The
Health Consequences

of SMOKING
1975

U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
Center for Disease Control
Atlanta, Georgia 30333
July 23, 1975

Honorable Carl Albert
Speaker of the House of Representatives
Washington, D.C, 20515

Dear Mr. Speaker:

As required by Section 8(a) of the Public Health Cigarette Smoking Act of 1969,
enclosed is the 1975 report on the health consequences of smoking. The recent
scientific information reviewed in the report reaffirms the previous evidence that
cigarette smoking is a serious public health problem. It is a major contributor to
the development of cardiovascular disease, various types of cancer, and
respiratory disease. Its toll in illness and premature death is needless and
preventable. The recent literature further refines our understanding of the
mechanisms by which smoking influences these disease states.

Under this Act, I am also required to submit to you such recommendations for
legislation as I deem appropriate. This Department has previously taken a
position in support of legislation which would authorize the regulation of
cigarettes through the power to ban the manufacture and sale of cigarettes
exceeding what are considered excessively hazardous levels of tar, nicotine,
carbon monoxide, and other ingredients shown to be injurious to health. The
extent to which the cigarette smoking public has over the years spontaneously
moved towards this kind of self protection suggests that it would welcome the
additional protection such legislation would bring. This Department, therefore,
recommends to the Congress that it consider legislation providing this
Department or some other appropriate agency with the authority to set
maximum permissible levels of hazardous ingredients in cigarettes.

With kindest regards.

Sincerely,

Caspar W. Weinberger
Secretary

Enclosure

 

For sale by the Superintendent of Documents, U.S. Government Printing
Office, Washington, D.C. 20402 -
PREFACE

Each year the Public Health Service reviews the scientific data
related to the health consequences of smoking and submits its review
to the Congress. This report, the ninth in the series, summarizes
recent research in four major areas: cardiovascular disease, cancer,
respiratory disease, and the effects of smoking on the nonsmoker
who shares the environment of those who smoke.

As has been the case with each of the previous reports in the
series, the research summarized herein further confirms the relation-
ships between cigarette smoking and disease and premature death
and refines our understanding of the mechanisms underlying these
relationships.

Cigarette smoking remains the largest single unnecessary and
preventable cause of illness and early death. In the eleven years since
the report of the Advisory Committee to the Surgeon General in
1964, there has been progress toward reducing this toll. Millions of
Americans have stopped smoking cigarettes, and millions more have
not taken up smoking. Even for those who continue to smoke, there
has been a striking reduction in the “‘tar” and nicotine content of
cigarettes used by the vast majority. At the same time, however.
counter-balancing these gains, there has been an increase in cigarette
smoking by women and young people, especially teen-age girls.

To eliminate the needless death and disability attributable to
cigarette smoking, the Public Health Service remains committed
today, as in the past, to increasing the knowledge about the health
consequences of smoking and to educating the American people as to
the nature and extent of the hazards of smoking. This is a task, not
for government alone, but for the great institutions of society as a
whole — the family, the schools, the health care system. Through
concerted effort, a climate of respect for our own health and that of
others can be created. Such a climate must certainly be conducive to
reducing and eventually eliminating the needless burden of disease
and premature death imposed by cigarette smoking.

‘ i ? host / rte. __
heodore abe

Assistant Secretary for Health

June 1975

iil
TABLE OF CONTENTS

 

Page
Preface 2.0... ee iii
Table of Contents .......02000 0000000000 ee ee v
Preparation of the Report and Acknowledgments ................ vii
INTRODUCTION: Overview — The Health Consequences of
Smoking «2.2.0... 2.2 eee 1
CHAPTER 1. Cardiovascular Diseases 5.2.2... eee 9
CHAPTER 2. Cancer 2... ee 39
CHAPTER 3. Non-Neoplastic Bronchopulmonary Diseases ...... 57
CHAPTER 4. Involuntary Smoking ..................-04. 83
Index 1975 0... ee eee 113
Index (Cumulative 1964-1975) 2.002. ee ee 118
PREPARATION OF THE REPORT
AND ACKNOWLEDGMENTS

Previous Reports

Reviews of the scientific evidence linking smoking to health
effects began in 1964 with Smoking and Health, Report of the
Advisory Committee to the Surgeon General of the Public Health
Service or as subsequently referred to “the Surgeon General’s
Report.” After this report, Public Law 89-92 was passed requiring
supplemental reports to Congress on this subject. In compliance,
three reports were submitted:

|. The Health Consequences of Smoking, A Public Health
Service Review: 1967.

bh

_ The Health Consequences of Smoking, 1968 Supplement
to the 1967 PHS Review.

ioe)

. The Health Consequences of Smoking, 1969 Supplement
to the 1967 PHS Review.

In April 1970, Public Law 91-222 amended the previous law
and called for an updated report on the health effects of smoking no
later than January 1, 1971, with annual reports thereafter. The
Health Consequences of Smoking, A Report of the Surgeon General:
/97], a comprehensive review of all the scientific literature available
to the National Clearinghouse for Smoking and Health and with
emphasis on the most recent additions to the literature. was that
updated report. Since then, the following annual reports on the
health consequences of smoking have been submitted:

1. The Health Consequences of Smoking, A Report of the
Surgeon General, 1972.

bo

. The Health Consequences of Smoking, 1973.
3. The Health Consequences of Smoking, 1974.

Each report since the original “Surgeon General's Report” has
reviewed the scientific literature relevant to the association between

Vil
smoking and cardiovascular diseases, non-neoplastic broncho-
pulmonary diseases, and cancer. Smoking as related to the following
diseases and conditons has been reviewed periodically in the reports:

Pregnancy (1967, 1969, 1971, 1972, 1973)

Peptic Ulcer Disease (1967, 1971, 1972, 1973)

Noncancerous Oral Disease (1969)

Tobacco Amblyopia (1971)

Allergy (1972)

Public Exposure to Air Pollution From Tobacco Smoke
(1972)

Harmful Constituents of Cigarette Smoke (1972)

Pipe and Cigar Smoking (1973)

Exercise Tolerance (1973)

The 1975 Report

The present document, The Health Consequences of Smoking,
1975, begins with an overview of the health consequences of
smoking and contains the current data on relationships between
smoking and cardiovascular diseases, non-neoplastic broncho-
pulmonary diseases, and cancer. A fourth chapter, “Involuntary
Smoking,” reviews the effects to nonsmokers of exposure to
smoke-filled environments. Although emphasis is on the latest
additions to the literature, where necessary to provide the back-
ground or framework, research from earlier years is included.

This report was prepared by the staff of the National
Clearinghouse for Smoking and Health in the following way:

1. The Technical Information Center of the Clearinghouse
continually monitors and collects the scientific literature on
the health consequences of smoking through several estab-
lished mechanisms:

a. An information science corporation is on contract to
extract articles on smoking and health from the scientific
literature of the world.

b. The National Library of Medicine, through the MEDLARS
system, provides a monthly listing of articles on smoking
and health. Articles not provided by the information
science corporation are ordered.

Viil
c. Staff members review current medical literature and
identify pertinent articles.

) The literature was reviewed by the Medical Staff Director
who wrote first drafts for this report. These drafts were sent
to reviewers for criticism and comment regarding the format.
the appropriateness of the articles selected for discussion, and
the conclusions. The final drafts of the total report were
reviewed by the Director of the National Clearinghouse for
Smoking and Health, the Director of the National Cancer
Institute. the Director of the National Institute of Environ-
mental Health Sciences, the Director of the National Heart
and Lung Institute, and by additional experts both inside and
outside the Public Health Service.

ACKNOWLEDGEMENTS

The National Clearinghouse for Smoking and Health, Daniel
Horn. Ph.D., Director, and Charles A. Althafer, Acting Director, are
responsible for the preparation of this report. Medical Staff Director
for the report was David M. Burns. M.D. Consulting editors were
Elvin E. Adams, M.D., Daniel P. Asnes, M.D., John il. Holbrook,
M.D., Paul Schneiderman, M.D.. and H. Stephen Williams, M.D.
Technical Editor was Priscilla B. Holman, and Technical Information
Officer responsible for the literature collection was Donald R.
Shopland.

The professional staff has had the assistance and advice of the
following experts in the scientific and technical fields whose
contributions are gratefully acknowledged.

Reviewers

ANDERSON, Wilham H.. M.D. - Chief. Section of Respiratory and Environmental
Medicine, University of Louisville. Louisville. Ky.

AUERBACH, Oscar. M.D. — Senior Medical Investigator, Veterans Administration Hospital,
East Orange, N.J.

BOCK. Fred G., Ph.D. - Director, Orchard Park Laboratories. Roswell Park Memorial
Institute, Orchard Park, N.Y.

BOREN, Hollis G.. M.D. Assistant Director of the Medical Center and Associate Dean of
the College of Medicine, University of South Florida. Tampa. Fla.
FALK, Hans L., Ph.D. - Associate Director for Program, National Institute of Environ-
mental Health Sciences, Research Triangle Park, N.C.

FERRIS, Benjamin G., Jr., M.D. — Professor of Environmental Health and Safety, School of
Public Health, Harvard University, Boston, Mass.

GOLDSMITH, John R., M.D. — Medical Epidemiologist, Epidemiological Studies Labora-
tory, California State Department of Health, Berkeley, Calif.

GORI, Gio B., Ph.D. — Deputy Director, Division of Cancer Cause and Prevention, National
Cancer Institute, National Institutes of Health, Bethesda, Md.

HARKE, H.-P., Ph.D., — Forschunginstitut der Cigarettenindustrie, e.V., Hamburg,
Germany.

HIGGINS, Ian T. T., M.D. — Professor of Epidemiology, School of Public Health, University
of Michigan, Ann Arbor, Mich.

HOFFMANN, Dietrich, Ph.D. — Member, and Chief, Division of Environmental Carcino-
genesis, Naylor Dana Institute for Disease Prevention, American Health Foundation,
Valhalla, N.Y.

KELLER, Andrew Z., D.M.D. — Chiet, Research in Geographic Epidemiology Medical
Research Service, Veterans Administration Central Office, Washington, D.C.

KRUMHOLZ, Richard A.. M.D. — Medical Director, Institute of Respiratory Diseases,
Kettering Medical Center, Kettering, Ohio.

LENFANT, Claude J. M.. M.D. — Associate Director for Lung Programs, National Heart and
Lung Institute, National Institutes of Health, Bethesda, Md.

MacMAHON, Brian, M.D. — Professor, Department of Epidemiology, School of Public
Health, Harvard University, Boston, Mass.

McMILLAN, Gardner, C., M.D. — Associate Director for Etiology of Arteriosclerosis and
Hypertension, National Heart and Lung Institute, National Institutes of Health,
Bethesda, Md.

NETTESHEIM, Paul, M.D. — Group Leader, Respiratory Carcinogenesis Group, Biology
Division, Oak Ridge National Laboratory, Oak Ridge, Tenn.

PAFFENBARGER, Ralph S., Jr.. M.D. — Epidemiologist, Resource for Cancer Epidemi-
ology, California State Department of Health, Berkeley, Calif.

PETTY, Thomas L., M.D. — Professor of Medicine and Head, Division of Pulmonary
Diseases, University of Colorado Medical Center, Denver, Colo.

RALL, David P., M.D. — Director, National Institute of Environmental Health Sciences,
National Institutes of Health, Research Triangle Park, N.C.

RAUSCHER, Frank J., M.D. -- Director, National Cancer Institute, National Institutes of
Health, Bethesda, Md.

RENZETTI, Attilio D., Jr.. M.D. -— Professor of Medicine and Head, Pulmonary Disease
Division, University of Utah Medical Center, Salt Lake City, Utah.

RINGLER, Robert L., Ph.D. — Acting Director, National Heart and Lung Institute, National
Institutes of Health, Bethesda, Md.

SAFFIOTTI, Umberto, M.D. - Associate Director for Carcinogenesis, National Cancer
Institute. National Institutes of Health, Bethesda, Md.
SCHMELTZ, Irwin, Ph.D. — Associate Member and Head, Section of Bio-organic Chemistry,
Division of Environmental Carcinogenesis, Naylor Dana Institute for Disease
Prevention, American Health Foundation, Valhalla, N.Y.

SCHUMAN, Leonard M., M.D. — Professor and Director, Division of Epidemiology, School
of Public Health, University of Minnesota, Minneapolis, Minn.

SHIMKIN, Michael B., M.D. — Professor of Community Medicine and Oncology, School of
Medicine, University of California, La Jolla, Calif.

WYNDER, Ernst L., M.D. — President and Medical Director, American Health Foundation,
Valhalla, N.Y.

Special assistance for the Cardiovascular Chapter was provided by:

JENNINGS, Michael, M.D. — Epidemic Intelligence Service Officer, CDC, located at Ohio
Department of Health, Columbus, Ohio, and

MANNING, Kathleen, M., R.N. — Department of Staff Development, Boston City Hospital,
Boston, Mass.

The following staff members of the Center for Disease Control also contributed to
the preparation of this report: Bureau of Training — Julia M. Fuller, Winthrop N. Davey,
M.D., and Seth N. Leibler, Ed.D.; National Clearinghouse for Smoking and Health — Nancy
M. Johnston and Sanda Lager.

x}
INTRODUCTION
Overview — The Health Consequences of Smoking_
OVERVIEW — HEALTH CONSEQUENCES OF SMOKING

The statement, ‘Warning: The Surgeon General Has Determined
That Cigarette Smoking Is Dangerous to Your Health,’ has been
required by law on cigarette packaging since 1970 as a part of the
Public Health Cigarette Smoking Act of 1969. This Act was a
response by the U.S. Congress to the scientific information on the
health consequences of cigarette smoking summarized in reports then
available (the Surgeon General’s Report of 1964 and the subsequent
1967, 1968, and 1969 PHS Health Consequences of Smoking). This
Act was passed because a series of important questions concerning
cigarette smoking and health had been answered.

The following discussion summarizes the basic questions, the
methodology used to determine the answers, and the answers
themselves.

The initial question to be answered concerning the health
consequences of smoking was ‘“‘Are there any harmful health effects
of smoking cigarettes?’’ The answer to this question was provided in
two ways. First, it was demonstrated that some diseases occurred
more frequently in smokers than in nonsmokers. Second, a causal
relationship was established between smoking and these diseases.

Concern about the possible health effects of smoking started
When scientists began looking for an explanation to account for the
Tapidly increasing death rate from lung cancer. The early retrospec-
tive studies showed a link between fung cancer and smoking. The
first Prospective studies, however, found that only one-eighth of the
€xcess overall mortality found among smokers could be accounted
for by lung cancer; the rest was largely due to coronary heart disease,
chronic respiratory disease, and other forms of cancer. They also
found that the effect on overall mortality was largely confined to
“igarette smokers rather than the users of other forms of tobacco.

_ However, demonstrating an association by statistical probability
's not enough to establish the causal nature of a relationship.
Determining that the association between smoking and excess death
Tates is cause and effect was a judgment made after a number of
‘teria had been met, no one of which by itself is sufficient to make
this judgment. These criteria as listed in the Surgeon General’s
Advisory Committee Report (1964) were the consistency, strength, -
specificity, temporal relationship, and coherence of the association.

In addition, convincing theories about the mechanisms whereby
smoking contributes to the various diseases responsible for the excess -
mortality among cigarette smokers were developed from the evidence
on the biochemical, cytologic, pathologic, and pathophysiologic
effects of cigarette smoking, thereby providing the necessary support
for the decision that the relationship was causal.

The most important specific health consequence of cigarette
smoking in terms of the number of people affected is the
development of premature coronary heart disease (CHD). Both -
prospective and retrospective studies clearly established that cigarette
smokers have a greater risk of death due to CHD and have a higher
prevalence of CHD than nonsmokers. Long-term followup of healthy
populations has confirmed that a cigarette smoker is more likely to
have a myocardial infarction and to die from CHD than a
nonsmoker. Cigarette smoking has been shown to be one of the
major independent CHD risk factors and to act in combination with
other major alterable CHD risk factors (high blood pressure and
elevated serum cholesterol). Autopsy studies have shown that
persons who smoked cigarettes have more severe coronary athero-
sclerosis than persons who did not smoke. Physiologic studies and
animal experiments have indicated several mechanisms whereby these
effects can take place.

A second major health consequence of smoking is the develop-
ment of cancer in smokers. Cigarette smoking was firmly established
as the major risk factor in lung cancer. The risk of developing lung
cancer was found to be 10 times greater for cigarette smokers than
for nonsmokers. The risk of developing lung cancer increases with
the number of cigarettes smoked per day and is greater in cigarette
smokers who report inhaling, who started smoking at an early age, or
who have smoked for a greater number of years. Smokers of filter
cigarettes have been shown to have a lower risk of developing lung
cancer than smokers of nonfilter cigarettes, but the risk remains well
above that for nonsmokers. The risk of developing cancer of the
larynx, pharynx, oral cavity, esophagus, pancreas, and urinary
bladder was also found to be significantly higher in cigarette smokers
than in nonsmokers. Pipe and cigar smokers were found to have
elevated risks for the development of cancer of the oral cavity,
pharynx, larynx, and esophagus when compared to nonsmokers.
Fewer pipe and cigar smokers than cigarette smokers report that they
inhale. As a result lungs of pipe and cigar smokers receive much less

4
exposure to smoke than the lungs of cigarette smokers. This is
probably the primary reason for the lower incidence of cancer of the
lung for pipe and cigar smokers compared to cigarette smokers.

Women have had far lower rates of lung cancer than men. This
has been attributed to the fact that fewer women than men smoke
and the fact that women smokers generally select filter and low tar
and nicotine cigarettes. However, the percentage of women smokers
in the United States has increased steadily in the last 30 years, and
since 1955 the death rates from lung cancer in women have increased
proportionately more rapidly than the rates for men, reflecting this
increased proportion of women smokers.

The tar from cigarette smoke has been found to induce
malignant changes in the skin and respiratory tract of experimental
animals, and a number of specific chemical compounds contained in
cigarette smoke were established as potent carcinogens or co-carcino-
gens. Malignant changes including carcinoma in situ were found in
the larynx and in the sputum exfoliative cytology of experimental
animals exposed to cigarette smoke.

Nonmalignant respiratory disease is a third area of smoking-
induced morbidity and mortality. Cigarette smokers have been
shown to have more frequent minor respiratory infections, miss more
days from work due to respiratory illness, and report symptoms of
cough and sputum production more frequently than nonsmokers.
Retrospective and prospective studies with long-term followup have
found that cigarette smoking is the primary factor in the develop-
ment of chronic bronchitis and emphysema in the United States.
Cigarette smokers have also been found to be more likely to have
abnormalities of pulmonary function and have higher death rates
from respiratory diseases than nonsmokers. Data from autopsy
studies have shown that cigarette smokers were more likely to have
the macroscopic changes of emphysema, and that these changes are
closely related to the number of cigarettes smoked per day. Mucous
cell hyperplasia has been found more often in cigarette smokers.
Cigarette smoke also inhibits the ciliary motion responsible for
cleansing the respiratory tract.

An additional area of health concern has been the effect of
cigarette smoking during pregnancy. Mothers who smoke cigarettes
during the last two trimesters of their pregnancy have been found to
have babies with a lower average birth weight than nonsmoking
mothers. In addition cigarette smoking mothers had a higher risk of
having a stillborn child, and their infants had higher late fetal and
neonatal death rates. There are some data to show that these risks
due to cigarette smoking are even greater in women who have a high
risk pregnancy for other reasons. These effects may occur because
carbon monoxide passes freely across the placenta and is readily
bound by fetal hemoglobin, thereby decreasing the oxygen carrying
capacity of fetal blood.

Having established that cigarette smoking is a significant causal
factor in a number of serious disease processes, two additional
questions became important. They are “Can the health consequences
to the individual be averted by stopping smoking or by changing the
cigarette,’’ and “What are the overall public health consequences of
cessation and of the changes made in cigarettes?”

The first question is the simpler of the two to answer. In the
individual, cessation of cigarette smoking results in a rapid decline of
the carbon monoxide level in the blood over the first 12 hours.
Symptoms of cough, sputum production, and shortness of breath
usually improve over the next few weeks. A woman who stops
smoking by the fourth month of her pregnancy has no increased risk
of stillbirth or perinatal death in her infant related to smoking. The
deterioration in pulmonary function tests that occurs in some
smokers becomes less rapid than that of continuing smokers. The
death rates from ischemic heart disease, chronic bronchitis, and
emphysema also become less than those of the continuing smoker.
The risk of developing cancer of the lung, larynx, and oral cavity
declines relative to the continuing smoker in the first few years after
cessation and 10 to 15 years after stopping smoking approximates
that of nonsmokers. A smoker who switches to filter cigarettes and
has smoked them for 10 years or longer has a lower risk of
developing lung cancer than a smoker who continues to smoke
nonfilter cigarettes. The risk to a filter cigarette smoker, however,
still remains well above that of a nonsmoker.

The public health benefits of cessation are more difficult to
determine than the effects of cessation on the individual. Just as
cause-specific death rates have reflected the effect of cigarette
smoking on certain diseases, they should also reflect any substantial
benefits to be gained by cessation or reduction in cigarette smoking.
Several factors combined to produce a reduction in per capita dosage
of tobacco exposure in the United States for the years 1966-1970.
First, per capita consumption of cigarettes declined from 4,287
cigarettes per person in 1966 to 3,985 in 1970. Second, during this
period there was a slow but significant decrease in the average tar and
nicotine content of cigarettes as well as a decrease in the amount of

6
tobacco contained in the average cigarette. The decline in per capita
consumption during those years occurred in the face of a substantial
increase in the proportion of young women becoming smokers as
compared to women of previous generations and so reflected
predominantly a decrease in cigarette consumption by men.

Since 1970, although the per capita consumption of cigarettes
has increased, the average levels of tar and nicotine have continued to
decline, making it more difficult to predict what has happened to per
capita dosage.

Examination of cause-specific death rates for the period of this
declining per capita consumption reveals that there was a downturn
in the male death rate from ischemic heart disease beginning in 1966
which reversed the upward trend that had occurred over the previous
two decades. This decline in the death rate from ischemic heart
disease has not occurred in women.

The male death rate from chronic bronchitis has also been
declining since 1967, and the male death rate for emphysema has
declined since 1968 when it was first recorded as a separate category.
Female death rates for these two diseases have not shown these
trends.

Despite the impressive coincidences of the decline in death rates
among males occurring at the same time that there was a decline in
per capita cigarette consumption, it is impossible to be certain of the
exact cause of the decline in the death rates. These diseases are
influenced by a variety of factors in addition to cigarette smoking
such as blood pressure and air pollution. Some of these factors have
also been subject to major control efforts which may have
contributed to the decline in the death rates. In addition, there have
been therapeutic advances in the treatment of these problems which
may also have helped lower the death rates.

A decline in male death rates from lung cancer should also
follow the decline in per capita consumption. This rate would not be
influenced as much by changes in other etiologic factors or changes in
therapy because cigarette smoking causes from 85 to 90 percent of
all lung cancer and there have been no major improvments in survival
due to changes in therapy. With lung cancer, however, two
additional considerations must be kept in mind. A decline in death
fates from lung cancer would be expected to lag several years behind
a decline in per capita consumption. In addition, the decline in
Consumption and switch to low tar and nicotine cigarettes occurred
predominantly in the younger age groups where death rates from
lung cancer are low. For these reasons, it is necessary to look at lung
cancer death rates by age group rather than total lung cancer death
rates. The lung cancer rates by age groups for 1971 suggest a decline
in the lung cancer rates for the younger males (under 45), but the
confidence limits on these trends at present remain wide enough
that it is impossible to say whether this is a real decline or merely
a leveling off. The national health statistics broken down by 5-year
age groups are currently available only through 1971. The data by
age group from a few more years will be necessary to determine
whether the changes in smoking behavior which have taken place
have reversed the trend of the preceding 40 years of continually
increasing lung cancer rates in men. In 1971, the last year for
which detailed mortality statistics are available, the accumulated
exposure to cigarettes reached its peak among men born between
1915 and 1919, a group then in their early 50’s. Cumulative
exposure has continued to decline with each successive 5-year birth
cohort born since then. The trends of the last few years offer some
hope that the peak of the “lung cancer epidemic,” as some have
termed this phenomenon, may have been reached with this group
and that future years will show a slow but consistent decline.
CHAPTER 1
Cardiovascular Diseases
CHAPTER 1
Cardiovascular Diseases

 

CONTENTS
Page
Coronary Heart Disease (CHD) ............0... 0.0. cece ueeeuee 13
Introduction... 2.2... ee eee 13
Cigarette Smoking as a Major Risk Factor for
Coronary Heart Disease... 0... .00.0000 000000. e eee 14
Cigarette Smoking in Relation to Other Risk
Factors for Coronary Heart Disease ................... 15
Hypertension ...........0.....000.0.0.0- 0s eee 15
Coffee Drinking ..............0.0.0...0.00000. 19
Ventricular Premature Beats .................... 20
Carbon Monoxide ........0.000 000000 cece cece cent eas 20
Introduction... 2... ce eee 20
Sources of Carbon Monoxide Exposure and
Human Absorption ............. 000000 c eee 21
Effects on Healthy Individuals ...................... 26
Effects on Persons With Atherosclerotic
Cardiovascular Disease. ........20.0..0.0.0...00- 27
Studies on the Pathogenesis of Cardiovascular
Disease... ee ene 28
Nicotine 2... ee eee nena 29
Acrolein 2.0... eee een ne eas 29
Cerebrovascular Disease... 2... 20 eee eee 29
Effects of Smoking on the Coagulation System ................... 32
Summary of Recent Cardiovascular Findings ..................... 33

Bibliography . 2.2... cee ee een nee 34
List of Tables

Table 1. — Age-standardized blood pressure changes (mm Hg)
at followup for continuing cigarette smokers and

quitters according to weight changes ...............04.

Table 2. — Number of subjects who had developed hypertension
at followup for continuing cigarette smokers and
quitters

Table 3. — Mean percent of carboxyhemoglobin saturation in
smokers and nonsmokers by sex and race

Table 4. — Mean percent of carboxyhemoglobin saturation in
smokers and nonsmokers by employment status

Table 5. — Median percent carboxyhemoglobin (COHb) saturation
and 90 percent range for smokers and nonsmokers by
location

Table 6. — Mean percent carboxyhemoglobin (COHb) saturation
in cigarette smokers 1 hour after last cigarette

Table 7. — Age-standardized death rates and mortality ratios
for cerebral vascular lesions for men and women by type
of smoking (lifetime history) and age at start of
study

Page
CORONARY HEART DISEASE (CHD)

Introduction

Coronary Heart Disease (CHD) is the most frequent cause of
death in the United States and is the most important single cause of
excess mortality among cigarette smokers. The evidence relating
smoking to CHD has been reviewed in previous reports on the health
consequences of smoking (6/, 62, 63, 64, 65, 66, 67, 68). The
following is a brief summary of the relationships between smoking
and CHD presented in these reports.

Cigarette smoking, hypertension, and elevated serum cholesterol
are the major alterable risk factors for myocardial infarction and
death from CHD. Cigarette smoking acts both independently as a risk
factor and synergistically with the other CHD risk factors. The
magnitude of the risk increases directly with the amount smoked.
The excess risk of CHD among smokers has been demonstrated in
some Asian, Black, and Caucasian populations and is proportionately
greater for younger men, especially those below age 50. Cessation of
cigarette smoking results in a reduced mortality rate from CHD
compared with the mortality rate for those who continue to smoke.

Pipe and cigar smokers have a slightly higher risk of death from
CHD than nonsmokers, but they incur a much lower risk than ciga-
rette smokers. This has been attributed to the lower levels of inhala-
tion that characterize most pipe and cigar smoking.

Data from autopsy studies have shown coronary atherosclerosis
to be more frequent and more extensive in cigarette smokers than in
nonsmokers, and experimental work in humans and animals has
Suggested several mechanisms by which smoking may influence the
development of atherosclerosis and CHD. The formation of carboxy-
hemoglobin, release of catecholamines, creation of an imbalance
between myocardial oxygen supply and demand, and increased
platelet adhesiveness leading to thrombus formation have all been
demonstrated in smokers and proposed as explanations for the excess
CHD mortality and morbidity among smokers.

13
Cigarette Smoking as a Major Risk Factor
for Coronary Heart Disease

The evidence establishing smoking as a major risk factor in CHD
has been reviewed in previous reports (6/, 62, 63, 64, 65, 66, 67,
68). During the last year new epidemiologic data have been published
on the relationship between coronary artery disease and smoking.

Bengtsson (9, /0) studied the smoking habits of women with
myocardial infarction (MI) in Goteborg, Sweden. He found that
smoking was significantly more common in a group of 46 women (80
percent smokers), ages 50-54, who had a myocardial infarction than
in a control group of 578 healthy nonhospitalized women (37.2
percent smokers).

Other investigators examined the effect of cigarette smoking on
survival of people with acute myocardial infarction. In a study of
400 patients with documented myocardial infarction who survived to
be admitted to a coronary care unit, Helmers (26, 27, 28) found no
significant difference between the percentages of smokers and
nonsmokers among survivors studied after the first 24 hours, from 2
days until discharge, and from discharge to 3 years. Reynertson and
Tzagournis (52), in a 5-year prospective study of 137 patients with
documented CHD at age 50 or less, were also unable to find any
relationship between CHD mortality rates and smoking habits.
Smoking habits after entrance into the study were also considered
and again no difference in mortality rates was found.

The Coronary Drug Project (/7) found an effect of cigarette
smoking on mortality after myocardial infarction. This group studied
2,789 men ages 30-64 years for 3 years after myocardial infarction
and found a statistically significant correlation between cigarette
smoking determined 3 months after a myocardial infarction and
mortality (t-value of 2.94). None of these studies (17, 26, 27, 28, 52)
were able to examine the smoking habits of the group of people who
die suddenly as a first manifestation of CHD, and therefore may have
excluded that group in which there is the highest excess mortality
due to cigarette smoking (3/).

Additional data from the Swedish twin study of Friberg, et al.
(23) have been reported. They found an excess CHD mortality
among smokers in dizygotic twins with different degrees of smoking,
but no similar excess in monozygotic twins. Although the numbers
were too small to be significant, the authors suggest that this tends to
support the theory that both smoking and CHD are constitutionally

14
determined. These data must be viewed with caution, however, since
the difference was demonstrable only in the older age group (born
1901 - 1910). When the younger age group (born 1911 - 1925) was
considered, no excess CHD mortality was seen in the dizygotic group
but a small excess was noted in the monozygotic group (three CHD
deaths in the high smoking group and one in the low smoking group).
Also the difference in cigarette consumption between the high and
low smoking groups was relatively small (seven cigarettes per day).
Consequently, data from this study are not sufficient to warrant the
conclusion that both smoking and excess CHD mortality are
constitutionally determined rather than smoking being a cause of the
excess CHD mortality.

Cigarette Smoking in Relation to Other Risk Factors
for Coronary Heart Disease

Cigarette smoking, elevated serum cholesterol, and elevated
blood pressure are generally accepted as the three major modifiable
risk factors for CHD. However, there is less agreement concerning
other CHD risk factors — obesity, physical inactivity, diabetes
mellitus, elevated resting heart rate, psychologic type A behavior,
etc. The following studies present recent evidence on the relation-
ships between smoking and hypertension, coffee drinking, and
ventricular premature beats.

Hypertension

Results from several studies have shown that smokers on the
average have slightly lower blood pressure than nonsmokers. Some
investigators have attributed this finding to the fact that smokers on
the average weigh slightly less than nonsmokers. Three current
studies (24, 36, 55) discuss this relationship. Gyntelberg and Meyer
(24), based on their evaluation of 5,249 men ages 40-59, were of the
opinion that lower blood pressure in smokers could not be accounted
for by differences in weight, age, or physical fitness. Kesteloot and
Van Houte (36), in a study of 42,804 men, performed a multiple
regression analysis on age, weight, and height and found that
cigarette smokers had lower blood pressure than nonsmokers;
however, when they included serum cholesterol values in the
analysis, the difference in blood pressure was reduced to approxi-
mately | mm Hg. Although this difference was statistically signifi-
cant based on the large population, the actual difference in blood
pressure was too small to be of clinical importance.

15
Seltzer (55) studied 794 men selected for their initial good
health and normal blood pressure (below 140 systolic and 90
diastolic) and followed them for changes in cigarette smoking habits,
weight, and blood pressure. During the 5-year period of the study
104 men gave up smoking. For every age group except those over 55,
there was a significantly greater weight gain (8 lb) among the
“quitters” than among the continuing smokers (3.5 Ib). Blood
pressure increased 4 mm Hg systolic and 2.5 mm Hg diastolic in the
quitters with no change in systolic and a slight reduction in diastolic
(-1.1 mm Hg) in persons who continued to smoke. In order to
examine blood pressure changes in relation to weight change, both
continuing smokers and quitters were grouped according to their
weight changes during the period of study (Table 1). The most
significant finding was an increase in the systolic blood pressure
(+1.77 mm Hg) among the quitters even in that group with significant
weight loss. In contrast, the continuing smokers with significant
weight loss had a decline in systolic blood pressure (-3.28 mm Hg).
Diastolic blood pressure in quitters showed an increase with weight
gain and no change with weight loss, while continuing smokers
showed a decrease in diastolic pressure with weight loss and no
change with weight gain. The data on subjects whose blood pressure
had increased to hypertensive levels (systolic > 150 and diastolic >
95) were evaluated, and it was found that quitters had a much higher
frequency of becoming hypertensive than continuing smokers (Table
2).

Seltzer, in interpreting these data, suggested that cigarette
smoking tends to inhibit blood pressure increases, with only minimal
pressure rises occurring even in instances of substantial weight gain.
When this inhibiting effect of cigarette smoking is removed as in the
case of the quitters, sharp rises in blood pressure become evident. He
cautioned, however, that the development of hypertension in some
quitters may have been responsible for decisions to lose weight and
that his data do not allow an evaluation of the degree of blood
pressure changes according to how recently cigarettes were given up.

The results of the ischemic heart disease study by Kahn, et al.
(34) raise additional questions about Seltzer’s data. Kahn followed
10,000 Israeli male civil service employees for 5 years to determine
what factors were associated with an increased incidence of
hypertension. He presented no data concerning persons who stopped
smoking, but he did show that the incidence of hypertension
increased with age and that the age-adjusted incidence of hyper-
tension in smokers was over twice that of nonsmokers (76.9/ 1000
for smokers versus 35.4/1000 for nonsmokers). Seltzer reported no

16
Li

TABLE 1. — Age-standardized blood pressure changes (mm Hg)! at followup for
continuing cigarette smokers and quitters according to weight changes

 

 

 

 

 

 

 

 

Weight Change (LB)
Significant No Significant Moderate Significant
Smoking Class Wt Loss Wt Change Wt Gain Wt Gain
Ib lb Ib Ib
No. -25 to -5 No. -4to+4 No. +5 to +12 No. +13 to +30
Mean systolic BP changes:
Continuing smokers 32 —4,00 84 —1.52 71 2.85 24 1.50
Quitters 13 1.77 27 2.22 27 4.04 32 3.69
Mean diastolic BP changes:
Continuing smokers 32 —3.28 84 ~2.04 71 0.73 24 --0.04
Quitters 13 —0.31 27 —1.96 27 4.30 32 3.94

 

 

 

 

 

' Standardized on basis of age distribution of current cigarette smokers.

Source: Seltzer, C.C. (55).
sl

TABLE 2. — Number of subjects who had developed hypertension at

followup for continuing cigarette smokers and quitters

 

 

 

Blood pressure Continuing cigarette smokers Quitters
levels
Number Percent Number Percent
Systolic blood pressure 150+ 6 2.8 9 8.7
Systolic blood pressure 160+ 2 0.9 5 4.8
Diastolic blood pressure 95+ 3 1.4 5 4.8

 

 

 

Source: Seltzer, C.C. (55).
data on the incidence of hypertension in nonsmokers, and the age
distribution for his group of smokers (the original source of the
quitters) is heavily weighted toward younger age groups (with only
33 of 214 men age 50 years or over). According to Kahn’s data, this
age group would be expected to have a lower incidence of
hypertension, and, in fact, Seltzer found only small numbers of men
who developed hypertension (eight with diastolic hypertension)
(Table 2). Making interpretations based on such small numbers is
hazardous; for example, the difference between current smokers and
quitters in the incidence of diastolic hypertension could have been
produced by only three men quitting smoking because they
developed hypertension.

Coffee Drinking

The Boston Collaborative Drug Study (/ 2) recently reported a
correlation between coffee drinking (> 6 cups per day) and
myocardial infarction that persisted after controlling for the effect of
cigarette smoking. This was a retrospective study of 276 patients
with a hospital discharge diagnosis of myocardial infarction and
1,104 age, sex, and hospital-matched controls discharged with other
diagnoses. In addition to the usual limitations of retrospective
studies, this study has several characteristics that make interpretation
difficult. In controlling for the effect of cigarette smoking, the
investigators divided the smokers into those who smoked one pack or
less per day and those who smoked more than one pack per day.
Because cigarette consumption is highly correlated with coffee
consumption (29, 39), it can be expected that within such broad
smoking categories those who were heavy coffee drinkers tended to
be heavier smokers than those who consumed smaller amounts of
coffee. It is also possible that the hospitalized controls represented
persons who drank less coffee than the general population because of
serious chronic illnesses. These characteristics of the study design do
not allow firm conclusions to be made concerning the extent to
which the relationship between coffee drinking and myocardial
infarction is independent of the relationship of both variables to
cigarette smoking.

The question of the independent nature of this relationship is
also dealt with in a prospective study by Klatsky, et al. (39) of 464
Patients with myocardial infarction who previously had had multi-
phasic health checkups. Both ordinary controls and CHD risk
factor-matched controls were drawn from 250,000 people who had
undergone the same multiphasic health checkups. The investigators
did not find an independent correlation between coffee drinking and
myocardial infarction when risk-matched controls were used.

19
The Framingham Study (/8) recently published data on coffee
drinking based on a 12-year followup of 5,209 men and women ages
30-62. An increased risk of death from all causes was demonstrated in
coffee drinkers, but this relationship was accounted for by the associ-
ation between coffee consumption and cigarette smoking. No
association between coffee drinking and myocardial infarction or
between coffee drinking and the development of CHD, stroke, or
intermittent claudication was demonstrated. Heyden, et al. (29) also
found no relationship between excessive coffee consumption (> 5
cups per day) and atherosclerotic vascular disease.

Ventricular Premature Beats

Ventricular premature beats have been shown to be a risk factor
for sudden death from CHD. Vedin, et al. (69), in a study of 793
men in Goteborg, Sweden, examined the frequency of rhythm and
conduction disturbances at rest and during exercise. They found no
statistically significant correlation between cigarette smoking habits
and the presence of supraventricular or ventricular premature beats
at rest or during exercise.

CARBON MONOXIDE

Introduction

Carbon monoxide has long been recognized as a dangerous gas,
but until recently concentrations which produced carboxyhemo-
globin levels below 15 to 20 percent were thought to have little
effect on humans. Currently there is considerable interest in
determining the effect of chronic exposure to low levels of carbon
monoxide (65, 66, 67, 68).

Carbon monoxide is present in concentrations of 1 to 5 percent
of the gaseous phase of cigarette smoke (//, 45). The concentration
varies with temperature of combustion as well as with factors which
control the oxygen supply such as the porosity of the paper and
packing of the tobacco. The amount of carbon monoxide produced
increases as the cigarette burns down. Carboxyhemoglobin levels in
smokers vary from 2 to 15 percent depending on the amount
smoked, degree of inhalation, and the time elapsed since smoking the
last cigarette.

Carbon monoxide, which has 230 times the affinity of oxygen
for hemoglobin, impairs oxygen transportation in at least two ways:

20
First, it competes with oxygen for hemoglobin binding sites. Second,
it increases the affinity of the remaining hemoglobin for oxygen,
thereby requiring a larger gradient in Poz between the blood and
tissue to deliver a given amount of oxygen; this increased gradient is
usually produced by a lowering of the tissue Poo.

Carbon monoxide also binds to other heme-containing pig-
ments, most notably myoglobin, for which it has even a greater
affinity than for hemoglobin under conditions of low Pox. The
significance of this binding is unclear, but may be important in
tissues, such as the heart muscle, which have both high oxygen
requirements and large amounts of myoglobin.

Sources of Carbon Monoxide Exposure and Human Absorption

Several researchers (13, 32, 35, 57, 60, 70) have estimated the
relative contribution of cigarette smoking and air pollution to the
human carbon monoxide burden as measured by carboxyhemoglobin
levels (COHb). Kahn, et al. (35), in a study of 16,649 biood donors,
determined that smoking was the most important contributing
factor, followed by industrial work exposure. Nonsmoking industrial
workers had COHb levels of 1.38 percent, and nonsmokers without
industrial exposure had levels of .78 percent. Cigarette smokers, on
the other hand, had very high levels. Smokers with industrial
exposure had levels of 5.01 percent, while smokers without industrial
exposure had levels of 4.44 percent (Tables 3 and 4). Stewart, et al.
(57) found similar results in a nationwide survey of blood donors and
noted marked variation in mean COHb levels in residents of different
cities measured at different times of the year (Table 5). However, in
all areas, smokers still had COHb levels two to three times higher
than nonsmokers and had increasing COHb levels with increasing
level of cigarette consumption (Table 6). Similar findings were
reported by Torbati, et al (60) in a study of 500 male Israeli blood
donors.

Nonsmoking workers exposed to automobile exhaust — London
taxi drivers (32) and garage and service station operators (/3) — have
higher baseline levels of carboxyhemoglobin than nonsmokers of the
general population. But even in these high exposure occupations
smokers have markedly higher COHb levels (8.1 and 10.8 percent)
than nonsmokers (6.3 and 5.5 percent). An extreme is represented
by New York City tunnel workers who are exposed to an average of
63 ppm CO with peak exposure levels as high as 217 ppm CO;
cigarette smokers still maintained much higher COHb levels (5.01
percent) than nonsmokers (2.93 percent) (8).

2]
cc

TABLE 3. — Mean percent of carboxyhemoglobin saturation in smokers and
nonsmokers by sex and race

 

 

 

 

 

 

 

Total Sample Nonsmokers Smokers!
No. X+Sz No. X+$5 No. X£Sz
Total Sample 16,649 2.30 £ 0.02 10,157 0.85 +0.01 6,492 4.58 £0.03
Male 10,542 2.66 + 0.03 §,888 1.00 + 0.01 4,654 4.76 £0.04
Female 6,107 1.68 + 0.03 4,269 0.64 +0.01 1,838 4.10 + 0.06
White 15,167 2.28 + 0.02 9,474 0.85 + 0.01 5,693 4.66 + 0.04
Male 9,669 2.65 + 0.03 5,508 1.00 + 0.01 4,161 4.83 + 0.04
Female 5,498 1.63 £0.03 3,966 0.64 + 0.01 1,532 4.19 + 0.06
Black 1,429 2.59 + 0.06 641 0.86 + 0.03 788 4.00 + 0.08
Male 829 2.91 £0.10 347 1.07 + 0.05 482 4.24+0.10
Female 600 2.15 + 0.09 294 0.62 + 0.04 306 3.63 + 0.12

 

 

Ismokers are defined as those who smoked on the day of giving blood.
NOTE. — X = mean percent; sy= standard error of mean percent.
Source: Kahn, A., et al. (35).
€C

TABLE 4. — Mean percent of carboxyhemoglobin saturation in smokers

and nonsmokers by employment status

 

 

 

 

Nonsmokers Smokers!
No. X +S; No. X tS;

Persons employed 8,478 0.89 + 0.01 $,962 4.61 £0.03

Classed as

industrial workers! 1,523 1.38 + 0.04 1,738 5.01 + 0.06

Classed as workers

other than industrial 6,955 0.78 £0.01 4,224 4.44 + 0.04
Persons not employed 1,678 0.63 + 0.02 $31 4.2440.11

 

 

 

ladustrial workers are employed in either durable or nondurable goods manufacturing (craftsmen, operatives, or laborers). Smokers

are defined as those who smoked on the day of giving blood.
NOTE. — X = mean percent; Sx = standard error of mean percent.

Source: Kahn, A., et al. (35).
TABLE 5. — Median percent carboxyhemoglobin (COHb) saturation and 90 percent
range for smokers and nonsmokers by location

 

 

 

Cigarette Smokers Nonsmokers
Location
Median Range Median Range

Anchorage 47 0.9 - 9.5 1.5 0.6 — 3.2
Chicago 5.8 2.0 — 9.9 1.7 1.0 ~ 3.2
Denver 5.5 2.0 - 9.8 2.0 0.9 - 3.7
Detroit 5.6 1.6 — 10.4 1.6 0.7 — 2.7
Honolulu 4.9 1.6 - 9.0 1.4 0.7 — 2.5
Houston 3.2 1.0 — 7.8 1,2 0.6 — 3.5
Los Angeles 6.2 2.0 — 10.3 1.8 1.0 - 3.0
Miami 5.0 1.2 - 9.7 1.2 0.4 — 3.0
Milwaukee 4.2 1.0 — 8.9 1.2 0.5 — 2.5
New Orleans 5.5 2.0 — 9.6 1.6 1.0 — 3.0
New York 4.8 12-91 1.2 0.6 — 2.5
Phoenix 4.1 0.9 ~ 8.7 1.2 0.5 — 2.5
St. Louis 5.1 1.7 - 9,2 1.4 0.9 - 2.1
Salt Lake City §.1 1.5 — 9.5 1.2 0.6 — 2.5
San Francisco 5.4 1.6 — 9.8 1.5 0.8 — 2.7
Seattle 5.7 17-96 1.5 0.8 — 2.7
Vermont,

New Hampshire 4.8 1.4 ~—9.0 1.2 0.8 — 2.1
Washington, DC 4.9 1.2 - 8.4 1.2 0.6 - 2.5

 

 

 

Source: Stewart, R.D., et al

. (57).
Sc

TABLE 6. — Mean percent carboxyhemoglobin (COH}) saturation in cigarette

smokers I hour after last cigarette

 

Packs of Cigarettes Smoked Per day

 

 

Location Nonsmoker
<% YVri 1 1% 2
Milwaukee 1.3 3.0 4.2 5.3 6.2 4.7
New Hampshire,

Vermont 1.4 3.3 4.4 5.7 6.7 5.3
New York City 1.4 3.1 4,3 4.7 5.8 6.3
Washington, DC 1.4 3.8 4.6 5.2 5.8 6.6
Los Angeles 2.0 4.0 5.2 6.0 7.4 7.5
Chicago 2.0 4.8 5.4 6.3 7A 77

 

 

 

Source: Stewart, R.D., et al.

(57).
Studies on the CO burden of each cigarette have determined the
body burden of CO per cigarette to be 7.10-8.66 ml (40), and the
increase in COHb level produced by smoking one cigarette to be .94
to 1.6 percent after 12 hours of abstinence (40, 53). The half-life for
the washout of CO in healthy college smokers (40) was calculated to
be from 3 to 5 hours.

Effects on Healthy Individuals

Several studies have been published on the effects of carbon
monoxide on healthy individuals. Small doses of CO (COHb levels
2.4-5.4 percent) were found to have no effect on heart rate (56).
Raven, et al. (5/7), in a study of young men exposed during exercise
on a treadmill to 50 ppm CO (COHb levels 2.5 percent in
nonsmokers and 4.1 in smokers), found no decrease in maximum
aerobic capacity when the subjects were tested at 25°C. In a similar
experiment conducted at 35°C by the same researchers (20), there
was a decrease in maximum aerobic capacity in nonsmokers exposed
to 50 ppm CO, but not in smokers despite an increase in the
carboxyhemoglobin levels of 1.5 percent in both groups. They
postulated a possible physiologic adaptation of smokers to carbon
monoxide. Ekblom and Huot (22) studied five young men who
inhaled CO to reach given COHb levels. They reported that as COHb
levels increased, there was a decrease in maximal oxygen uptake and
lower heart rates at maximal treadmill exercise.

Sagone, et al. (54), in a study of 9 cigarette smokers and 18
nonsmokers ages 20-32, showed significantly higher values for COHb,
red cell mass, hemoglobin, and hematocrit in the smokers. Levels of
2,3 DPG were unaltered while oxyhemoglobin affinity P50 and ATP
levels were significantly lower in the smokers. The three smokers
with highest red cell mass had normal arterial blood gases and one
smoker had very high values of red cell mass which returned to
normal after he stopped smoking. The authors interpret these data as
evidence of tissue hypoxia.

Millar and Gregory (43), in a study of both fresh heparinized
blood and ACD-stored blood from a blood bank, showed a reduction
in the oxygen carrying capacity of up to 10 percent in the blood of
cigarette smokers; this reduction persisted for the full 21-day storage
life of blood bank blood.

Cole, et al. (76), in a study of pregnant women, found COHb
levels in the fetus to be 1.8 times as great as those in the

26
simultaneously measured blood of the mother. Fetal blood was
exposed to carbon monoxide in vitro, and fetal hemoglobin was
found to have a shift of the oxyhemoglobin disassociation curve to

the left as occurs with adult hemoglobin. The higher fetal COHb
levels were attributed to the lower fetal Poy and a resultant decrease
in the ability of oxygen to compete for the fetal hemoglobin. It was
felt by the authors that the high COHb levels may be responsible for
the lower birth weight of infants born to mothers who smoke.

Effects on Persons with
Atherosclerotic Cardiovascular Disease

Aronow and Isbell (5) and Anderson, et al. (7) have shown a
decrease in the mean duration of exercise before the onset of pain in
patients with angina pectoris exposed to low levels of carbon
monoxide (50 and 100 ppm). Carboxyhemoglobin levels were
significantly elevated (2.9 percent after 50 ppm; 4.5 percent after
100 ppm) and the systolic blood pressure, heart rate, and product of
systolic blood pressure times heart rate (a measure of cardiac work)
were all significantly lower at onset of angina pectoris.

In a continuation of this work, Aronow, et al. (2, 3) studied
eight patients during two separate cardiac catheterizations, one
during which each patient smoked three cigarettes and one during
which each patient inhaled carbon monoxide until the maximal
coronary sinus COHb level equalled that produced by smoking
during the first catheterization. All eight had angiographically
demonstrated CHD (> 75 percent obstruction of at least one
coronary artery). Smoking increased the systolic and diastolic blood
pressure, heart rate, left ventricular end-diastolic pressure (LVEDP),
and coronary sinus, arterial, and venous CO levels. No changes were
noted in left ventricular contractility (dp/dt), aortic systolic ejection
period, or cardiac index, and decreases were found in stroke index
and coronary sinus, arterial, and venous Poz. When carbon monoxide
was inhaled, increased LVEDP and coronary sinus, arterial, and
venous CO levels were noted; there were no changes in systolic and
diastolic blood pressure, heart rate, or systolic ejection period; and
decreases in left ventricular dp/dt, stroke index, cardiac index and
coronary sinus, arterial, and venous Poz were found. These data
suggest that carbon monoxide has a negative inotropic effect on
myocardial tissue resulting in the decrease in contractility (dp/dt)
and stroke index. When the positive effect of nicotine on contrac-
tility and heart rate is added by cigarette smoking, the net effect is
increased cardiac work for the same cardiac output. In the heart with

27
coronary artery disease there is a greatly restricted capacity to
increase blood flow in response to this increase in cardiac work. The
result is early cardiac decompensation manifested by elevation in
LVEDP and angina pectoris.

Aronow, et al. have also shown decreased exercise time prior to
onset of angina pectoris in persons exercised after riding for 90
minutes on the Los Angeles Freeway (4). In a related study, they
demonstrated a decrease in exercise time before claudication in a
group of patients with intermittent claudication who were exposed

to 50 ppm CO (6).

Studies on the Pathogenesis of Cardiovascular Disease

In a review of some of their work on carbon monoxide, Astrup
and Kjeldsen (7) noted that in cholesterol-fed rabbits exposed to 170
ppm carbon monoxide for 7 weeks (COHb 16 percent) and then to
340 ppm for 2 weeks, the cholesterol content of the aorta was 2.5
times higher than that of cholesterol-fed, air breathing controls.
Groups of cholesterol-fed rabbits intermittently exposed to carbon
monoxide for 12 or 4 hours per day produced three- to fivefold
increases in the cholesterol content of their aortas. Cholesterol-fed
rabbits made hypoxic at 10 and 16 percent oxygen had 3 to 3.5
times the aortic cholesterol content, while those exposed to 26 and
28 percent oxygen had a considerable decrease in cholesterol
accumulation.

Theodore, et al. (58) studied the aortas of monkeys, baboons,
dogs, rats, and mice fed a normal diet but exposed to very high levels
of CO (COHb levels 33 percent) and found no atheromatous changes
in their aortas.

Further work by Astrup and Kieldsen (38) revealed that in rab-
bits fed normal diets but exposed to 180 ppm carbon monoxide for 2
weeks, there were local areas in their hearts of partial or total necrosis
of myofibrils; in the arteries there was endothelial swelling, formation
of subendothelial edema, and degeneration of the myocytes. When
the aortas of these rabbits were examined (37), the luminal coats
showed pronounced changes characterized by severe edematous
reaction with extensive swelling and formation of subendothelial
blisters and plaques. The authors postulate that carbon monoxide
increases endothelial permeability to albumin which results in
formation of edema leading to changes indistinguishable from early
atherosclerosis.
Evidence that this mechanism may occur in humans is provided
by the findings of Parving (50) who showed an increased trans-
capillary escape rate for 13! J- labeled albumin in humans exposed to
.43 percent CO (COHb 20 percent) for 3 to 5 hours, but not in those
made hypoxic to an altitude of 4300 meters (hemoglobin 75 percent
saturated).

By exposing rabbits to different concentrations of carbon
monoxide (50, 100, and 180 ppm) for varying periods (.5, 2, 4, 8,
24, and 48 hours), Thomsen and Kjeldsen (59) were able to show a
threshold of 100 ppm of CO for myocardial damage. The demonstra-
tion of damage at this level of CO (COHb 8-10 percent) is possibly
explained by the ratio of carboxymyoglobin to carboxyhemoglobin
which is about 3 to 1 in myocardium at ambient Po2. Thus, a
COHb level of 10 percent would be accompanied by a carboxymyo-
globin level of 30 percent in heart muscle. This ratio is even greater
under hypoxic conditions with a ratio of 6 to | when the arterial Po
is below 40 mm Hg (/5).

Nicotine

In a study of the effects of smoking cigarettes with low and
high nicotine content, Hill and Wynder (30) noted increasing serum
epinephrine levels with increasing nicotine content of the smoke, but
serum norepinephrine levels were unchanged. However, increasing
serum epinephrine levels with increasing number of low nicotine
content cigarettes smoked were also noted.

Acrolein

Egle and Hudgins (2/) did inhalation studies with acrolein on
rats. Inhalation of this aldehyde at concentrations below those
encountered in cigarette smoke resulted in a significant increase in
blood pressure and heart rate in rats.

CEREBROVASCULAR DISEASE

There has been conflicting evidence on whether there is an
increased risk of cerebrovascular disease due to smoking (6/, 62, 63,
64, 65, 66, 67, 68). A prospective study by Paffenbarger, et al. (48)
of 3,991 longshoremen followed for 18 years showed no correlation
between fatal strokes and smoking. However, both the Dorn study of

29
U.S. veterans (33) and Hammond’s study of one million men and
women (25) showed a small but significant increase in the death rates
from cerebrovascular disease among cigarette smokers. The Framing-
ham 18-year followup of men ages 45 to 54 (42) and Paffenbarger’s
study of men who entered Harvard between 1916 and 1940 (49) also
showed an excess risk of cerebrovascular disease associated with
cigarette smoking.

Two recent studies provided more data on this topic. Ostfeld, et
al. (46, 47), in a study of 2,748 people ages 65-74 receiving old age
assistance in Cook County, Illinois, were unable to find any relation
between cigarette smoking habits at the start of the study and
incidence of new strokes or prevalence of transient ischemic attacks.
Nomura, et al. (44), in a study of the population of Washington
County,. Maryland, ages 25 and older, were unable to find any
relation between cigarette smoking and either mortality or morbidity
from stroke. Nomura noted that “in atherosclerotic strokes the
Framingham study and Paffenbarger’s investigation of former college
students included a great percentage of stroke cases under the age of
55. Because these two studies found an association between cigarette
smoking and atherosclerotic strokes and the present study did not, it
may be that the association is age-dependent.”

Hammond (25) provides some data which may clarify this
relationship. Analysis of his data shows that the difference between
cerebrovascular death rates in cigarette smokers and nonsmokers
increases as persons get older except in males ages 75-84 (Table 7),
indicating that the excess death rates associated with cigarette
smoking increase with advancing age. The ratio of the death rates for
smokers and nonsmokers (mortality ratio), however, decreases with
age, reflecting the fact that cerebrovascular disease death rates
attributable to other causes increase with age more rapidly than
death rates attributable to smoking. Cigarette smoking may well be a
risk factor for stroke at all ages, but other causes of strokes become
proportionally so important in older age groups that in studies not
based on very large populations the risk due to cigarette smoking is
masked by the large total number of strokes due to other causes.

30
le

TABLE 7. — Age-standardized deaths rates and mortality ratios for cerebral vascular lesions
for men and women by type of smoking (lifetime history) and age at start of study

 

 

 

 

 

 

Age Groups
Type of Smoking
45-54 55-64 65-74 75-84
CVL Death Rates per 100,000 Person-Years
Men
Never smoked regularly 28 92 349 1,358
Pipe, cigar 25 100 369 1,371
Cigarette and other 28 129 361 990
Cigarette only 42 130 477 1,168
Total 35 116 391 1,272
Women
Never smoked regularly 18 57 228 1,082
Cigarette 38 88 315 1,277
Total 25 64 238 1,091
CVL Mortality Ratios
Men
Never smoked regularly 1.00 1.00 1.00 1.00
Pipe, cigar 0.89 1.09 1.06 1.01
Cigarette and other 1.00 1.40 1.03 0.73
Cigarette only 1.50 1.41 1.37 0.86
Women
Never smoked regularly 1.00 1.00 1.00 1.00
Cigarette 2.11 1.54 1.38 1,18

 

 

NOTE. — CVL = Cerebral vascular lesions.
Source: Hammond, E.C, (25).
EFFECTS OF SMOKING ON THE COAGULATION SYSTEM

Several studies have contributed to an understanding of the role
of smoking in thrombogenesis. Levine (4/), in a controlled double
blind study, showed that smoking a single cigarette increased the
platelet’s response to a standard aggregating stimulus (ADP). This
phenomenon did not occur when lettuce leaf cigarettes were smoked
and was independent of a rise in free fatty acids in the plasma. The
author postulates that this may be due to increasing epinephrine
levels.

These data may have relevance for two other studies. In the
clinical trial of the possible prevention of heart attack by
hyperlipidemic drugs in Newcastle, England, (/9) it was found that
cigarette smokers were at increased risk of sudden death. This
increased risk was not present in smokers treated with clofibrate.
However, the researchers were unable to relate this reduction in risk
to any effect of clofibrate on serum lipids. Recently Carvalho, et al.
(7/4) evaluated 29 patients with familial hyperbetalipoproteinemia
and noted that their platelets had an increased sensitivity to
aggregating stimuli (ADP). Treatment with clofibrate returned the
ADP sensitivity to normal without significantly altering serum lipids.
This demonstrated effect of clofibrate may provide some insight into
the Newcastle study. The reduction in the excess risk of sudden
death could be due to a clofibrate induced reversal of increased
sensitivity to aggregating stimuli produced by smoking.
SUMMARY OF RECENT CARDIOVASCULAR FINDINGS

1. Data from one recent incidence study suggest that cigarette
smokers are more likely to develop hypertension than are
nonsmokers. There is some evidence that suggests that stopping
smoking may be accompanied by a rise in blood pressure.

2. Cigarette smoking has been shown to be the major source of
elevated carboxyhemoglobin levels, with occupational exposure and
air pollution being far less important in most circumstances.
Carboxyhemoglobin levels in cigarette smokers are two to three
times the levels in nonsmokers and increase with the amounts
smoked.

3. Elevated carboxyhemoglobin levels have been shown to
decrease maximal oxygen uptake in healthy people as well as to
decrease the exercise tolerance of persons with angina pectoris and
intermittent claudication. The carboxyhemoglobin levels at which
these effects take place are well within the range produced by
cigarette smoking.

4. Carbon monoxide at levels of exposure commonly reached
by cigarette smokers has been shown to decrease cardiac contractility
in persons with coronary heart disease.

5. Carbon monoxide has been shown to produce changes like
those of early atherosclerosis in the aortas of rabbits.

33
10

11

12

14

15

34

BIBLIOGRAPHY

ANDERSON, E.W., ANDELMAN, R.J., STRAUCH, J.M., FORTUIN, N. J.,
KNELSON, J.H. Effect of low level carbon monoxide exposure on onset and
duration of angina pectoris. A study of ten patients with ischemic heart disease.
Annals of Internal Medicine 79(1):46-50, July 1973.

ARONOW, W.S., CASSIDY, J., VANGROW, J.S., MARCH, H., KERN, J.C.,
GOLDSMITH, J.R., KHEMKA, M., PAGANO, J., VAWTER, M. Effect of
cigarette smoking and breathing carbon monoxide on cardiovascular hemo-
dynamics in anginal patients. Circulation 50(2):340-347, August 1974.

ARONOW, W.S., GOLDSMITH, J.R., KERN, J.C., JOHNSON, L.L. Effect of
smoking cigarettes on cardiovascular hemodynamics. Archives of Environmental
Health 28(6): 330-332, June 1974.

ARONOW, W.S., HARRIS, C.N., ISBELL, M. W., ROKAW, S.N., IMPARATO, B.
Effect of freeway travel on angina pectoris. Annals of Internal Medicine 77(5):
669-676, November 1972.

ARONOW, W. S., ISBELL, M. W. Carbon monoxide effect on exercise-induced angina
pectoris. Annals of Internal Medicine 79(3): 392-395, September 1973.

ARONOW, W.S., STEMMER, E.A., ISBELL, M.W. Effect of carbon monoxide
exposure on intermittent claudication. Circulation 49(3): 415-417, March 1974.

ASTRUP, P., KJELDSEN, K. Carbon monoxide, smoking, and atherosclerosis. Medical
Clinics of North America 58(2): 323-350, March 1974.

AYERS, S. M., EVANS, R., LICHT, D., GRIESBACH, J., REIMOLD, F,, FERRAND,
E. F., CRISCITIELLO, A. Health effects of exposure to high concentrations of
automotive emissions. Studies in bridge and tunnel workers in New York City.
Archives of Environmental Health 27(3): 168-178, September 1973.

BENGTSSON, C. Smoking habits in a population sample of women and in women with
ischaemic heart disease. Acta Medica Scandinavica (Supplementum 549): 60-64,
1973.

BENGTSSON, C. Prevalence of multiple “risk factors” for ischaemic heart disease in
women with and without known ischaemic heart disease. Acta Medica
Scandinavica (Supplementum 549): 97-105, 1973.

BOKHOVEN, C., NIESSEN, H.J. Amounts of oxides of nitrogen and carbon
monoxide in cigarette smoke, with and without inhalation. Nature 192(4801):
458-459, November 4, 1961.

BOSTON COLLABORATIVE DRUG SURVEILLANCE PROGRAM. Coffee drinking
and acute myocardial infarction. Lancet 2(7790): 1278-1281, December 16,
1972.

BUCHWALD, H. Exposure of garage and service station operatives to carbon
monoxide: A survey based on carboxyhemoglobin ievels. American Industrial
Hygiene Association Journal 30(6): 570-575, November-December 1969.

CARVALHO, A.C. A., COLMAN, R. W., LEES, R.S. Clofibrate reversal of platelet
hypersensitivity in hyperbetalipoproteinemia. Circulation 50(3): 570-574,
September 1974.

COBURN, R. F. The carbon monoxide body stores. Annals of the New York Academy
of Sciences 174:11-22, October 5, 1970.
16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

COLE, P. V., HAWKINS, L.H., ROBERTS, D. Smoking during pregnancy and its
effects on the fetus. Journal of Obstetrics and Gynaecology of the British
Commonwealth 79(9): 782-787, September 1972.

CORONARY DRUG PROJECT RESEARCH GROUP. Factors influencing long-term
prognosis after recovery from myocardial infarction— Three-year findings of the
coronary drug project. Joumal of Chronic Diseases 27(6): 267-285, August 1974.

DAWBER, T.R., KANNEL, W. B., GORDON, T. Coffee and cardiovascular disease.
Observations from the Framingham Study. New England Journal of Medicine
291(17): 871-874, October 24, 1974.

DEWAR, H. A. Trial of clofibrate in the treatment of ischaemic heart disease. Five-year
study by a group of physicians of the Newcastle upon Tyne Region. British
Medical Journal 4 (5790): 767-775, December 25, 1971.

DRINKWATER, B. L., RAVEN, P. B., HORVATH, S. M., GLINER, J. A., RUHLING,
R.O., BOLDUAN, N. W., TAGUCHI, S. Air pollution, exercise, and heat stress.
Archives of Environmental Health 28(4): 177-181, April 1974.

EGLE, J.L., Jr., HUDGINS, P.M. Dose-dependent sympathomimetic and cardio-
inhibitory effects of acrolein and formaldehyde in the anesthetized rat.
Toxicology and Applied Pharmacology 28: 358-366, 1974.

EKBLOM, B., HUOT, R. Response to submaximal and maximal exercise at different
levels of carboxyhemoglobin. Acta Physiologica Scandinavica 86(4): 474-482,
December 1972.

FRIBERG, L., CEDARLOF, R., LORICH, U., LUNDMAN, T., DEFAIRE, U.
Mortality in twins in relation to smoking habits and alcohol problems. Archives of
Environmental Health 27(5): 294-304, November 1973.

GYNTELBERG, F., MEYER, J. Relationship between blood pressure and physical
fitness, smoking and alcohol consumption in Copenhagen males aged 40-59. Acta
Medica Scandinavica 195(5): 375-380, May 1974.

HAMMOND, E.C. Smoking in relation to the death rates of one million men and
women. Jn: Haenszel, W. (Editor). Epidemiological Approaches to the Study of
Cancer and Other Chronic Diseases. Bethesda, Md., U.S. Public Health Service,
National Cancer Institute Monograph No. 19, January 1966, pp. 127-204.

HELMERS, C. Prognosis for the first day after admission. Acta Medica Scandinavica
(Supplementum $55): 14-26, 1974.

HELMERS, C. Prognosis for the hospital period from the second day after admission.
Acta Medica Scandinavica (Supplementum 555): 31-41, 1974.

HELMERS, C. Long-term prognosis. Acta Medica Scandinavica (Supplementum 555):
54-65, 1974.

HEYDEN, S., BARTEL, A., CASSEL, J.C., HAMES, C.G., TYROLER, H. A.,
MEIER, R. Kaffeekonsum Gefasserkrankungen und Risikofaktoren in der
Evans-County/Georgia-Studie. (Coffee consumption, vascular diseases, and risk
factors in the Evans County, Georgia, study.) Zeitschrift fur Ernahrungswissens-
chaft (Supplement 14): 1-10, 1972.

HILL, P., WYNDER, E. L. Smoking and cardiovascular disease. Effect of nicotine on

the serum epinephrine and corticoids. American Heart Journal 87(4): 491-496,
April 1974.

35
31

32

33

34

35

36

37

38

39

40

41

42

43

44

36

INTERSOCIETY COMMISSION FOR HEART DISEASE RESOURCES. Atherosclero-
sis Study Group and Epidemiology Study Group. Primary prevention of the
atherosclerotic diseases. Circulation 42(6): A-54-A-95, December 1970.

JONES, R. D., COMMINS, B. T., CERNIK, A. A. Blood lead and carboxyhemoglobin
levels in London taxi drivers. Lancet 2(7772): 302-303, August 12, 1972.

KAHN, H. A. The Dorn study of smoking and mortality among U.S. veterans: Report
on 8% years of observation. Jn: Haenszel, W. (Editor). Epidemiological
Approaches to the Study of Cancer and Other Chronic Diseases. Bethesda, Md.,
U.S. Public Health Service, National Cancer Institute Monograph No. 19, January
1966, pp. 1-125.

KAHN, H. A., MEDALIE, J. H., NEUFELD, H.N., RISS, E., GOLDBOURT, U. The
incidence of hypertension and associated factors: The Israel ischemic heart disease
study. American Heart Journal 84(2): 171-182, August 1972.

KAHN, A., RUTLEDGE, R.B., DAVIS, G.L., ALTES, J. A., GANTNER, G. E.,
THORNTON, C.A., WALLACE, N.D. Carboxyhemoglobin sources in the
Metropolitan St. Louis population. Archives of Environmental Health 29(3):
127-135, September 1974.

KESTELOOT, H., VAN HOUTE, O. An epidemiologic survey of arterial blood pressure
in a large male population group. American Journal of Epidemiology 99(1):
14-29, January 1974.

KJELDSEN, K., ASTRUP, P., WANSTRUP, J. Ultrastructural intimal changes in the
rabbit aorta after a moderate carbon monoxide exposure. Atherosclerosis 16(1):
67-82, July-August 1972.

KJELDSEN, K., THOMSEN, H.K., ASTRUP, P. Effects of carbon monoxide on
myocardium. Ultrastructural changes in rabbits after moderate, chronic exposure.
Circulation Research 34(3): 339-348, March 1974.

KLATSKY, A. L., FRIEDMAN, G. D., SIEGELAUB, A. B. Coffee drinking prior to
acute myocardial infarction. Journal of the American Medical Association 226(5):
540-543, October 29, 1973.

LANDAY, S. A. The effects of cigarette smoking on total body burden and excretion
rates of carbon monoxide. Journal of Occupational Medicine 15(3): 231-235,
March 1973.

LEVINE, P.H. An acute effect of cigarette smoking on platelet function. A possible
link between smoking and arterial thrombosis. Circulation 48(3): 619-623,
September 1973.

McGEE, D. Section 28. The probability of developing certain cardiovascular diseases in
eight years at specified values of some characteristics. Ja: Kannel, W. B., Gordon,
T. (Editors). The Framingham Study: An epidemiological investigation of
cardiovascular disease. U.S. Department of Health, Education, and Welfare, Public
Health Service, National Institutes of Health, Publication No. (NIH) 74-618, May
1973, 152 pp.

MILLAR, R.A., GREGORY, I.C. Reduced oxygen content in equilibrated fresh
heparinized and ACD-stored blood from cigarette smokers. British Journal of
Anaesthesia 44(10): 1015-1019, October 1972.

NOMURA, A., COMSTOCK, G. W., KULLER, L. TONASCIA, J. A. Cigarette smoking
and strokes. Stroke 5(4}:483-486, July-August 1974.
45

46

47

48

49

50

$1

52

53

54

55

56

37

58

$9

50

OSBORNE, J.S., ADAMEK, S., HOBBS, M. E. Some components of gas phase of
cigarette smoke. Analytical Chemistry 28(2): 211-215, February 1956.

OSTFELD, A.M., SHEKELLE, R. B., KLAWANS, H. L. Transient ischemic attacks
and risk of stroke in an elderly poor population. Stroke 4(6): 980-986,
November-December 1973.

OSTFELD, A. M., SHEKELLE, R. B.. KLAWANS, H., TUFO, H. M. Epidemiology of
stroke in an elderly welfare population. American Journal of Public Health 64(5):
450-458, May 1974.

PAFFENBARGER, R.5S., Jr. Factors predisposing to fatal stroke in longshoremen.
Preventive Medicine 1(4): 522-528, December 1972.

PAFFENBARGER, R.5S., Jr., WING, A. L. Chronic disease in former college students,
XI. Early precursors of nonfatal stroke. American Journal of Epidemiology 94(6):
524-530, December 1971.

PARVING, H.-H. The effect of hypoxia and carbon monoxide exposure on plasma
volume and capillary permeability to albumin. Scandinavian Journal of Clinical
and Laboratory Investigation 30(1): 49-56, September 1972.

RAVEN, P. B., DRINKWATER, B. L., RUHLING, R. O., BOLDUAN, N., TAGUCHI,
S., GLINER, J., HORVATH, S. M. Effect of carbon monoxide and peroxyacetyl
nitrate on man’s maximal aerobic capacity. Journal of Applied Physiology 36(3):
288-293, March 1974.

REYNERTSON, R.H., TZAGOURNIS, M. Clinical and metabolic characteristics.
Effects on mortality in coronary disease. Archives of Internal Medicine 132(5):
649-653, November 1973.

RUSSELL, M.A.H. Blood carboxyhaemoglobin changes during tobacco smoking.
Postgraduate Medical Journal 49(576): 684-687, October 1973.

SAGONE, A. L., Jr., LAWRENCE, T., BALCERZAK, S. P. Effect of smoking on tissue
oxygen supply. Blood 41(6): 845-851, June 1973.

SELTZER, C.C. Effect of smoking on blood pressure. American Heart Journal 87(5):
558-564, May 1974.

SHEPHARD, R. J. The influence of small doses of carbon monoxide upon heart rate.
Respiration 29(5/6): 516-521, 1972.

STEWART, R.D., BARETTA, E.D., PLATTE, L.R., STEWART, E.B.,
KALBFLEISCH, J.H., VAN YSERLOO, B., RIMM, A. A. Carboxyhemoglobin
levels in American blood donors. Journal of the American Medical Association
229(9): 1187-1195, August 26, 1974.

THEODORE, J., ODONNELL, R. D., BACK, K. C. Toxicological evaluation of carbon
monoxide in humans and other mammalian species. Journal of Occupational
Medicine 13(5): 242-255, May 1971.

THOMSEN, H.K., KJELDSEN, K. Threshold limit for carbon monoxide-induced
myocardial damage. An electron microscopic study in rabbits. Archives of
Environmental Health 29(2): 73-78, August 1974.

TORBATI, [. D., HAR-KEDAR, I., BEN-DAVID, A. Carboxyhemoglobin levels in
blood donors in relation to cigarette smoking and to occupational exposure to
carbon monoxide. Israel Journal of Medical Sciences 10(3): 241-244, March
1974.

37
61

62

63

64

65

66

67

68

69

70

38

US.

US.

USS.

US.

US.

US.

US.

US.

PUBLIC HEALTH SERVICE. Smoking and Health. Report of the Advisory
Committee to the Surgeon General of the Public Health Service. Washington, U.S.
Department of Health, Education, and Welfare, Public Health Service Publication
No. 1103, 1964, 387 pp.

PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Public
Health Service Review: 1967. U.S. Department of Health, Education, and
Welfare. Washington, Public Health Service Publication No. 1696, Revised
January 1968, 227 pp.

PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. 1968.
Supplement to the 1967 Public Health Service Review. U.S, Department of
Health, Education, and Welfare. Washington, Public Health Service Publication
1696, 1968, 117 pp.

PUBLIC HEALTH SERVICE. The Health Consequences of Smoking 1969.
Supplement to the 1967 Public Health Service Review. U.S. Department of
Health, Education, and Welfare. Washington, Public Health Service Publication
1696-2, 1969, 98 pp.

PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Report of
the Surgeon General: 1971. U.S. Department of Health, Education, and Welfare.
Washington, DHEW Publication No. (HSM) 71-7513, 1971, 458 pp.

PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Report of
the Surgeon General: 1972. U.S. Department of Health, Education, and Welfare.
Washington, DHEW Publication No. (HSM) 72-6516, 1972, 158 pp.

PUBLIC HEALTH SERVICE. The Health Consequences of Smoking: 1973. U.S.
Department of Health, Education, and Welfare. Washington, DHEW Publication
No. (HSM) 73-8704, 1973, 249 pp.

PUBLIC HEALTH SERVICE. The Health Consequences of Smoking: 1974. U.S.
Department of Health, Education, and Welfare. Washington, DHEW Publication
No. (CDC) 74-8704, 1974, 124 pp.

VEDIN, J. A., WILHELMSSON, C. E.. WILHELMSEN, L., BJURE, J., EKSTROM-

JODAL, B. Relation of resting and exercise-induced ectopic beats to other
ischemic manifestations and to coronary risk factors. Men born in 1913.
American Journal of Cardiology 30(1): 25-31, July 11, 1972.

WALLACE, N.D., DAVIS, G.L., RUTLEDGE, R.B., KAHN, A. Smoking and

carboxyhemoglobin in the St. Louis Metropolitan population. Theoretical and
empirical considerations. Archives of Environmental Health 29(3): 136-142,
September 1974.
CHAPTER 2
Cancer
CHAPTER 2

 

Cancer
CONTENTS

Page
Introduction ..... 2.0.2... 00 eee ee ee eee 43
Lung Cancer 2.0.0.0 0c et tenes 44
Epidemiologic Studies ...- 2... 20-0 44
Smoking and Air Pollution... 2.2... 2-26-02 bee ee eee 44
Exfoliative Cytology... 0.2.06 e ee ees 47
Experimental Carcinogenicity .... 2.2... 6-662 e eee ees 48
Carcinogens in Cigarette Smoke ....-------- 6220s 48
Asbestos ... 2.000. ee eee eee 49
Infection and Carcinogenicity ... 2... 6-2... eee ee ee eee 49
Other Cancers ..........-.- ee eee ee eee eee 50
Oral and Laryngeal Cancer... 0... eee es 50
Genitourinary Cancer 2.22.6... e eee ees 50
Nasopharyngeal Cancer ... 0-00-00 ee ee eee eee ees 50
Aryl Hydrocarbon Hydroxylase (AHH) .......-----+-+ eee cere 50
Summary of Recent Cancer Findings ........-.--- 6-22-22 eee eee? 54
Bibliography ... 2... tee 55
List of Figures

Page
Figure 1.—Production of aryl hydrocarbon hydroxylase
(AHH) in macrophages from one person in response
to cigarette smoking .. 0... 6. ee ee ee 52
List of Tables
Page
Table 1.—Distribution by type of lung cancers in a
composite series of nonsmokers and a representative
hospital series 22... ee eee 45
Table 2.—Distribution by type of lung cancer in
populations with specific occupational
EXPOSULES 2... ee ee eee ee 46

Table 3.—Aryl hydrocarbon hydroxylase (AHH) inducibility
in patients with lung cancer, with other tumors, and
in healthy controls
INTRODUCTION

The major relationships between smoking and various cancers
have been documented in previous reports on the health
consequences of smoking (/8, 19, 20, 2], 22, 23, 24, 25). Based on
evaluations of detailed epidemiologic, clinical, autopsy, and
experimental data accumulated over the last 30 years, cigarette
smoking has been clearly identified as a causative factor for lung
cancer. The risk of developing lung cancer increases directly with
increasing cigarette smoke exposure as measured by number of
cigarettes smoked per day, total lifetime number of cigarettes
smoked, number of years of smoking, age at initiation of smoking,
and depth of inhalation. Lung cancer death rates for women are
lower than for men but have increased dramatically over the last 15
years coincident with the increasing number of women smokers. This
increase has occurred in spite of the fact that women smokers use
fewer cigarettes per day, more frequently choose cigarettes with
filter tips and low tar and nicotine delivery, and tend to inhale less
than men. A person who stops smoking has a decreased risk of
developing lung cancer compared to the continuing smoker, but the
risk remains greater than the nonsmoker’s for as long as 10 to 15
years after the person stops smoking.

Cigarette smoking is a significant etiologic factor in the
development of cancer of the larynx, oral cavity, pharynx,
esophagus, and urinary bladder and is associated with cancer of the
pancreas.

Certain occupational exposures have been found to be
associated with an increased risk of dying from lung cancer. Cigarette
smoking interacts with these exposures to produce a greater risk of
developing lung cancer than from occupational exposure alone.
Uranium mining and the asbestos industries are occupations which
have only slightly increased lung cancer rates for nonsmokers but
dramatically elevated rates for cigarette smokers.

Pipe and cigar smokers experience mortality rates from cancer
of the oral cavity, larynx, pharynx, and esophagus approximately
equal to those of cigarette smokers. Their risk of developing cancer
of the lung is lower than the risk of cigarette smokers, but it is
significantly above that of nonsmokers. This is probably due to the

43
fact that pipe, cigar, and cigarette smokers experience similar smoke
exposure of the upper respiratory tract, while cigarette smokers (due
to their greater tendency to inhale) have a greater exposure of their
lungs to smoke than pipe or cigar smokers.

The bronchial epithelium of smokers often shows premalignant
changes such as squamous metaplasia, atypical squamous metaplasia,
and carcinoma in situ. The pathogenesis of these changes is related to
the various carcinogenic and co-carcinogenic substances in cigarette
smoke; the exact mechanism of these carcinogens remains under
investigation.

LUNG CANCER

Epidemiologic Studies

Harris (3) has reviewed the reports of lung cancer in
nonsmokers and compared them to a representative hospital series
and has shown marked differences in the pathological types between
the two groups (Table 1). When only nonsmokers are examined, the
excess of squamous and oat cell carcinoma in men compared to
women is not observed. Adenocarcinoma is by far the most common
type of lung cancer in nonsmokers while squamous cell is by far the
most common when smokers are included. The strength of the
relationship between smoking and the development of lung cancer
differs markedly with the type of lung tumor. Squamous and oat cell
carcinoma are very closely related to smoking behavior while,
according to this study, bronchiolar carcinoma shows no excess risk
attributable to smoking. Harris also presented the percentages of
different histologic types of cancer found in several industrial
exposures (Table 2); these percent distribution patterns resembled
those found in smokers far more closely than those found in
nonsmokers.

Wynder, et al. (26), in a retrospective study of 350 lung cancer
patients and hospitalized controls, noted that the relative risk of
developing lung cancer was far less in those smokers who had smoked
filter cigarettes for more than 10 years than in smokers of plain
cigarettes (26.8 and 46.2, respectively). Even with smokers of filter
cigarettes, the risk increased with increasing number of cigarettes
smoked and was significantly greater than the risk of nonsmokers.

Smoking and Air Pollution

Because of the magnitude of the association between smoking
and the development of epidermoid lung cancer, it is difficult to

44
SP

TABLE 1. — Distribution by type of lung cancers in a composite series

of nonsmokers and a representative hospital series

 

 

 

 

 

Distribution (Percent)
Type of Nonsmokers All Patients
cancer
Men Women Men Women

Squamous cell carcinoma 14 12 47 22
Oat cell carcinoma 4 4 17 11
Bronchiolar carcinoma - 5 8 23
Adenocarcinoma $7 54 10 20
Large cell anaplastic carcinoma 8 8 17 19
Carcinoid 14 16 0.6 4
Other specific types _ <i 1 2
Undifferentiated ! 4 2 ~ -
Total number of cases $1 274 1,903 315

 

 

 

‘includes oat cell carcinoma and large cell anaplastic carcinoma.

Source: Harris, C.C. (3).
oP

TABLE 2. — Distribution by type of lung cancer in populations
with specific occupational exposures

 

Type of cancer

Distribution (%) in populations with exposure to—

 

 

Arsenic Nickel Chromium Hematite Asbestos
Squamous cell carcinoma 40 57 48 33 44
Oat cell carcinoma 13 43 16 60 6
Adenocarcinoma 7 - 24 - 25
Oat cell or anaplastic 40 - ~ - 24
carcinoma
Anaplastic - - 12 7 i

 

 

 

 

 

 

Source: Harris, C.C. (3).
evaluate the effects of other possible causes of lung cancer such as air
pollution. Higgins (4) recently analyzed respiratory cancer mortality
in Great Britain and the United States. In the United States, although
‘the age-specific death rates for males continued to increase, the rate
of increase was not as great as in the past. Female lung cancer
mortality rates, by contrast, have increased steadily since about
1955. If these increases continue, the American Cancer Society
estimates that lung cancer among women will move from fourth to
third place in 1975 as the site responsible for the greatest number of
deaths due to cancer among women (/). In England and Wales,
Higgins noted that between 1940 and 1969 lung cancer rates for men
declined in the age group under 55 and increased only in men over
65. After adjusting for cigarette smoking, an independent effect of
air pollution was sought. It was found that the lung cancer death
rates for men ages 25-64 in greater London decreased more than the
rates in the rest of the country; he attributed this decrease to the
greater decline in smoke pollution in London than elsewhere.

Exfoliative Cytology

Microscopic examination of respiratory epithelial cells shed into
the sputum has become a useful aid in the diagnosis of lung cancer
and has been employed in many lung cancer screening programs for
selected high risk groups. Saccomanno, et al. (J/) have conducted
Periodic cytologic examinations of the sputum of uranium miners
and a group of nonmining controls. Many of these individuals
developed abnormal squamous cell metaplasia that progressed in
several cases to become invasive carcinoma. Both cigarette smoking
and radiation exposure from uranium mining were associated with an
increased prevalence of these cytologic changes. Of the two factors,
cigarette smoking was noted to be the more important (in both
miners and nonminers) for the development of atypia and carcinoma
in situ. Neither cigarette smoking nor uranium mining could be
correlated with the length of time it took for these changes to
Progress from one pathologic stage to the next.

Schreiber, et al. (/5) studied exfoliative cytology of the lungs of
hamsters treated with intratracheal injection of the carcinogen
benzo(a)pyrene. They noted progression from mild atypia to
Squamous metaplasia, to moderate and marked atypia, to changes
indicative of cancer. These cytologic changes in animals exposed to
carcinogens are comparable to those found in humans who smoke
cigarettes.

47
EXPERIMENTAL CARCINOGENICITY

Carcinogens in Cigarette Smoke

A great deal of effort has been expended to identify those
substances in cigarette smoke that cause malignant changes. The
hope is that, if these carcinogenic substances can be identified and
removed from cigarette smoke, the risk of developing lung cancer as
a result of smoking can be reduced. Carcinogenic substances which
act as tumor initiators, accelerators, and promoters in experimental
animal systems have been identified in cigarette smoke.

Hoffman and Wynder (6) conducted an extensive analysis of the
tumorigenicity of tobacco smoke. Using the gas phase of cigarette
smoke, they identified certain known carcinogens but were unable to
induce carcinoma in the respiratory tract of experimental animals.
They interpreted these results as indicating that the levels of
carcinogens present in the gas phase alone are below the
concentrations necessary for tumor activity.

In the same study, Hoffmann and Wynder examined the
particulate phase of tobacco and identified several carcinogens. The
majority of tumor initiators in the particulate phase were
polynuclear aromatic hydrocarbons and alkylated polynuclear
aromatic hydrocarbons. They found that a significant inhibition of -
pyrosynthesis of these substances leads to a significant reduction of
the tumorigenicity of tobacco smoke. They also identified several
tumor accelerators — substances which accelerate the carcinogenicity
and tumor initiating activity of the polycyclic aromatic hydro-
carbons. The tumor accelerators found were trans-4, 4’-dichloro-
stilbene, N-alkyl indoles, and N-alkyl carbazoles. They also reported
that the tumor promoters in cigarette smoke occur in the acidic
portion of the particulate matter but did not further characterize
them.

Hoffmann, et al. (5) reported identifying the nitrosamine,
N’-nitrosonornicotine, in concentrations of 1.9 to 6.6 micrograms
per gram in unburned tobacco and levels of 88.6 pg/g in one sample
of finely cut chewing tobacco. This is one of the highest
concentrations of an environmental nitrosamine (a family of
compounds containing several organic carcinogens) yet identified;
concentrations in food and drink rarely exceed 0.1 ug/g. This
substance is readily extractable from tobacco by water and so would
be present in high concentrations in the saliva of persons who chew

48
tobacco. As yet, N’-nitrosonornicotine has not been established as
carcinogenic, and even the known carcinogenic nitrosamines are not
felt to act topically.

Asbestos

The combination of cigarette smoking and asbestos exposure
has been shown to result in a particularly high risk of developing lung
cancer. Selikoff, et al. (16) have shown that asbestos workers who
smoke have 90 times greater risk of developing lung cancer than
nonsmoking, nonexposed people. Shabad, et al. (/ 7) recently studied
the possible causes of the synergistic effect of cigarette smoke and
asbestos. They studied the carcinogenic activity of different types of
asbestos in the U.S.S.R. and noted that all samples of chrysotile
asbestos had traces of benzo(a)pyrene (a polycyclic aromatic
hydrocarbon carcinogen found in cigarette smoke). In addition, they
noted that chrysotile asbestos had a high adsorption activity for
benzo(a)pyrene. This was not found in the other types of asbestos
tested (anthophyllite and magnesiaarfvedsonite). In these animal
studies, 20 percent of the rats exposed to chrysotile asbestos
developed precancerous lesions; inhalation of chrysotile plus
benzo(a)pyrene or of chrysotile plus cigarette smoke increased the
frequency of the lesions to 57 and 38 percent, respectively. The
synergism between asbestos and smoking may be the result of the
adsorption of carcinogens onto asbestos, therefore prolonging their
retention in the lung.

Infection and Carcinogenicity

There has been some discussion concerning the association
between lung cancer and chronic bronchitis. Both diseases can be
Caused by cigarette smoking; however, chronic bronchitis may also
influence the development of lung cancer by some independent
mechanism. Schreiber, et al. (14) administered N-nitrosoheptamethy-
leneimine to germfree rats, specific-pathogen-free rats, and rats with
chronic murine pneumonia. The incidence of lung neoplasms was 17
Percent in germfree males, 37 percent in specific pathogen-free
males, and 83 percent in infected males. An incidence of 90 to 100
percent occurred among females in all three experimental groups.
They concluded that chronic respiratory infection may enhance the
neoplastic response of the lungs to a systemic carcinogen.

49
OTHER CANCERS

Oral and Laryngeal Cancer

Schottenfeld, et al. (73) have studied the role of smoking on the
development of multiple primary cancers of the upper digestive
system, larynx, and lung. They followed 733 patients surviving a first
primary epidermoid cancer of the oral cavity, pharynx, or larynx for
5 years. The average annual incidence for a second primary was
higher in men (18.2/1000) than in women (15.4/1000). Both men
and women who developed a second primary tumor had heavier
tobacco exposure prior to their first cancer than those who did not
develop a second malignancy. The authors were unable to show a
significant relationship between smoking habits after removal of the
first primary and development of a second primary. They postulate
that this failure to show an association is due to the long induction
period between presence of a carcinogen and occurrence of the
cancer, and they expect that a relationship, if present, may become
apparent after 7 or 8 years of followup.

Genitourinary Cancer

Schmauz and Cole (/2) studied 43 persons with cancer of the
renal pelvis or ureter and noted that smoking was only a risk factor
at very high levels of consumption (over 24% packs per day), despite
its being related to cancer of the bladder at all levels of smoking.
They postulate that, due to the rapid transit of urine through the
renal pelvis and ureter, very high levels of exposure are required to
have any effect whereas the bladder stores urine for some time and
even small amounts of carcinogens in the urine may be sufficient to
influence the bladder epithelium.

Nasopharyngeal Cancer

Lin, et al. (/0), in a retrospective study of nasopharyngeal
cancer in Taiwan using neighborhood controls, found smoking to be
significantly associated with the development of nasopharyngeal
carcinoma. A person smoking over 20 cigarettes per day had twice
the risk of a nonsmoker of developing nasopharyngeal cancer.

ARYL HYDROCARBON HYDROXYLASE (AHH)

Due to the great variation in the amount of smoking exposure
before the development of lung cancer, attempts have been made to

50
identify groups of people who may have a greater sensitivity to the
carcinogenic effect of cigarette smoke. Interest has developed in the
possibility that aryl hydrocarbon hydroxylase (AHH) may be a
genetically determined enzyme that mediates such increased
susceptibility to certain environmental carcinogens.

AHH is an enzyme system which metabolizes polycyclic
aromatic hydrocarbons; some of the resulting metabolites are
carcinogenic. It has been postulated that persons with high levels of
this enzyme may be at greater risk of developing cancer from
exposure to the polycyclic hydrocarbons in cigarette smoke than
those with low levels.

The amount of AHH produced in response to an inducing
stimulus can be used to separate a population into three groups
(those capable of being induced to produce high, medium, and low
levels of AHH). Kellerman, et al. (8) studied the induction of AHH
activity in 353 healthy subjects (67 families with 165 children). They
felt that the enzyme was controlled by a single gene locus with two
alleles (one able to be induced to produce high AHH levels with a
gene frequency of .283 and one, to produce low levels with a gene
frequency of .717). All six possible crossmatings were found in the
families studied, and no deviations from the expected phenotypes
were found in the children.

Cantrell, et al. (2), studied 19 healthy volunteers and found that
cigarette smokers had higher levels of AHH in their pulmonary
aveolar macrophages than nonsmokers. In one subject they showed
an increase in AHH activity starting 1 week after he began to smoke
10 to 15 cigarettes per day (2, Fig. 1). Holt and Keast (7) also
showed increased levels of AHH activity in homogenates of lung
tissue from mice exposed to cigarette smoke.

Kellermann (9) also studied the inducibility of AHH in the
lymphocytes of 50 patients with bronchogenic carcinoma and
compared them to a healthy white population and to a group of
patients with nonrespiratory malignancies (Table 3). They found that
lung cancer patients had a statistically significant, higher percentage
of persons homozygous for the high allele, i.e., able to be induced to
high AHH levels, than either the healthy or tumor controls. They
postulated that the reason for the greater frequency of persons
homozygous for the high AHH inducibility allele in the lung cancer
group was that this group was more susceptible to lung cancer due to
their increased ability to convert polycyclic aromatic hydrocarbons
into carcinogenic metabolites. The incidence of lung cancer,

5]
however, does not show a markedly familial occurrence pattern;
therefore, a single genetic locus can not be the major factor
determining susceptibility. Persons with increased ability to
metabolize polycyclic aromatic hydrocarbons may well be a group at
increased risk of developing lung cancer if they smoke; however,
prospective studies of random populations controlled for smoking
and environmental factors will be necessary before this genetic
susceptibility can be confirmed.

FIGURE 1.—Production of aryl hydrocarbon hydroxylase (AHH) in macrophages
from one person in response to cigarette smoking

 

 

0.05
.
€
o 0.04 _
3
a
E
% 0.03_]
°
&
a
2
= 0.02 _]
3
=x
=
< 0.01 fom
AN
q AN T J t ! t J I t T t
—115 0 10 20 30 40 50 60 70 80 90
DAYS

NOTE.—Shaded bar indicates duration of smoking; the vertical lines indicate
the range of duplicate determinations at each time period.

Source: Cantrell, E.T., et al. (2),

52
es

TABLE 3. — Aryl hydrocarbon hydroxylase (AHH) inducibility in patients
with lung cancer, with other tumors, and in healthy controls

 

 

NUMBER IN DISTRIBUTION OF GENE FREQUENCIES
GROUP GROUP GENOTYPES ( PERCENT)! OF A AND B ALLELES

AA AB BB A B
Healthy control 85 44.7 45.9 9.4 0.676 0.324
Tumor control 46 43.5 45.6 10.9 0.663 0.337
Lung cancer 50 4.0 66.0 30.0 0.370 0.630

 

 

 

 

TAA = low inducibility; AB = intermediate inducibility; BB = high inducibility

Source: Kellerman, G., et al. (9).
SUMMARY OF RECENT CANCER FINDINGS

1. Filter cigarette smokers have a lower risk of developing lung
cancer than nonfilter cigarette smokers, but that risk is still greater
than the risk to nonsmokers and increases with increasing number of
filtered cigarettes smoked.

2. Cigarette smoking and exposure to radioactivity by uranium
mining have been related to cytologic changes in the respiratory tract
epithelium including carcinoma in situ. Cigarette smoking has been
more strongly related to these changes than mining exposure.

3. Crysotile asbestos has been shown to contain traces of the
carcinogen benzo(a)pyrene, and the combination of the two has been
shown to be a more potent carcinogen in rats than either alone.

4. Heavy smoking prior to a first primary oral or respiratory
cancer has been shown to be related to the development of a second
primary in the respiratory tract or oral cavity.

5. Results from one study have shown a greater proportion of
lung cancer patients having high levels of aryl hydrocarbon
hydroxylase activity than among either healthy persons or persons
with other cancers. Persons with high levels of AHH may be a group
which has a genetically determined increased risk of lung cancer if
they smoke, but no excess risk if they do not smoke.

54
10

12

13

BIBLIOGRAPHY

AMERICAN CANCER SOCITY. ’75 Cancer Facts and Figures. New York, N.Y., 1974,
31 pp.

CANTRELL, E. T., MARTIN, R. R., WARR, G. A., BUSBEE, D. L., KELLERMANN,
G., SHAW, C. Induction of aryl hydrocarbon hydroxylase in human pulmonary
alveolar macrophages by cigarette smoking. Transactions of the Association of
American Physicians, 86th Session, Atlantic City, New Jersey, May 1-2, 1973. 86:
121-130.

HARRIS, C.C. The epidemiology of different histologic types of bronchogenic
carcinoma. Cancer Chemotherapy Reports 4(2, Part 3): 59-61, March 1973.

HIGGINS, I. T. T. Trends in respiratory cancer mortality: In the United States and in
England and Wales. Archives of Environmental Health 28(3): 121-129, March
1974.

HOFFMANN, D., HECHT, S.S., ORNAF, R.M., WYNDER, E. L. N’-nitrosonor-
nicotine in tobacco. Science 186(4160): 265-267, October 18, 1974.

HOFFMANN, D., WYNDER, E.L. Chemical composition and tumorigenicity of
tobacco smoke. In: Schmeltz, I. (Editor). The chemistry of tobacco and tobacco
smoke. Proceedings of the symposium on the chemical composition of tobacco
and tobacco smoke held during the 162nd National Meeting of the American
Chemical Society in Washington, D.C., September 12-17, 1971. Plenum Press,
New York, 1972, pp. 123-147.

HOLT, P.G., KEAST, D. Induction of aryl hydrocarbon hydroxylase in the lungs of
mice in response to cigarette smoke. Experientia 29: 1004, August 15, 1973.

KELLERMANN, G., LUYTEN-KELLERMANN, M., SHAW, C. R. Genetic variation of
aryl hydrocarbon hydroxylase in human lymphocytes. American Journal of
Human Genetics 25: 327-331, 1973.

KELLERMANN, G., SHAW, C.R., LUYTEN-KELLERMANN, M. Aryl hydrocarbon
hydroxylase inducibility and bronchogenic carcinoma. New England Joumal of
Medicine 289(18)}: 934-937, November 1, 1973.

LIN, T. M., CHEN, K. P., LIN, C.C., HSU, M. M., TU, S. M., CHIANG, T. C., JUNG,
P. F., HIRAYAMA, T. Retrospective study on nasopharyngeal carcinoma. Journal
of the National Cancer Institute 51(5): 1403-1408, November 1973.

SACCOMANNO, G., ARCHER, V.E.. AUERBACH, O., SAUNDERS, R. P.,
BRENNAN, L.M. Development of carcinoma of the lung as reflected in
exfoliated cells. Cancer 33(1): 256-270, January 1974.

SCHMAUZ, R., COLE, P. Epidemiology of cancer of the renal pelvis and ureter.
Journal of the National Cancer Institute 52(5): 1431-1434, May 1974.

SCHOTTENFELD, D., GANTT, R.C., WYNDER, E.L. The role of alcohol and

tobacco in multiple primary cancers of the upper digestive system, larynx, and
lung: A prospective study. Preventive Medicine 3(2): 277-293, June 1974.

55
14

15

16

17

18

19

20

21

22

23

24

25

26

56

SCHREIBER, H., NETTESHEIM, P., LIJINSKY, W., RICHTER, C. B., WALBURG,
H.E., Jr. Induction of lung cancer in germ-free specific-pathogen-free, and
infected rats by N-nitrosoheptamethyleneimine: Enhancement by respiratory
infection. Journal of the National Cancer Institute 49(4): 1107-1114, October
1972.

SCHREIBER, H., SACCOMANNO, G., MARTIN .D. H., BRENNAN, L. Sequential
cytological changes during development of respiratory tract tumors induced in
hamsters by benzo(a)pyrene-ferric oxide. Cancer Research 34(4): 689-698, April
1974.

SELIKOFF, I. J.. HAMMOND, E.C., CHURG, J. Mortality experiences of asbestos
insulation workers 1943-1968. Pneumoconiosis. Proceedings of the International
Conference on Pneumoconiosis, 3d, Johannesburg, 1969. Oxford University Press,
New York, 1970. Pp. 180-186.

SHABAD, L.M., PYLEV, L.N., KRFIVOSHEEVA, L.V., KULAGINA, T. F.,
NEMENKO, B. A. Experimental studies on asbestos carcinogenicity. Journal of
the National Cancer Institute $2(4): 1175-1187, April 1974.

U.S. PUBLIC HEALTH SERVICE. Smoking and Health. Report of the Advisory
Committee to the Surgeon General of the Public Health Service. Washington, U.S.
Department of Health, Education, and Welfare, Public Health Service Publication
No. 1103, 1964, 387 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Public
Health Service Review: 1967. U.S. Department of Health, Education, and
Welfare. Washington, Public Health Service Publication No. 1696, Revised
January 1968, 227 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. 1968.
Supplement to the 1967 Public Health Service Review. U.S. Department of
Health, Education, and Welfare. Washington, Public Health Service Publication
1696, 1968, 117 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. 1969.
Supplement to the 1967 Public Health Service Review. U.S, Department of
Health, Education, and Welfare. Washington, Public Health Service Publication
1696-2, 1969, 98 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Report of
the Surgeon General: 1971. U.S. Department of Health, Education, and Welfare.
Washington, DHEW Publication No. (HSM) 71-7513, 1971, 458 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking: A Report of
the Surgeon General: 1972. U.S. Department of Health, Education, and Welfare.
Washington, DHEW Publication No. (HSM) 72-6516, 1972, 158 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking: 1973. U.S.
Department of Health, Education, and Welfare. Washington, DHEW Publication
No. (HSM) 73-8704, 1973, 249 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking: 1974. U.S.
Department of Health, Education, and Welfare. Washington, DHEW Publication
No. (CDC) 74-8704, 1974, 124 pp.

WYNDER, E. L., MABUCHI, K., BEATTIE, E. J., Jr. The epidemiology of lung cancer.
Journal of the American Medical Association 213(13): 2221-2228, September 28,
1970.
CHAPTER 3
Non-Neoplastic Bronchopulmonary Diseases
CHAPTER 3
Non-Neoplastic Bronchopulmonary Diseases

Contents

Page

Introduction .. 0.0.0... 02 eee ete 61
Smoking and Respiratory Morbidity ...........--2 +++ eee e rere 62
Smoking and Air Pollution... 2.6... 0-2-0. 63
Smoking and Occupational Disease ....-..--- 2-02 e eee certs 68
Mill Workers — Byssinosis. ©... 2... +--+ ee rece reer 68
Firemen 2.0... cee ee eee eee 68
Smoking and Pulmonary Function Tests ..... 2.2... 2602 - cere eeee 71
a,-Antitrypsin 0. ens 72
Autopsy and Pathophysiologic Studies .....--. 2-6 +--+ e sere eres 74
Autopsy Studies... 2.26.0 ee ee eee 74
Pathophysiologic Studies in Humans .....-.-..--- 2-0 --5-- 76
Pathophysiologic Studies in Animals ....-..--------+ +00 0-> 77
Summary of Recent Bronchopulmonary Findings ........--.--.-+-- 78

Bibliography .... 2.022 ee eens 79
List of Figures

Figure 1.—Respiratory bronchiolitis in smokers and

control groups .... 0.2.0.0... 00. eee eee eee nee

List of Tables

Table 1.—Levels of sulfur dioxide (SO, ) and total
suspended particulates (TSP) in four Utah
communities, 1971, and in five Rocky Mountain

communities, 1970 ........0..00 000... cc eee eee

Table 2.-Mean annual levels of sulfur dioxide (SO.) and
total suspended particulates (TSP) in four

C7: Sr

Table 3.—Age-adjusted percentage of cigarette smokers
and nonsmokers in each race-sex group responding
positively to exposure to chemicals, fumes, sprays,

and dusts 2... 2.0... cee eee ee eee eee

Table 4.—The a, -antitrypsin levels and frequency of
protease inhibitor (Pi) phenotypes in healthy

populations... 2.0... ee ee eee

Table 5.—Means of the numerical values given lung
sections at autopsy of male current smokers and non-

smokers, standardized forage ..................4..

Table 6.—Means of the numerical values given lung sections .
at autopsy of female current smokers and nonsmokers,

standardized for age .....................000000.

Table 7.—Means of the numerical values given lung
sections at autopsy of male former cigarette

smokers, standardized forage ...0................0.

Page
INTRODUCTION

Chronic non-neoplastic lung diseases are major causes of
permanent and temporary disability in the United States. Chronic
obstructive pulmonary disease (COPD) is the largest subgroup of
these diseases and in this report refers to chronic bronchitis and/or
emphysema. Relationships between smoking and non-neoplastic lung
diseases have been reviewed in previous reports on the health
consequences of smoking (36, 37, 38, 39, 40, 41, 42, 43).

Cigarette smoking is the most important cause of COPD.
Cigarette smokers have higher death rates from chronic bronchitis
and emphysema, more frequently report symptoms of pulmonary
disease, and have poorer performance on pulmonary function tests
than do nonsmokers. These differences become even more marked as
the number of cigarettes smoked increases. The relationship between
cigarette smoking and COPD has been demonstrated in many
different national and ethnic groups and is more striking in men than
in women. Pipe and cigar smokers have higher morbidity and
mortality rates from COPD than do nonsmokers but are at lower risk
than cigarette smokers. Cessation of cigarette smoking often results
in improved pulmonary function tests, decreased pulmonary symp-
toms, and reduced COPD mortality rates.

In addition to an increased risk of COPD, cigarette smokers are
more frequently subject to and require longer convalescence from
other respiratory infections than nonsmokers. Also, if they require
surgery, they are more likely to develop postoperative respiratory
complications.

The relative importance of air pollution in the development of
COPD remains controversial, but it is clearly less significant under
most circumstances than cigarette smoking. The combination of
cigarette smoking and polluted air, however, may produce higher
rates of COPD than either factor alone.

Several occupational exposure groups incur an increased risk of
COPD, and cigarette smoking adds significantly to this risk. In
particular, exposure to cotton fiber and coal dust appears to act in
concert with cigarette smoking to promote the development of
pulmonary disease.

61
Autopsy studies have demonstrated a dose-related effect of
cigarette smoking on the severity of macroscopic emphysema.
Increased goblet cell density, alveolar septal rupture, bronchial
epithelial thickening, and mucous gland hypertrophy are more
commonly found in the lungs of smokers than in those of
nonsmokers.

Many pathophysiologic mechanisms by which smoking may
cause COPD have been proposed. Decreased overall pulmonary
clearance, reduced ciliary motion, and impaired alveolar macrophage
functions have all been related to cigarette smoking and probably
play a role in the development of COPD. The exact mechanisms
whereby cigarette smoking contributes to the development of COPD,
however, remain only partially understood.

SMOKING AND RESPIRATORY MORBIDITY

An increased prevalence of respiratory symptoms in smokers
from early teens to those past the age of 80 has been well
established. Bewley, et al. (5), in a study in Derbyshire County,
England, extended these findings to include younger children. In a
questionnaire study of 7,115 schoolchildren ages 10 to 11% years, he
found that 6.9 percent of the boys and 2.6 percent of the girls
smoked more than one cigarette per day. The boys who smoked
reported more morning cough (21.5% to 6.1%), cough during the day
or night (48.0% to 20%), and cough of 3-months duration (18.0% to
4.1%) than their nonsmoking schoolmates. The percentages for the
girls were similar although based on smaller numbers of smokers. As
in many studies of this type, it was impossible to control for air
pollution, social class, or smoking habits of the parents; nevertheless,
the results suggest that cigarette smoking even in this young age
group produces respiratory symptoms.

Fridy, et al. (/2), in a somewhat older population (average age
25 years), examined the effect of smoking on airway function during
mild viral illness. They measured closing volumes for 22 subjects (9
cigarette smokers — average age 29.1, and 13 nonsmokers — average
age 25.7) before onset and at weekly intervals from the beginning of
a mild respiratory illness until all symptoms had subsided. The
closing volumes for smokers prior to illness were higher than those
for nonsmokers, but the difference was not statistically significant.
In the tests done during the illness, the smokers had a statistically
significant increase in the closing volumes (from 37.0 to 45.8 percent
of their total lung capacity, while nonsmokers had no change, 32.7

62
and 31.7 percent). Smokers remained symptomatic more than twice
as long as nonsmokers (35.7 and 16.5 days, respectively), and the
mean duration. of pulmonary function abnormalities in smokers was
29.7 days. Nonsmokers had no change in pulmonary function tests
during illness.

SMOKING AND AIR POLLUTION

The relationships among air pollution, smoking, and COPD
remain controversial. Reasons for this controversy include difficulties
in controlling such variables as socioeconomic class, degree of
crowding, ethnic differences, and age distribution as well as
determining the exact type and amount of individual pollution
exposure. Measuring individual pollution exposure even within a
small area is difficult since both amount and type can vary
dramatically from street to street (e.g., proximity of a street to a
heavily traveled expressway).

In an effort to control as many of these variables as possible,
two basic approaches in study design have been tried. The first
approach is to find areas where pollution levels have been well
measured and then to select study populations that are as similar as
possible in areas with different pollution levels. Thus, effects on a
population in a low pollution area can be compared to those on a
similar population in a high pollution area. The second approach is to
select a population that is as uniform as possible, for example, twins,
and then measure individual responses to different pollution expo-
sures. Both approaches have drawbacks as will be evident from the
following studies.

Using the first approach, the Community Health and Environ-
mental Surveillance System of the Environmental Protection Agency
(6, 11), has conducted surveys in areas with different types and levels
of pollution in four different parts of the United States (Chicago,
New York City, the Salt Lake Basin, and the Rocky Mountain area).
Within each part of the country, the researchers identified communi-
ties of similar socioeconomic status but different pollution levels.
They then administered a questionnaire through the school systems
to determine the frequency of lower respiratory tract infection in the
children and their families. They reported an increased incidence of
lower respiratory tract illness in children in high pollution communi-
ties compared to children in low pollution communities. This
difference was demonstrable only in children whose families had
lived in the high pollution communities for more than 3 years. They
also reported an increased prevalence of chronic bronchitis in parents

63
who lived in high pollution communities compared to parents from
low pollution communities. They calculated the excess risk of
chronic bronchitis produced by air pollution to be one-third of that
produced by smoking but to be additive with smoking.

Several major problems in these surveys make it difficult to
evaluate the results. The authors describe the areas as having
different kinds of pollution. The Salt Lake Basin and Rocky
Mountain areas were felt to be high in sulfur dioxide (SO) and low
in total suspended particles (TSP), while New York and Chicago were
high in both these pollutants. As a result, in the Salt Lake Basin and
Rocky Mountain areas, communities were separated into low and
high pollution communities only on the basis of their SO, levels.
Many communities classified as low pollution communities on the
basis of their SO, levels had higher levels of total suspended particles
than the communities classified as high pollution communities by
SO, level (Table 1). In fact, the average total suspended particles
level for the low pollution communities in the Salt Lake Basin was
higher than that for the high pollution communities (Table 2) in the
Salt Lake Basin. These differences exemplify the difficulties of using
only one pollutant as a marker of total pollution exposure.

Additional problems with these studies were the differences in
socioeconomic class measurements between low and high pollution
communities in some of the regions. In the Rocky Mountain area,
the percentage of fathers who completed high school varied from 91
percent in one of the low communities to 58 percent in one of the
high pollution communities. There were also major differences
between high and low pollution communities in the percentage of
families with more than one person per room in the Salt Lake Basin
(59.6% to 51.2%), Rocky Mountain area (87.0% to 68.0%), and New
York (85.0% to 72.0%). Residential stability (percentage of families
living in the community for more than 3 years) was different in the
high and low pollution communities in New York (58.0% to 36.0%)
and Chicago (56.0% to 46.0%). The percentage of parents who
currently smoke also differed for high and low pollution communi-
ties in New York (53% to 45% for the fathers and 47% to 37% for
the mothers). These differences raise questions as to whether the
high and low pollution communities were really similar enough
populations to justify the claim that differences in incidence of
respiratory tract illness could be attributable to differences in air
pollution.

64
$9

TABLE 1. — Levels of sulfur dioxide (SO2) and total suspended particulates (TSP)
in four Utah communities, 1971, and in five Rocky Mountain

communities, 1970

 

 

 

 

Community Pollution levels
Area Pollution in pg/m3

Classification S03 TSP
Utah (Salt Lake Basin) Low 8 78
Intermediate 1 15 81
Intermediate 2 22 45
High 62 66
Rocky Mountain Area Low 1 10 50
Low 2 26 68
Low 3 46 110
High 1 109 43
High 2 186 102

 

 

 

Source: Chapman. R.S., et al. (6).
99

TABLE 2. — Mean annual levels of sulfur dioxide (SO2) and total suspended

particulates (TSP) in four areas

 

Pollution tevels in ug/m3

 

 

 

Area SO? TSP
Decade Decade
During Study Preceding Study During Study Preceding Study
Low High Low High Low High Low High
Five Rocky
Mountain Areas 10 275 10 263 45 110 50 101
Salt Lake Basin 9 65 < 20 144 78 66 82 62
New York 23 63 < 30 431 34 104 40 201
Chicago 57 106 109 250 111 151 121 165

 

 

 

NOTE. — Area includes highest- and lowest-polluted communities,

Source: French, J.G., et al. (17).
Increased prevalence of COPD has also been demonstrated in
areas of high pollution in the Netherlands (44), Yokkaichi, Japan
(25), and Cracow, Poland (30). Again, however, these studies were
poorly controlled for socioeconomic status.

Several recently published studies have used the second major
method of investigating the relationship between smoking, air
pollution, and COPD, i.e., to select a uniform population and then to
measure individual differences to pollution exposure. Comstock, et
al. (8), in an attempt to control for occupational exposure and
socioeconomic class, studied three separate, uniform populations of
telephone workers and used as a measure of pollution the location of
the place of work and residence. The populations studied were
telephone installers and repairmen in Baltimore, New York City,
Washington, D.C., and rural Westchester County in 1962 (survey 1)
and in 1967 (survey 2); and telephone installers and repairmen in
Tokyo in 1967 (survey 3). They were unable to find any relation
between pulmonary symptoms and degree of urbanization of place
of work or place of residence (either current or past). They were,
however, able to establish a strong correlation between smoking
habits and pulmonary symptoms. Given the crude estimation of
pollution exposure used in this study (all workers in each city were
treated as though they received the same exposure), a small
difference in symptoms due to air pollution could have been missed,
whereas the difference due to smoking could be detected both
because it was larger and because it was possible to determine
individual exposure more exactly.

Hrubec, et al. (75), in a study of twins from the U.S. Veterans
Registry, were unable to show a difference in respiratory symptoms
either between individuals with different exposure to air pollution or
between members of twin pairs with different air pollution ex po-
sures. However, they too used a crude measure of air pollution
exposure (by each zip code area), and so could have missed a small
difference due to air pollution despite being able to relate respiratory
symptoms to smoking, socioeconomic status, and alcohol intake.

Colley, et al. (7), in a study of 3,899 persons (20-year-olds born
during the last week of March 1946 in the United Kingdom), were
also unable to show a relation between COPD and air pollution. They
used as their estimates of air pollution exposure the domestic coal
consumption in the towns where the subjects lived. This method of
estimating air pollution exposure is subject to the same limitation
cited for the previous two studies — limited sensitivity to small risks
due to air pollution.

67
In summary, if an increased risk of COPD due to air pollution
exists, it is small compared to that due to cigarette smoking under
conditions of air pollution to which the average person is exposed.
The possibility remains that the two different kinds of exposure may
interact to increase the total effect beyond that contributed by each
exposure.

SMOKING AND OCCUPATIONAL DISEASE

Friedman, et al. (/3), in a study of 70,289 men and women
who had had Kaiser-Permanente multiphasic health checkups, noted
that smokers were more likely to report occupational exposure on a
questionnaire (Table 3) than nonsmokers. The differences are small
but statistically significant and need to be considered when investi-
gating the relationship of smoking to occupational diseases. They
were not able to determine whether smokers’ responses reflect actual
differences in exposure or an increased awareness of and sensitivity
to occupational exposure.

Exposure to coal and granite dust and cotton fiber carries an
increased risk of COPD. This risk is further increased by cigarette
smoking. Other new data have been published which clarify the risk
in certain occupational groups.

Mill Workers — Byssinosis

Berry, et al. (4), in a study of 595 workers in the Lancashire
cotton mills over a 3-year period, found that the decline in forced
expiratory volume in one second (FEV) was 19 ml/year greater in
smokers than in nonsmokers (59 ml/year compared to 40 ml/year, P
> .02) but they could not demonstrate a dose-response relationship.

Firemen

Sidor and Peters (32, 33), in a cross-sectional study of 1,768
Boston firemen, were unable to show a significant relationship
between severity of fire exposure and impairment of pulmonary
function tests or prevalence of COPD; there was a clear harmful
effect of cigarette smoking on both. They postulate that they were
unable to show an increased prevalence of COPD in this cross-sec-
tional study because firemen who developed COPD were no longer
capable of meeting the physical demands of the job and had retired,
thus removing them from the study population. They were able,
however, to show a higher incidence of COPD in men under the age
of 35 years who had been on the force more than 6 months when
compared to persons of the same age who had just been hired.

68
69

TABLE 3. — Age-adjusted percentage of cigarette smokers and nonsmokers in each race-sex group

responding positively to exposure to chemicals, fumes, sprays, and dusts

 

 

 

 

 

 

 

Whites Blacks Yellows
Exposure Time period! Smoking status
% % % % % %
Men Women Men Women | Men Women
Chemicals, cleaning Before | year ago Smokers 24.0 6.4 26.0 11.8 16.7 4.1
fluids or solvents (or Nonsmokers 18.9 5.1 19.2 6.7 12.9 5.1
chemical sprays)2
In the past year Smokers 12.1 3.0 14.2 5.1 13.1 3.5
Nonsmokers 9.7 2.6 11.6 4.5 9.4 3.8
Insect or plant sprays Before | year ago Smokers 4.0 1.0 6.6 2.1 3.8 0.3
Nonsmokers 3.5 0.9 5.1 19 2.5 1.0
In the past year Smokers 2.9 . 4.8 2.9 3.0 1.3
Nonsmokers 2.9 1.8 4.8 3.0 3.6 1.8
Ammonia, chlorine, Before 1 year ago Smokers 79 2.3 10.3 48 6.2 0.9
ozone or nitrous gases Nonsmokers 6.2 1.9 7.0 3.2 4.5 1.7
(nitrous oxides or
other irritating gases)2 In the past year Smokers 5.4 1.9 76 3.9 8.0 0.5
Nonsmokers 3.7 1.5 5.8 3.1 3.5 1.7
Engine or exhaust fumes Before | vear ago Smokers 11.8 1.0 17.6 1.9 4.0 0.0
(more than 2 hours a Nonsmokers 6.9 0.5 13.1 0.6 3.6 0.1
day)2
In the past year Smokers 8.7 0.7 17.6 1.0 4.3 0.5
Nonsmokers $.2 0.5 13.3 1.2 3.9 0.2

 

 
OL

TABLE 3. — Age-adjusted percentage of cigarette smokers and nonsmokers in each race-sex group

responding positively to exposure to chemical, fumes, sprays, and dusts — Continued

 

 

 

 

 

 

Whites Blacks Yellows
Exposure Time period! Smoking Status % % % % % %

Men Women Men Women| Men Women

Plastic or resin fumes Before | year ago Smokers 5.1 1.1 3.3 1.2 3.1 0.1

Nonsmokers 3.5 0.8 3.0 0.6 2.2 0.3

In the past year Smokers 3.3 0.8 3.9 0.9 3.0 0.1

Nonsmokers 2.5 0.6 4.3 0.6 1.3 0.3

Lead fumes or metal Before 1 year ago Smokers 8.2 0.9 9.1 1.5 4.1 0.1

fumes (leaded sprays Nonsmokers 4.3 0.5 5.8 0.6 2.6 0.1
or paint sprays) 2

In the past year Smokers 5.5 0.7 V7 1.3 3.3 0.5

Nonsmokers 3.1 0.5 6.8 0.8 2.4 0.4

Asbestos, cement or Before 1 year ago Smokers 7 0.6 11.5 1.2 2.7 0.0

grain (or flour) dusts2 Nonsmokers 4.4 0.3 8.8 0.8 1.6 0.1

In the past year Smokers 2.8 0.4 75 1.0 2.7 0.1

Nonsmokers 1.8 0.3 6.2 0.8 0.3 0.8

Silica, sandblasting, Before 1 year ago Smokers 6.9 0.6 10.5 1.3 3.5 0.3

grinding or rock drill- Nonsmokers 4.0 0.5 6.8 0.7 2.9 0.0
ing dust (sand or

coal)2 In the past year Smokers 3.9 0.5 8.0 1.0 3.3 0.4

Nonsmokers 2.3 0.4 6.6 0.9 3.5 0.4

Total number of subjects Smokers 14,485 16,059 2,609 2.869 654 446

Nonsmokers 8,282 18,526 1,116 3,218 712 1,313

 

 

 

 

 

lwith a few slight variations, the questions were worded as follows:

Before 1 year ago: ‘“‘Before 1 year ago have you ever worked ina place where you were often or daily around

In the past year: ‘‘In the past year have you worked in a place where you were often or daily around

2rA4ateriol in OMrentheses appears in Cast year’) uwntiae tue mes io tafore ¢

 

war mages” spurmatderc-

ge
SMOKING AND PULMONARY FUNCTION TESTS

It is recognized that smokers as a group have poorer pulmonary
function tests than nonsmokers. The standard pulmonary function
tests generally only become abnormal late in the pathologic process
of COPD and usually only after irreversible changes in the lungs have
occurred. As a result, tests are needed that will identify persons at
risk of developing COPD before they have irreversible loss of lung
function. Standard tests of pulmonary resistance are inadequate for
this purpose because they measure predominately resistance in the
large airways while the first changes of COPD occur in bronchioles
that are 2 mm and smaller. Small airway resistance may be measured
through evaluating frequency dependent compliance, but this is often
cumbersome to perform. Closing volume and maximum ex piratory
flow rates at 25 and 50 percent of vital capacity have the advantage
of being relatively easy to perform, yet are still able to measure
changes in the small airways. Closing volume is the lung volume at
which the alveoli in the dependent portions of the lung begin to
close, and it is usually expressed as a percent of vital capacity.
Elevated closing volume is considered evidence of small airway
dysfunction. Maximum expiratory flow rates at 25 and 50 percent of
vital capacity measure air flow at low lung volumes where the
resistance of the small airways makes up a much larger proportion of
the measured resistance.

Several recently published studies contain data on small airway
dysfunction in smokers. Lim (20) studied 50 smoking and 50
nonsmoking high school students and found in smokers a statistically
significant reduction in the forced expiratory volume in one second
when the test was started at normal end expiration (i.e., low lung
volumes). Stanescu, et al. (34) noted elevated closing volumes in 16
healthy asymptomatic smokers when compared to 16 nonsmokers,
but were unable to show any difference in maximum expiratory flow
rates at 25 and 50 percent vital capacity. Ruff, et al. (28) studied 50
subjects ages 18 to 82 and showed increasing closing volumes with
age and smoking. Martin, et al. (2/), in a study of 50 subjects ages 12
to 68, found that 25 percent of the smokers had abnormal closing
volumes, and Oxhoj, et al. (26) noted elevated closing volumes for
50-year-old smokers compared to nonsmokers. Dirksen, et al. (0)
reported higher closing volumes in smokers and noted no change
with cessation of smoking. Hoeppner, et al. (/4) also showed elevated
closing volumes in healthy smokers ages 16 to 6 1, but found these to
be closely related to decreases in the static transpulmonary pressure.
They postulate that the elevated closing volumes may be related to
decreased elastic recoil rather than changes in small airway resistance.

71
The data have established the fact that a greater percentage of
smokers than nonsmokers have elevated closing volumes, but the
number of smokers with elevated closing volumes who will develop
COPD remains to be determined.

Stebbings (35), in a further analysis of Densen’s data (9) on
the changes in pulmonary function test values in male postal workers
and transit workers in New York City, noted significantly less decline
in FEV; among Black smokers when compared to White smokers.
This difference persisted even when corrections were made for
differences in amount smoked, age at which smoking began,
inhalation patterns, and smaller initial lung volumes in Blacks. Black
and White nonsmokers did not differ in the rate of decline in FEV.
By age 60 years, Blacks who smoked one pack per day had a .34 liter
smaller cumulative decrease in FEV, than Whites who smoked the
same amount.

a ,-ANTITRYPSIN

It would be useful to identify the populations at excessive risk
of developing COPD from smoking. They then might be made aware
of the hazard before they develop symptomatic lung disease. Persons
with a, -antitrypsin deficiency may be such a population.

a,-antitrypsin deficiency is a rare homozygous recessive genetic
defect which occurs in approximately one out of every 3,600 people
and results in an increased susceptibility to and premature develop-
ment of COPD. There is some evidence that smoking hastens the
development of COPD in these people. The heterozygous state
(producing intermediate levels of the a, -antitrypsin in serum) is far
more common than the homozygous state and is found in approxi-
mately 10 percent of the population. It is uncertain whether the
heterozygous deficiency state predisposes to COPD.

a,-antitrypsin inheritance patterns suggest multiple codominant
alleles at one gene locus, some of which (most notably the S and Z
alleles) produce lower serum protease levels than the normal M-allele
(Table 4). The pathophysiologic mechanism of the deficiency state is
felt to be the inability to inhibit the proteases found in the
granulocytes and pulmonary macrophages which go on to damage
essential constituents of lung tissue. Several recent reviews of the
enzyme and the clinical syndrome produced by its deficiency have
been published (76, 77, 78).

72
TABLE 4.— The 4 ,-antitrypsin levels and frequency of
protease inhibitor (Pi) phenotypes in healthy populations

 

 

 

Healthy popuiations
Protease Expected
inhibitor ay-antitrypsin frequency of
concentration Pi types
(Pi) type (% normal) (per 1,000 people)
MM 100 898
(FM,FF,IM,MV,MX) 100 28
MW 80 -a
MP 80 I
MS 80 41
(FS,IS) 80 i
MZ 60 29
(FZ) 60 i
SS 55 1
SZ 40 1
ZZ 15 <1

 

 

4 Seen rarely in Spanish populations.
Source: Mittman, C., Lieberman, J. (22).

In most studies of patients with COPD, investigators have found
an increased prevalence of the partially deficient heterozygote
phenotypes when compared to healthy control populations. In the
few studies not finding this relationship, only a ,-antitrypsin levels
were measured. Because a,-antitrypsin is an acute phase protein and
increases with infection, it is difficult to separate out the partially
deficient heterozygote phenotypes by measuring only a,-antitrypsin
levels. It is necessary to identify the products of each allele
electrophoretically in order to identify the deficient phenotypes.

Two recent studies using this technique showed an increased
prevalence of deficient phenotypes in patients with COPD but not
among control populations. Mittman, et al. (23) studied 240 patients
with COPD admitted to LaVina Hospital in Altadena, California, and
found that 19.1 percent had deficient phenotypes compared to only
7.1 percent of a control Scandinavian population. Keuppers and
Donhardt (79) found prevalence rates for deficient phenotypes of
3.5 percent in healthy controls, 12.9 percent in persons retired from
work because of COPD, and 15.7 percent in patients hospitalized for
COPD.

73
Additional population studies have been done to determine the
effect of the heterozygous state on the development of COPD. Webb,
et al. (47) studied 500 persons visiting a multiphasic screening clinic
in Monroe County, New York, and found that 11.6 percent had
deficient phenotypes. He was unable to show differences in
symptoms or in pulmonary function test values between persons with
normal and deficient phenotypes. In a study of 451 randomly
selected adults from the same county (3/), pulmonary function
studies were done on 40 deficient heterozygote phenotypes (20 MS
and 20 MZ) and on normal phenotype (MM) controls matched for
age, sex, and smoking habits. When total pulmonary resistance was
measured by a forced oscillometric technique, the nonsmoking MZ
subjects had significant impairment compared to their normal
phenotype controls. All cigarette smokers, regardless of phenotype,
had abnormal values.

Although the data are still inconclusive, it may well be that
heterozygous deficient persons are a group at excessive risk of
developing COPD especially if they smoke.

AUTOPSY AND PATHOPHYSIOLOGIC STUDIES
Autopsy Studies

Auerbach, et al. (3) have previously shown dose-related macro-
scopic emphysematous changes in the lungs of smokers. Now in an
autopsy study (2) of 1,582 men and 388 women, they have
examined microscopic lung parenchymal changes in relation to
cigarette smoking. They were able to show that rupture of alveolar
septa (emphysema) and fibrosis and thickening of the small arteries
and arterioles are far greater in smokers than nonsmokers and
increase with increasing amount smoked (Tables 5 and 6).

When these researchers examined former cigarette smokers,
they found that those who had stopped more than 10 years prior to
death had fewer pathologic changes than those who had stopped less
than 10 years before death. But even in those who had stopped for
more than 10 years, there was a greater degree of pathologic change
in those who had been smoking more than one pack per day than in
those who had been smoking less than one pack per day (Table 7).

Niewoehner, et al. (24), in an autopsy study of 39 men who

died suddenly from various causes and who were below 40 years of
age (20 nonsmokers and 19 smokers), observed a respiratory

74
SL

LABLE 5, — Means of the numerical values given Ming sections at autopsy of
male current smokers and nonsmokers, standardized for age

 

 

 

 

 

 

Subjects Who Current Pipe Current Cigarette Smokers
Never Smoked or Cigar

Regularly Smokers <5 5-1 1-2 >2

Pk. Pk. Pk. Pk.
Number of Subjects 175 141 66 115 440 216
Emphysema 0.09 0.90 1.43 1.92 2.17 2.27
Fibrosis 0.40 1.88 2.78 3.73 4.06 4.28
Thickening of arterioles 0.10 ai 1.35 1.66 1.82 1.89
Thickening of arteries 0.02 0.23 0.42 0.68 0.83 0.90

 

NOTE. — Numerical values were determined by rating each tung section on scales of 0—4 for emphysema and thickening of
arterioles, O—7 for fibrosis, and 0—3 for thickening of the arteries.

Source: Auerbach, O,, et al. (2).

TABLE 6. — Means of the numerical values given lung sections at autopsy
of female current smokers and nonsmokers, standardized for age

 

 

 

Subjects Who Current Cigarette
Never Smoked Smokers
Regularly
<1 Pk. 21°Pk.
Number of Subjects 252 33 64
Emphysema 0.05 1.37 1.70
Fibrosis 0.37 2.89 3.46
Thickening of arterioles 0.06 1.26 1.57
Thickening of arteries 0.01 0.40 0.64

 

 

 

NOTE. — Numerical values were determined by rating each lung section on scales of O0—4 for

emphysema and thickening of the arterioles, O—7 for fibrosis, and 0-3 for thickening of the
arteries.

Source: Auerbach, O., et al. (2).
TABLE 7. — Means of the numerical values given lung sections at autopsy
of male former cigarette smokers, standardized for age

 

 

 

Stopped = 10 yr. Stopped <10 yr.
Formerly Smoked
<1 Pk Pk. <1 Pk. Pk.
Number of Subjects 35 66 51 131
Emphysema 0.24 0.70 1.08 1.69
Fibrosis 1.14 1.74 2.44 3.30
Thickening or arterioles 0.57 0.93 1.25 1.59
Thickening of arteries 0.04 0.16 0.36 0.61

 

 

 

NOTE. — Numerical values for each finding were determined by rating each lung section on
scales of O—4 for emphysema and thickening of the arterioles, O—7 for fibrosis,
and 0—3 for thickening of the arteries.

Source: Auerbach, O., et al. (2).

bronchiolitis associated with clusters of pigmented alveolar macro-
phages in the lungs of smokers. They found these changes only rarely
in the lungs of nonsmokers (Fig. 1). The smokers were young
(average age 25.7 years), were a heavy smoking population (average
20.1 pack years), but did not differ significantly from the non-
smokers in age, social class, or pollution exposure. However, 12 of
the 19 smokers had had productive cough or frequent cold compared
to only 3 of the 20 nonsmokers. These authors postulated that
bronchiolitis may be responsible for the abnormalities in the tests of
small airway function of smokers.

Pathophysiologic Studies in Humans

Yeager, et al. (48) showed decreased pinocytosis in human
alveolar macrophages obtained from asymptomatic cigarette smoking
volunteers when compared to those obtained from nonsmoking
controls.

Warr and Martin (46) studied alveolar macrophages lavaged
from four healthy smokers and four healthy nonsmokers. Only two
members of each group were reactive to delayed hypersensitivity skin
tests for Candida albicans. Macrophages from nonsmokers responded
to Migration Inhibitory Factor (MIF) by a depression in migration of
at least 30 percent, whereas macrophages from smokers did not
respond to MIF. The cells from smokers were noted to migrate three
times faster than those from nonsmokers. When Candida antigen was
added to the medium, cells from the nonreactive subjects (both

76
FIGURE 1.—Respiratory bronchiolitis in smokers and control group

 

 

 

 

T
5. eo | sesecoee

\ eeocesee
|

7 I

2 4E ° ! ee

3 |

E I

o I

w I

7. 1

¥ 3 ° I e

FE i

B !

9 i

“ 2 !

° I

oc ’

w i

@

= i

5 1 e t

é 1
'

OL ocveesece |
NONSMOKERS SMOKERS

NOTE .—The position of each symbai represents the number of sections
per case in which bronchiolitis was identified.

Source: Niewoehner, D.E., et al. (24).

smokers and nonsmokers) were not inhibited, the cells from the
reactive nonsmokers were inhibited, but the cells from reactive
smokers were not inhibited. Thus, macrophages from smokers did
not respond normally to either MIF or antigenic challenge.

Pathophysiologic Studies in Animals

Roszman and Rogers (27) noted that either the nicotine or the
water soluble fraction of whole cigarettes smoked suppressed the
immunoglobulin response of lymphoid cell cultures. When concentra-
tions of over 200 micrograms per milliliter of nicotine of the water
soluble fraction were added, they were able to completely suppress
the immunoglobulin response and to observe this suppression even in
cells exposed for 2 hours prior to the antigenic challenge.

Guinea pigs (29) exposed to the smoke of five cigarettes and
then lavaged 2 hours later had fewer pulmonary macrophages and
leukocytes in the lavage fluid than did controls not exposed to
smoke. The decrease in the number of macrophages was highly
correlated with acetaldehyde, tar, nicotine, hydrogen cyanide, and

77
acrolein concentrations in the cigarette smoke. The decrease in the
number of leukocytes was more closely correlated with pH of the
particulate phase and concentrations of acetaldehyde and tar.

Tracheal mucous velocity has been shown to be decreased in
purebred beagle dogs (45) exposed to 100 cigarettes per week for
13.5 months. In donkeys (/) low level exposure to whole cigarette
smoke accelerated tracheobronchial clearance, whereas at inter-
mediate and high levels of exposure, clearance was decreased. At high
exposure levels whole cigarette smoke had twice the effect of filtered
smoke in decreasing clearance.

SUMMARY OF RECENT BRONCHOPULMONARY FINDINGS

1. Cigarette smokers with mild viral respiratory illnesses have
been shown to develop abnormal but reversible changes in certain
pulmonary function tests while nonsmokers show no changes in
these tests. Cigarette smokers have also been shown to have a
significantly longer duration of respiratory symptoms following mild
viral illness than nonsmokers.

2. Cigarette smoking is more closely related to COPD than is air
pollution under the conditions of air pollution encountered by the
average person. The possibility remains that the two kinds of
exposure may interact to increase the total effect beyond that
contributed by each exposure.

3. Cigarette smokers without respiratory symptoms have evi-
dence of small airway dysfunction (elevated closing volumes) more
frequently than do nonsmokers without respiratory symptoms.

4. Autopsy studies have shown a dose-response relationship
between cigarette smoking and the microscopic changes of COPD.
Data from one study indicate that bronchiolitis may be a far more
common finding in cigarette smokers than in nonsmokers.

5. Pulmonary macrophages from cigarette smokers’ lungs have

a decreased ability to respond to in vitro antigenic stimuli as
compared to macrophages from smokers.

78
10

11

12

BIBLIOGRAPHY

ALLBERT, R.E., BERGER, J., SANBORN, K., LIPPMANN, M. Effects of cigarette
smoke components on bronchial clearance in the donkey. Archives of Environ-
mental Health 29 (2): 96-101, August 1974.

AUERBACH, O., GARFINKEL, L., HAMMOND, E. C. Relation of smoking and age to
findings in lung parenchyma: A microscopic study. Chest 65(1): 29-35, January
1974,

AUERBACH, O., HAMMOND, E. C., GARFINKEL, L., BENANTE, C. Relation of
smoking and age to emphysema: Whole-lung section study. New England Journal
of Medicine 286(16): 853-857, April 20, 1972.

BERRY, G., McKERROW, C.B., MOLYNEUX, M.K.B., ROSSITER, C. E.
TOMBLESON, J.B. L. A study of the acute and chronic changes in ventilatory
capacity of workers in Lancashire cotton mills. British Journal of Industrial
Medicine 30 (1): 25-36, January 1973.

BEWLEY, B.R., HALIL, T., SNAITH, A. H. Smoking by primary schoolchildren —
prevalence and associated respiratory symptoms. British Journal of Preventive and
Social Medicine 27 (3): 150-153, August 1973.

CHAPMAN, R.S., SHY, C. M., FINKLEA, J. F., HOUSE, D. E., GOLDBERG, H. E.,
HAYES, C.G. Chronic respiratory disease in military inductees and parents of
schoolchildren. Archives of Environmental Health 27(3): 138-142, September
1973.

COLLEY, J.R.T., DOUGLAS, J. W. B., REID, D. D. Respiratory disease in young
adults: Influence of early childhood lower respiratory tract illness, social class, air
pollution, and smoking. British Medical Journal 3(5873): 195-198, July 28, 1973.

COMSTOCK, G. W., STONE, R. W., SAKAI, Y., MATSUYA, T., TONASCIA, J. A.
Respiratory findings and urban living. Archives of Environmental Health 27(3):
143-150, September 1973.

DENSEN, P.M., JONES, E. W., BASS, H. E., BREUER, J., REED, E. A survey of
respiratory disease among New York City postal and transit workers. 2.
Ventilatory function test results. Environmental Research 2(4): 277-296, July
1969.

DIRKSEN, H., JANZON, L., LINDELL, S. E, Influence of smoking and cessation of
smoking on flung function. Scandinavian Journal of Respiratory Diseases

(Supplementum 85): 266-274, 1974.

FRENCH, J.G., LOWRIMORE, G., NELSON, W.C., FINKLEA, J. F., ENGLISH, T.,
HERTZ, M. The effect of sulfur dioxide and suspended sulfates on acute
respiratory disease. Archives of Environmental Health 27(3): 129-133, September
1973.

FRIDY, W.W., Jr, INGRAM, R.H., Jr, HIERHOLZER, J.C., COLEMAN, M.T.
Airways function during mild viral respiratory illnesses. The effect of rhinovirus
infection in cigarette smokers. Annals of Internal Medicine 80(2): 150-155,
February 1974.

79
13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

80

FRIEDMAN, G.D., SIEGELAUB, A. A., SELTZER, C.C. Cigarette smoking and
exposure to occupational hazards. American Journal of Epidemiology 98(3):
175-183, September 1973.

HOEPPNER, V.H., COOPER, D.M., ZAMEL, N., BRYAN, A.C., LEVISON, H.
Relationship between elastic recoil and closing volume in smokers and non-
smokers. American Review of Respiratory Disease 109(1): 81-86, January 1974.

HRUBEC, Z., CEDERLOF, R., FRIBERG, L., HORTON, R., OZOLINS, G.
Respiratory symptoms in twins. Archives of Environmental Health 27(3):
189-195, September 1973.

HUTCHISON, D.C.S. Alpha-l-antitrypsin deficiency and pulmonary emphaysema:
The role of proteolytic enzymes and their inhibitors. British Journal of Diseases
of the Chest 67(3): 171-196, July 1973.

KUEPPERS, F. a@;-antitrypsin and its deficiency. American Journal of Human Ge-
netics 25(6): 677-686, 1973.

KUEPPERS, F., BLACK, L. F. ay-antitrypsin and its deficiency. American Review of
Respiratory Disease 110(2): 176-194, August 1974.

KUEPPERS, F., DONHARDT, A. Obstructive lung disease in heterozygotes for
alpha,-antitrypsin deficiency. Annals of Internal Medicine 80(2): 209-212,
February 1974.

LIM, T. P. K. Airway obstruction among high school students. American Review of
Respiratory Disease 108(4): 985-988, October 1973.

MARTIN, R.R., LEMELIN, C., ZUTTER, M., ANTHONISEN, N. R. Measurement of
“closing volume”: Application and limitations. Bulletin de Physio-Pathologie
Respiratoire 9(4): 979-995, July-August 1973.

MITTMAN, C. LIEBERMAN, J. Screening for a,-antitrypsin deficiency. Israel Journal
of Medical Science 9(9/10): 1311-1318, September-October 1973.

MITTMAN, C., LIEBERMAN, J., RUMSFELD, J. Prevalence of abnormal protease
inhibitor phenotypes in patients with chronic obstructive lung disease. American
Review of Respiratory Disease 109(2): 295-296, February 1974.

NIEWOEHNER, D.E., KLEINERMAN, J., RICE, D.B. Pathologic changes in the
peripheral airways of young cigarette smokers. New England Journal of Medicine
291(15): 755-758, October 10, 1974.

OSHIMA, H., IMAI, M., KAWAGISHI, T. Effects of air pollution on the respiratory
symptoms in Yokkaichi, Central Japan. Mie Igaku 16(1): 25-29, June 1972.

OXHO], H., BAKE, B., WILHELMSEN, L. Closing volume in 50- and 60-year-old men.
A preliminary report. Scandinavian Journal of Respiratory Diseases
(Supplementum 85): 259-265, 1974.

ROSZMAN, T.L., ROGERS, A.S. The immunosuppressive potential of products
derived from cigarette smoke. American Review of Respiratory Disease 108(5):
1158-1163, November 1973.

RUFF, F., SALEM, A., BUSY, F., de VERNEJOUL, P., EVEN, P., BROUET, G, La
fermeture des voies aeriennes peripheriques. Son augmentation chez les fumeurs.
(Closing of the peripheral airways. Its increase in smokers.) Revue de Tuberculose
et de Pneumologie 36(2): 308-311, March 1972.
29

30

31

32

33

34

35

36

37

38

39

40

41

RYLANDER, R. Toxicity of cigarette smoke components: Free lung cell response in
acute exposures. American Review of Respiratory Disease 108(5): 1279-1282,
November 1973.

SAWICKI, F. Air pollution and prevalence of chronic nonspecific respiratory diseases.
In: Brzezinski, Z., Kopcezynski, J., Sawicki, F. (Editors). Ecology of chronic
nonspecific respiratory diseases, International Symposium, September 7-8, 1971,
Warsaw, Poland, Panastwowy Zaklad Wydawnictw Lekarskich, Warsaw, 1972, pp.
3-13.

SCHWARTZ, R.H. Alpha-t-antitrypsin deficiency and chronic respiratory disease.
Annual Report June 28, 1972-June 20, 1973. University of Rochester, Rochester,
N.Y. Prepared for Respiratory Diseases Branch, National Heart and Lung
Institute, National Institutes of Health, Bethesda, Maryland.

SIDOR, R., PETERS, J. M. Fire fighting and pulmonary function. An epidemiologic
study. American Review of Respiratory Disease 109(2): 249-254, February
1974,

SIDOR, R., PETERS, J. M. Prevalence rates of chronic nonspecific respiratory disease
in fire fighters. American Review of Respiratory Disease 109(2): 255-261,
February 1974.

STANESCU, D.C., VERITER, C., FRANS, A., BRASSEUR, L. Maximal expiratory
flow rates and “closing volume” in asymptomatic healthy smokers. Scandinavian
Journal of Respiratory Diseases 54: 264-271, 1973.

STEBBINGS, J.H., JR. A survey of respiratory disease among New York City postal
and transit workers. FV. Racial differences in the FEV 1. Environmental Research
6: 147-158, June 1973.

U.S. PUBLIC HEALTH SERVICE. Smoking and Health. Report of the Advisory
Committee to the Surgeon General of the Public Health Service. Washington, U.S.
Department of Health, Education, and Welfare, Public Health Service Publication
No. 1103, 1964, 387 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Public
Health Service Review: 1967. U.S. Department of Health, Education, and
Welfare. Washington, Public Health Service Publication No. 1696, Revised
January 1968, 227 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. 1968.
Supplement to the 1967 Public Health Service Review. U.S. Department of
Health, Education, and Welfare. Washington, Public Health Service Publication
1696, 1968, 117 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. 1969.
Supplement to the 1967 Public Health Service Review. U.S. Department of
Health, Education, and Welfare. Washington, Public Health Service Publication
1696-2, 1969, 98 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Report of
the Surgeon General: 1971. U.S. Department of Health, Education, and Welfare.
Washington, DHEW Publication No. (HSM) 71-7513, 1971, 458 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Report of

the Surgeon General: 1972. U.S. Department of Health, Education, and Welfare.
Washington, DHEW Publication No. (HSM) 72-6516, 1972, 158 pp.

81
42

43

44

45

46

47

48

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking: 1973. U.S.
Department of Health, Education, and Welfare. Washington, DHEW Publication
No. (HSM) 73-8704, 1973, 249 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking: 1974. U.S.
Department of Heaith, Education, and Welfare. Washington, DHEW Publication
No. (CDC) 74-8704, 1974, 124 pp.

VAN DER LENDE, R., DE KROON, J. P. M., TAMMELING, G. J., VISSER, B. F., DE
VRIES, K., WEVER-HESS, J., ORIE, N. G. M. Prevalence of chronic nonspecific
lung disease in a nonpolluted and air-polluted area of the Netherlands. In:
Brzezinski, Z., Kopczynski, J., Sawicki. F. (Editors). Ecology of chronic
nonspecific respiratory diseases, International Symposium, September 7-8, 1971,
Warsaw, Poland, Panstwowy Zaklad Wydawnictw Lekarskich, Warsaw, 1972, pp.
27-33.

WANNER, A., HIRSCH, J. A.. GREENELTCH, D. E., SWENSON, E. W., FORE, T.
Tracheal mucous velocity in beagles after chronic exposure to cigarette smoke.
Archives of Environmental Health 27(6): 370-371, December 1973.

WARR, G.A., MARTIN, R.R. In vitro migration of human alveolar macrophages:
Effects of cigarette smoking. Infection and Immunity 8(2): 222-227, August
1973.

WEBB, D.R., HYDE, R.W., SCHWARTZ, R.H., HALL, W. J., CONDEMI, J. J.,
TOWNES, P.L., Serum @,-antitrypsin variants. Prevalence and clinical
spirometry. American Review of Respiratory Disease 108(4): 918-925, October
1973.

YEAGER, H.., JR., ZIMMET, S. M., SCHWARTZ, S. L. Pinocytosis by human alveolar
macrophages. Comparison of smokers and nonsmokers. Journal of Clinical
Investigation 54(2): 247-251, August 1974.
CHAPTER 4.
Involuntary Smoking
CHAPTER 4
Involuntary Smoking

 

Contents

Page

Introduction 2... 2... tees 87
Constituents of Tobacco Smoke ............0.00 00.00 cee eee ee 88
Carbon Monoxide ...............0 0.0.02 cee eee eens 90
Nicotine... 0.022. ee ee ee eee 97
Other Substances .. 2... 2. ke ee 98
Effects of Exposure to Cigarette Smoke ..............0200000000e 98
Cardiovascular Effects of Involuntary Smoking ............... 98
Effects of Carbon Monoxide on Psychomotor Tests ............ 99
Pathologic Effects of Exposure to Cigarette Smoke ............. 99
Summary of Involuntary Smoking Findings..................... 108

Bibliography . 2.0... teens 109
List of Tables

Table 1.—Comparison of mainstream and sidestream

cigarette smoke 2... 2. ee

Table 2.—-Measurements of constituents released by
the combustion of tobacco products in various

Situations 2... 0... ee eee ee eee

Table 3.—Median percent carboxyhemoglobin (COHb)
saturation and 90 percent range for nonsmoker

by location... 2... . ee ees

Table 4.-Effects of carbon monoxide on psychomotor

functions ....... 0.0.0.0. 00 ce eee eee eee

Table 5._Admission rates (per 100 infants) by
diagnosis, birth weight, and maternal

smoking . 0... Lee ee

Table 6.—Pneumonia and bronchitis in the first
5 years of life by parents’ smoking habit

and morning phlegm ..... 2.0... 0.0.00. 000 cece
INTRODUCTION

The effects of smoking on the smoker have been extensively
studied, but the effects of tobacco smoke on nonsmokers have
received much less attention. The 1972 Health Consequences of
Smoking (49) reviewed the effects of public exposure to the air
pollution resulting from tobacco smoke. This exposure has been
called ‘‘passive smoking” by many authors, but will be referred to in
this report as “Involuntary Smoking.” The term involuntary smoking
will be used to mean the inhalation of tobacco combustion products
from smoke-filled atmospheres by the nonsmoker. This type of
exposure is, in a sense, “smoking” because it provides exposure to
many of the same constituents of tobacco smoke that voluntary
smokers experience. It is also “involuntary” because the exposure
occurs as an unavoidable consequence of breathing in a smoke-filled
environment.

The chemical constituents found in an atmosphere filled with
tobacco smoke are derived from two sources — mainstream and
sidestream smoke. Mainstream smoke emerges from the tobacco
product after being drawn through the tobacco during puffing.
Sidestream smoke rises from the burning cone of tobacco. Main-
stream and sidestream smoke contribute different concentrations of
many substances to the atmosphere for several reasons: Different
amounts of tobacco are consumed in the production of mainstream
and sidestream smoke; the temperature of combustion differs for
tobacco during puffing or while smouldering; and certain substances
are partially absorbed from the mainstream smoke by the smoker.
The amount of a substance absorbed by the smoker depends on the
characteristics of the substance and the depth of inhalation by the
smoker. As discussed in the 1972 Report, when the smoker does not
inhale the smoke into his lungs, the smoke he exhales contains less
than half its original amount of water-soluble volatile compounds,
four-fifths of the original nonwater-soluble compounds and
particulate matter, and almost all of the carbon monoxide (/5).
When the smoker inhales the mainstream smoke, he exhales into the
atmosphere less than one-seventh of the amount of volatile and
particulate substances that were originally present in the smoke and
also reduces the exhaled CO to less than half its original concentra-
tion (/6). As a result, different concentrations of substances are
found in exhaled mainstream smoke depending on the tobacco
product, composition of the tobacco, and degree of inhalation by the
smoker.

87
Several minor symptoms (conjunctival irritation, dry throat,
etc.) are caused by levels of cigarette smoke encountered in everyday
life, and serious allergic-like reactions to cigarette smoke may occur
in some sensitive individuals. A major concern, however, about
atmospheric contamination by cigarette smoke has been due to the
production of significant levels of carbon monoxide. Cigarette
smoking in poorly ventilated enclosed spaces may generate carbon
monoxide levels above the acceptable 8-hour industrial exposure
limits (50 ppm) — set by the American Conference of Government
Industrial Hygienists (/). Exposure to this level of carbon monoxide
even for short periods of time has been shown to reduce significantly
the exercise tolerance of some persons with symptomatic cardio-
vascular disease. There is also some evidence that prolonged exposure
to this level of carbon monoxide in combination with a high
cholesterol diet can enhance experimental atherosclerosis in animals

(Chapter |, Cardiovascular Diseases).

In the present chapter, the effects of cigarette smoke on the
environment and on the nonsmoker in that environment will be
examined by reviewing data on (1) the constituents of cigarette
smoke measured under various conditions, and (2) the physiologic
effects of this ‘involuntary smoking” on individuals.

CONSTITUENTS OF TOBACCO SMOKE

In a recent workshop on the effects of environmental tobacco
smoke on the nonsmoker (4/), Corn (/4) presented a compilation
adapted from Hoegg (32) of some of the substances in mainstream
cigarette smoke and the ratio of sidestream to mainstream levels for
some of these substances (Table 1). The actual numerical value of the
sidestream to mainstream concentration ratio will vary with different
types of tobacco tested, but Table | gives values generally consistent
with those found by others (34, 42). Many of these substances
including nicotine and carbon monoxide are found in much higher
concentrations in sidestream smoke than in mainstream smoke,
establishing that the smoke exposure received by both the smoker
and nonsmoker due to breathing in a smoke-filled environment
differs qualitatively as well as quantitatively from the smoke
exposure received by the smoker who inhales through a lighted
cigarette. A more comprehensive recent review of the constituents of
mainstream and sidestream smoke has also been provided by
Schmeltz, et al. (42) and Johnson, et al. (34).

88
68

TABLE 1. — Comparison of mainstream and sidestream cigarette smoke '-?

 

 

Ratio
Compound Mainstream Sidestream Sidestream/ Comment
(mg/cig) (mg/cig) Mainstream
A General characteristics
Duration of smoke production 20 sec 550 sec 27
Tobacco burnt 347 411 1.2
Particulates, no. per cigarette 1.05 x 101? 3.5 x 101? 3.3
B Particulate phase
2Tar (chloroform extract) 20.8 44.1 2.1
10.2 34.5 3.4 Filter cigarette
Nicotine 0.92 1.69 1.8
0.46 1.27 2.8 Filter cigarette
Benzo(a)pyrene 3.5 x 105 13.5 10° 3.7
Pyrene 13x 105 39x 10° 3.0
Total phenols 0.228 0.603 2.6
Cadmium 12.5 x 105 45 x 10°5 3.6
Cc Gases and vapors
Water 7.5 + 298 39.7 3.5 mg of Mainstream
and 5.5 mg of
Sidestream in
particulate phase,
rest in vapor phase
Ammonia 0.16 7.4 46
Carbon monoxide 31.4 148 4.7
Carbon dioxide 63.5 79.5 1.3
Oxides of Nitrogen 0.014 0.051 3.6

 

' Adapted from Hoegg, U.R. (31, 32).
2 For 35 ml puff volume, 2 sec puff duration, one puff per minute and 23 or 30 mm butt length and 10 percent tobacco moisture.
Source: Corn, M. (14).
A number of other researchers have attempted to measure the
levels of some of the substances in cigarette smoke encountered in
everyday situations (Table 2). They have also tried to determine the
factors controlling the atmospheric concentrations of these
substances as well as the amount absorbed by nonsmokers under
these conditions. Carbon monoxide, nicotine, benzo(a)pyrene,
acrolein, and acetaldehyde have been of particular concern.

Carbon Monoxide

Levels of carbon monoxide (CO), a major product of tobacco
combustion, have been studied in a variety of situations, and
concentrations ranging from 2 to 110 ppm have been measured
(Table 2). The major determinants of the CO levels in these
situations are size of the space in which the smoking occurs (dilution
of CO), the number and type of tobacco products smoked (CO
production), and the amount and effectiveness of ventilation (CO
removal).

The type of tobacco product smoked is important as a
determinant of CO exposure because it has been found that
mainstream smoke from regular and small cigars contains more CO
pre puff and per gram of tobacco burned than filtered or unfiltered
cigarettes (8). This greater production of CO by cigars was confirmed
by Harke (23). He measured the CO produced by 42 cigarettes, 9
cigars, and 9 pipefuls of tobacco, each product evaluated separately
but under the same room conditions. The cigars produced the highest
CO level (60 ppm).

In addition to the effect of type of tobacco product on CO
levels, data on the effects of room size, amount of tobacco burned,
and ventilation are included in Table 2. Only under conditions of
unusually heavy smoking and poor ventilation did CO levels exceed
the maximum permissible, 8-hour industrial exposure limit of 50
ppm CO (/); however, even in cases where the ventilation was
adequate, the measured CO levels did exceed the maximum
acceptable ambient level of 9 ppm (/8).

Harke (27) also showed that in small enclosed ventilated spaces
(an automobile) the CO level is determined more by the number of
cigarettes being smoked at one given time than by the cumulative
number of cigarettes that have been smoked; also the CO level
decreases rapidly once the smoking stops.

90
16

TABLE 2. — Measurements of constituents released by the combustion of tobacco products in various situations

 

 

 

 

[Cig = cigarettes; — = unknown; TPM = total particulate matter |
Reference, Location, and Amount of
Dimensions If Known Ventilation Tobacco Burned Constituents
Harke, H.-P., et al. (27)
Mid-size European car, None 9 cig 30 ppm CO
engine off, in wind
tunnel at 50 km/hr Air jets open & 6 cig 20 ppm CO
wind speed blower off
Air jets open & 6 cig 10 ppm CO
blower on
Mid-size European car, None 9 cig 110 ppm CO
engine off, in wind
tunnel at zero km/hr None 6 cig 80 ppm CO
wind speed
Air jets open & 6 cig 8-10 ppm CO
blower on
Harke, H.-P., Peters, H. (28)
Car in traffic None 4 cig 21.4 ppm CO
Srch, M. (45)
Car, engine off— None 10 cig in 1 hr 90 ppm CO, Smokers 10% COHb
2.09 m Nonsmokers 5% COHb

 

Seiff, H-E. (44)
Intercity buses 15 air changes per hr 23 cig 33 ppm CO (at driver’s seat)
(burning continuously)

3 cig 18 ppm CO (at driver’s seat)
(burning continuously)

 
iS TABLE 2. — Measurements of constituents released by the combustion of tobacco products in various situations — Continued

[ Cig = cigarettes; — = unknown; TPM = total particulate matter]

 

Reference, Location, and
Dimensions If Known

U.S. Dept. Transportation,
et al. (48)
Airplane flights:
Overseas—100% filled
Domestic—66% filled

Cano, LP., et al. (//)
Submarines—66 m2

Godin, G., et al. (21)

Ferry boat compartments:

Smoking
Nonsmoking

Theater:
Foyer
Auditorium

Bridge, D.P., Corn, M. (7)
Party rooms:
145 m3
101 m3

Ventilation

15-20 air changes per hr
do.

7 ait changes per hr
10.6 air changes per hr

Amount of
Tobacco Burned

157 cig per day
94-103 cig per day

30 cig & 17 cigars in 1.5 hr
63 cig & 10 cigars in 1.5 hr

Constituents

2-5 ppm CO, <.120 mg/m? TPM
<2 ppm CO, <.120 mg/m> TPM

<40 ppm CO, 32 ug/m3 Nicotine
<40 ppm CO, 15-35 g/m? Nicotine

18.4 +8.7 ppm CO
3.0+2.4 ppm CO

3.4+0.8 ppm CO
1.4+0.8 ppm CO

7 ppm CO
9 ppm CO
£6

TABLE 2. -- Measurements of constituents released by the combustion of tobacco products in various situations — Continued
[ Cig = cigarettes; — = unknown; TPM = total particulate matter]

 

Reference, Location, and

Dimensions If Known

Ventilation

Amount of
Tobacco Burned

Constituents

 

Harke, H.-P., et al. (25)
Room—38.2 m3

None

30 cig per 13 min (by machine)

5 cig per 13 min (by machine)

64 ppm CO, 510 ug/m?3 Nicotine
.46 mg/m? Acrolein
6.5 me/m3 Acetaldehyde

11.5 ppm CO, 60 pe/m3 Nicotine,
-07 mg/m? Acrolein,
1.3 mg/m?> Acetaldehy de

 

Harke, H.-P. (24)
Office Bldg
Office Bldg
Room ~78.3 m3

Air conditioned
Not air conditioned

3 smokers

<5 ppm CO
<5 ppm CO
15.6 ppm CO

 

Harke, H.-P., (23)
Room-§7 m3

None
7.2 air changes per hr
8.4 air changes per hr

None
7.2 air changes per hr

None
7.2 air changes per hr

42 cig (by machine)

42 cig do.
42 cig do.
9 cigars do.
9 cigars do.
9 pipes do.
9 pipes do.

50 ppm CO, 530 ug/m> Nicotine
10 ppm CO, 120 ug/m3 Nicotine
<10 ppm CO, <100 ug/m3 Nicotine

60 ppm CO, 1040 ug/m3 Nicotine
20 ppm CO, 420 ug/m3 Nicotine

10 ppm CO, 520 ug/m> Nicotine
<10 ppm CO, <100 ug/m?> Nicotine

 
v6

TABLE 2. — Measurements of constituents released by the combustion of tobacco products in various situartions — Continued

[Cig = cigarettes; — = unknown; TPM = total particulate matter ]

 

Reference, Location, and

 

Amount of
Dimensions If Known Ventilation Tobacco Burned Constituents
Harke, H.-P. (23) None 105 cig 30 ppm CO, Smokers 7.5% COHb
Room-—170 m3 Nonsmokers 2.1% COHb
1.2 air changes per hr ~ 107 cig SppmCO, Smokers 5,8% COHb
. Nonsmokers 1.3% COHb
2.3 air changes per hr 101 cig 75 ppm CO, Smokers 5.0% COHb

Anderson, G., Dalhamn, T. (3)
Room—80 m

Russell, M.A.H., et al. (40)
Room-—43 m

Harmsen, H., Effenberger, E.
(30)
Room—93 m3

Hoegg, U.R. (31, 32)
Sealed test chamber—25 m3

6.4 air changes per hr

None

None

None

46 cig & 3 pipefuls

80 cig & 2 cigars per hr

62 cig in 2 hrs

4 cig
8 cig
16 cig
24 cig

Nonsmokers 1.6% COHb

4.5 ppm CO, 377 ug/m? Nicotine,
3.0 mg/m? TPM

38 ppm CO, Smokers 9.6% COHb
Nonsmokers 2.6% COHb

80 ppm CO, 5200 ug/m> Nicotine

12.2 ppm CO, 2,28 mg/m3 TPM
25.6 ppm CO, 5,39 mg/m3 TPM
47.0 ppm CO, 11.41 mg/m3 TPM
69.8 ppm CO, 16.65 mg/m? TPM
One must be careful when using the levels recorded in Table 2
as measures of individual exposure because the CO levels were
usually measured at points several feet from the nearest smoker and
probably would have been higher if measured at points correspond-
ing to the position of a person sitting next to someone actively
smoking (17, 35). In addition, it is the CO absorbed by the body
that causes the harmful effects and not that which is measured in the
atmosphere. This absorption can vary from individual to individual,
depending on factors such as duration of exposure, volume of air
breathed per minute, and cardio-respiratory function.

Several investigators have tried to determine the amount of
carbon monoxide absorbed in involuntary smoking situations by
measuring changes in carboxyhemoglobin levels in nonsmokers
exposed to cigarette smoke-filled environments. Anderson and
Dalhamn (3) were unable to find any change in the COHb levels of
nonsmokers in a well ventilated room where the CO level was 4.5
ppm. When Harke (23) studied nonsmokers under similar conditions
(good ventilation and less than 5 ppm CO), he was able to show an
increase in COHb level from 1.1 to 1.6 percent; without ventilation
the CO levels rose to 30 ppm and the COHb level increased from .9
to 2.1 percent in 2 hours. Russell, et al. (40) also found that COHb
levels increased from 1.6 to 2.6 percent in nonsmokers exposed toa
smoke-filled room where the CO level was measured at 38 ppm;
however, he cautioned that nearly all persons in the room felt that
the conditions were worse than those experienced in most social
situations.

Stewart, et al. (46) measured COHb levels in a group of
nonsmoking blood donors from several cities and found that 45
percent exceeded the Clean Air Act’s Quality Standard of 1.5
percent with the 90 percent range as high as 3.7 percent for
individual cities (Table 3). These levels represent the total CO
exposure from all sources, involuntary smoking, and other sources of
pollution as well as establishing the levels which would be added to
any new involuntary smoking exposure.

Increases in the COHb levels of this magnitude are probably
functionally insignificant in the healthy adult, but in persons
with angina pectoris, any reduction of oxygen-carrying capacity is of
great importance. In this disease, the volume of blood able to be
pumped through the diseased coronary artery is already unable to
meet the demands of the heart muscle under exercise stress. Aronow,
et al. (4) examined the effect of exposure to carbon monoxide on
persons with angina pectoris. They exercised persons with angina

95
96

TABLE 3. — Median percent carboxyhemoglobin (COHb) saturation and 90 percent
range for nonsmokers by location

 

 

 

Percent of
ovation Nonsmokers No. of Nonsmokers
J Nonsmokers With COHb
Median Range > 1.5%

Anchorage 1.5 0.6 -— 3.2 152 56
Chicago 1.7 1.0 - 3.2 401 74
Denver 2.0 0.9 — 3.7 744 16
Detroit 1.6 0.7 — 2.7 1,172 42
Honolulu 1.4 0.7 — 2.5 503 39
Houston 1.2 0.6 — 3.5 240 30
Los Angeles 1.8 1.0 - 3.0 2,886 716
Miami 1.2 0.4 — 3.0 398 33
Milwaukee 1,2 0.5 - 2.5 2,720 26
New Orleans 1.6 1.0 - 3.0 159 59
New York 1.2 0.6 — 2.5 2,291 35
Phoenix 1,2 0.5 — 2.5 147 24
St. Louis 1.4 0.9 — 2.1 671 35
Salt Lake City 1.2 0.6 — 2.5 544 27
San Francisco 1.5 0.8 — 2.7 660 61
Seattle 1.5 0.8 — 2.7 535 55
Vermont,

New Hampshire 1,2 0.8 — 2.1 959 18
Washington, D.C. 1.2 0.6 — 2.5 850 35

 

 

 

 

 

Source: Stewart, R.D., et al. (46).
pectoris before and after exposure to carbon monoxide. The average
amount of excercise that was able to be performed before a person
developed chest pain was significantly shortened from 226.7 seconds
before exposure to 187.6 seconds after CO exposure. This change
occurred after a 2-hour exposure to 50 ppm CO and with an increase
in COHb level from 1.03 percent to 2.68 percent; these COHb levels
are within the range produced by involuntary smoking.

These data indicate that exposure to CO at levels found in some
involuntary smoking situations may well have a significant impact on
the functional capacity of persons with angina pectoris. Carbon
monoxide has also been shown to decrease cardiac contractility in
persons with coronary heart disease at COHb levels similar to those
produced due to involuntary smoking situations (5). It is reasonable
to assume that any significant CO exposure to the diseased heart
reduces its functional reserve.

Nicotine

Nicotine in the atmosphere differs from CO in that it tends to
settle out of the air with or without ventilation (thereby decreasing
its atmospheric concentration), whereas the CO level will remain
constant until the CO is removed. The concentrations of both
substances are decreased substantially by ventilation. As can be seen
from data in Table 2, under conditions of adequate ventilation
neither exceeds the maximum threshold limit values for industrial
exposure (nicotine, 500 yg/m3; CO, 50 ppm, /): whereas in
conditions without ventilation, smoking produces very high con-
centrations of both (nicotine, up to 1,040 ng/m3: CO, 110 ppm).

Nicotine in the environment is of concern because nicotine
absorbed by cigarette smokers is felt to be one factor contributing to
the development of atherosclerotic cardiovascular disease. Several
researchers have attempted to measure the amount of. nicotine
absorbed by nonsmokers in involuntary smoking situations. Cano, et
al. (J7) studied urinary excretion of nicotine by persons on a
submarine. Despite very low levels measured in the air (15 to 32
ug/m3), nonsmokers did show a small rise in nicotine excretion;
however, the amount excreted was still less than | percent of the
amount excreted by smokers. Harke (23) measured nicotine and its
metabolite cotinine in the urine of smokers and nonsmokers exposed
to a smoke-filled environment and reported that nonsmokers
2xcreted less than 1 percent of the amount of nicotine and cotinine
2xcreted by smokers. He feels that at this low level of absorption
licotine is unlikely to be a hazard to the nonsmoker.

97
Other Substances

In two studies environmental levels of the experimental
carcinogen benzo(a)pyrene were measured. Galuskinova (20) found
levels of benzo(a)pyrene from 2.82 to 14.4 mg/m? in smoky
restaurants, but it is not clear how much of this was due to cooking
and how much was due to smoking. In a study of the concentration
of benzo(a)pyrene in the atmosphere of airplanes (48), only a
fraction of a microgram per cubic meter was detected. The effect of
chronic exposure to very low levels of this carcinogen has not been
established for humans.

Acrolein and acetaldehyde have also been measured in smoke-
filled rooms (25, Table 2) and may contribute to the eye irritation
commonly experienced in these situations.

EFFECTS OF EXPOSURE TO CIGARETTE SMOKE

Cardiovascular Effects of Involuntary Smoking

The effects of cigarette smoking on the cardiovascular system of
the smoker are well established, but very little is known about the
cardiovascular response of the nonsmoker to cigarette smoke. Harke
and Bleichert (26) studied 18 adults (11 smokers and 7 nonsmokers)
in a room 170 m3 large in which 150 cigarettes were smoked or
allowed to burn in ashtrays for 30 minutes. They noted that the
subjects who smoked during the experiment had a significant
lowering of skin temperature and a rise in blood pressure. Non-
smokers who were exposed to the same smoke-contaminated
environment showed no change in either of these parameters.
Luquette, et al. (36) performed a similar experiment with 40
children exposed alternately to smoke-contaminated and clean
atmospheres, but otherwise under identical experimental conditions.
They found that exposure to the smoke caused increases in heart rate
(5 beats per minute) and in systolic (4 mm Hg) and diastolic (5 mm
Hg) blood pressure. The differences in results between these studies
may be due, in part, to the age of the subjects — i.e., children may be
more sensitive to the cardiovascular effects of involuntary smoking
than adults, or the increase in heart rate and blood pressure may be
due to a difference between children and adults in the psychologic
response to being in a smoke-filled atmosphere.

98
Effects of Carbon Monoxide on Psychomotor Tests

Carbon monoxide from tobacco smoke, automobile exhaust,
and industrial pollution is an important component of air pollution.
There has been some concern over the effect of relatively low levels
of carbon monoxide on psychomotor functions (the ability to
perceive and react to stimuli), especially those functions related to
driving an automobile (Table 4).

Carbon monoxide levels occasionally reached in some involun-
tary smoking situations result in measurable cognitive and motor
effects, but these effects generally are measurable only at the
threshold of stimuli perception. One study (Wright, et al., (50))
found that the safe driving habits measured on a driving simulator
did not improve as much with practice in a group exposed to CO as
did the habits of a control group. Another study (37) with a
different experimental design but at the same levels of CO did not
find any effect on complex psychomotor activity such as driving a
car. Thus, the role of CO alone in motor vehicle accidents remains
unclear. The effect on judgement and reactions of CO in combina-
tion with factors such as fatigue and alcohol, conditions known to
influence judgement and reaction time, has not been determined.

Pathologic Effects of Exposure to Cigarette Smoke

The effect of involuntary smoking on an individual is deter-
mined not only by the qualitative and quantitative aspects of the
smoke-filled environment, but also largely by the characteristics of
the individual. Reactions may vary with age as well as with the
sensitivity of an individual to the components of tobacco smoke. The
severity of possible effects range ffom minor eye and throat
irritations experienced by most people in smoke-filled rooms, to the
anginal attacks of some persons with cardiovascular disease.

The minor symptomatic irritation experienced by nonsmokers
in a smoke-filled environment is influenced by the humidity of the
air as well as the concentration of irritating substances found in the
atmosphere. Johansson and Ronge (33) have shown that irritation
due to cigarette smoke is maximal in warm, dry air and decreases
with a small rise in relative humidity. A change from acceptable to
unpleasant was reported at 4.7 mg/m? of particulate matter for
nonsmokers and eye irritation was noted at 9 mg/m? for both
smokers and nonsmokers. The authors concluded that a ventilation
rate of 12 m3/hr/cig was necessary to avoid eye irritation and 50
m3 /hr/cig was necessary to avoid unpleasant odors.

99
00!

TABLE 4. -— Effects of carbon monoxide on psychomotor functions

 

 

co COHb
Test or level level
Reference
ererenc Measurement (ppm) (Percent) Effect
McFarland, R.A. Ability of drivers to stay 6 None
(37) between two-lane markers 11 None
while being permitted only 17 None
brief glimpses of the road
Ray, A.M., Reaction time to 10 Prolonged
Rockwell, T.H. car taillights
(39)
McFarland, R.A. Performance of two tasks at 700 17 None
(38) same time
Dark adaptation and glare 700 17 None
recovery
Peripheral vision at 10° 700 17 None
and 30°
Peripheral vision at 20° 700 17 Decreased
Depth perception 700 17 None
Stewart, R.D., et al. Time perception $00 20 None

(47)
10!

TABLE 4. — Effects of carbon monoxide on psychomotor junctions — Continued

 

 

co COHb
Test or level level
Reference Measurement ppm (Percent) Effect
Fodor, G.G., Attentiveness to 50x 5 hrs. 2-5 Decreased
Winneke, G. auditory stimuli
a9)
Flicker fusion $0 x 5 hrs. 2-5 No change
Speed of motor performance $0 x 5 hrs. 2-5 No change
Perception of complex $0 x 5 hrs. 2-5 Improved
visual patterns
Schulte, J.H. Cognitive function 100 5 Decreased
(43)
Reaction time 20 No change
Bender, W., et al. Threshold for temporal 100 7.25 Raised
(6) resolution of visual stimuli
Manual dexterity 100 7.25 Decreased
Learning meaningless syllables 100 7.25 Decreased
Retention of 10 syllables 100 7.25 No change
for 1 hr
Groll-Knapp, E., et al. Attentiveness to auditory 50 Deterioration at
(22) stimuli 100 50 ppm, worse at
100 ppm, worst
150 at 150 ppm
Wright, G., et al. Reaction time 6.3 Prolonged
50
(90) Glare recovery 6.3 Prolonged
Careful driving habits 6.3 Failure to improve

with practice

 
Two government sponsored studies have attempted to evaluate
the degree of minor irritation due to cigarette smoke experienced by
bus and plane passengers. The U.S. Department of Transportation
(44) studied the environment on two ventilated buses — one with
simulated unrestricted smoking and another with simulated smoking
limited to the rear 20 percent of the seats. In one bus, lighted
cigarettes were placed at every other seat (23 cigarettes) to simulate a
bus filled with smokers. In the other bus, cigarettes were placed only
in the rear 20 percent of the bus (five cigarettes) to simulate a bus
where smoking was limited to the rear 20 percent of the seats. When
smoking was limited, the CO level at the driver’s seat was only 18
ppm (ambient air 13 ppm) compared to the level of 33 ppm
(ambient air 7 ppm) measured in the unrestricted smoking situation.
Four of the six subjects seated in the bus reported eye irritation
during the unrestricted smoking simulation. None of the six subjects
reported any eye irritation in the restricted smoking situation (not
even those seated in the rear 20 percent of the bus).

Several Federal agencies (48) cooperated to survey the symp-
toms experienced by travelers on both military and commercial
aircraft. They distributed a questionnaire to passengers on 20
military and 8 commercial flights; 57 percent of the passengers on
the military flights and 45 percent of the passengers on the
commercial flights were smokers. The planes were well ventilated
and CO levels were always below 5 ppm with low levels of other
pollutants as well. In spite of the low level of measurable pollution,
over 60 percent of the nonsmoking passengers and 15 to 22 percent
of the smokers reported being annoyed by the other passengers’
smoking. Seventy-three percent of the nonsmoking passengers on the
commercial flights and 62 percent of the nonsmoking passengers on
the military flights suggested that some remedial action be taken; 84
percent of those suggesting remedial action felt that segregating the
smokers from nonsmokers would be a satisfactory solution. These
feelings were even more prevalent among those nonsmokers who had
a history of respiratory disease.

Children have been found to have a higher incidence of
respiratory infections than adults and are thought to be more
sensitive to the effects of air pollution due to their greater minute
ventilation per body weight than adults. Several researchers have
investigated the effects of parental smoking on the health of
children. Cameron, et al. conducted two telephone surveys of Detroit
families to determine the relationship between children’s respiratory
illness and parental smoking habits. In the first survey (9) they found

a statistically significant relationship between the prevalence of

102
children’s respiratory infection and parental smoking habits only
when all children under 16 were considered (not when only those
under 9 or under 5 were considered). In a larger survey of the same
city (10) they found a relationship between parental smoking and
prevalence of respiratory illness in the 10- to 16-year age group and
in the birth to 5-year age group. Neither study controlled for
smoking by the children which might be a factor in the 10- to
16-year age group or for socioeconomic status which has an effect on
both smoking habits and illness. However, the data were consistent
with a higher prevalence of respiratory disease in families where there
are smokers than in nonsmoking families.

Colley (/2) also found a relationship between parental smoking
habits and the prevalence of respiratory illness in the children. He
found an even stronger relationship between parental cough and
phlegm production and respiratory infections in children. He
postulates this latter relationship to result from the greater infec-
tivity of these parents due to their cough and phlegm production.
The relationship between parental cigarette smoking and respiratory
infection in their children would then occur because cigarette
smoking caused the parents to cough and produce phlegm and would
not be indicative of a direct effect of cigarette smoke-filled air on the
children.

Harlap and Davies (29) studied infant admissions to Hadassah
Hospital in West Jerusalem and found a relationship between
admissions for bronchitis and pneumonia in the first year of life and
maternal smoking habits during pregnancy. Data on maternal
smoking habits after the birth of the child were not obtained, but it
can be assumed that most of the mothers who smoked during
pregnancy continued to smoke during the first year of the infant’s
life. A relationship between infant admission and maternal smoking
habits was demonstrable only between the sixth and ninth months of
infant life and was more pronounced during the winter months
(when the effect of cigarette smoke on the indoor environment
would be greatest). Mothers who smoke during pregnancy are known
to have infants with a lower average birth weight than the infants of
nonsmoking mothers. The relationship between maternal smoking
and their infants’ admission to the hospital found in this study was
greater for low birth weight infants, but was also found for normal
birth weight infants (Table 5) (29). Harlap and Davies (29)
demonstrated a dose-response relationship for maternal smoking and
infant admission for bronchitis and pneumonia; however, they also
found a relationship between maternal smoking and infant admis-
sions for poisoning and injuries. This may indicate a bias in the study

103
701

TABLE 5.- Admission rates (per 100 infants) by diagnosis, birth weight, and maternal smoking

 

 

 

 

Birth weight (g) Total

Diagnosis <2,999 3,000 - 3,499 3,500+ (including unknown)
s NS S NS S NS Ss NS

(297) (2,326) (415) (4,098) (264) (3,195) (986) (9,686)

Bronchitis and

pneumonia 19.2 12.3 9.6 8.2 12.1 9.0 13.1 9.5
All other 22.6 19.9 14.5 14.6 15.2 13.3 16.9 15.5
Total 41.8 32.2 24.1 22.8 27.3 22.3 30.0 24.9

 

NOTE. — S=Smokers; NS=Nonsmokers.
Source: Harlap, S., Davies, A.M. (29).
due to relationships which may exist between smoking and factors
such as parental neglect or socioeconomic class. In addition, hospital
admission rates may not be an accurate index of infant morbidity.

Colley, et al. (73) studied the incidence of pneumonia and
bronchitis in 2,205 children over the first 5 years of life in relation to
the smoking habits of both parents. They found that a relationship
between parental smoking habits and respiratory infection in
children occurred only during the first years of life (Table 6). They
also showed a relationship between parental cough and phlegm
production and infant infection (Table 6) which was found to be
independent of the effect of parental smoking habits. The relation-
ship between parental smoking and infant infection was greater when
both parents smoked and increased with increasing number of
cigarettes smoked per day. The relationship persisted after social
class and birth weight had been controlled for.

Thus, respiratory infections during the first year of life are
closely related to smoking habits independent of parental symptoms,
social class, and birth weight. Because of the dose-response relation-
ship between parental smoking and infant respiratory infection
established by Colley, et al. (/3), it is reasonable to suspect that
cigarette smoke in the atmosphere of the home may be the cause of
these infections; however, other factors such as parental neglect may
also play a role.

The above studies examined the effects of involuntary smoking
on relatively healthy people. A substantial proportion of the U.S.
population suffers from chronic cardiovascular and pulmonary
diseases, however, and they represent the segment of the population
most seriously jeopardized by conditions found in involuntary
smoking situations. In Chapter 1 of this report (Cardiovascular
Diseases) evidence was presented which showed that levels of CO
sometimes experienced in smoke-filled environments (50 ppm) are
capable of significantly decreasing the exercise tolerance of persons
with angina pectoris and intermittent claudication. In addition, these
levels of CO have been shown to decrease cardiac contractility and to
raise left ventricular end-diastolic pressure (an indication of heart
failure) in persons with cardiovascular disease.

Persons with chronic bronchitis and emphysema have consider-
able excess mortality under conditions of severe air pollution. In
smoke-filled environments levels of CO and several other pollutants
may be as high or higher than occur during air pollution emergencies.
The effects of short-term exposure of persons with chronic obstruc-

105
901

TABLE 6. — Pneumonia and bronchitis in the first 5 years of life by parents’ smoking habit and morning phlegm

 

Year of

Annual incidence of pneumonia and bronchitis per 100 children

(Absolute numbers in parentheses)

 

Both ex-smokers
of one ex-smoker

 

 

Followup Both nonsmokers One smoker Both smokers or smoking habit All
changed
N O/B N O/B N O/B N O/B N O/B
1 1.6 10.3 10.4 14.8 15.3 23.0 8.2 13.2 10.1 16.7
(343) (29) (424) (128) (339) (139) (546) (129) (1,652) (425)
2 8.1 8.3 71 15.5 8.7 9.2 6.5 10.7 74 11.3
(322) (36) (365) (129) (286) (152) (599) (159) (1,572) (476)
3 6.9 8.1 10.5 9.4 79 11.0 8.2 11.6 8.4 10.6
(305) (37) (353) (107) (242) (154) (661) (173) (1,561) (471)
4 8.0 11.1 7.5 10.8 716 11.6 8.2 9.1 7.9 10.3
(287) (36) (306) (102) (236) (121) (695) (187) (1,524) (446)
5 6.7 14.7 5.6 9.4 3.9 10.6 6.4 7.3 5.9 9.1
(285) (34) (267) (107) (208) (132) (737) (219) (1,497) (492)

 

 

 

 

 

 

 

 

 

 

 

NOTE. — N=neither with winter morning phlegm. O/B=one or both with winter morning phlegm.

Source: Colley, J.R.T., et al. (13).

 
tive bronchopulmonary disease (COPD) to these conditions have not
been evaluated. Persons with COPD are also possibly at increased risk
to CO exposure because of their low alveolar Po2. Due to the
reduced amount of oxygen available to compete with the CO for
~ hemoglobin binding sites, these persons might experience a carboxy-
hemoglobin to oxyhemoglobin ratio higher than those in healthy
subjects under the same conditions of CO exposure. The retention of
CO may also be prolonged due to both this increased binding of CO
to hemoglobin under low alveolar Po, and decreased ventilatory
capacity to excrete CO.

In summary, the effects of cigarette smoke on healthy
nonsmokers consists mainly of minor eye and _ throat irritation.
However, people with certain heart and lung diseases (angina
pectoris, COPD, allergic asthma) may suffer exacerbations of their
symptoms as a result of exposure to tobacco smoke-filled environ-
ments. These effects are dependent on the degree of individual
exposure to cigarette smoke which is determined by proximity to the
source of the tobacco smoke, the type and amount of tobacco
product smoked, conditions of room size and ventilation as well as
the amount of time the individual spends in the smoke-filled
environment, and his physiologic condition at the time of exposure.

107
SUMMARY

1. Tobacco smoke can be a significant source of atmospheric
pollution in enclosed areas. Occasionally under conditions of heavy
smoking and poor ventilation, the maximum limit for an 8-hour
work exposure to carbon monoxide (50 ppm) may be exceeded. The
upper limit for CO in ambient air (9 ppm) may be exceeded even in
cases where ventilation is adequate. For an individual located close to
a cigarette that is being smoked by someone else, the pollution
exposure may be greater than would be expected from atmospheric
measurements.

2. Carbon monoxide, at levels occasionally found in cigarette
smoke-filled environments, has been shown to produce slight
deterioration in some tests of psychomotor performance, especially
attentiveness and cognitive function. It is unclear whether these
levels impair complex psychomotor activities such as driving a car.
The effects produced by CO may become important when added to
factors such as fatigue and alcohol which are known to have an effect
on the ability to operate a motor vehicle.

3. Unrestricted smoking on buses and planes is reported to be
annoying to the majority of nonsmoking passengers, even under
conditions of adequate ventilation.

4. Children of parents who smoke are more likely to have
bronchitis and pneumonia during the first year of life, and this is
probably at least partly due to their being exposed to cigarette
smoke in the atmosphere.

5. Levels of carbon monoxide commonly found in cigarette

smoke-filled environments have been shown to decrease the exercise
tolerance of patients with angina pectoris. ,

108
10

11

BIBLIOGRAPHY

AMERICAN CONFERENCE OF GOVERNMENT INDUSTRIAL HYGENISTS.
TLVs® threshold limit values for chemical substances in workroom air adopted
by the American conference of government industrial hygienists for 1973. Journal
of Occupational Medicine 16(1): 39-49, January 1974.

ANDERSON, E. W., ANDELMAN, R. J., STRAUCH, J. M., FORTUIN, N. J., KNEL-
SON, J. H. Effect of low-level carbon monoxide exposure on onset and duration
of angina pectoris. A study of ten patients with ischemic heart disease. Annals of
Internal Medicine 79(1): 46-50, July 1973.

ANDERSON, G., DALHAMN, T. The risks to health of passive smoking. Lakartid-
ningen 70: 2833-2836, August 15, 1973.

ARONOW, W.S., CASSIDY, J., VANGROW, J.S., MARCH, H., KERN, J.C.,
GOLDSMITH, J.R., KHEMKA, M., PAGANO, J., VAWTER, M. Effect of
cigarette smoking and breathing carbon monoxide on cardiovascular hemo-
dynamics in anginal patients. Circulation 50(2): 340-347, August 1974.

ARONOW, W.S., ISBELL, M. W. Carbon monoxide effect on exercise-induced angina
pectoris. Annals of Internal Medicine 79(3): 392-395, September 1973.

BENDER, W., GOTHERT, M., MALORNY, G. Effect of low carbon monoxide
concentrartions on psychological functions. Staub Reinhaltung der Luft 32(4):
54-60, April 1972.

BRIDGE, D. P., CORN, M. Contribution to the assessment of exposure of nonsmokers
to air pollution from cigarette and cigar smoke in occupied spaces. Environmental
Research 5:192-209, 1972.

BRUNNEMANN, K. D., HOFFMANN, D. Chemical studies on tobacco smoke. XXIV.
A quantitative method for carbon monoxide and carbon dioxide in cigarette and
cigar smoke. Journal of Chromatographic Science 12(2): 70-75, February 1974.

CAMERON, P., KOSTIN, J. S., ZAKS, J.M., WOLFE, J. H., TIGHE, G., OSELETT,
B., STOCKER, R., WINTON, J. The health of smokers’ and nonsmokers’ children.
Journal of Allergy 43(6): 336-341, June 1969.

CAMERON, P., ROBERTSON, D. Effect of home environment tobacco smoke on
family health. Journal of Applied Psychology 57(2): 142-147, 1973.

CANO, J.P., CATALIN, J., BADRE, R., DUMAS, C., VIALA, A., GUILLERME, R.
Determination de la nicotine par chromatographie en phase gazeuse. II —
Applications Annales Pharmaceutiques Francaises 28(11): 633-640. 1970.

COLLEY, J. R. T. Respiratory symptoms in children and parental smoking and phlegm
production. British Medical Journal 2: 201-204, April 27, 1974.

COLLEY, J. R. T., HOLLAND, W. W. CORKHILL, R. T. Influence of passive smoking
and parental phlegm on pneumonia and bronchitis in early childhood. Lancet
2(7888): 1031-1034, November 2, 1974.

CORN, M. Characteristics of tobacco sidestream smoke and factors influencing its
concentration and distribution in occupied spaces. Scandinavian Journal of
Respiratory Diseases (Supplementum 91): 21-36, 1974.

DALHAMN, T., EDFORS, M.. RYLANDER, R. Mouth absorption of various

compounds in cigarette smoke. Archives of Environmental Health 16(6):
831-835, June 1968.

109
16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

110

DALHAMN, T., EDFORS, M., RYLANDER, R. Retention of cigarette smo
components in human lungs. Archives of Environmental Health 17(5): 746-145
November 1968.

DUBLIN, W.B. Secondary smoking: A problem that deserves attention. Pathology
26(9):244-245, September 1972. .

ENVIRONMENTAL PROTECTION AGENCY. National primary and Secondar,
ambient air quality standards. Federal Register 36(84-Part I1):8186-820), Apri
30, 1971.

FODOR, G.G., WINNEKE, G. Effect of low CO concentrations on Tesistance .,
monotony and on psychomotor capacity. Staub Reinhaltung der Lun
32(4):46-54, April 1972.

GALUSKINOVA, V. 3,4 — Benzpyrene determination in the smoky atmosphere ay
social meeting rooms and restaurants. A contribution to the problems of SO-calleg
passive smoking. Neoplasma 11:465-468, 1964.

GODIN, G., WRIGHT, G., SHEPHARD, R. J. Urban exposure to carbon Monoxide
Archives of Environmental Health 25(5):305-313, November 1972,

GROLL-KNAPP, E., WAGNER, H., HAUCK, H., HAIDER, M. Effects of low Carbor
monoxide concentrations on vigilance and computer-analyzed brain potentiay
Staub Reinhaltung der Luft 32(4):64-68, April 1972.

HARKE, H.-P. The problem of “passive smoking.” Munchener Medizinische Wochen
schrift 112(51): 2328-2334, December 18, 1970.

HARKE, H. -P. The problem of passive smoking. I. The influence of smoking on the
CO concentration in office rooms. Internationales Archiv fur Arbeitsmedizy
33(3): 199-206, 1974.

HARKE, H. -P., BAARS, A., FRAHM, B., PETERS, H., SCHLUTZ, C. Zum Probier
des Passivrauchens (The problem of passive smoking.) Internationales Archiv te
Arbeitsmedizin 29-323-339, 1972,

HARKE, H. -P., BLEICHERT, A. Zum Problem des Passivrauchens (The problem .:
passive smoking.) Internationales Archiv fur Arbeitsmedizin 29::312-322. 1972

HARKE, H.-P, LIEDL, W., DENKER, D. The problem of passive smoking. 1!
Investigations of CO level in the automobile after cigarette smoking. inte:
nationales Archiv fur Arbeitsmedizin 33(3):207-220, 1974.

HARKE, H. -P., PETERS, H. The problem of passive smoking HI. The influence -
smoking on the CO concentration in driving automobiles. Internationales Atc!:
fur Arbeitsmedizin 33(3):221-229, 1974.

HARLAP, S., DAVIES, A.M. Infant admissions to hospital and maternal smokirz
Lancet 1(7857):529-532, March 30, 1974.

HARMSEN, H., EFFENBERGER, E. Tobacco smoke in transportation vehicles, livin:
and working rooms. Archiv fur Hygiene and Bakteriologic 141(5):383-400, 195°

HOEGG, U.R. The significance of cigarette smoking in confined spaces. Thess
University of Cincinnati, Division of Graduate Studies, Department of Envues
mental Health. 1972,137 pp.

HOEGG, U. R. Cigarette smoke in closed spaces. Environmental Health Perspectne
2:117-128, October 1972.
33

34

35

36

37

38

39

40.

41

42

43

44

45

46

47

JOHANSSON, C.R., RONGE, H. Acute irritation effects of tobacco smoke in the
room atmosphere. Nordisk Hygienist Tidskrift 46 :45-50, 1965.

JOHNSON, W. R. HALE, J. W.. NEDLOCK. J.W.. GRUBBS. H. J.. POWELL, D. H.
The distribution of products between mainstream and sidestream smoke. Tobacco
175(21):43-46, October 12. 1973.

LAWTHER, P.J., COMMINS. B.T. Cigarette smoking and exposure to carbon
monoxide. Annals of the New York Academy of Sciences 174:135-147, October
5,1970.

LUQUETTE, A.J., LANDISS, C.W.. MERKI, D. J. Some immediate effects of a
smoking environment on children of elementary school age. The Journal of
School Health 40(10):533-536, December 1970.

McFARLAND, R.A. A study of the effects of low levels of carbon monoxide upon
humans performing driving tasks at the Harvard School of Public Health. 1973
Automotive Air Pollution Research Symposium, Washington, D.C., March 7-9,
1973.

McFARLAND, R. A. Low level exposure to carbon monoxide and driving perfor-
mance. Archives of Environmental Health 27(6):355-359, December 1973.

RAY, A.M., ROCKWELL, T.H. An exploratory study of automobile driving
performance under the influence of low levels of carboxyhemoglobin. Annals of
the New York Academy of Sciences 174:396-408, October 5, 1970.

RUSSELL, M. A. H., COLE, P. V., BROWN, E. Absorption by non-smokers of carbon
monoxide from room air polluted by tobacco smoke. Lancet 1(7803):576-579,
March 17, 1973.

RYLANDER, R. (Editor). Environmental tobacco smoke effects on the non-smoker.
Scandinavian Journal of Respiratory Diseases (Supplementum 91): 1-90, 1974.

SCHMELTZ, I., HOFFMANN, D., WYNDER, E. L. The influence of tobacco smoke on
indoor atmospheres. I. An overview. Preventive Medicine 4:66-82, 1975.

SCHULTE, J.H. Effects of mild carbon monoxide intoxication. Archives of
Environmental Health 7(5):30-36, November 1963.

SEIFF, H. E. Carbon monoxide as an indicator of cigarette-caused pollution levels in
intercity buses. U.S. Department of Transportation, Federal Highway Administra-
tion, Bureau of Motor Carrier Safety, April 1973, 11 pp.

SRCH, M. Uber die Bedeutung des Kohlenoxyds beim Zigarettenrauchen im Personen-
kraftwageninnern. Deutsche Zeitschrift fur gerichtliche Medizin 60:80-89, 1967.

STEWART, R.D., BARETTA, E.D., PLATTE, L.R., STEWART, E.B., KALB-
FLEISCH, J. H., VAN YSERLOO, B., RIMM, A. A. Carboxyhemoglobin levels in
American blood donors. Journal of the American Medical Association
229(9):1187-1195, August 26, 1974.

STEWART, R. D., NEWTON, P. E., HOSKO, J. J., PETERSON, J. E. Effect of carbon

monoxide on time perception. Archives of Environmental Health 27(3):155-160,
September 1973.

111
48 U.S. DEPARTMENT OF TRANSPORTATION, FEDERAL AVIATION ADMINIS-
TRATION, U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE.
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH.
Health aspects of smoking in transport aircraft. Rockville, Md. AD-736097,

December 1971, 85 pp.

49 U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Report of
the Surgeon General: 1972. U.S. Department of Health, Education, and Welfare.

Washington, DHEW Publication No. (HSM) 72-6516, 1972, 158 pp.

50 WRIGHT, G., RANDELL, P., SHEPHARD, R. J. Carbon monoxide and driving skills.
Archives of Environmental Health 27(6): 349-354, December 1973.

112
INDEX 1975

Acetaldehyde
levels, effects of room size, amount of
tobacco burned, and ventilation, 90, 93,
98
Acrolein
effects of inhalation of, in rats, 29
levels, effects of room size, amount of
tobacco burned, and ventilation, 90, 93,
98
AHH activity
see Ary] hydrocarbon hydroxylase activity
Air pollution
effects of exposure levels on respitatory
symptoms in twins, 67
exposure levels and coal consumption, 67
and human CO burden, 20
levels, exposure of telephone workers and
pulmonary symptoms, 67
and smoking, in COPD development,
6368
and smoking, in lung cancer development,
44,47
summary of recent findings, 108
survey data for four U.S. locations, 63-66
Airways
dysfunction of, in smokers, 71
function during viral illness, in smokers vs.
nonsmokers, 62, 63
Alveolar macrophages
decrease in pinocytosis, in smokers vs.
nonsmokers, 76
response to migration inhibition factor or
antigens, in smokers vs. nonsmokers, 76,
77
Angina pectoris
effects of increased carboxyhemoglobin
levels, in passive smokers, 95, 97
Antigens
effect on alveolar macrophages, in smokers
vs. nonsmokers, 76, 77
Antitrypsin deficiency
and smoking, in COPD etiology, 72-74
Arteries
thickening of, in smokers vs. nonsmokers,
74-76
Arterioles
thickening of, in smokers vs. nonsmokers,
74-16
Aryl hydrocarbon hydroxylase activity
role in lung cancer development, 50-53
Asbestos
chrysotile, effects on lungs, 49
Atherosclerosis, coronary
see Coronary heart disease
Autopsy findings
and smoking, 74-76

Benzo(a)pyrene
levels, effects of room size, amount of

tobacco burned, and ventilation, 91-94,
98
Birth weight
effects of maternal smoking, 27
Bladder cancer
see Genitourinary cancer
Blood pressure
levels, in smokers, nonsmokers, and
ex-smokers, 15-17
Body weight
and hypertension, in smokers, non-
smokers, and ex-smokers, 15-17
Bronchiolitis
autopsy studies, in male smokers vs.
nonsmokers, 74, 76, 77
Bronchitis -
chronic, incidence of, in high pollution
areas, 63, 64
chronic, and lung cancer development, 49
chronic, summary of previous findings, 5,
7,61, 62
development in infants of maternal
smokers, 103
incidence in children of smokers, 105, 106
in passive smokers, summary of recent
findings, 108
Bronchopulmonary diseases, chronic ob-
structive
see also Emphysema, Bronchitis
air pollution and smoking in etiology of,
6368 :
effects of antitrypsin deficiency in
smokers vs. nonsmokers, 72-74
effects of partially deficient heterozygote
phenotypes, 73,74
incidence in firemen, 68
summary of previous findings, 61, 62
summary of recent findings, 78
Byssinosis
development in cotton mill workers, in
smokers vs. nonsmokers, 68

Cancer
see also specific site, e.g., Lung cancer
summary of previous findings, 3-8
summary of recent findings, 43, 54
Carbon monoxide
cholesterol levels in aorta of rabbits, after
exposure to, 28
and decrease in exercise time before
claudication, 18
effects on aortas in animals, 28
effects on healthy smokers vs. non-
smokers, 26
exposure to, and human absorption, 21-28
levels, effects of room size, amount of
tobacco burned, and ventilation, 90-95
Jevels, effects on exercise performance, 97
levels, from smokers in buses and planes,
102

113
myocardial effects on rabbits, 29
summary of previous findings on
relationship to passive smoking, 87, 88,
108
summary of recent findings, 33
from tobacco smoke, effects of psycho-
motor performance, including attentive-
ness and cognition function, 99-101
Carboxyhemoglobin levels
in cigarette smokers, one hour after last
cigarette, 25-26
and CO burden in smokers vs. non-
smokers, 21, 26-29
effects on CO absorption, in passive
smoking, 95, 96
effects on exercise performance, 97
in fetuses, 26, 27
in smokers vs. nonsmokers, by sex, race,
employment status, or urban location,
22-24
summary of recent findings, 33
in workers exposed to exhaust gases, 21
Carcinogenesis
aryl hydrocarbon hydroxylase activity,
and susceptibility to carcinogens, 50-53
experimental, 48-50
summary of previous findings, 43
Carcinogens
benzo(a)pyrene, and exfoliative cytology
of hamster lungs, 47
benzo(a)pyrene and chrysotile asbestos, in
animals, 49
in cigarette smoke, 49, 50
Cardiovascular diseases
see also Coronary heart disease, Cerebro-
vascular disease
atherosclerotic, effects of CO, 27, 28
pathogenesis of, 28, 29
Cerebrovascular disease
epidemiological studies, 29, 30
mortality by age, sex, and smoking habit,
31
CHD
see Coronary heart disease
Chemicals
exposure to, in smokers vs. nonsmokers,
by race and sex, 69, 70
Children
of smokers, incidence of pneumonia and
bronchitis, 105, 106
of smokers, prevalence of respiratory
symptoms, 102, 103
Cholesterol levels
after CO exposure, in rabbits, 28
and hypertension, in smokers vs. non-
smokers, 15
Chronic bronchitis
see Bronchitis
Chronic obstructive bronchopulmonary
disease
see Bronchopulmonary disease, chronic
obstructive
Cigar smoking
autopsy studies, in smokers with emphy-
sema, fibrosis, or thickening of arterioles
or arteries, 75
CO levels in mainstream smoke, 90
relationship to cancer, 43, 44

114

summary of previous findings on effects
on smokers, 4, 13
Cigarette smoke
see Smoke, cigarette
Cigarettes, filter
decrease in lung cancer risk, 44
summary of previous findings, 4
Clofibrate
and reduction in risk of sudden death in
cigarette smokers, 32
Closing volume abnormalities
as indicator of small airways disease, in
smokers vs. nonsmokers, 71, 72
co
see Carbon monoxide
Coffee drinking
and myocardial infarction in smokers vs.
nonsmokers, 19, 20
COPD
see Bronchopulmonary disease, chronic
obstructive
Coronary heart disease
see also Angina pectoris, myocardial
infarction
effects of coffee drinking and cigarette
smoking, 20
epidemiological studies, 14, 15
summary of previous findings, 4, 7
Cough
of parental smokers, and respiratory
symptoms in children, 103, 105
in school-age smokers vs. nonsmokers, 62
Cytologic studies
exfoliative, and lung cancer diagnosis, 47

Dust exposure
in smokers vs. nonsmokers, by race and
sex, 69, 70
and smoking as risk factors in byssinosis
development, among mill workers, 68

Emphysema
autopsy studies, in smokers vs. non-
smokers, 74-76
summary of previous findings, 5, 7, 61, 62
Epidemiological studies
cerebrovascular disease and smoking, 29,
30
CHD and smoking, 14, 15
lung cancer and smoking, 44
Epinephrine levels
effects of nicotine, 29
Epithelium
bronchial, and premalignancy in smokers,
44
Exercise performance
effects of CO exposure and increased
carboxyhemoglobin levels, 95, 97
Ex-smokers
decrease in risk of developing lung cancer,
43
effects of cessation on body weight, blood
pressure, and hypertension, develop-
ment, 16-19
effects of cessation on closing voluine
abnormalities, 71
effects of cessation on pathologic changes,
74

summary of previous findings on health
consequences of cessation, 6

summary of previous findings on
relationship to COPD, 61

Eye irritation

effects of exposure to cigarette smoke, in

passive smokers, 99, 100

Fibrosis
autopsy studies, in smokers vs. non-
smokers, 74-76
Forced expiratory volume
decline in smokers, by race, 72
Framingham Study
effect of coffee drinking on mortality in
smokers vs. nonsmokers, 20
Fume exposure
in smokers vs. nonsmokers, by race and
sex, 69, 70

Genetics
role of antitrypsin deficiency and smoking
in COPD development, 72-74
Genitourinary cancer
smoking as risk factor, 50

Histological studies
lung cancer and smoking, 44-46
Humidity
and pathologic effects of exposure to
cigarette smoke, 99
Hypertension
effects of smoking, 15-19
summary of recent findings, 33

Infants
maternal smoking, and development of
bronchitis and pneumonia, 103
Inhalation patterns
summary of previous findings, 4
Immune sy stem
suppression of immunoglobulin response,
by nicotine or water-soluble fraction of
cigarettes, 77
Intermittent claudication
decrease in exercise time after exposure to
CO, 28
effects of coffee drinking and cigarette
smoking, 20
Involuntary smoking
see Passive smoking

Laryngeal cancer
incidence of second primary, in smokers
vs. nonsmokers, 50
Leukocytes
effects of cigarette smoke, in guinea pigs,
77, 78
Lung cancer
decreased risk of, in ex-smokers, 43
and development of chronic bronchitis, 49

effects of air pollution and smoking, 44,
47

effects of asbestos exposure and smoking,
49

epidemiological studies, 44

histological types, in smokers vs. non-
smokers, 44-46

increase in mortality of, in female
smokers, 47

summary of previous findings, 3, 5-8

summary of recent findings, 43

Mainstream smoke
see Smoke streams
Migration inhibition factor
effects of alveolar macrophages, in
smokers vs. nonsmokers, 76, 77
Morbidity
from respiratory symptoms, 62, 63
Mortality
from cerebrovascular disease by age, sex,
and smoking habit, 31
from CHD, 14
from lung cancer, of female smokers, 47
from myocardial infarction, 14
summary of previous findings, 3-8, 13
Myocardial infarction
damage to rabbits after exposure to
carbon monoxide, 29
effects of coffee drinking and cigarette
smoking, 19, 20
mortality, in smokers vs. nonsmokers, 14
summary of previous findings, 4, 13
in Swedish women, smokers vs. non-
smokers, 14

Nasopharyngeal cancer
in smokers vs. nonsmokers, in Taiwan, 50
Nicotine
effects on epinephrine and norepinephrine
levels, 29
excretion, by passive smokers, 97
levels, effects of room size, amount of
tobacco burned, and ventilation, 91-94,
97
suppression of immunoglobulin response,
in cell cultures, 77
N-Nitrosamines
N'-nitrosonornicotine, in tobacco, 48, 49
N-Nitrosoheptamethyleneimine
incidence of lung neoplasms, in rats, 49
Norepinephrine
effects of nicotine, 29

Occupational diseases
byssinosis in cotton mill workers, 68
COPD, in firemen, 68
effects of asbestos exposure and smoking
on lung cancer development, 49
lung cancer, in uranium miners, 47
and risk of cancer, 43
smoking and, 68-70
Occupational hazards
carboxyhemoglobin levels in workers
exposed to exhaust gases, 21

115
exposure to chemicals, fumes, sprays, and
dusts, in smokers vs. nonsmokers, by
race and sex, 69, 70
higher reporting of exposure to, by
smokers vs, nonsmokers, 68
Oral cancer
incidence of second primary, in smokers
vs. nonsmokers, 50

Parents
cough and phlegm production, and
respiratory symptoms in children, 103
incidence of pneumonia and bronchitis in
children of smokers, 105, 106
prevalence of respiratory symptoms in
children of smokers, 102, 103
Particulate matter
pollution levels in four U.S. locations, 65,
66
Passive smoking
CO, nicotine, benzo(a)pyrene, acrolein,
and acetaldehyde levels, 90-95
effects on bus and plane passengers, 102
effects of carboxyhemoglobin levels, in
persons with angina pectoris, 95, 97
effects of carboxyhemoglobin levels on
CO absorption, 95, 96
effects of CO in tobacco smoke on
psychomotor performance, 99-101
effects of tobacco smoke constituents,
88-98
excretion of nicotine, 97
exposure to cigarette smoke, and
development of eye and throat irita-
tions, 99, 100
incidence of pneumonia and bronchitis in
children of parental smokers, 105, 106
maternal smoking, and development of
bronchitis and pneumonia in infants,
103, 104
parental cough and phlegm production,
and respiratory symptoms in children,
103
pathological studies, 99
prevalence of respiratory symptoms in
children of smokers, 102, 103
summary of previous findings, 87, 88
summary of recent findings, 107, 108
Pathological studies
effects of exposure to cigarette smoke, in
passive smokers, 99
Pathophysiological studies
alveolar macrophages and smoking, 76, 77
effects of cigarette smoke on leukocytes,
in guinea pigs, 77, 78
effects of cigarette smoke on pulmonary
macrophages, in guinea pigs, 77, 78
effects of smoking on tracheal mucous
velocity, in dogs, 78
suppression of immunoglobulin response
by nicotine or water-soluble fraction of
cigarettes, 77
Pharyngeal cancer
incidence of second primary, in smokers
vs. nonsinokers, 50

116

Phenotypes
partially deficient heterozygote, in COPD
etiology, 73, 74
Phiegm
production by parental smokers, and
development of respiratory symptoms in
children, 103
production by parental smokers, and
incidence of pneumonia and bronchitis
in children, 105, 106
Pinocy tosis
decrease in alveolar macrophages, in
smokers vs. nonsmokers, 76
Pipe smoking
autopsy studies, in smokers with emphy-
sema, fibrosis, or thickening of arterioles
or arteries, 75
summary of previous findings on effects,
4,13
relationship to cancer, 43, 44
Pneumonia
incidence in children of smokers, 105, 106
maternal smoking, and development in
infants, 103
in passive smokers, summary of recent
findings, 108
Polynuclear aromatic hydrocarbons
tumor initiators in tobacco, 48
Pregnancy
carboxyhemoglobin levels in fetuses, 26,
27
maternal smoking, and development of
bronchitis and pneumonia in infants,
103, 104
summary of previous findings, 5, 6
Psychomotor performance
effects of CO in tobacco smoke, 99-101
in passive smokers, summary of recent
findings, 108
Public transportation
effects of passive smoking on bus and
plane passengers, 102
Pulmonary function
abnormalities, during viral illness, in
smokers vs. nonsmokers, 63
closing volume abnormalities as indicator
of small airways disease, 71, 72
decline in forced expiratory volume, in
smokers by race, 72
prevalence of deficient heterozygote
phenotypes, in smokers vs. nonsmokers,
74
small airways disease, smoking and, 71, 72
summary of recent findings, 78
Pulmonary macrophages
effects of cigarette smoke, in guinea pigs,
77, 78
summary of recent findings, 78
Pulmonary symptoms
effects of air pollution exposure levels on
telephone workers, 67

Respiratory symptoms
see also Cough, Phlegm
in smokers vs. nonsmokers, 62, 63

summary of previous findings, 5

summary of previous findings on
relationship to passive smoking, 88

summary of recent findings, 78

Sidestream smoke
see Smoke streams
Smoke streams
CO levels in mainstream cigar smoke, 90
constituents of tobacco smoke, 88-98
summary of previous findings, 87, 88
Smoke, cigarette
carcinogenic content of, 48
and decrease in pulmonary macrophages,
in guinea pigs, 77, 78
effects on tracheobronchial clearance, in
donkeys, 78 .
suppression of immunoglobulin response
in cell cultures, 77
Smoke, tobacco
effects of constituents on passive smokers,
88-98
summary of recent findings, 108
summary of previous findings on

relationship to passive smoking, 87, 88°

Smoking, maternal
during pregnancy, and development of
bronchitis and pneumonia in infants,
103, 104
Sudden death
reduction of risk of, in cigarette smokers,
using clofibrate, 32
Sulfur dioxide
pollution levels in four U.S. locations, 65,
66

Tars, cigarette
summary of previous findings on effects
on smokers, 5

Throat irritation
effects of exposure to cigarette smoke, in
passive smokers, 99
Thrombogenesis
effects of smoking, 32
Tracheal mucous velocity
effects of smoking, in dogs, 78
Tracheobronchial clearance
effects of cigarette smoke, in donkeys, 78
Tumorigenic activity
in experimental animals, 48
of polynuclear hydrocarbons and tumor
accelerators, 48
Twins
air pollution exposure levels and respira-
tory symptoms, 67
mortality from CHD, in smokers vs.
nonsmokers, 14, 15

Ventilation
effects on constituents of tobacco smoke,
90-95
Ventricular premature beats
effect of cigarette smoking, 20

Water
soluble fraction of cigarettes, suppression
of immunoglobulin response, 77
Women
autopsy studies, in smokers vs. non-
smokers with emphysema, fibrosis, or
thickening of arterioles or arteries, 75
exposure to chemicals, fumes, sprays, and
dusts, in smokers vs. nonsmokers, 69, 70
incidence of lung cancer in, 43
increase in mortality from lung cancer, 47
myocardial infarction, in Swedish smokers
vs. nonsmokers, 14
summary of previous findings on effects of
smoking, 5-7

117
CUMULATIVE INDEX
1964—1975

Since the original report on the health consequences of smoking
in 1964 entitled Smoking and Health, Report of the Advisory Com-
mittee to the Surgeon General of the Public Health Service, eight
additional reports on the topic have been prepared for the U.S. Con-
gress. The nine reports are for the years 1964, 1967, 1968, 1969,
1971, 1972, 1973, 1974, and 1975.

To facilitate use of this accumulated scientific evidence on the
health consequences of smoking, the following cumulative index of
the nine reports was prepared. It should be noted that before this
cumulative index, the 1964 and 1968 Reports had not been indexed;
thus, this compilation provides the only indexes for these two re-
ports. The concept headings in this index are essentially the same as
those used in the individual report indexes. However, an effort was
made to use only one term per concept and to select the most com-
monly used terminology in the scientific literature for the concept.

The user of this index is referred to information in the different
reports by the report year followed by the page numbers in that re-
port. The year of the report is set in boldface type to stand out from
the page numbers. The following excerpt from the index exemplifies
this:

 

Abortion
comparison of stillbirth and neonatal
death with, in smoking and nonsmok-
ing mothers

YCAT nt :[390,405-406 -— pages

effect of maternal smoking
74:13; 72:5, 84, 85; 73:123,124

 

 

 

 

71:390,405-406 (This entry refers the user to the 1971
Report, pages 390, 405, and 406.)

71:13; 72:5,84.85; 73:123-124 (This entry refers the
user to the 1971 Report, page 13; to the 1972
Report, pages 5, 84, and 85; and to the 1973
Report, pages 123 and 124.)

118
INDEX
(Cumulative 1964-1975)

Abortion
comparison of stillbirth and neonatal
death with, in smoking and nonsmok-
ing mothers
71:390, 405406
effect of maternal smoking
71:13; 72:5, 84, 85; 73:123, 124
frequency, and cigarette consumption
72:85
Absenteeism
smoking and
67:19
Abstinence syndrome
64:352
Academic underachievement
64:372, 373
Acenaphthylene
in cigar, pipe, and cigarette smoke
73:178
Acenapthene
64:55
Acetaldehyde
64:52, 60, 61
as ciliatoxic agent in cigarette smoke
73:51
levels, effects of room size, amount of
tobacco burned and ventilation
75:91-94, 98
as suspected contributor to health haz-
ards of smoking
72:145
Acetic acid
as ciliatoxic agent
67:107-108
in tobacco smoke
67:107-108
Acetone
64:52, 60
as suspected contributor to health haz-
ards of smoking
72:145
Acetonitrile
as suspected contributor to health haz-
ards of smoking
72:145
Acetylcholine
effect on nicotine pharmacology
67:60
sensitivity to
64:69
Acetylene
64:60
Acidosis
metabolic, maternal smoking effect on
infant
71:407
Acinus
smoke clearance from
64:267, 269
Acrolein
64:60, 61, 266, 268

ciliastatic effect from
64:266, 267, 268
as ciliatoxic agent
67:107-108
effect on Dunaliella bioculata
69:42
effect on respiratory tract
64:266, 267
effect on respiratory tract, in rats
74:104
effects of inhalation of, in rats
75:29
as irritant in tobacco smoke
72:101
levels, effects of room size, amount of
tobacco burned and ventilation
75:91-94, 98
as probable contributor to health haz-
ards of smoking
72:144
Acrylonitrile
as suspected contributor to health haz-
ards of smoking
72:145
Additives, tobacco
see Tobacco additives
Adenocarcinoma
beryllium induced
64:166
classification of
64:173
hydrocarbon induced
64:228
increased frequency of
64:35, 174,175, 231
kidney, smoking and
69:60
nonsmokers incidence of
64:160
prevalence in male and female smokers
and nonsmokers
71:250
relationship of cigarette smoking to
71:246-249, 296
risk ratio of smokers
69:56
smoking and
64:159;67:107-108
smoking and, for men
69:57
Adenoma
papillary, induction in rats by exposure
to cigarette tars
71:348
pulmonary
64:34, 165
pulmonary, genetic factors in
64:34, 167
pulmonary, induction in mice by ciga-
rette smoke inhalation
71:349
pulmonary, induction of
64:143
renal, relationship of smoking to
71:296
Adipose tissue
effect of nicotine, in rats
74:13
Adrenalectomy
effect on nicotine pharmacology
67:60
Adrenat glands
catecholamine release from, nicotine ef-
fects on
71:36
epinephrine discharge from
64:318
nicotine effect on
64:69
Advertising
curtailment of
64:8

Advisory Committee on Smoking and
Health
64:13, 14,173
establishment and conclusions of study
by
71:3
evaluation of studies by
64:8,9, 14, 15,19
formation of
64:7,8,9
members of
64:9, 10
report on cigarette smoke and conden-
sates effects on oral cavity of animals
71:288

Aerobic capacity
effect of cessation of smoking
73:243
effect of exercise and smoking
73:243, 244

Aerosol
irritation by
64:295
tobacco smoke as
64:263

Aflatoxins
64:145
Age

atypical nuclei in esophageal epithelium
arranged by smoking and
71:379-380

bed days by, and smoking history
67:20-21

bladder neoplasm mortality rates by
67:154

bronchitis mortality rates by
67:29, 92

bronchitis mortality ratios by
67:94

cerebrovascular disease mortality ratios
by
67 :66-68

coronary disease excess morbidity rates
by
67:54

120

coronary disease incidence rates and
smoking history by
69:13-14, 17

coronary disease incidence rates by
67:54, 58

coronary disease morbidity ratios by
67:54

coronary disease mortality rates by
67:25-26, 50

coronary disease mortality ratios by
67:26, 47, 49, 51-52; 69:13, 18

coronary thrombosis mortality by
67:26

current cigarette smokers by sex and
71:6

effects on CHD
74:27-39

emphysema mortality rates by
67:29, 92

emphysema mortality ratios by
67:94

esophageal neoplasm mortality rates by
67:150

esophageal neoplasm mortality ratios by
67:150

expiratory flow rate by
64:291

forced expiratory volume by
64:291

increased smoking by
64:361, 362

laryngeal neoplasm mortality rates by
67:148-149

larnygeal neoplasm mortality ratios by
67:148-149

liver cirrhosis mortality rates by
67.184

liver cirrhosis mortality ratios by
67:184

lung functions for smokers vs. non-
smokers by
67:100

lung neoplasm mortality rates by
67:134-138, 140

lung neoplasm mortality ratios by
67:134-136, 138, 140

mortality ratios by
64:36, 87

mouth neoplasm mortality rates by
67:146

mouth neoplasm mortality ratios by
67:145-146

nonsmokers by
64:117

pancreatic neoplasm mortality rates by
67:158-159

pancreatic neoplasm mortality ratios by
67:158-159

peptic ulcer mortality rates by
67:181

peptic ulcer mortality ratios by
67:181

peptic ulcer mortality ratios for smokers
vs. ex-smokers by
67:181

pharyngeal neoplasm mortality rates by
67:146
pharyngeal neoplasm mortality ratios by
67:146

pulmonary fibrosis by
64:274

respiratory symptoms in smokers vs.
nonsmokers by
67:96-98, 100

restricted activity days by, and smoking
history
67:20-21

smokers by
64:117

smoking and, effect on clinical labora-
tory tests in healthy male veterans
73:11

statistics, errors in
64:117, 118

stomach neoplasm mortality rates by
67:157

stomach neoplasm mortality ratios by
67:157

stroke mortality rates by
69:13, 17

stroke mortality ratios by
69:13

urinary tract neoplasm mortality rates
by
67:154

urinary tract neoplasm mortality ratios
by
67:154

urogenital neoplasm mortality ratios by
67:154

work-loss days by, and smoking history
67:20, 21

Age-adjusted death rates

64:31, 36, 82, 84, 100, 101

by country
64:127

in heavy smokers
64:100

in males
64:95, 101,127

in nonrespondents
64:114

sex ratios in
64:133

in survey respondents
64:114

in United States
64:127

variables affecting
64:100

weighting of
64:114

in white males
64:95

Aged

prevalence of COPD in, smokers vs.
nonsmokers
74:78

Age started smoking

64:89, 111, 361, 362, 368, 371-374,
376
lung neoplasm association with
64:158, 230
mortality rates and
64:29, 158

mortality rates in Japanese by
73:7, 8

socioeconomic factors in
64:368

Agricultural workers

64.290

Air pollution

64:150, 177, 186, 195, 232, 295, 296,
297, 298
arsenic in
64:61
and bronchitis, in smokers vs. nonsmok-
ers
73:36, 37
bronchopulmonary effects on smokers
vs, nonsmokers
68:69
carbon monoxide from cigarette smoke
72:7, 121-123, 125
as cause of chronic bronchopulmonary
disease
67:29, 108-110
as cause of COPD
71:152, 175, 216-217
in chronic bronchitis
64:297, 298
ciliastasis from
64:268
effect of exposure levels on respiratory
symptoms in twins
75:67
effect on mortality rates from lung
cancer
73:73
effect on nonsmokers
72:121-125
effect on smokers
67:108-110
and emphysema
64:297
in etiology of bronchitis
67:108-110
in etiology of emphysema
67:108-110
in etiology of lung neoplasms
64:172; 67:140; 68:98, 99; 71:11,
276; 73:72, 73
exposure levels and coal consumption
75:67
exposure magnitude in
64:296, 297, 298
and human CO burden
75:20
levels, exposure of telephone workers
and pulmonary symptoms
75:67
lung damage from
64:301
in Osaka, Japan
73:44
prevalence of respiratory diseases and
73:44
relationship of lung neoplasms, smoking
and place of residence
71:252-255
respiratory diseases in
64:295-298
smoking and, in COPD development
74:82, 83; 75:63-68
smoking and, in lung neoplasms develop-
ment
74:45, 46; 75:44,47
smoking and, in military and civilian
aircraft
73:45
sulfur dioxide in
64:295
summary of recent findings
75:108
survey data for four U.S. locations
75:63-66
tobacco smoke as a factor
72:7, 121-124
“Tokyo-Yokohoma asthma” from
64:276
urban-rural effects of
64 :298
Air quality
standards for carbon monoxide
72:128
Airway conductance
64:292
Airway obstruction
emphysema in
64:297
measurement of
64:292
ozone induction of
64:296
smoking effect on
64.292, 293, 297, 300
sulfur dioxide effect on
64:295
Airway resistance
to smoke inhalation in guinea pigs
68:72
Airways, large
effect of smoking one nonfilter cigarette
74:99
Airways, small
abnormalities, in smokers vs. nonsmok-
ers, autopsy studies
74:97, 98
dysfunction of, in smokers
75:71
effect of smoking one nonfilter cigarette
74:99
function during viral illness, in smokers
vs. nonsmokers
75:62, 63
Albany prospective studies
64:323, 325
Alcohol
ethanol, penetrability of dissolved
benzo(a)pyrene in mice esophageal
epithelium
71:293
Alcohol consumption
64:91, 101, 224, 302, 385
effect on esophageal neoplasms in smok-
ers
71:289, 293
effect on laryngeal neoplasms in tobacco
users
71:280
effect on mortality rates from esoph-

122

ageal neoplasms in Japanese males
72:71
effect on tobacco amblyopia
71:435-436
in esophageal neoplasms
64:213, 217, 218
in heavy smokers
64:342
and heavy smoking, effect on oral neo-
plasms
71:288
interaction with smoking and other risk
factors in CHD
73:10
in laryngeal neoplasms
64:210, 211
in liver cirrhosis
64:342
in oral neoplasms
64 :204
smoking and, in esophageal neoplasm
etiology
67:152; 71:3, 68, 70, 71; 73:76, 200
smoking and, in laryngeal neoplasm eti-
ology
73:197
smoking and, in neoplasm development
73:76, 200
smoking and, in oral neoplasm etiology
68:100, 101; 73:193; 74:53-55
smoking and, in relation to cirrhosis of
liver
67:40, 185
in tuberculosis
64:277; 71:172
see also Alcoholism
Alcoholic beverage workers,
neoplasm risk ratios in
64:134
Alcoholics Anonymous
64:354
Alcoholism
mortality in, relation to smoking
67:10, 184
patients, smoking and ventilatory func-
tion in
74:213
Alcohols, aliphatic
64:51
Aldehydes
64:52, 296
Aldrin
64:62, 145
Alkaline dusts
64:298
Alkaloids
64:54
Alkaloids, tabacco
and experimental bladder neoplasms
69:64
N-Alkanes
64:51
Alkylbenzenes
64:55
Alkylphenols
64:54
Allergy
effect on cardiovascular abnormalities
72:411
tests of
64:276
tobacco and
72:7, 103-11
tobacco-induced
64:276, 301, 319
tobacco smoke irritants and
72:110
Alpha-l-antitrypsin deficiency
COPD predisposition from
71:150
determination using immunoelectro-
phoresis
71:151
in emphysema etiology
71:10-11; 72:110
smoking and
72:110
smoking and, in COPD etiology
74:87-90; 75:72-74
Altitude
effect on arterial oxygen tension
72:22
Aluminum
in main stream smoke
64:55
Alveolar bone loss
smoking and
69:85-87
Alveolar macrophages
see Macrophages, alveolar
Alveoli
see Pulmonary alveoli
Amblyopia, tobacco
64:39, 73, 341, 342
alcohol consumption effect on
71:435-436
characterization of
71:435
and cigar smoking
67:39
developmen: from cyanide component
of tobacco smoke
71:14; 72:6
diet and
72:6
effect on optic pathways
67:183
incidence of
71:435
pathogenesis
67:183
and pipe smoking
67:39
potentiation of cyanide toxicity by vita-
min B-12 deficiency in
67:183
smoking and
72:6
vitamin B deficiency and tobacco smoke
in
67:40, 183
American Cancer Society
64:6, 7, 81,93, 96, 101, 363
American College of Chest Physicians
64:8
American Heart Association
64:6,7

pooling project on CHD
71:23, 28, 30, 39
American Medical Association
64:8
American Thoracic Society
64:275, 278, 279
Amino acids
64:54
Aminoazo dyes
activity in placenta of smoking mothers
71:410
o-Aminophenols
concentration in urine of cancer patients
and smokers
69:64
experimental bladder neoplasm induc-
tion
67:156
Ammonia
64:60, 61
ciliastatic effect of
64:268
as suspected contributor to health haz-
ards of smoking
72:145
Amphetamine
64:71
Anabasine
64:49
Analytic methods
arsenic determination
64:61, 62
fluorescence properties
64:51
mass spectrometry
64:51
paper chromatography
64:51
ultraviolet absorption
64:51
Anger
personality traits, smokers
64-326
Angina pectoris
64:275, 319, 320, 323, 325
carbon monoxide exposure and
74:14, 12
carbon monoxide inhalation and
73:17, 18
coffee drinking, smoking, and
74:8
and coronary disease incidence
67:53
effects of increased carboxyhemoglobin
levels, in passive smokers
75:95,97
Health Insurance Plan Study and inci-
dence in males
68:19, 20
and heavy cigarette smoking, findings of
Framingham Heart Study
68:19
incidence in Norwegian men
68:19
incidence in pipe and cigar smokers
73:215
incidence rates and smoking history
69:21-22

123
morbidity ratios
67:59
morbidity ratios among persons 30-59
years old
68:20
smoking and
69:18; 74:8
smoking and, in twins
67:59; 69:25; 72:18
Aniline dyes
64:222
Animals
esophageal neoplasms in, induction by
nitrosamines
71:292
experiments, as evidence
64:26
respiratory tract of, neoplastic changes
following cigarette smoke inhalation
71:238-239
skin of, carcinogenicity of tobacco tars
71:238, 267
tests of, with smoke carcinogens
74:12
ventilatory function change from smok-
ing
71:10
Annandale study
64:286
Anoxia
64:70, 344
cerebral
64:70
effect on myocardial tissue function
68:38-40, 43
relation to smoking
67:183
Anthanthrene
64:147
Anthracene
in cigar, pipe, and cigarette smoke
73:178
oil, carcinogenic activity of
64:147
Anthranilic acid, 3-hydroxy-
urinary excretion of, smoking effects on
71:296
Anticarcinogens
64:143, 144
Antidiuretic hormone
64:69, 320
Antigen-antibody reactions
allergy and
72:103-107
smokers vs. nonsmokers
72:7, 105, 111
tobacco and
72:7, 104-107
Antigenic properties
of tobacco
64:319
Antigens
effect on alveolar macrophages, in smok-
ers vs. nonsmokers
75:76, 77

Antioch College study
64:370

124

Antismoking campaigns
64:354
Aortic aneurysm
mortality, for men by amount smoked
69:16
mortality rates
64:103, 325; 67:69
mortality ratios
67:69
nonsyphilitic, mortality rates, smokers
vs. nonsmokers
72:2
smoking and
67:27; 71:9, 67, 71, 75
Aortic arch reflexes
64:70
Aortic bodies,
nicotine induced stimulation of
64:317
Appetite reduction
64:71, 355
Areca nut
see Betel nut
Arecoline
64:351
Argon
in gas phase, in smoke
64:60
Aromatic alcohols
64:51
Aromatic compounds
carcinogenic properties in cigarette
smoke from
71:264, 265
detection in urine using chemilumines-
cence technique
71:297
polycyclic, carcinogenicity of
64:142, 146, 165, 166, 189, 229,
230
polycyclic, pyrolytic formation of
64:59

polycyclic, structure of
64:54, 56

stimulation of placental BP-hydroxylase
activity in pregnant rats by
71:414

Aromatic hydrocarbons
64:55
carcinogenicity
67:129;69:61
role in lung neoplasm development
74:49-52
in tobacco smoke
64:55; 67:127
Aromatic hydrocarbons, polycyclic
binding to DNA and RNA
73:86, 87

effect during pregnancy in laboratory
animals
73:117, 118
effect on tobacco carcinogenicity
72:66
maternal-fetal exchange and
73119

tumor initiators in tobacco
75:48
Arousal effects
nicotine induction of
64:70, 350
Arrhythmias
formation in nicotine stimulated dam-
aged myocardium
71:58
nicotine toxicity in
64:73
smoke induction of
64:319
smoking and
69:4
Arsenic
64:55, 61, 62
carcinogenicity of
64:167
determination of
64:61, 62
lung neoplasm mortality in smelter
workers exposed to
71:257
lung neoplasm risk from
64:193, 194
respiratory tract carcinoma in workers
exposed to
71:256, 257

Arterial diseases
carboxyhemoglobin levels and
72:26
smokers vs. nonsmokers
72:26
smoking and
72:25, 26
see also Arteriosclerosis; Atherosclerosis

Arteries
64:274

aneurysm in aortic, cigarette smoking
effects on
71:9, 67, 71, 75

atherosclerotic, increased by cigarette
smoking
71:8, 63

flow of carotid, cigarette smoking effects
on
71:67

hypoxemia, development from cigarette
smoking
71:9

occlusions of, cigarette smoking effects
on
71:73

thickening of, in smokers vs. nonsmokers
75:74-76

walls of, mechanism of lipoprotein infil-
tration
71:63

walls of, nicotine-induced necrosis
71:63

Arterioles
effect of smoking
73:22, 23
thickening of, in smokers vs. nonsmokers
75:74-16
Arteriosclerosis
64:32, 320-325

in aorta and coronary arteries, cigarette
smoking effects on
71:45, 52-56

aortic
69:26

autopsy studies and
72:19, 20

cigarette smoking effects on
71:8

cigar smoking and
72:19

coronary
69:26

coronary, mortality rate in
64:317, 320, 321

development by increased carboxyhemo-
globin formation
71:9

development of, carbon monoxide ef-
fects on
74:63

development of, effects of nicotine on
71:38

and effect of smoking on blood circula-
tion
67:62

experimentally induced in dogs
72:19, 20

experimental studies
69:26-27

hypoxia and, hypercholesterolemia in
69:26

tesion development in, smoking enhance-
ment
74:36

mortality rates
64:25; 67:26

obliterans
64:326

obliterans, smoking as a cause
73:19, 20

pathogenesis of, relating to smoking
67:65-66

peripheral, cigarette smoking effects on
71:72-73; 73:21

pipe smoking and
72:19

severity of, and smoking
69:26

smokers vs. nonsmokers
72:19, 22, 23, 27

smoking and
67:28; 69:4-5

smoking classification and
72:19

see also Atherosclerosis

Arthritis, rheumatoid

pulmonary function abnormalities,
smoking, and
74:92, 93

Aryl hydrocarbon hydroxylase

effect of benzo(a)pyrene in pregnant rats
73:119

role in lung neoplasm development
74:49-52:75:50-53

125
role in metabolism of chemical carcin-
ogens
73:82, 83

Asbestos

chrysotile, effects on lungs
75:49

effect on pulmonary function in smokers
vs, nonsmokers
73:41

effect on radiological findings in smokers
vs. nonsmokers
73:41

effect on respiratory symptoms in smok-
ers vs. nonsmokers
73:41

pulmonary fibrosis and
72:44

smoking and, effect on mortality rates
from lung neoplasms
73:73

synergistic effect with smoking in lung
neoplasm development
74:4143
Asbestosis
64:167
in smokers vs. nonsmokers, asbestos
workers in Singapore
74:95
Asbestos workers
64:193, 232; 74:95
Asia
Central and Southeast, relationship of
tobacco use and neoplasms of oral
cavity
71:366
Asthma
bronchial, cigarette smoking effects on
71:10, 175
cigarette smoking in
64:38, 302
definition of
64:27
smoking and
67:29; 72:37
tobacco allergy in
64:276
“TFokyo-Yokohama”
64:276
Atelectasis
64:272
Atherosclerosis
64:318, 319, 320
aortic, long term smoking effects
71:52-56
coronary blood flow in, in rabbits
64:318
experimental induction of, in rats
64:319
see also Arteriosclerosis
Athletic performance
running, effect of smoking
73:243, 244
smokers vs. nonsmokers
73:243, 244
swimming, effect of smoking
73:244
Atropine
64:354

126

effects on bronchoconstriction in dogs
71:163
mucus secretion blockage by
64 :269
Atypical cells
64:231
hyperchromatic nuclei in
64:34
smoke-induced, in epithelium
64:168, 169, 170, 172, 173
Australia
COPD morbidity in smokers in
71:203
coronary death rate in
64:320
laryngeal neoplasms in; relationship to
tobacco use
71:357
lung neoplasms death rate in
64:176
lung neoplasms in, retrospective studies
of
71:327
peptic ulcer in, methods for retrospec-
tive and cross-section studies of
smoking and
71:426, 428
Automobile driving
64:322
Autonomic nervous system
effect of nicotine on
67:60
Autopsy studies
64:150
arteriosclerosis and
72:19, 20
bronchiolitis development and smoking
75:74, 76
COPD and smoking
73:4548
coronary heart disease and
72:19, 20
emphysema development and smoking
74:97; 75:74-76
fibrosis development and smoking
75:74-76
lung neoplasms in U.S. veterans
73:73, 74
mucous gland abnormalities and smoking
74:97
small airway abnormalities and smoking
74:97, 98
thickening of arteries, arterioles and
smoking
7§:74-76
Aviators
prevalence of CHD
68:19
smoking effect on blood pressure
68:22

Bacteria
effect of cigarette smoke on action of
macrophages
71:165
pneumonia, mice resistance following
cigarette inhalation
71:173
Bacterial flora
in smokers vs. nonsmokers with COPD
73:54
Ballistocardiography
64:319
findings in cardiac disease after cigarette
smoking
68:37
Bank employees
chronic cough in
64:281
Barbiturates
64:352
Bartenders
esophageal neoplasms in
64:134
oral neoplasms in
64:134
Bauhinia
64:21]
Bed days
by age, sex and smoking history
67:19-21
definition of
67:19
Behavior
and coronary disease
67:56; 69:20, 24
of heavy smokers
64:372
patterns, in smokers vs. nonsmokers
68:26-28
Behavioral research
smoking habit
67:38, 188-192
Belfast
lung neoplasm mortality in
64:195
Benz(e)acephenanthrylene
carcinogenic properties in cigarette
smoke from
71:264, 265
see also Aromatic hydrocarbons
Benzanthracene (9-10 dimethyl-1!, 2-)
64:203
Benz(a)anthracene
alcoholic solution of, penetrability of
mice esophageal epithelium
71:292
carcinogenicity
67:127
carcinogenicity, as component of ciga-
rette smoke
72:66
in tobacco smoke
67:127

Benz(a)anthracene, 7, 12-dimethyl

carcinoma induction in hamsters follow-
ing instillation of
71:346

skin painting with, papilloma and carci-
noma induction in mice by
71:341

see also Aromatic hydrocarbons

Benzene
64:55, 59
as suspected contributor to health haz-
ards of smoking
72:145
Benzocaine lozenges
64:354
Benzo(b)fluoranthene
carcinogenicity
67:127
in tobacco smoke
67:127
see also Aromatic hydrocarbons
Benzo(j)fluoranthene
64:57
carcinogenicity
67:127
carcinogenic properties in cigarette
smoke from
71::265
see also Aromatic hydrocarbons
Benzo(k)fluoranthene
carcinogenicity
67:127
in tobacco smoke
67:127

see also Aromatic hydrocarbons

Benzo(rst)pentaphene
carcinogenic properties in cigarette
smoke from
71:265
see also Aromatic hydrocarbons

Benzo(g,h,i)perylene
64:147
carcinogenicity
67:127
in tobacco smoke
67:127
see also Aromatic hydrocarbons

Benzo(c)phenanthrene

64:56

carcinogenicity
67:127

carcinogenic properties in cigarette
smoke from
71:265

in tobacco smoke
67:127

see also Aromatic hydrocarbons

Benzo(a)pyrene

64:147, 148, 233

ability of smoking mothers to hydroxy-
late
71:407

as air pollutant from cigarette smoke
72:123

and air pollution, in lung neoplasm
development
74:45, 46

alcoholic solution of, penetration of
mice esophageal epithelium
71:292

carcinogenic effect in laboratory animals
73:78-80

carcinogenicity of
64:33, 144, 145, 146,67:127

127
carcinogenicity of, in relation to asbestos
in hamsters
71:257

carcinogenic properties in cigarette
smoke from
71:264, 265

carcinoma induction by
64:166

in cigar, pipe, and cigarette smoke
73:177, 178

cocarcinogenic effect on respiratory
tract in rabbits
72:67

determination of
64:57

detoxification by lung aryl hydroxylase
71:257

effect on DNA and RNA
73:86, 87

effects during pregnancy in laboratory
animals
72:89; 73:117, 118

effects of instillation or implantation in
animal tracheobronchial tree
71:346-347

effects on animal tissue and organ cul-
tures in
71:343-345

effects with influenza virus on cigarette
inhalation by mice
71:352

in ethanol, effect on esophageal tissue
67:153-154

hydroxylation by pulmonary benzo-
pyrene hydroxylase
69:62

hydroxylation by the placenta
69:80; 72:89

isolation of
64:55

levels, effects of room size, amount of
tobacco burned and ventilation
75:91-94, 98

in olive oil, effect on esophageal tissue
67:152-153

oral neoplasm induction by
64:203, 204

pyrolytic formation of
64:59

reduction of, by copper nitrate
64:60

role in respiratory tract carcinogenesis,
in animals
74:46, 47

sarcoma induction in rats following in-
stillation of
71:346

skin painting with, papilloma induction
in mice by
71:337-338

in smoke streams
72:123

in soot
64:148

squamous cell carcinoma from
64:166

structural formula of
64:56

128

threshold levels of
64:143
in tobacco smoke
67:127
from vegetable fibers
64:59
see also Aromatic hydrocarbons
Benzo(e)pyrene
64:147
carcinogenicity
67:127
in tobacco smoke
67:127
see also Aromatic hydrocarbons
Benzopyrene hydroxylase
inhibition of nickel carbony! in cigarette
smoke
69:62
Beryllium
64:55
carcinoma induction by
64:166
epidermoid neoplasms from
64:166
lung neoplasm risk from
64:193
oxide
64:166
sulfate aerosol
64:166
Betanaphthylamine
content of cigarettes
69:64
Betel nut
64:203, 349, 351
Betel nut chewing
64:211, 351
in Bombay, India
72:69
in head and neck neoplasm etiology
72:69
laryngeal neoplasms from
64:211
oral neoplasms from
64:197; 71:366, 369-370
smoking and

72:69
smoking and oral leukoplakia
69:58
and tobacco chewing
64.203
Biased measurements
64:36, 98
Bicarbonate
in pancreatic secretions, effect of smok-
ing
73:159, 160

Bicycle ergometer performance
cardiovascular parameters in smokers vs.
nonsmokers
73:242-244
Bioassay methods
in carcinogenesis
64:59, 143, 147
Biometry Branch, National Cancer Institute
64:137, 138, 139
Biri
64:211
Birth weight
effect of maternal smoking
64:39, 343; 67:39, 185-186; 69:5,
77-80; 71:389, 397-399; 72:5, 83-87;
73:103-114, 119-122: 75:27
effect of maternal smoking before and
during current pregnancy by cigarette
consumption
73:107-109
effect of maternal smoking during pre-
vious pregnancies
73:112-114
effect of paternal smoking
73:110,111
effect of tobacco smoke, nicotine, or
carbon monoxide in laboratory ani-
mals
73:114-118
gestation duration in smokers vs. non-
smokers
73:103-106
mortality risk of low birth weight infants
of smoking vs. nonsmoking mothers
73:126-132
timing of influence of smoking
73:120, 121
Bitters
64:354
Blacks
maternal smoking and infant weight
71:397
maternal smoking and prematurity
69:78; 71:400-401
Bladder neoplasms
64:37, 218-235
aniline dyes in
64:222
blood groups in
64:224
carcinogenesis, tobacco smoke constit-
uents and tars
67:156
cotinine and
69:64
dose effect in
64:223
experimental aspects of
69:64
experimental induction by hydro-
quinone
67:156
experimental induction by 3-hydroxy-
anthranilic acid
67:156
experimental induction by 3-hydroxy-
kynurenine
67:156
experimental induction by ortho-amino-
phenols
67:156
experimental induction by tars
64:219, 223
experimental induction in mice
64:223
frequency in smokers vs, nonsmokers
71:238, 293-295; 73-77, 78
in heavy smokers
64:219, 224

in men, relation to smoking
67:153
morbidity, effect of smoking on
67:155
mortality rates
64:133, 148, 149; 71:293, 294
mortality rates, female
64:132, 137, 219, 220, 221, 224,
225; 67:154
mortality rates, foreign-born
64:134
mortality rates, male
64:130, 132, 137;67:154
mortality ratios
64:148, 149, 222; 67:33
mortality ratios, male smokers by age
67:154
mortality trends, by sex
64.137
occupational risk
64.134, 222,224
relationship of cigarette smoking to
71:13, 299
relative risk in females by amount smok-
ed
72:73
relative risk in males by amount smoked
72:72, 73
relative risk ratios from, in smokers
64:223
retrospective studies of, and smoking
64:218-222; 71:293, 381-384
sarcoma
64:223
smokers vs. nonsmokers
72:293-295, 381-384

smoking and
64:32; 67:33; 69:60, 64; 72:68,
72-74

smoking in etiology of
72:5; 73:77, 78
and tobacco alkaloids

69:64
and tryptophan metabolites in urine

67:36, 156; 71:296-297
urban-rural prevalence of
64:225
U.S. incidence of
64:127
in women
64:132, 219, 220, 221, 224, 225
see also Urogenital neoplasms
Bladder stones
64:224
Blood
gas exchange in
64:292
groups, in bladder neoplasms
64:224
plasma, and thrombus formation
69:27-28
Blood chemical analysis
comparison for smoking and nonsmok-
ing mothers and their infants
69:80
Blood cholesterot levels
and coronary disease
64:321; 67:58; 71:21-22, 23-24, 43

129
and coronary disease mortality
69:17
effect of carbon monoxide in rabbits
73:18; 75:28
effect of diet
64:322
effect of smoking
67:66; 71:8,41,43; 74:17, 18
effect of smoking and body weight
73:11
effect of smoking and clinical parameters
in British business executives
73:11
effect of smoking in peripheral vascular
disease
71:72
and hypertension, in smokers vs. non-
smokers
75:15
increase in smokers
64:326
and lung neoplasms in male smokers
69:57
myocardial infarction morbidity ratios in
males from Framingham study
68:24
in pipe and cigar smokers
73:215, 216
in smokers vs. nonsmokers
68:22, 23, 29, 43; 71:41, 98-102
see also Cholesterol
Blood circulation
effect of cigarette smoke inhalation
67:26, 63; 71:58
effect of cigarette smoke inhalation, in
dogs
67:62
effect of nicotine on
67:60-64
effect of smoking on
67:60-64; 69:11, 27-28: 73:19, 22,
23
effect of variations in hemoglobin and
hematocrit
71:66
peripheral
64:318
Blood coagulation
clotting time
64:319
effect of smoking
67:64; 71:9, 36; 74:18, 19
Blood lipids
effect of nicotine in rabbits
68:31
effect of smoking
74:65-66, 123-128; 73-11, 12; 74-17
effect of smoking and nicotine
68:30, 31
effect of smoking and relative weight, in
male Parisian civil servants
73:51
effect of smoking in middic-aged pa-
tients with angina pectoris
73:12
effect of smoking in young Norwegian
military recruits
73:11

130

elevated, as risk factor in CHD
73:11

elevated, as risk factor in CHD
73:11

free fatty acids, effect of smoking
64:319; 67:64-65

smokers vs. nonsmokers
71:41, 98-102

and thrombogenesis
68:32, 33

Blood platelets

adhesiveness, effect of cigarette smoking
on
TE:9, 36

counts
64:319

effect of smoking
67:64; 69:27-28: 71:66, 75

survival
64:319

Blood pressure

coronary disease
67:54-55, 58; 68:22

coronary disease and smoking
69:14; 71:43, 47

coronary disease mortality and
69:14, 17

diastolic, cigarette smoking effects
71:8, 23

diastolic, in smokers with CHD
71:21-22, 24, 42

effect of catecholamines on
67:60

effect of cigarette smoke inhalation on
67:54

effect of CO exposure
74:11, 12

effect of exercise and smoking
73:242, 244-246

effect of nicotine
64:318; 67:60; 71:36; 74:13

effect of pipe and cigar smoking
73:216

effect of smoking
67:54-55, 60; 74:17

effect of smoking in middle-aged pa-
tients with angina pectoris
73:12

high risk in mortality from CVD
71:67

hypertensive vs. nonhypertensive, mor-
tality rates of CHD in
71:42

myocardial infarction morbidity ratios in
males
68:24

risk factors in arteriosclerosis obliterans
F372

in smokers, nonsmokers, and ex-smokers
75:15-17

smokers vs. nonsmokers
68:22, 29:71:41, 42, 103-104

smoking and, effects on pregnancy out-
come
69:77-78

systolic, mortality from elevated, with
CHD
71:42
Blood sugar
elevation, by tobacco
64:355
Blood vessels
effect of nicotine on
67:62
effect of smoking on pulmonary arterial
capillaries
67:111
Blood viscosity
and arteriosclerosis
69:27
Body constitution
64:321
and bronchitis
67:30, 102-103, 108
and cough development
67:102-103, 111
and emphysema
67:30, 111
and respiratory tract diseases
67:30
smokers vs. nonsmokers
67:54, 99
Body height
effect of maternal smoking
74:407,; 72:88
interaction with smoking as factor in
cerebrovascular disease
73:19
in respiratory function tests
64:290
Body size
in male smokers vs. nonsmokers
68:28
Body weight
64 :384, 385
and coronary disease
67:58
and hypertension, in smokers, nonsmok-
ers, and ex-smokers
75:15-17
increase in, on cessation of smoking
64:326
interaction with smoking as factor in
cerebrovascular disease
73:19
relationship to coronary disease mortal-
ity rates and smoking
69:14
tisk factor in CHD
68:29, 43
in smokers vs. nonsmokers
68:21
and smoking, as factors in CHD inci-
dence
73:44
and smoking, effect on blood lipids
73:11
Boilermakers
neoplasm risk in
64:134
Boston Collaborative Drug Surveillance Pro-
gram
role of coffee drinking and smoking in
myocardial infarction
74:8

Bowel habits
tobacco effects on
64:355
Bradycardia
development in dogs given nicotine
74:57
Breast feeding
duration of
64:368
Breathlessness
64:27, 38, 301
prevalence of
64:285, 286, 287
Britain
chronic bronchitis studies in
64:271, 280
coronary death rates in
64:320
curtailment of advertising in
64:8
lung neoplasm death rate in
64:176
mortality rates, in laryngeal neoplasms
64:205
risk ratios in
64:127
urban-rural mortality ratios in
64:186
British agricultural workers
forced expiratory flow rates in
64:290
British air pollution
disease factors in
64:194, 195, 298
British doctors study
64:97, 102, 114, 162, 180, 230, 322
expected deaths in
64:109
mortality ratios in
64:109, 149
nonresponse rates in
64:113
observed death rates in
64:109
British General Post Office
64:281, 286
British Medical Research Organization
64:6
British miners
forced expiratory flow rate in
64:290
British Perinatal Mortality Survey
results of
71:390
British smokers
age distribution of
64:177
cough prevalence in
64:281
inhalation practices among
64:177
Bronchi
abnormalities in smokers vs, nonsmokers
72:45
histopathologic change in
64:170
hyperplasia in
64:271

13]
morphology
64:271
mucus secretion in, nicotine-induced
64:268
physiology, in animals and humans
68:71-74
Bronchial epithelium
changes after nitrogen dioxide exposure,
in animals
74:102, 103
changes in, in smokers
64:171,172
disintegrating nuclei in
64:170
effect of cigarette smoke on
67-107, 140, 144; 69:40
effect of filtered gas-phase cigarette
smoke, in rabbits
74:104, 105
effect of nitrogen dioxide on, in rats
69:41
effect of smoking on
67:104, 106
effect of tobacco smoke on
67:129
histological changes at autopsy and
smoking habit
73:74
histological changes in cigar, pipe, ciga-
rette smokers vs. nonsmokers
73:203, 204, 209
premalignant changes in smokers
73:67; 75:44
Bronchial glands
64:168
Bronchial mucosa
effect of cigarette smoke on
67:30, 104-107, 144
effect of tobacco smoke constitutents on
67:30
Bronchial neoplasms
experimentally induced by cigarette
smoke
67:144
risk ratio of smokers
69:56
Bronchiectasis
64:277-294
induction of, in mice
64:272
Bronchiolar dilations
64:272
Bronchiolar neoplasms
64:159
Bronchiolitis

autopsy studies, in male smokers vs.

nonsmokers
75:74, 76,77
ozone induction
64:295
purulent, in mice
64:272
Bronchiolo-alveolar neoplasms
smoking and
73:71
Bronchitis
64:277-294

132

definition of
64:289; 67:89

development in infants of maternal
smokers
75:103

diagnosis
67:90

and disability, in smokers vs. nonsmok-
ers
73:43

dust exposure as a factor
73:44

and emphysema
64:113, 280

etiology of
64:8

fibrotic, induction by sulfur dioxide
64:295

incidence in British males by cigarette
consumption
72:62

incidence in children of parental smokers
75:105, 106

incidence of among smokers
69:37

morbidity, and cigar smoking
67:29-30, 94

morbidity, and pipe smoking
67:29-30, 94

morbidity, and smoking
67:3, 22, 96

morbidity, in smoking-discordant twin
pairs
67:103

mortality, and smoking
67:3, 30, 90-96

mortality, in United States
67:9,90

mortality rates
67:8, 29

mortality rates, by sex and smoking
classification
67:95

mortality rates, effect of cessation of
smoking on
67:2, 29,94, 96

mortality ratios, by amount smoked
67:90-92

mortality ratios, cigar smokers
67:94

mortality ratios in male pipe and cigar
smokers
73:217, 219

mortality ratios, male smokers by a-
mount smoked
67:93

mortality ratios, pipe smokers
67:94

occupational diseases and
72:42

in passive smokers, summary of recent
findings
75:108

post-operative, incidence in smokers vs.

nonsmokers
74:92
prevalence in cement and rubber indus-
try workers, smokers vs. nonsmokers
74:95, 96

prevalence in Duisburg, Germany, by age
and cigarette consumption
73:39

prevalence in ex-coal miners and non-
miners by smoking habit
73:42

prevalence in heavy smokers
64:298

prevalence in male smokers by smoking
patterns
74:79

prevalence in miners and farmers in
Hungary, by smoking habit
73:42

prevalence in moderate smokers
64:298

prevalence in pipe and cigar smokers
73:220, 221

prevalence in rubber industry workers,
smokers vs. nonsmokers
74:96

prevalence in smokers in Glenwood
Springs, Colorado
72:39

prevalence in smokers vs. nonsmokers in
Bordeaux, France
73:36

prevalence in smokers vs. nonsmokers in
mountainous and low-lying areas
73:36, 37

prevalence in smokers vs. nonsmokers in
Osaka, Japan
73:44

prevalence in smokers vs, nonsmokers in
Yugoslavia
72:40

prevalence in smoking vs. nonsmoking
yarn mill workers
73:40

prevalence in the elderly, smokers vs.
nonsmokers
74:78, 79

prevalence in urban vs. rural population
in Mongolia
74:80

prevalence in U.S., statistics
74:75

prevalence in wool and cotton textile
workers in North Carolina
74:93

prevalence of
64:25, 288

prevalence of, by sex
64:289

prevalence rates by sex and smoking
history
67:96, 99

and respiratory symptoms
68:74

and respiratory symptoms by smoking
classification
67:97-98

role of constitutional factors in patho-
genesis of
67:30, 102-103, 108-109

role of hereditary factors in pathogenesis
of
67:30, 101-104, 108
and small airway abnormatities, in smok-
ers vs. nonsmokers
74:97, 98
in smokers vs. nonsmokers
68:69, 70
in smokers vs. nonsmokers, autopsy
studies
73:45, 46
smoking and
69:4
smoking and, effect on pulmonary func-
tion
74:80
smoking in etiology of
67:29, 31, 96, 103, 104-106; 69:4;
72:37
smoking vs. coal mining in etiology of
73:42
smoking vs. dust inhalation in etiology
of
73:42
summary of previous findings on rela-
tionship to smoking
74:75-78
see also Bronchitis, chronic

Bronchitis, chronic

64:31, 38, 271, 272, 277-302
air pollution in
64:297, 298
British incidence of
64:280, 297, 298
cigarette smoking cause and effect rela-
tionship
71:3,9
cigarette smoking in
64:31, 277-302
definition of
64:278; 71.139
diagnosis of
64:278, 280
emphysema relation to
64:279, 280, 297, 298
epidemiology of
64:280-294, 301
etiology of 64
64:38, 280-294, 298, 299,
302
histopathologic change in
64:271, 272, 300
incidence of, in high pollution areas
75:63, 64
lung neoplasms related to
64:195; 75:49
mortality in cigarette smokers
TL175
mortality rates
64:25; 68:66, 67; 71:139
mortality ratios in
64:29, 277, 293, 301
mucus production in
64:272
occupational exposure in
64:298, 299, 300, 302
ozone induction of
64:295
pathology of
64:271, 272, 274, 275
prospective studies in
64:293, 294
risk ratios in
64:31
smokers vs, nonsmokers
71:195-205
symptoms of
64:27, 278-294

Bronchoconstriction
from cigarette smoke in animals
68:72

Bronchogenic carcinoma
see Carcinoma, bronchogenic

Bronchopneumonia
development in dogs following cigarette
smoke inhalation
71:271

Bronchopulmonary diseases, chronic ob-
structive
64:272, 277-297, 298
air pollution relationship in
64:38; 71:152, 216-217
alpha-1-antitry psin deficiency and
autopsy studies
73.4548
as cause listed on death certificates vs.
findings at autopsy
73:47
characterization of
71:139
cigarette smoking effects on develop-
ment
71:4,9-11,175
definition
67:89-90
disabilities from
64:277

effect of smoking cessation on develop-
ment
71:10

epidemiology
64:280-294, 297, 298; 73:3645

epidemiology in Tecumseh, Michigan
72:39, 40

genetic factors in pathogenesis of
71:148, 150-152, 205

increased prevalence of heterozygotes in
71:151-152

morbidity, smokers vs. nonsmokers in
Berlin, New Hampshire
72:39

mortality
64:277

mortality and morbidity studies
73:36-39

mortality rates
71:139-145

mortality rates for ex-smokers, and
smokers vs, nonsmokers
72:3

mortality rates for pipe/cigar smokers vs.
cigarette smokers
72:3

134

mortality rates in British citizens by
migration patterns
73:36

mortality rates in pipe, cigar, and ciga-
rette smokers
71:175

mortality rates, smokers vs. nonsmokers
72:38, 39

mortality ratios in male pipe and cigar
smokers
73:216, 217, 219

occupational hazards and
72:4244

prevalence of
69:38

relation to pulmonary hypertension and
cor pulmonale
68:74-76

smoking effect on
64:31, 277-302

smoking effects on ventilation-perfusion
measurments in
71:163

smoking in etiology of
72:3, 37

summary of previous findings
73:35, 36

summary of recent findings
73:55

see also Bronchopulmonary diseases,
non-neoplastic

Bronchopulmonary diseases, non-neoplastic

air pollution and smoking in etiology of
74:82, 83; 75:63-68

alpha-1-antitrypsin deficiency and smok-
ing in etiology of
74:87-90

closing volume abnormalities, in smokers
vs. nonsmokers
74:84-87

effects of alpha-l-antitrypsin deficiency
in smokers vs. nonsmokers
75:72-74

effects of partially deficient hetero-
zygote phenotypes
75:73, 74

history of respiratory diseases and smok-
ing in etiology of
74:90

incidence in autoworkers
74:80

incidence in firemen
75:68

mortality and morbidity
68:66-7!

occupational exposure and smoking
74:80

prevalence in Boston policemen, smokers
vs. nonsmokers
74:82, 83

prevalence in the elderly, smokers vs.
nonsmokers
74:78

prevalence in urban vs. rural population,
in Mongolia
74:80

reference listings
74:107-118
small airways disease, pulmonary func-
tion, and
74:84, 87
small airways disease, smoking, and
74:84-87
summary of previous findings
68:65; 75:61, 62
summary of recent findings
74:106, 107; 75:78
Bronchospasm
64:296
Buechley, Drake, and Breslow study
64:324
Buerger’s disease
smoke toxicity in
64:73, 326
Bullous disease
incidence in men by age, race, and
smoking habit
74:90-92
Bureau of State Services, USPHS
64:13
Burma
methods used in study of smoking and
human pregnancy
71:393
Burns
neoplasm initiation by
64:142
2, 3-Butadione
as suspected contributor to health haz-
ards of smoking
72:145
Butane
64:60
Butytamine
as suspected contributor to health haz-
ards of smoking
72:145
Butylamine, N-methy!-nitroso
suspected carcinogenic properties in ciga-
rette smoke from
71:265
Butylmethylnitrosamine
in cigarette smoke
67:29, 31, 96, 103
Byssinosis
development in smoking vs. nonsmoking
cotton mill workers
75:68
dust exposure and smoking in etiology
of
74:94-96
prevalence in men by index of severity
and smoking habits
73:40, 41
prevalence in smoking vs. nonsmoking
cotton mill workers
73:39, 55
smoking and
73:39-41

Cachexia
64:73

Cadmium
in cigarette smoke, relation to patho-
genesis of emphysema
71:154
in emphysema etiology, in animals
74:104
Caffeine
64:349, 351, 352
California
cancer registries

64:127

California Legion Study
expected deaths in
64:110
mortality ratios in
64:110, 149
nonresponse rates in
64:113

California Occupational Study
64:95, 106, 217, 342
bladder neoplasm prevalence in
64:222
expected deaths in
64:109
mortality ratios in
64:109, 149
nonresponse rates in
64:113
observed deaths in
64:109, 110
Canada
COPD morbidity of smokers in
71:204
coronary death rate in
64:320
human experimental data on smoking
and pregnancy
71:409
infectious respiratory disease in, relation-
ship to smoking
71:228
kidney and bladder neoplasms in smok-
ers in
71:294
jung neoplasm death rate in
64:176
mortality rates from COPD
71:139-141, 145
mortality ratios from COPD
71:143
mortality ratios in smokers and non-
smokers from pancreatic neoplasms
71:298
National Department of Health and Wel-
fare
64:6
neoplasm risk in
64:127
prospective study, bladder neoplasm
prevalence in
64:222
thrombosis in, smoking relationship
71:132
Canadian veterans study
64:91, 94, 342
expected deaths in
64:110
lung neoplasm mortality ratios in, smok-
ers vs. nonsmokers
71:241
mortality ratios in
64:110, 149
nonresponse rates in
64:113
observed deaths in
64:110
Cancer
see Neoplasms and specific neoplasm
terms, e.g., Lung neoplasms
Cancer registries
64:128, 135
in California
64:127
completeness of
64:128
in Connecticut
64:128
in Denmark
64:220
mortality rates, by site, in
64:132
in New York
64:129
Cannibinols
64:349
Capillaries
effect of smoking
73:22
Carbazole, 9-methyl-
possible importance in tobacco carcino-
genesis
71:266
Carbon-14
labeled smoke particulate deposition in
hamster respiratory tract
71:281-282
Carbon black
neoplasm risk from
64:147
Carbon dioxide
in gas phase, in smoke
64:60
as suspected contributor to health haz-
ards of smoking
723145
Carbon monoxide
64:70, 296, 297
as air pollutant from cigarette smoke
72:7, 121-123, 125
and carboxyhemoglobin levels
69:28-29; 72:21-23, 127
and carboxyhemoglobin levels in smok-
ers vs, nonsmokers
67:63
cardiovascular effects, experimental
studies
TBAT-19
cholesterol levels in rabbits, after ex-
posure to
75:28
in cigarette smoke
67:63, 183
in cigarette smoke, formation of
carboxyhemoglobin
71::8-9

136

coronary heart disease and
74:10-12

and decrease in exercise time before
claudication
75:28

effect during pregnancy in laboratory
animals
73:116, 117, 132, 133

effect on aortas in animals
75:28

effect on birth weight and neonatal
mortality in animals
73:133

effect on blood circulation in human
beings
67:63

effect on cardiovascular system
72:22; 74:10-12

effect on cholesterol biosynthesis, in
vitro
73:18

effect on cholesterol-fed rabbits
71:65-66

effect on cholesterol level in aorta in
rabbits
73:18

effect on coronary hemodynamics and
ventricular function in dogs
73:18

effect on exercise performance in smok-
ers vs. nonsmokers
73:18

effect on healthy smokers vs. nonsmok-
ers
75:26

effect on human physiology
71:60-62

effect on myocardium
68:3840, 43-44; 69:28; 75:29

effect on nonsmokers
72:126

effect on platelet stickiness in rabbits
73:18

effect on psychomotor performance
72:126

effect on reflex vasoconstrictor re-
sponses
73:18, 23

effect on vascular resistance
73:22, 23

effect on vision
72:126

exposure to, and human absorption
75 :21-28

from freeway traffic, effect on myocar-
dial work capacity and angina
74:11

inhalation of, and effect on blood circu-
lation in dogs
67:63

as most likely contributor to health
hazards of smoking
72:8, 143

neonatal mortality effect from
64:343

psychological and physiological effects
72:125-128
summary of previous findings on rela-
tionship to passive smoking
75:87, 88, 108
summary of recent findings
75:33
from tobacco smoke, effects on psycho-
motor performance, including atten-
tiveness and cognition function
75:99-101
see also Carbon monoxide levels
Carbon monoxide levels
in cigarette smoke
71:59
effect of room size, amount of tobacco
burned and ventilation
75:90-95
effect on exercise performance
75:97
in fetal blood of smoking mothers
71:407-410
from smokers in buses and planes
75:102
Carboxyhemoglobin
effect on fetal tissues
71:407
formation from CO in cigarette smoke
71:8-9
formation in blood of smokers
71:60, 75
see also Carboxyhemoglobin levels
Carboxyhemoglobin levels
69:26, 28
blood cholesterol and
72:23
blood circulation and
67:63
in cigarette smokers, one hour after last
cigarette
75:25, 26
and CO burden in smokers vs. nonsmok-
ers
78:25, 26
coronary heart disease and
74:10-12, 19
during and following exposure to carbon
monoxide
72:124,125
effect on CO absorption, in passive
smokers
75:95, 96
effect on exercise performance
73:246, 247; 75:97
in fetuses
75:26, 27
following smoking of non-nicotine ciga-
rettes
73:17, 18
in neonates of smoking mothers
73:118,119
in nonsmokers exposed to cigarette
smoke
72:125
occlusive peripheral vascular disease and
72:26
in smokers
69:28-29, 80

in smokers, and carbon monoxide in
tobacco smoke
67:183

smokers vs. nonsmokers
67:63, 100; 72:21-23

in smokers vs. nonsmokers, by sex, race,
employment status or urban location
75 :22-24

summary of recent findings
75:33

in workers exposed to exhaust gases
7§:21

Carboxylic acids

as Cocarcinogens

67:131
Carcinogenesis

aryl hydrocarbon hydroxylase activity,
and susceptibility to carcinogens
75:50-53

bladder neoplasms, and tobacco smoke
constituents
67:156

bladder neoplasms, and tobacco tars
67:156

bladder neoplasms, by o-aminophenols
in laboratory animals
67:156

bladder neoplasms, by hydroquinone in
laboratory animals
67:156

bladder neoplasms, by 3-hydroxyan-
thranilic acid in laboratory animals
67:156

bladder neoplasms, by 3-hydroxy-
kynurenine in laboratory animals
67:156

cell and tissue culture studies
73:84-86

effect of tobacco curing methods
73:212

epidermoid carcinoma, experiments in
laboratory animals
67:35

experimental
68:90-93; 69:62-64,
72:65-67; 73:78-87; 74:46, 47;
75:48, 49,50

initiating and promoting agents in ciga-
rette smoke
73:68

initiating agents
64:142

initiating agents in cigarette smoke
72:66

lung neoplasms by cigarette smoke in
laboratory animals
67:144

mechanism of action
73:78, 80-87

mechanism of action, in lung neoplasm
induction, in animals
74:46, 47

and occupational asbestos exposure of
smokers
67:35

and occupational uranium exposure of
smokers
67:35

137
possible role of tobacco alkaloids in
69:61

promoters
64:142

of respiratory tract in laboratory animals
73:78-80

role of cigarette smoke condensate
73:80-84

skin neoplasms by cigarette smoke
67:144

summary of recent findings
75:43

by tobacco smoke constituents in labora-
tory animals
67:35, 144

Carcinogens

64:172
action on oral cavity, effect of saliva
71:288
anthracene oil as
64:172
aromatic hydrocarbons, unspecified
69:61
benz(a)anthracene
67:127
benzo(b)fluoranthene
67:127
benzo(j)fluoranthene
67:127
benzo(g,h,i)perylene
67:127
benzo(c)phenanthrene
67:127
benzo(a)pyrene, and chrysotile asbestos,
in animals
75:49
benzo(a)pyrene, and exfoliative cytology
of hamster lungs
75:47
benzo(a)pyrene as
64:55
bladder, in tobacco smoke
69:64
in cigarette smoke
67:15, 34; 75:49, 50
in cigarette smoke condensate
74:47
cigar, pipe, and cigarette smoke conden-
sate, in skin painting experiments in
animals
73:210-214
creosote oil as
64:147
dibenz({a,h)acridine
67:127
dibenz(a,j)acridine
67:127
dibenz(a,h)anthracene
67:127
dibenzanthracene as
64:143
dibenzo(a,h)acridine as
64:59
dibenzo(a,j)acridine as
64:59
dibenzo(a,h)anthracene as
64:55, 229

138

7H-dibenzo-(c,g)carbazole
67:127
dibenzo(a,i)pyrene
67:127
effect on cell transformations
73:84-86
effect on oral mucosa in taboratory
animals
72:70
effect on respiratory tract in laboratory
animals
73:78-80
heterocyclics as
64:54
hydrocarbons, extraction of
64:147
hydrocarbons, polynuclear, and tumor
accelerators
75:48
hydrocarbons, reduction of
64:60
implantation
69:64
indeno(1 ,2,3-c,d)pyrene
67:127
listing of, in cigarette smoke
71:265-266
metals as
64:166, 167, 189, 193, 194, 232
N-nitrosamines
67:127, 128
oral administration of, in mice
64:228
polycyclic aromatic compounds as
64:26
polycyclic, order of potency
64:56
polycyclic, structure of
64:56
pyrolytic formation of
64:59
role in tumor induction in animals
74:46, 47
in smoke, effect on oral cavity
71:12
sterol hydroperoxides as
64:52
tobacco smoke constituents as
64:26, 33, 34, 51-60, 141-148;
68:90, 91; 73:210-214
use in experimental bronchogenic carci-
noma
69 63-64
see also Carcinogenesis, and specific
compound listings

Carcinoid tumor

prevalence in male and female smokers
and nonsmokers
71:250

risk ratio of smokers
69:56

Carcinoma

64:165, 166

benzo(a)pyrene induction of
64:166

beryllium induction of
64:166
chromium induction of
64:167
classification of, in smokers vs. non-
smokers
67:140
formation following animal skin painting
with smoke condensates
71:337-342
induction in rats exposed to cigarette
tars
71:348
induction in rhesus monkeys
64:166
in situ
64:172, 203
tobacco tar induction of
64:143
undifferentiated, and pipe smoking
64:143
undifferentiated, and smoking
64:140-143
undifferentiated, relationship to ciga-
rette smoking
71:248-249
see also Specific histologic types
Carcinoma, alveolar cell
64:159
induction in mice by cigarette smoke
inhalation
71:349
risk ratio of smokers
69:56
and smoking
64:143
Carcinoma, anaplastic
64:231
classification of
64:173
prevalence in male and female smokers
and nonsmokers
71:250
Carcinoma, bronchogenic
64:229
animal models for
69:63-64
development in dogs following cigarette
smoke inhalation
71:269, 272-273
experimental induction of
64:33, 165, 189; 69:63-64
in dogs
64:33
mortality from, relationships to smoking,
air pollution and residence
71:253
mortality in smoking vs. nonsmoking
asbestos workers
71:257
mortality trends in
64:141
multiple primary
67:142-143
risk ratio of smokers
69:56
Carcinoma, epidermoid
64:165, 231
experimental induction of
69:63-64

mortality from, relationship to smoking,
air pollution and residence
71:254
pipe smoking and
67:143
prevalence in male and female smokers
and nonsmokers
71:250
relationship of cigarette smoking to
71:246-249
risk ratio of smokers
69:56
smoking and
67:35, 140-143
in women
64:159
Carcinoma, epithelial
induction in mice by cigarette smoke
inhalation
71:350
Carcinoma, oat cell
64:159, 231
relationship of cigarette smoking to
71:247
smoking and
67:140-141
Carcinoma, oval cell
64:175
Carcinoma, smali cell
tisk ratio of smokers
69:56
Carcinoma, squamous cell
64:166, 231
development in mice drinking alcoholic
benzo(a)pyrene
71:292
increase in
64:175
induction of
64:189, 228
in oral cavity, relationship to tobacco

use
71:366-367
smoking in etiology of
72:69
Carcinoma, tracheobronchial!
induction in hamsters by cigarette smoke
instillation
71:346-347
Cardiac index
effect of exercise and smoking
73:242-244
Cardiovascular diseases
64:38, 317-327
atherosclerotic, cigarette smoking rela-
tionship
71:4
atherosclerotic, effects of CO
75:27, 28
glucose metabolism
68:40,41
mortality rates
64:25, 317; 69:17
mortality ratios in male pipe and cigar
smokers
73:215, 216
pathogenesis of
75:28, 29

139
pyschosocial factors in
64:327

response to smoking and nicotine
68:3442

in smokers vs, nonsmokers
68:37

smoking and
64:32, 38, 317-327; 67:3, 25-28,
47-69; 69:3-5; 73:3-23; 74:3-19

smoking effects in
64:38, 317-327

and sudden death
68:36

summary of previous findings
73:3; 74:3,4

summary of prospective epidemiological
studies for cigar and pipe smokers
73:216

summary of recent findings
73:23; 74:19

see also Arteriosclerosis; Atherosclerosis;
Coronary diseases

Cardiovascular system

effect of carbon monoxide exposure
74:10-13

effect of catecholamines on
67:60

effect of cigarette smoke on
71:56-58, 107-118

effect of nicotine on
67:60; 71:56-58, 107-118; 74:13

effect of smoking on
67:26, 60

Carotid body
64:69, 318
Catecholamine levels
effect of cigar, pipe, and cigarette smoke
in dogs
73:216
effect of nicotine, in rats
74:13
Catecholamines
64:70, 318
effect of nicotine on release of
67:60; 71:36, 57, 119
effect of smoking on release of
69:60; 71:8
effect on blood circulation
67:60
effect on blood circulation in coronary
arteries
71:58
effect on blood pressure
67:60
effect on cardiovascular system
67:60
effect on heart rate
67:60
effect on myocardium
67:60
and thrombogenesis
68:32
see also Catecholamine levels
Catholics
smoking prevalence in
64:364

140

Cats
cardiovascular function in, smoking and
nicotine effects on
71:110, 111
ciliary function in, effect of cigarette
smoke on
71:222-224
lungs of, cigarette smoke effect on sur-
factant activity
71:225
mucus secretion in
64:268
mucus secretion in, nicotine-induced
effects
64:318
Cattle
ciliary function in, effect of cigarette
smoke on
71:221
Causality
definition of
64:20, 21
epidemiological methods in determining
64:20
statistical methods in determining

temporal factors in
64:185
Cell cultures
malignant transformations induced by
tobacco tars on carcinogens
73 :84-86
tobacco carcinogenesis and
73:84-86
Cells
atypical, in ex-smokers, smokers, and
nonsmokers at autopsy
73:74
pathology of, in smokers
64:26, 27, 167-173
respiration of, cyanide effect on
64:266
stimulation of, by nicotine
64:349
Cellulose
pyrolysis of
64:60
Cembrene
64:49
Central nervous system
effect of carbon monoxide in smoke on
71:60
nicotine effects on
64:69, 70, 317, 318
Cerebrovascular diseases
64:103
definition of
71:66
epidemiological studies
74:16, 17; 75:29, 30
incidence in longshoremen
74:17
incidence in men, Framingham study
74:17
incidence in women, smokers vs. non-
smokers
74:16, 17
interaction of smoking and other risk
factors
73:19

mortality rates
64:325

mortality rates by age, sex and smoking
classification
67:66; 75:31

mortality rates, effects of cigarette
smoking
71:9

mortality rates, smokers vs. nonsmokers
71:66-70; 72:2

mortality ratios by age, sex and smoking
classification
67:66

mortality ratios in pipe and cigar smok-
ers
73:215, 216

oral contraceptives and smoking in etiol-
ogy of
74:16, 17

smoking and
67:27-28, 66, 68; 72:24, 25

thrombosis, smoking and
67:27, 68

see also Arteriosclerosis

Cerium

neoplasm induction by
64:166

Cervix

carcinoma in situ of
64:172

Cesium

64:137
tobacco plant uptake of
64:146

Cessation of smoking

64:31, 37, 87, 188, 374, 375, 376

in adults
64:375

body weight increase following
64:326

compared benefits in cigarette vs.
pipe/cigar smokers
73:172, 173

death rate reduction following
64:29, 92

decreased clinical symptoms following
64:271, 301

effect on absolute aerobic power
73:243

effect on bladder neoplasm mortality
rate
67:155

effect on bronchitis mortality rate
67:29, 94, 96

effect on COPD development
71:140

effect on COPD development in British
physicians
72:142

effect on COPD morbidity and mortality
71:175; 72:41, 42

effect on COPD morbidity in smokers vs.
nonsmokers
71:146

effect on coronary disease mortality rate
67:25, 28, 50; 71:32, 46-48, 106

effect on emphysema mortality rate
67:29, 94

effect on esophageal neoplasms
67:147

effect on infant birth weight
73:107-109, 112-114

effect on laryngeal neoplasm mortality
rate
67:149

effect on lung neoplasm mortality rate
64:163, 187, 188; 67:24, 33,
137-140

effect on lung neoplasm mortality rate in
men
67:134, 136

effect on morbidity
67:24

effect on mortality rates
67:4, 7, 15-16, 24, 139

effect on mortality ratios
64:29, 163

effect on mouth neoplasm mortality rate
67:147

effect on pharyngeal neoplasm mortality
trate
67:147

effect on pulmonary surfactant levels
73:55

effect on respiratory symptoms
72:41, 42

effect on respiratory tract neoplasm
mortality rate
67:147

effect on risk of lung neoplasms
69:55, 57

effect on stomach neoplasm mortality
rate
67:158

effect on tryptophan metabolism dis-
orders
67:89-90

emotional disturbances following
64:350

gastric ulcer recovery following
64:337

genetic factors in
64:191

group psychotherapy in
64:354

health improvement following
64:187, 188, 271, 294

illness as a reason for
64:92

improvements in respiratory system
71:148, 149

lung neoplasm development and
72:62

methods for
64:354

myocardial infarct and
72:17, 18

as preventive measure in CHD
72:17, 18

as preventive measure in occlusive dis-
ease
73:21, 22

14]
psychosocial aspects of
64:374, 375, 376
reduction of risk following
64:37, 163, 187, 188
reinforcing factors in
64:34
relation to incidence of CHD
71:32, 46-48, 106
stomatitis nicotina resolution following
64:271; 69:87
as therapy for peptic ulcer
67:182
as therapy in arterial diseases
72:26
thromboangiitis obliterans treatment by
64:326
Channe! blacks
64:147
Chemicals
exposure to, in smokers vs. nonsmokers,
by race and sex
75:69, 70
Chemoreflex
nicotine induction of
64:318
Chest illnesses
prevalence of
64:287, 288, 301
prevalence of, in pipe and cigar smokers
73:220, 221
prevalence of, in smokers
64:27, 297, 298
in women
64:288
‘Chewing tobacco
see Tobacco chewing
Chickens :
ciliary function in, effect of cigarette
smoke on
71:223
Ciliastasis in
64:268
effect of cigarette smoke on embryos
71:344
effect of nicotine on embryos CNS
71:411
Children
effect of parental smoking
64:369; 72:129
epithelial tissues in
64:170, 173
passive smoking and
72:129
respiratory illness and
72:129
of smokers, incidence of pneumonia and
bronchitis
75:105, 106
of smokers, prevalence of respiratory
symptoms
75:102, 103
smoking patterns in
64:368, 369
Chile .
atherosclerosis autopsy studies in
71:55, 56
Chimney sweeps
scrotal cancer in
64:147

142

skin cancer in
64:147
China
ginseng root consumption in
64:355
Chiordane
64:62, 145
Chlorinated hydrocarbons
pesticide use of
64:62, 145
Chlorogenic acid
64:54
Chlorpromazine
64:70
Cholesterol
64:326, 385
biosynthesis, effect of carbon monoxide,
in vitro
73:18
rabbits fed, carbon monoxide effects on
71:65-66
synergistic relationship of carbon mon-
oxide in coronary atheromatosis
71:63
in tobacco
72:24
in tobacco smoke
72:24
see also Blood cholesterol levels
Chromaffin tissue
64:69, 318
Chromium
carcinogenesis by
64:167
lung neoplasm induction by
64:189, 193, 194
lung neoplasm mortality from
71:257-258
in mainstream smoke
64:55
neoplasm prevalence in workers exposed

to
64:193, 194, 232
respiratory tract carcinoma in workers
exposed to
71:256
Chronic diseases
smokers vs. nonsmokers
67:22
Chrysene
” carcinogenicity
67:127
carcinogenicity, as component of ciga-
rette smoke
71:265,; 72:66
in tobacco. smoke
67:127
Cigar and pipe smokers
see Smokers, cigar and pipe
Cigarette ash
nickel in
64:167
Cigarette butts
lengths
64:177
Cigarette filters
see Filters —
Cigarette paper

increase of cigarette burning rate
68:91

Cigarettes

definition and processing
73:175

and development of esophageal neo-
plasms
71:12, 293

flavor, terpenoids as source of
64:52

low nicotine, and respiratory symptoms
64:289

low nicotine, ciliastatic effect of
64:268

modified, effect on respiratory symp-
toms and ventilatory capacity
73:37, 38

portion smoked, dosage score as func-
tion of
67:15

similarities with little cigars
73:224, 225

tar and nicotine content
72:142, 143

tar levels of, relationship to lung neo-
plasm development
71:275, 276

taxation
69:4,57

see also Cigarettes, filter; Cigarettes, low-
Nicotine; Cigarettes, non-nicotine;
Cigarettes, non-tobacco

Cigarettes, daily consumption

aortic aneurysm mortality by
69:16

and atypical nuclei in larynx
69:59

average, dosage score as function of
67:15

bladder neoplasms mortality rates by
67:155

bronchitis mortality ratios by
67:90

coronary disease incidence rates
67:58; 69:15; 21-24

coronary disease mortality rates by
67:51; 69:13

coronary disease mortality ratios by
67:49

coronary disease mortality ratios for
male smokers by
67:48

digestive tract neoplasm mortality rates
by
67:147

effect on lung neoplasm mortality in
Poland
72:61, 62

esophageal neoplasm mortality ratios by
67:150

increase in, by women
64:363

laryngeal neoplasm mortality rates by
67:147

liver cirrhosis mortality rates by
67:184

liver cirrhosis mortality ratios by
67:184

lung neoplasm morbidity rates by
67:33-34

lung neoplasm mortality rates
67:135-137

lung neoplasm mortality ratios
67:34, 135-140

mouth neoplasm mortality rates by
67:146

mouth neoplasm mortality ratios by
67:146

pancreatic neoplasm mortality rates in
men by
67:159

pancreatic neoplasm mortality ratios in
men by
67:159

peptic ulcer mortality rates in male
smokers by
67:182

per capita
64:26, 45, 46, 185

pharyngeal neoplasm mortality rates by
67:146

pharyngeal neoplasm mortality ratios
by
67:146

prevalence of
64:361-374

respiratory tract neoplasm mortality
rates by
67:147

stomach neoplasm mortality rates by
67:157

stomach neoplasm mortality ratios by
67:157

tracheal neoplasm mortality rates by
67:147

in tuberculars
64:277

urogenital neoplasm mortality ratios for
male smokers by
67:154

Cigarettes, filter

decrease in tar yields
68:91

effect on respiratory symptoms
73:55

increase in

64:46
and polonium-210 content in tobacco
smoke
68:92
production of, in U.S., by year
64:46
and risk of lung neoplasms
69:57; 73:44
summary of previous findings
75:4

vs. nonfilter, and risk of tung neoplasms
74:40, 41

vs. nonfilter, comparison of safety
69:57

vs. nonfilter, effect on sputum produc-
tion
73:37, 38

Cigarettes, low-nicotine

respiratory symptoms trom
64:268
Cigarette smoke
see Smoke, cigarette
Cigarette smokers
see Smokers, cigarette
Cigarette smoking
see Smoking
Cigarettes, non-nicotine
effect on apexcardiogram
72:21
effect on carboxyhemoglobin levels
73:17, 18
Cigarettes, non-tobacco
64:59
Cigars
definition and processing
73:175, 176
per capita consumption
64:26, 45
Cigars, little
chemical composition of
73:224, 225, 228
evaluation of potential public health
impact
73:222-228
shipment for domestic consumption
(1970-1972)
73:222-224, 227
similarity to cigarettes
73:224, 225
sugar and pH differences with large cigar
and cigarettes
73:222-224
tar and nicotine content
73:224-226, 228

Cigar smoke
see Smoke, cigar
Cigar smokers
see Smokers, cigar; Smokers, cigar and
pipe
Ciliary activity
64:61
clearance mechanism by
64:267, 268
effect of cigarette smoke in animals
68:71, 72
effect of nitrogen dioxide, in rats
74:103
effect of pipe/cigar smoke vs. cigarette
smoke in cats
73:217, 218
effect of smoke on
64:27, 34, 35, 61, 168, 169, 170,
172, 173, 267; 67:107-108; 69:42
effect of smoking on
74:101, 102
loss of, in smokers
64:168, 169, 170, 172, 173
morphological changes in cilia
64:267, 268, 271
transport
64:61, 267, 268
Ciliary depressants
64:27, 33, 34, 61, 267, 268
acrolein as
64:267, 268
ammonia as
64:268

144

cigarette smoke as
64:33, 35, 370
formaldehyde gas as
64:268
gas phase as
64:34
hydrogen cyanide as
64:268
nicotine as
64:268
nitrogen dioxide as
64:268
ozone as
64:268
sulfur dioxide as
64:268, 295
Ciliatoxic agents
acetic acid
67:108
acrolein
67:107
in cigarette smoke
67:107
crotonaldehyde
67:108
cyanides
67:107
effect on adenosine triphosphatase
67:108
effect on oxidative enzymes
67:108
formaldehyde
67:107
formic acid
67:108
phenols
67:108
propionic acid
67:108
Circulatory diseases
64:113
Circumcision
64:224
Clofibrate
and reduction in risk of sudden death in
cigarette smokers
75:32
Closing volume abnormalities
as indicator of small airways disease, in
smokers vs, nonsmokers
74:84-87; 75:71, 72
Coal dust
effect on pulmonary function in smokers
vs. nonsmoker
73:4143
effect on respiratory symptoms in smok-
ers vs. nonsmokers :
73:4143
Coal gas workers
64:232
lung neoplasms in
64:193
Coal miners
pneumoconiosis and
72:42-44
respiratory function tests in
64:289, 293, 294
respiratory symptoms in
64:298, 299
Coal tar
benzo(a)pyrene content of
64:148
neoplasm induction by
64:33, 147, 167, 229
Cocaine |
64:349
Coca leaves
64:349
Cocarcinogens
64:33, 58, 142, 144, 145
benz(a)anthracene as
64:58
carboxylic acids as
67:131
croton oil as
64:58
fatty acids as
64:58, 59
nickel carbonyl] as
69:62
phenols as
64:54, 58, 59; 67:31
in tobacco smoke
- 64:33; 69:61
in tobacco tars
67:131
Cocoa
64:349
Coffee drinking
-  64:349
angina pectoris, smoking, and
74:8
myocardial infarction, smoking and, in
smokers vs. nonsmokers
74:8; 75:19, 20
Cognition
and smoking habit
67:189-191
Cologne,
autopsy records in
64:150
Colonic polyposis
64:191
Combustion temperature
effect on tumorigenic activity of pipe
and cigarette tobacco
73:210, 211
Common colds
64:276
Compensatory behavior,
smoking as
64:372
Congenital malformations
maternal smoking and
72:87; 73:136, 137
Congestive heart failure
64:320
Connecticut Cancer Registry
64:127, 128
data from
64:135
figures on age-adjusted larynx neoplasm
incidence
71:277

figures on incidence of oral neopiasms
71:284
Constitutional hypothesis
64:190, 191, 192, 193
refutation of
64:192
relationship to CHD and smoking
71:48-49, 105-106
Contraceptives, oral
incidence of stroke and, in women smok-
érs vs. nonsmokers |
74:16, 17
smoking and
72:26
thrombophlebitis and
72:26
Control populations
bias in selection of
64:181, 217, 231
Copenhagen
neoplasm study in
64:220, 222, 224
Tuberculosis Station
64:141
Copper
64:193
nitrate
64:60
sulfate
64:354
Coppersmiths
64:134
Cornfield method
64:155, 159, 160
Cornsilk
smoking, lack of arterial epinephrine
level increase
71:57
Coronary circulation
64:318; 68:41-43
Coronary diseases
64:8, 29, 36, 38 103, 106, 108, 317,
320-327, 384, 385
age-adjusted rates in smokers
71:23
by amount smoked
69:12-13, 18
arteriosclerotic, mortality rates in U.S.
74:21
associated risk factors and smoking
74:17
atherosclerosis
64:320
atherosclerosis, effects of smoking on
71:4, 63
autopsy studies
72:19, 20; 74:4
and behavior
67:57
blood pressure of smokers vs. nonsmok-
ers
71:43, 47
carbon dioxide effects on oxygen uptake
in
71:62
carbon monoxide and
74:4

145
carboxyhemoglobin levels and
72:27

cross-sectional study in Bergen, Norway
72:16

death ratios of paired combinations of
high risk
71:25

effect of coffee drinking and cigarette
smoking
75:20

effect of norepinephrine levels
68:38

effect of smoking on blood circulation in
67:26, 61-62

effect on blood circulation
67:62-63

effect on blood pressure
67:54

epidemiological studies
64:320, 321, 322; 69:25; 72:14-16;
73:4-11; 75:14, 15

etiology of
64:320, 321, 322

excess deaths in
64:113

experimental studies
73:13-19

heredity as a factor
72:18

high blood pressure in
64:38

high serum cholestero} in
64:38

incidence and education level
68:24

incidence and mortality rates in former
smokers
71:46, 4748

incidence in European vs. American men
73:9

incidence in farmers vs. nonfarmers by
smoking habit
73:7

incidence in Hawaiian men of Japanese
ancestry
73:10

incidence in Japanese male smokers vs.
nonsmokers
68:17

incidence in lawyers
68:25

incidence in male bank employees in
Brussels, Belgium
73:10

incidence in males by smoking habits or
physical activity
68:20, 25

incidence in male smokers vs. nonsmok-
ers
68:17, 18, 20, 23, 25, 27, 28, 37

incidence in men in Yugoslavia
73:9

incidence in men under 60, in New
South Wales
74:6

incidence in men with and without
ventricular premature beats
74:44

146

incidence in middle-aged men from var-
ious countries
74:6

incidence in miners in Sardinia
73:10

incidence in Minnesota men by age and
smoking habit
72:14-16

incidence in pipe and cigar smokers
73:215, 216

incidence in smokers vs. nonsmokers,
Peoples Gas Co. Study
74:6,7

incidence in smokers vs. nonsmokers,
Stockholm Prospective Study
74:6

incidence in tribal population area, New
Guinea
74:9

incidence in twins
68:29

incidence in white males by body weight
and smoking habit
73:5

incidence in whites vs. blacks in Evans
County, Georgia
73:4,5

incidence in women, smokers vs. non-
smokers
74:9,10

incidence of, relation to angina pectoris
67:53

incidence of, relation to blood cholester-
ol levels
67:58

incidence of, relation to blood pressure
67:58

incidence of, relation to body weight
67:58

incidence of, relation to electrocardio-
graphic abnormalities
67:58

incidence of, relation to hemoglobin
levels
67:58

incidence of, relation to myocardial in-
farct
67:53

incidence of, relation to socioenviron-
mental stress
67:56

incidence rates, by age
67:54, 57-58; 68:21; 69:21-22, 24

incidence rates, by amount smoked
67:54, 57-58

incidence rates, by behavior type
69:20, 24

incidence rates, by smoking and other
risk factors
69:23

incidence rates, by smoking history
69:21-24

incidence rates in men
67:65; 69:21-22

incidence rates in twins, smokers vs.
nonsmokers
67:59
incidence rates, smokers vs. nonsmokers
69:18, 20-22

in India
73:11

infarction in NYC pipe and cigar smok-
ers
71:32, 38-39

infarction, relationship to physical act-
ivity, smokers vs. nonsmokers
71:44

interaction of smoking and other risk
factors
72:16-18; 73:4-11

in Irish smokers vs. nonsmokers
68:18

morbidity ratios
67:59; 69:19

morbidity ratios, and blood pressure
67:55

morbidity ratios, and Jung function
67:56

morbidity ratios, by age
67:54

morbidity ratios, by blood cholesterol
levels
67:55

morbidity ratios, by personality charac-
teristics
67:57

morbidity ratios, by sociocultural mobil-
ity status
67:57

morbidity ratios, in New Delhi, India
72:16

morbidity, relationship of smoking to
71:32-35, 37, 39, 93-97

mortality and morbidity retrospective
studies
71:40, 93-97

mortality rates
64:25, 29, 32, 38, 39, 184, 320, 321,
324; 67:8, 25-26

mortality rates among former college
students
69:16, 18

mortality rates and per capita cigarette
consumption in several countries
72:16

mortality rates, by age
67:25, 28, 47, 49-51; 69:13-14

mortality rates by blood pressure
69:14

mortality rates by relative weight
69:14

mortality rates, by sex
67:25, 27, 28, 47, 49-50; 69:13-14

mortality rates, by smoking
67:25, 28, 49-51; 69:13-14

mortality rates, effect of associated dis-
eases on
67:51-52

mortality rates, effect of cessation of
smoking on
67:25, 27-28, 50

mortality rates, ex-smokers by smoking
history
67:51

mortality rates in heavy smokers
64:322

mortality rates in hypertensives vs. non-
hypertensives
71:42

mortality rates in industrial workers
64:323

mortality rates in Japanese men and
women by cigarette consumption and
age started smoking
73:7, 8

mortality rates in longshoremen
72:14

mortality rates in obese vs, nonobese
71:45

mortality rates in smokers vs. nonsmok-
ers
71::21-22, 24, 26-29

mortality rates in smoking men in Fin-
land
73:9

mortality rates in United States
67:47, 68:16

mortality rates in, with increased carbon
monoxide
71:62

mortality rates of cigarette smokers
from, AHA pooling project
71:28, 30, 39

mortality rates of paired combinations
of high risk
71:25

mortality rates of U.S. veterans
71:26, 38

mortality rates, relationship to electro-
cardiographic findings
71:42

mortality ratios, by age
67:25, 26, 28, 49-50, 52; 69:13

mortality ratios, by age and blood pres-
sure
67:53

mortality ratios, by age and smoking
history
67:51-52

mortality ratios, by amount smoked
67:48-49; 69:13

mortality ratios, by sex
67:25, 28; 69:13-14

mortality ratios, by smoking history
67:25, 28

mortality ratios, effect of associated
diseases
67:51-52

mortality ratios in pipe and cigar smok-
ers
73:215, 216

and multiple risk factors
68:28-30

in Nepal
73:11

in New Zealand
73311

nicotine and
74:13

nicotine effect on coronary blood flow
in
71:58

147
obesity in
64:38
occlusion in
64:320
occupational risks in
64:321, 322
pathophysiology of, effect of carbon
monoxide exposure
74:10
and personality characteristics
64:321, 326; 67:57
predisposing characteristics
67:58
prevalence of
64:320, 321
relationship of blood pressure and smok-

ing
71:45, 47

relationship of heart rate and smoking
71:45, 47

relationship of physical activity and
smoking
71:41, 43, 44

relationship of triglycerides to
71:65

relationship to constitutional makeup
and smoking
71:48-49, 105-106

relationship to ECG abnormalities and
smoking
71:45, 47

relationship to obesity and smoking
71:43-45

retrospective studies in Goteborg, Swe-
den
72:16

retrospective studies in Prague, Czech-
oslovakia
72:16

risk factors
71:23-24, 4041

risk factors and personal characteristics
68:26

role of glucose metabolism
68:40, 41

in Seventh Day Adventists
64:322

smokers’ age effects on development
71:27, 39

in smokers vs. nonsmokers
68:26, 42, 43

in smokers with predisposing factors
71:24

smoking and
67:26, 54, 64-65; 69:3-5, 11, 20;
71:5

smoking and, in individuals under 40
years
73:10

smoking and, in myocardial ischemic
patients in Italy
73:10

smoking as cause of death
67:25-27

smoking as etiologic agent in
67:26, 54, 62, 65, 66; 69:11; 72:1,
2,13, 14

148

smoking in thrombus formation
67:26, 64-65
smoking risk factor
71:8
sudden death, and smoking
67:53; 71:52
summary of previous findings
68:16; 75:4, 7
summary of relationship to smoking
74:3,4,19
symptoms of
64:320
twin studies
72:18
in women
64:321
see also Angina pectoris; Arteriosclerosis;
Atherosclerosis; Cardiovascular diseases
Coronary Drug Project Research Group
epidemiologic study of smoking and
CHD
74:46
Coronary heart disease
see Coronary diseases
Coronary vessels
effect of cigarette smoking on
67:65
Coronene
64:147
Cor pulmonale
and chronic obstructive pulmonary dis-
ease
74:76
Cotinine
64:71
desmethyl-
64:72
effect on rats and mice
69:61-62
in experimental induction of bladder
adenomas
69:64
methonium ion, structure of
64:72
Cough
64:280, 281, 282, 283
chronic
64:27, 280, 281, 282, 283, 299, 302
chronic, and cigarette smoking in males
68:69
chronic, in women
64:282, 285
effect of air pollution and smoking
64:297; 74:90, 91
effect of asbestos exposure in smokers
vs. nonsmokers
73:41
effect of coal dust exposure in smokers
vs. nonsmokers
73:41, 42
effect of filtered cigarettes
73:55
effect of modified cigarettes
73:38
epidemiology of
67:97
ex-smokers vs. nonsmokers
67:98
of parental smokers, and respiratory
symptoms in children
75:103, 105
prevalence in cement and rubber indus-
try workers, smokers vs, nonsmokers
74:95, 96
prevalence in pipe and cigar smokers
73:220, 221
prevalence in smoking vs. nonsmoking
women in Bordeaux, France
73:36
prevalence of
64:38, 280, 283, 284, 289, 291, 301,
302
prevalence of among smokers
67:103
prevalence of, in smoking-discordant
twin pairs
67:103
respiratory function in presence of
64:291, 292
in school-age smokers vs. nonsmokers
75:62
smokers vs. nonsmokers
67:29; 72:40
and smoking
64:297; 67:97
and smoking, by sex
67:98
and sputum
64:283-286
traumatic injury from
64:279
Coumarin
64:145
Creosote oil
carcinogenic activity of
64:147
Cresols
in cigar, pipe, and cigarette smoke
73:177
as probable contributors to health haz-
ards of smoking
72:144 .
suspected carcinogenic agent of cigarette
smoke
71:266
Crotonaldehyde
ciliatoxic agent
67:108
in tobacco smoke
67:108
Croton oil
64:58
Crotononitrile
as suspected contributor to health haz-
ards of smoking
72:145
Cuba
laryngeal neoplasms in
64:205, 207
laryngeal neoplasms in, relationship to
tobacco use
71:356
oral neoplasms in, by type of smoking
64:200, 201
oral neoplasms in, relationship of tobac-
co use
71:364

Current Population Survey of 1955
64:177, 180, 186
Curschmann’s spirals
in sputum of smokers
69:39-40
Customs and Excise Act of 1952, Great
Britain
64:62
Cyanides
detoxification, in pregnant smokers vs.
nonsmokers
73:119
in tobacco amblyopia etiology
67:40; 71:14, 435-436; 72:6
in tobacco smoke
67:40
in tobacco smoke, and optic atrophy
67:183
toxicity, potentiation by vitamin B12 in
tobacco amblyopia
67:183
and vitamin B deficiency in tobacco
amblyopia
67:40
Cysteine
inhibition of smoke cytotoxic action on
macrophages
69:42
Cystitis
64:224
Cytochrome oxidase
64:266
Cytologic studies
exfoliative, and lung neoplasm diagnosis
75:47
macrophage function and smoking
74:104, 105
Czechoslovakia
64:205
laryngeal neoplasms in, relationship to
tobacco use
71:354, 357
laryngeal neoplasms in, retrospective
study of
64:206
serum lipid difference in smokers vs.
nonsmokers
74:101

Danish Cancer Registry
64:141, 186, 220
Danish Morbidity Study
64:224
Data collection methods
in retrospective studies
64:206, 214, 215, 226
DDT
64:145
as suspected contributor to health haz-
ards of smoking
72:65, 145
Death certification
limitations of, in health statistics
64:101, 127
neoplasm diagnosis in
64:128

149
Death Registration Act
64:127
Deaths, accidental
64:39, 344, 345
Deaths, sudden
from cardiovascular disease
68:36, 42
incidence in men with and without
ventricular premature beats
74:5
incidence in pipe and cigar smokers
73:215
incidence in women, smokers vs. non-
smokers
74:9, 19
rate by smoking, cholesterol, and blood
pressure,
69:17
reduction of risk of, in cigarette smok-
ers, using clofibrate
75:32
smoking as a risk factor
74:4-6, 19
Defense mechanisms
64:264
Demographic factors
in smoking
64:361-365
enmark
advertising curtailment in
64:8
atherogenic effect of carbon monoxide
and hypoxia
71:64
bladder neoplasms in
64:219, 220, 221
bladder neoplasms in, methods and re-
sults in retrospective studies of smok-
ing and
71:381, 383
carbon monoxide effects on human
blood lipids in
71:129
carbon monoxide effects on rabbit blood
lipids in
71:129
coronary mortality in
64:320
cough prevalence in
64:281
Danish Cancer Registry
64:141, 186, 220
Danish Morbidity Study
64:224
lung neoplasm mortality in
64:176
respiratory function tests in
64:291
serum lipid differences in smokers vs.
nonsmokers in

71:102 .
twins in, angina pectoris in smokers vs.

nonsmokers
74:51
Deoxyribonucleic acid
see DNA
Dermatitis
among tobacco workers
72:111

150

Dermatologists
coronary disease incidence in
64:322
Dextroamphetamine
64:352
Diabetes mellitus
64:326
effect on CHD in smokers
71:24
relationship with cigarette smoking in
peripheral vascular disease
71:72
risk in mortality from CVD
71:67
Diarrhea
smoking and
64:71
Dibenz(a,h)acridine
64:56
carcinogenicity
67:127
carcinogenic properties in cigarette
smoke from
71:265
pyrolytic formation of
64:59
structural formula of
64:59
Dibenz(a,j)acridine
carcinogenicity
67:127
carcinogenic properties in cigarette
smoke from
71:265
pyrolytic formation of
64:59
structural formula of
64:56
in tobacco smoke
67:127
Dibenzanthracene
tumor induction by
64:143, 167
Dibenz(a,c)anthracene
carcinogenicity, as component of ciga-
rette smoke
72:66
Dibenz(a,h)anthracene
carcinogenicity
67:127
carcinoma induction by
64:229
structural formula of
64:56
7H-Dibenzo(c,g) carbazole
carcinogenic effect in laboratory animals
73:79
carcinogenic effect on respiratory tract
in hamsters
72:66, 67
carcinogenicity, as component of ciga-
trette smoke
67:127; 71:265; 72:66, 67
structural formula of
64:56
Dibenzo(a,i)pyrene
64:33, 57
carcinogenicity
67:127
structural formula of
64:26
Dicarbony! compounds
64:53
Dieldrin
64:62
Diet
influence of, in coronary disease
64:322
intervention and cholestero! levels in
postinfarction patients
68:23
and peptic ulcer
67:182
and smoking
67:66
and smoking, effect on blood lipids
73:12
as test constant
64:224
tobacco amblyopia
72:6
Diethylnitrosamine
suspected carcinogenic properties in ciga-
rette smoke from
71:265
Digestive tract neoplasms
mortality, and smoking
67:10, 147
Digital blood flow
effect of smoking
64:318
Digital temperatures
effect of smoking
64:318
Dihydric alcohols
64:52
Dimethylamine
as suspected contributor to health haz-
ards of smoking
72:145
9-10-Dimethyl-1, 2-benzanthracene
64:203
7, 12-Dimethylbenz(a)anthracene
effect on oral mucosa in hamsters
72:70
Dimethylnitrosamine
suspected carcinogenic properties in ciga-
rette smoke from
71:265
Dipalmityl ketone
64:53
Dipentene
64:52
2,3-Diphosphoglycerate
effects of carbon monoxide on
71:60-61
Disability
of emphysema patients
68:66
higher rates of smokers
68:7
DNA
alteration, and oral neoplasm carcino-
genesis
68:101
binding of polycyclic hydrocarbons to
73:86, 87

effect of aromatic hydrocarbons on
69:61

effect of cigarette smoke on synthesis
69:62-63

increases in smokers’ oral epithelial cells
71:288

levels in mice lung exposed to cigarette
smoke
71:161

Dogs

atherogenic effects of nicotine in
71:120

bladder neoplasms in, fed 2-naphthyl
amine
71:296

bradycardia and tachycardia in, follow-
ing nicotine injection
71:57-58

bronchogenic carcinoma induction in,
from cigarette smoke inhalation
71:269, 270

cigarette smoke instillation or implanta-
tion effects on tracheobronchial tree
of
71:268, 347

death in, causes from cigarette smoke
inhalation
71:271

effect of cigarette smoke on pulmonary
clearance in
71:164, 170

epinephrine release in
64:318, 319

experimental neoplasm induction in
64:146, 165, 189

fetal bronchial tubes of, effect of ciga-
rette smoke on
71:345

lung neoplasms following cigarette
smoke inhalation
71:239, 277

lung neoplasms in, types and lobes where
found
71:269, 272-273

lungs of, cigarette smoke effects on
surfactant activity
71:172, 225

myocardium, nicotine effects on
71:58

neoplasm development in smoking, per-
centages of
71:274

nicotine effect on
64:71, 318, 319

ozone effect on
64:295, 296

pulmonary histological changes in ciga-
tette smoke inhaling
71:158, 159-160

respiratory tract of, cigarette smoke in-
halation effects on
71:268, 352, 353

smoke deposition in
64:265

smoke-induced bronchoconstriction in,
atropine effects
71:163

151
smoking and nicotine effects on blood
lipids in
71:127-128
smoking and nicotine effects on cardio-
vascular function in
71:107-112
smoking and nicotine effects on cate-
cholamine levels in
TL:119
Doll & Hill study
64:324
Donkeys
effect of cigarette smoke on pulmonary
clearance in
71:164, 171
Dorn study
64:324
Dosage
measure of, in light and heavy smokers
67:14-15
measure of, in men and women
67:14-15
and mortality among women smokers
67:25
nicotine and tar content of cigarette
smoke as measurement of
67:15
score, for smoking
67:14-15
smoking exposure
67:25
Driving habits
and coronary disease
64:322
Drug addiction
64:350, 351, 352
definition of
64:351
distinction from drug habituation
64:351
psychology of
64:353
Dry mouth
64:354
Dublin
lung neoplasm mortality in
64:195
Ducks
cigarette smoke instillation or implanta-
tion effects on tracheobronchial tree
of
71:346
clearance products in
64:269
Duodenal ulcers
64:8, 337, 340
mortality rates in
64:37
mortality ratios in
64:103, 337
mortality ratios in male cigar and pipe
smokers
73:222
nicotine induced, in cats
73:158, 159
post-operative complications in smokers
vs. nonsmokers

73157

152

potentiating action of nicotine, in ani-

mal
73:161-163
prevalence in smokers, mechanism of
action
73:160
smoking and
72:6, 97, 98
Dust exposure
64:298, 299
bronchitis and
73:44
COPD development from
71:153, 218
as occupational hazard
73:43, 44
in smokers vs. nonsmokers, by race and
sex
75:69, 70
smoking and
73:44
smoking and, as risk factors in bronchitis
development
74:93, 94
smoking and, as risk factors in byssinosis
development
74:94-96; 75:68
Dysphoria
64:350
Dyspnea
64:286
prevalence in cigar and pipe smokers
73:220, 221

Ear neoplasm
64:147
Edentulism
smoking and
69:87; 72:6
Educational level
64:100, 101
and incidence of CHD, in males
68:24
smoking prevalence by

64:363
Egypt
relationship of human pulmonary his-
tology and smoking in
74:163
Electrocardiograms
abnormalities, and CHD
67:58; 68:29; 71:42, 45, 47
effect of smoking
64:319; 74:45, 47; 73:13
effect of smoking, in middle-aged Dutch
men
73:12
effect of smoking, in young military
recruits in Poland
73:12
Electroencephalograms
nicotine effect on
64:70
placebo effect on
64:70
smoking effect on
64:70

Electrophoresis

use in determining serum level of alpha-
l-antitrypsin
73:151

Emotional stress

64:373, 374

Emphysema

64:35, 38, 277-294, 302
air pollution in
64:297
alpha-l-antitrypsin deficiency and
71:150, 151; 72:44; 74:87-90
alveolar destruction in
64:294
asthmatic form of
64:294
autopsy studies, in smokers vs. nonsmok-
ers
75:74-16
bronchitic form of
64:294
and bronchitis mortality rates, for men
by amount smoked
67:93
and bronchitis mortality ratios, by age,
amount smoked, and sex
67:94
and bronchitis mortality ratios, for men
by amount smoked
67:93
bronchitis relation to
64:278, 279, 280
cadmium exposure in etiology of, in
animals
74:104
cigarette smoking effects on
71:9
definition of
64:278; 67:89; 71:139
development in dogs following cigarette
smoke inhalation

71:271 .
development of, relation of cadmium in
smoke to
71:154
diagnosis of
64:278, 279, 280; 67:90
disability payments in U.S.
68:66
dyspneic form of
64:297
epidemiology of
64:280-294
excess mortality from
64:25, 277
experimentally induced in smoking dogs

72:46

grade II or III, smokers vs. nonsmokers
71:162

in horses
69:40

hypersensitivity in development of
67:111

incidence in cigar/pipe smoking coal
miners vs. cigarette smokers and non-
smokers
73:217

morbidity, and cigar smoking
67:99
morbidity, and pipe smoking
67:99
morbidity, and smoking
67:3, 22, 29-30, 96-98
morbidity, body constitution as a factor
in

:30
morbidity, heredity as a factor in
67:30
mortality, and cigar smoking
67:30
mortality, and pipe smoking
67:30
mortality, effect of cessation of smoking
on
67:29
mortality, effect of cigarette smoking on
71:175
mortality rates
64:25, 29, 301; 67:29, 90-93; 68:66;
71:139
mortality ratios
64:103, 293; 67:8, 90
mortality ratios, and smoking
67:3, 91
mortality ratios, by amount smoked
67:90-93
mortality ratios, by sex in United States
67:91
mortality ratios, in cigar smokers
67:94
mortality ratios, in male pipe and cigar
smokers
73:217, 219
mortality ratios, in pipe smokers
67:94
nonsmoker prevalence of
64:297
occupational exposure in
64:298, 299, 300, 302
pathogenesis of

69:38-40
phases of

64:294

pigment deposition in
64:272, 273

premature development and smoking,
autopsy studies
74:97

prevalence in males by smoking cate-
gory, at autopsy
73:48

prevalence in pipe/cigar and cigarette
smokers vs. nonsmokers, autopsy
studies
73:45, 46

prevalence in smokers vs. nonsmokers
73:55

prevalence rates in U.S.
74:75
prospective studies on
64:293
pulmonary function studies and
74:80
respiratory symptoms, body constitution
as a factor in
67:30, 102-103, 108-109

153
respiratory symptoms, by smoking classi-
fication
67:99
Tespiratory symptoms, heredity as a fac-
tor in
67:30, 102-103, 108, 111
respiratory symptoms, in pipe smokers
67:99
respiratory symptoms, in smokers
64:27; 67:99; 68:74
in smokers vs. nonsmokers, autopsy
studies
73:45-47
smoking and etiology of
64:38, 294, 303; 67:30-31, 96,
104-107, 110-111; 69:37-38; 72:37;
74 :87-90
summary of previous findings on rela-
tionship to smoking
74:75-78; 75:5, 7, 61, 62
Emphysema Registry
64:294
Endrin
64:145
as suspected contributor to health haz-
ards of smoking
72:145
Enzymes
activity, effect of smoking
71:165
adenosine triphosphatase, effect of cilia-
toxic agents on
47:108
aryl hydrocarbon hydroxylase activity in
placentas at childbirth
71:410
aryl hydroxylase, effect of nickel in
cigarette smoke on induction
71:257
benzo(a)pyrene hydroxylase, activity in
placentas of smoking mothers
71:410
carbonic anhydrase, carbon monoxide
inhibition in fetal cord blood of
smoking mothers
71:407
carbonic anhydrase, decrease in activity
in fetal cord blood in smoking moth-
ers
71:409
effect of cigarette smoke, in rabbit lungs
74:104, 105
and macrophage function, in rabbit
lungs, .
74:104, 105
oxidative enzymes, effect of ciliatoxic
agents on
67:108
Epidemiological studies
bladder neoplasms and smoking
72:72-74
bronchopulmonary diseases and smoking
72:38-41; 73:36-45
cerebrovascular disease and smoking
75:29, 30
COPD and smoking
74:78-80

154

coronary diseases and smoking
69:12-25; 72:14-16; 73:4-13, 23;
75:14, 15
esophageal neoplasms and smoking
72:70, 71
laryngeal neoplasms and smoking
69:58-60; 72:68
lung neoplasms and smoking
69:55-56; 72:60-65; 73:68-72;
74:37; 75:44
lung neoplasms, by age and sex
68:94-99
lung neoplasms, in Iceland
68:94, 95
lung neoplasms, in Japan
68:95, 96
lung neoplasms, in Switzerland
68:95
maternal smoking and outcome of preg-
nancy
69:77-80; 72:83-87
oral neoplasms and smoking
69:58; 72:68-70; 74:53
pancreatic neoplasms and smoking
69:60-61; 72:74; 74:57
peptic ulcer and smoking
73:155-157
urinary tract neoplasms and smoking
69:60
Epiglottis
laryngeal neoplasms
64:212
Epinephrine
64:318
effect in thrombus formation
67:64-65
effect of nicotine
75:29
levels in arteries, cigarette smoking ef-
fects on
71:57
Epithelial lesions
in smokers
64:168, 170, 172, 173, 213
Epithelial tissues
age effects on
64:34
changes in female smokers
64:34
changes in male smokers
64:34
cigarette smoking and
64:34, 165, 167-173, 189, 213,
263-275
ciliary loss in
64:34
in ex-smokers
64:34
histopathologic changes in
64:167-173, 231, 263-275
hyperplasia in
64:34, 203
hypertrophy caused by nitrogen dioxide
69:41
in nonsmokers
64:189
pipe and cigar effects on
64:34
premalignant lesions in
64:34; 75:44
see also Bronchial epithelium; Esopha-
geal epithelium
Epithelial tumors
classification of
64:174
in man
64:146
Epitheliomas
of lip, relationship of tobacco use with
71:361
Epoxides
suspected carcinogenic agents in ciga-
rette smoke
71:265
Ergonovine
effect on blood circulation in laboratory
animals with coronary disease
67:62
Esophageal balloon technique
64:292
Esophageal epithelium
atypical nuclei in basal cells, male smok-
ers
71:292, 379-380
effect of smoking on
67:36, 150-153
pathological changes by age and smoking
history
67:150-162
pathological changes by amount smoked
67:152
pathological changes by smoking classi-
fication
67:150-151
pathological changes for male smokers
vs. nonsmokers
67:150-153
Esophageal neoplasms
64:37, 212-218, 234
alcohol consumption and smoking in
67:152-153; 72:4, 5, 71; 73:76, 200
frequency in smokers vs. nonsmokers
71:12, 238
geographical factors in
64:133
incidence of, by tobacco use
64:216
incidence of, in Jewish women
64:135
incidence of, in U.S.
64:127
income class gradients in
64:134
induction in animals by nitrosamine
71:292
inhalation patterns and
64:218; 73:197
methods and results of retrospective
studies of tobacco use in
71:289, 375-378
mortality rates
64:37, 133; 71:289
mortality rates, by amount smoked
67:147, 150
mortality rates, by smoking classification
67:147, 150

mortality rates in females
64:131, 132

mortality rates in Japanese males by
smoking and drinking characteristics
72:71

mortality rates in males
64:130, 132

mortality rates in migrants
64:134

mortality rates in pipe/cigar and ciga-
rette smokers
68:102

mortality ratios, by age
67:150

mortality ratios, by amount smoked
67:150

mortality ratios, by smoking classifica-
tion
67:150

mortality ratios for cigar, pipe, and
cigarette smokers vs. nonsmokers
73:197, 200

mortality ratios in
64:148, 149, 217; 71:289-291

mortality ratios in cigarette smokers
64:149

mortality ratios in Japanese male smok-
ers vs. nonsmokers
73:76

mortality ratios in nonwhites
64:218

prospective studies of
64:217

relative risk in cigar, pipe, and cigarette
smokers vs. nonsmokers
73:197, 200-202

retrospective studies of
64:212-217

risk gradients in, by amount smoked
64:217, 218

tisk ratios in
64:213

smoking in etiology of
64:37, 188; 67:33, 150, 151;
71:293; 72:4, 70, 71

summary of previous findings on rela-
tionship to smoking
68:89, 90; 74:55

summary of retrospective studies
73:201, 202

tobacco tars in
64:218

tobacco use and
64:32, 217, 218

trend in mortality
64:137

urban-rural differences in
64:133

Esophagus

effect of benzo(a)pyrene in laboratory
animals
67:152-153

histological changes in cigar, pipe, ciga-
rette sinokers vs. nonsmokers
73:200

Esters

in cigarette smoke

64:52

155
Ethane

64:60

Ethnic groups

neoplasm risks in
64:134, 135

neoplasm sites by
64:134, 135

Ethy! alcohol

carcinogenic promoter activity of
64:217

Ethylene

64:60
glycol
64:52

Euphoria

64:350

Executive Office of the President

64:15

Exercise

on bicycle ergometer, effect of smoking
73:242, 243

cardiac index, effect of smoking
73:242, 243

effect of carbon monoxide exposure
74:11, 12

effect of smoking and smoking absti-
nence
73:241, 242, 246, 247

effects of CO exposure and increased
carbo xyhemoglobin levels
75:95, 97

influencing factors
73:241, 246, 247

and pulmonary function, smokers vs.
nonsmokers
74:99

relationship to mortality rates
64:101

summary of findings and mechanism of
action
73:246, 247

on treadmill, effect of smoking
73:243, 245

Ex-smokers

atypical nuclei in esophageal epithelium,
in male
71:379-380

chronic cough
67:98

decrease of lung neoplasm risk
69:57; 75:43

effects of cessation on body weight,
blood pressure and hypertension de-
velopment
75:16-19

effects of cessation on closing volume
abnormalities
75:71

effects of cessation on pathologic
changes
75:74

histological changes in bronchial epi-
thelium at autopsy
73:74

low birth weight infants of
73:112-114

lung neoplasms in, lowered rates
Wh

156

lung neoplasms in, prevalence
64:192, 193
mortality rates in
64:36; 64:105
mortality rates in, by smoking history
67:8-11
mortality rates in, COPD
TL:175
mortality rates in, coronary disease
64:322, 323, 325; 71:46-48
mortality rates in, coronary disease, by
smoking history
67:51
mortality rates in, coronary disease, ciga-
rette vs. pipe/cigar smokers
73:172, 173
mortality rates in, coronary disease, for
men by amount smoked
69:15
mortality rates in, coronary disease, for
men, by years stopped smoking
69:15
mortality rates in, coronary disease, for
men, compared to nonsmokers
69:15
mortality rates in, gastric ulcer
64:104
mortality rates in, laryngeal neoplasms
64:104
mortality rates in, lung neoplasms
64:104; 71:276; 72:5; 73:71-72
mortality rates in, oral neoplasms
64:104
mortality rates in, stroke, for men, com-
pared to nonsmokers
69:15
mortality ratios in
64:36, 92,93, 103, 104, 105
mortality ratios in, circulatory disease
64:104
mortality ratios in, ex-cigar smokers
64:94 .
mortality ratios in, lung neoplasms
71::241-242
mortality ratios in, respiratory disease
64:104
pneumoconiosis incidence in, in miners
64:298
prevalence of respiratory symptoms
73:39
psychosomatic disorders in
64:367
pulmonary fibrosis in
64:274
pulmonary function in
73:39
relative risk in lung neoplasms develop-
ment
73:71-72
risk ratios in, from neoplasms
64:155, 158, 188
summary of previous findings on health
consequences of cessation
75:6
summary of previous findings on rela-
tionship to COPD
75:61
survival after treatment for pharyngeal,
laryngeal, or oral neoplasms
73:75
thickness of vocal cords in
69:60
Extroversion
64:365, 366
Eye irritation
effects of exposure to cigarette smoke,
in passive smokers
75:99, 100

Face
skin neoplasms of
64:147
Factory workers,
mean expiratory flow rates in
:290

False vocal cords
epithelial hyperplasia in
64:271
hyperkeratosis in
64:271
Farmers
coronary disease incidence in
64:321
decreased smoking by
64 :323
myocardial infarction in
64:323
smoking incidence in
64:187
Fats, saturated
64:322
Fatty acid levels
effect of cigar, pipe, and cigarette smoke
in dogs
73:216
effect of smoking
73:12
rise in, after smoking
71:36, 65
in smokers vs. nonsmokers
71:102
see also Fatty acids; Free fatty acids
Fatty acids
64:53
Suspected carcinogenic agents of Ciga-
Tette smoke
71:266
see also Fatty acid levels; Free fatty
acids
Federal insecticide regulations
64:61
Federal Trade Commission
64:8, 15
Fertility
and smoking
69:79-80
Fetal death
effect of maternal smoking
64:39, 343; 67:185; 69:77-78;
73:123-135
epidemiological studies, in smokers vs.
nonsmokers
73:126-132

Fetus
effect of maternal smoking
64:39, 343;72:5, 83-89
heart beats in, increase in smoking moth-
ers
71:408
morbidity, effect of maternal smoking
on
67:186
tissues of, effects of elevated carboxy-
hemoglobin on
71:407
Fibrosis
see Pulmonary fibrosis
Filters
advantages in reduction of particulates
71:269, 275
cellulose acetate
64:59
charcoal, and effect of cigarette smoke
on cell cultures
69:62
as a factor in reducing tung neoplasm
risk
74:40-41
reduction of lung neoplasms from,

blood pressure differences in smokers vs.
nonsmokers
71:103

COPD morbidity in smokers in
71:200

coronary death rate in
64:320

lung neoplasm mortality in, relationship
to tobacco use
64:176; 71:245-246

lung neoplasms in, retrospective study
of, methods
71:325, 327

peptic ulcer in, methods and results for
retrospective and cross section stud-
ies of smoking
71:426, 428

risk ratio in
64:127

serum lipid differences in smokers vs.
nonsmokers in
71:98, 99

smoking and nicotine effects on human
blood lipids
71:124

Fires

smoking as cause of

64:344, 345; 67:187-188
Fitness tests
smokers vs. nonsmokers

antismoking measures using
64:354
Flax mill workers
chronic respiratory diseases in
64:289, 299
Fluoranthene
alcoholic solution of, penetrability of
esophageal epithelium
71:292

157
in caffeine solution, effect on esophageal
tissue in laboratory animals
67:152-153
in carbon black
64:147
in ethanol, effect on esophageal tissue in
laboratory animals
67:152-153
Forced expiratory flow rates
64:288-293
Forced expiratory volume
64:288, 289, 290, 291, 293, 294, 298
decline in smokers, by race
75:72
Formaldehyde
64:60, 61, 268
ciliastatic action of
64:61, 268
ciliatoxic agent
67:107
as suspected contributor to health haz-
ards of smoking
72:145
in tobacco smoke
67:107
toxic action of
64:295
tracheobronchial irritation from
64:266
Formic acid
ciliatoxic agent
67:108
in tobacco smoke
67:108
Formosa
acute effect of cigarette smoke on hu-
man pulmonary function in
71:169
Framingham Study
64:291, 323
angina pectoris in
64:325
duration of smoking habit and incidence
of CHD
68:17
effect of coffee drinking on mortality in
smokers vs. nonsmokers
75:20
epidemiologic study of CHD, CDV, in-
termittent claudication, and smoking
74:14-16
interaction of smoking and other risk
factors in CHD
73:8
morbidity ratios for CHD, by smoking
habit
68:18; 71:24
mortality rates in
64:324
France
bladder neoplasms in, methods and re-
sults in retrospective studies of smok-

ing
71::381-383
bladder neoplasms in, retrospective
studies
64:219, 220, 221

158

CHD mortality and morbidity in
71:94, 97
cigarette smoke effects on animal tissue

in
71:343, 344, 349
COPD mortality of smokers in
71:201
esophageal neoplasms in, retrospective
studies of tobacco use
64:214; 71:378
laryngeal neoplasms in, relationship to
tobacco use
64:205, 207; 71:355, 357
lung neoplasms in, methods of retro-
spective study of smoking in
71:326
oral neoplasms in, by type of smoking
64:199, 201
oral neoplasms in, relationship of tobac-
co use and
71:363
Free fatty acids
64:52
plasma, effect of nicotine, in rats
74:13
plasma, effect of smoking on
69:27
see also Fatty acid levels; Fatty acids
Fried foods
64:100
Fume exposure
in smokers vs. nonsmokers, by race and
sex
75:69, 70
Fungi
carcinogenic contamination of tobacco
68:92, 93
Fungicides
concentration in cigarette smoke
71:265, 266
Furfural
as suspected contributor to health haz-
ards of smoking
72:145

Ganglia, parasympathetic
64:69, 71, 317, 318
Ganglion cells
nicotine effect on
64:69, 70
paralysis of
64:69, 70
Gas adsorbents
carbon granules as
64:61
Gas phase, cigarette smoke
69:63
effect on mucus flow rates in cats
72:47
harmful constituents in
72:143
Gas phase, tobacco smoke
64:60
acetaldehyde in
64:60
acetone in
64:60
acetylene in
64:60
acrolein in
64:60
ammonia in
64:60
argon in
64:60
butane in
64:60
carbon dioxide in
64:60
carbon monoxide in
64:60
ethane in
64:60
ethylene in
64:60
formaldehyde in
64:60
hydrogen cyanide in
64:60
hydrogen in
64:60
hydrogen sulfide in
64:60
methane in
64:60
methanol in
64:60
methy! chloride in
64:60
methyl ethyl ketone in
64:60
methyl nitrate in
64:60
nitric oxide in
64:266
nitrogen dioxide in
64:60
nitrogen in
64:60
oxygen in
64:60
phenol in
64:267
propane in
64:60
propylene in
64:60

Gastric acidity

effect of smoking on
67:182

Gastric motility

64:340

Gastric neoplasms

64:37, 38, 225-229, 235

decline in mortality from
64:133

geographic factors in
64:133

income class gradients in
64:134

migrant mortality in
64:134

mortality rates in
64:130, 133
mortality rates in, in smokers
64:149
mortality rates in, Japanese smokers vs.
nonsmokers
74:56, 57
mortality ratios in
64:148, 149, 228
prospective studies of
64:227
retrospective studies of
64:225, 226, 227, 228
retrospective studies of, by smoking pat-
tern
64:226, 227
summary of previous findings on rela-
tionship to smoking
68:90; 74:55
tea drinking and smoking in etiology of
74:56, 57
tobacco tars in
64:228
trends in prevalence of
64:135
U.S. incidence of
64:127
Gastric secretion
effect of nicotine
72:97
effect of nicotine in laboratory animals
73:158, 159
effect of smoking
64:340
effect of smoking in ulcer patients
73:157, 158
Gastric ulcers
64:8, 37, 337, 340
healing of, after cessation of smoking
64:337
mortality ratios in
64:37, 113, 337
Gastrointestinal disorders
prevalence in cigarette and pipe/cigar
smokers
73:222
smoking and
72:5, 6, 97, 98
General practitioners
coronary disease incidence in
64:321, 322
Genetic factors
64:321, 385
alpha-1-antitrypsin deficiency
72:44
alpha-l-antitrypsin deficiency and smok-
ing in COPD development
74 :87-90; 75:72-74
in bronchitis development
67: 102-104, 108-109
cessation of smoking and
64:191
COPD pathogenesis and
71:148, 150-152, 205
coronary disease and
72:18
in cough development
67:102, 111

159
in emphysema development
67:30, 102-103, 108-109, 111
and heart disease
67:53-54, 57
lung neoplasms and
64:167, 232
in respiratory tract disease development
67:30, 108
short run changes in, in humans
64:191
smoking and
64:190, 319; 71:5; 72:18, 44
smoking and, in lung neoplasm develop-
ment
74:37
susceptibility in neoplasm epidemiology
64:190, 191, 192, 193
twin studies, effects of smoking
71:49-52, 99
Genitourinary diseases
see Urogenital diseases
Genitourinary neoplasms
see Urogenital neoplasms
Geographic factors
neoplasm incidence by
64:133
neoplasm mortality by
64:133
Germany
CHD morbidity and mortality in
71:95-96, 97
cigarette smoke inhalation effects on
animal respiratory tract in
71:350
laryngeal neoplasms in
64:205
laryngeal neoplasms in, relationship to
tobacco use
71:355
laryngeal neoplasms in, retrospective
study of
64:206
lung neoplasms in, methods of retro-
spective study of smoking in
71:323, 325, 326
polonium-210 levels in tungs of smokers
in
71:336
smoking and nicotine effects on human
blood lipids
71:125
Gestational age
effect on perinatal mortality rates in
smoking vs. nonsmoking mothers
73:126-132
and low-birth-weight infants, effect of
maternal smoking
73:103-106
Gingival neoplasms
64:197, 202
cigar smoking in
64:202
pipe smoking in
64:202
retrospective study of, by type of smok-

ing
64:201

160

tobacco chewing in
64:202
see also Mouth neoplasms; Oral neo-
plasms
Gingivitis
incidence among Danish Royal Marines
69:86
incidence among Dutch Navy recruits
69:86
incidence among U.S. Naval trainees
69:86
smoking and
69:85-86; 72:6
Gingivitis, Vincent’s
relationship to smoking
69:86
Ginseng root
64:355
Glossary
terms used in smoking and ventilatory
function
71:215
Glucose intolerance
as a risk factor in CHD
73:8

Glucose metabolism
cardiovascular effects of
68:40, 41
and insulin response, alteration effects
on myocardial response
71:66
Glutamic acid
64:54
Glutamine
64:54
Glutathione
inhibition of smoke cytotoxic action on
macrophages
69:42
Glycerol
64:52, 62
Glycogen
levels in mice lung exposed to cigarette
smoke
71:161
Glyoxal
64:53
Goblet cells
morphological changes in
64:35, 268, 271
Graphite
respiratory tract carcinoma in workers
exposed to
71:256
Grief,
drug use in
64:353
Grip strength
effect of smoking
73:241, 242
Group psychotherapy
cure of tobacco habit by
64:354
Growth inhibitors
and carcinogenesis
68:92
Guanethidine

blockage of nicotine cardiac stimulation
by
71:57

Guinea pigs

64:296

induced pulmonary damage in
64:266

lung neoplasm development following
chronic nickel carbonyl or dust in-
halation
71:256

lungs of, cigarette smoke effects on
surfactant activity
71:255

respiratory changes in, exposed to ciga-
rette smoke
71:162

sulfur dioxide effect on
64:266

Habituation
64:350, 352, 354
definition of
64:351
Hamsters
benzo(a)pyrene inhalation by, effect of
asbestos dust on carcinoma induction
71:162
bladder neoplasms in, fed 2-naphthyl-
amine
71:296
cigarette smoke instillation or implanta-
tion effects on tracheobronchial tree
of
71:268, 346-348
induced carcinogenesis in
64:166
induced oral neoplasms in
64:202, 203, 204, 232
laryngeal neoplasms following smoke in-
halation
71:12
larynx of, effect of cigarette smoke
inhalation on
71:281, 284
lung and embryos, effects of cigarette
smoke tars on
71:343-344
pulmonary changes from chronic nitro-
gen dioxide inhalation
71:220
respiratory tract of, C-14 labeled particu-
lates deposition in
71:281-282
respiratory tract of, cigarette smoke in-
halation effects on
71:268, 351
Harvard College
alumni study
64:385, 386
student study
64:383
Health Insurance Plan
68:19, 20

myocardial infarction in pipe and cigar
smokers under
71:32, 38-39
Heart
effect of CO exposure
74:10-12
effect of nicotine
64:318; 67:60; 71:36; 74:13
effect of smoking
64:318; 67:60-62
see also Myocardium
Heart disease
64:320
description of
64:320
U.S. mortality rate from
64:25, 317, 320
see also Coronary diseases
Heart rate
64:318, 326
effect of catecholamines on,
67:60
effect of CO exposure
74:11, 12
effect of exercise and smoking
73:242-246
effect of nicotine on
67:60; 74:13
effect of smoking and -coronary disease
67:61; 71:45, 47
effect of smoking on
67:60
fetal, effect of maternal smoking
71:408
Hematite
64:193
dust, respiratory tract neoplasms in ham-
sters exposed to
71:348
Hematocrit
64:319
infant, smoking mother effects on
71:407, 409
variations in, effect on coronary blood
flow
71:66
Hemoglobin
64:319
affinity for oxygen, CO effects on 2,3-di-
phosphoglycerate control of
71:60-41
effect of smoking on oxygen affinity
69:29
levels, relation to incidence of coronary
disease
67:58
tisk factor in CHD

68:29
variations in, effect on coronary blood

flow
71:66
Hepatomas
64:145, 321
Heptachlor
64:62, 145
Heredity
see Genetic factors

161
Heterocyclic compounds
64:54
carcinogenic properties in cigarette
smoke
71:264, 265
Heterocyclic nitrogen compounds
carcinogenicity
67:127
in tobacco smoke
67:127
Hexamethonium
blockage of nicotine cardiac stimulation
by
71:57
High school students
smoking in
64:370
Hippocampus
nicotine effect on
64:71
Histiocytes
64:269
Histological studies
in laboratory animals
73:49, 50
lung neoplasms and smoking
74:38; 75:4446
lung neoplasms in U.S. veterans
73:73
macrophage function and
74:104, 105
in smokers vs. nonsmokers
74:8, 49
Holland
lung neoplasm mortality rate in
64:176
smoking habits in
64:177
Honolulu Heart Study
interaction of smoking and other risk
factors in CHD
73:8,9
Hookahs
smokers of, laryngeal neoplasm induc-
tion in
71:355
Humectants
64:52
Humidity
and pathologic effects of exposure to
cigarette smoke
75:99
Hungary
methods used for retrospective studies of
lung neoplasms in
71:328
Hunger
64:355
Hydrocyanic acid
as probable contributor to health haz-
ards of smoking
72:144
Hydrogen
in gas phase, cigarette smoke
64:60
Hydrogen cyanide
64:60

162

in cigarette smoke, effects on body
oxidative metabolism
71:62
ciliastatic action of
64:61, 268
as respiratory enzyme poison
64:60
toxicity of
64:265, 266
Hydrogen sulfide
64:60
as suspected contributor to health haz-
ards of smoking
72:145
Hydrolases
reduction of in smokers’ alveolar macro-
phages
69:42-43
Hydroperoxides
64:52, 72
Hydroquinone
64:54
bladder neoplasm induction in labora-
tory animals
67:156
as suspected contributor to health haz-
ards of smoking
72:145
3-Hydroxyanthranilic acid
biadder neoplasm induction in labora-
tory animals
67:156
urinary excretion, smokers vs. nonsmok-
ers
67:156
Hydroxy-cotinine
structure of
64:72
Hydro y-coumarin
64:145
3-Hydroxyk ynurenine
bladder neoplasm induction in labora-
tory animals
67:156
excretion of, smokers vs. nonsmokers
67:156
excretion of, smoking effects on
71:296
Hydroxy proline
level in mice lang exposed to cigarette
smoke
71:161
Hypercapnia
and chronic obstructive bronchopul-
monary disease
68:75, 76
Hy percholesterolemia
and hypoxia, in arteriosclerosis
69:26
incidence in Belgian military men
74:17, 18
incidence in male British business execu-
tives, by smoking habit and clinical
parameters
73:11
as a risk factor for coronary heart disease
72:16, 17; 73:8, 9, Lh
Hyperchromatic nuclei
in epithelial cells of smokers
64:168, 173
Hyperinsulinemia
during oral glucose tolerance tests after
smoking
68:41
Hyperplasia
64:168, 169, 170, 172, 203, 231
basal cell
64:168, 169, 170, 172, 173, 231
basal cell, and smoking
67:36
betel nut chewing and
64:203
bronchial mucosa, by smoking history in
men
67:105
nonspecificity of
64:172
precancerous aspects of
64:166
reversibility of
64:172
Hy perpnea
from nicotine
64:70
Hypersensitivity
effect in emphysema development
67:111
Hypertension
incidence in male Israeli civil servants
74:18
interaction with smoking as risk factor in
cerebrovascular disease
73:9
pulmonary, and chronic obstructive pul-
monary disease
68:74-76
as arisk factor for coronary heart disease
64:32, 321; 72:16, 17; 73:8, 9
risk of, in smokers vs. nonsmokers
68:22, 44
smoker mortality rates in
64:325
smoking effects in
64:325; 75:15-19
summary of recent findings
75:33
in women smokers with CHD
68:22
Hypnotism
cure of tobacco habit by

64:354
Hypothalamus

nicotine stimulation
64:71
Hypoxemia
carbon dioxide effects on
71:61, 75
and chronic obstructive bronchopul-
monary disease
68:75, 76
smoking and
72:22
Hypo xia
aortic atheromatosis development in rab-
bits exposed to
71:64

and arteriosclerosis
69:26

carbon monoxide-induced
73:18, 23

effect of nicotine
72:21

experimentally induced in rats
72:21

postoperative, in smokers
71:174, 230

postural, mechanism in asymptomatic
smokers vs. nonsmokers
71147

tissue, carbon monoxide effects on
71:61

Iceland
lung neoplasm mortality rate in
64:176
lung neoplasms in, relationship to to-
bacco smoking
74:244
Immune system
response to benzo(a)pyrene-induced lung
neoplasms
74:48, 49
suppression of immunoglobulin _ re-
sponse, by nicotine or water soluble
fraction of cigarettes
75:77
Income class
lung neoplasm mortality by
64:133, 134
smoking prevalence by
64:362
Indeno(1,2,3-cd)pyrene
carcinogenicity
67:127
carcinogenic properties in smoke
67:127; 71:265
India
64:205
esophageal neoplasms in, retrospective
studies of tobacco use with
64:214, 215; 71:378
laryngeal neoplasms in, relationship to
tobacco use
71:355, 356
laryngeal neoplasms in, retrospective
studies of
64:205
oral neoplasms in, relationship of tobac-
co use
71:362, 366
oral neoplasms in, retrospective studies
of, by type of smoking

64:199, 201

relationship of smoking to thrombosis in
71:131

relationship of smoking to tuberculosis
in
74:227

smoking and nicotine effects on human
cardiovascular system
T1117

163
Indole, 1-methyl-
possible initiator in tobacco carcino-
genesis
71:265
Industrial carcinogens
64:166
Industrial hazards
effect of dust on COPD development
71:175
effect on COPD development in smokers
71:153, 154, 218, 219
Industrial pollution
in etiology of bronchitis
67:108 110
in etiology of emphysema
67:108,110
Infant mortality
black vs. white smoking mothers
73:129, 132
comparison of stillbirth and abortions in
smoking and nonsmoking mothers
71:395, 405,406
differences of birth weight and, in smok-
ing and nonsmoking mothers
71:404
effect of genetic differences and smoking
73:132
effect of maternal smoking
67:185; 69:77,78; 71:415; 72:83,
87; 73:123,135
effect of previous obstetrical experience
and smoking
73:132
effect of socioeconomic background and
smoking
73:131, 132
epidemiological studies in smokers vs.
nonsmokers
73:126, 132
factors other than smoking
73:131, 132
low birth weight and
72:86
risk of low-birth-weight infants of smok-
ing vs. nonsmoking mothers
73:126, 132
sudden death, relation of smoking and
nonsmoking mothers
71:407
Infants
development of bronchitis and pneu-
monia, and maternal smoking
75:103
growth rate, effect of maternal smoking

on
69:78
Infectious diseases
64:38, 276, 277, 302
Influenza
64:195, 277, 302
incidence from antibody deficit in smok-

ing
72:109
mortality ratios in
64:276
prevalence in pipe and cigar smokers
73:220, 221

164

Influenza viruses
effect of cigarette smoke on, in mice
68:70, 71
effect on dogs inhaling cigarette smoke
71:351
enhancing effect in vitro on oxidized
nicotine
69:42
lung neoplasm induction by
64:172
neoplasm induction by
64: 166
resistance of mice following cigarette
smoke inhalation
71:173
Inhalation
64:91, 187, 188
amount smoked and
64:163
bladder neoplasm prevalence and
64:219, 223, 225
carbon monoxide, effect on blood circu-
lation in coronary disease patients
67:63
as carcinogen application method
64:166
cigarette smoke, and chronic cough
67:97
cigarette smoke, and coronary disease
67:54
cigarette smoke, and mortality
67:7,9
cigarette smoke, effect on blood pressure
67:54
coronary mortality and
64:324
effect of previous smoking habits on
patterns of
73:186, 189
effect on blood circulation in dogs
67:63
esophageal neoplasms and
64:213, 218
frequency-per-puff in cigar and cigarette
smokers
73:186, 189
laryngeal neoplasms and
64:209, 212
and lung neoplasms in animals
68:93
lung neoplasms prevalence by
64:159, 230
by male smokers, and mortality rate
67:11
as measures of exposure to cigarette
smoke
67:15
mortality rate from
64:36, 91, 92, 99, 111
mortality rate, inhalers vs. noninhalers
67:7; 68:5
mortality ratios
64:91, 111
particulate retention in
64:264, 350; 69:62
personality factors in
64:367
pipe, cigar, and cigarette smokers
73:184, 189
possible determining factors in patterns
of .
73:183, 184
of radon
64:145
risk in, in lung neoplasms
64:188
stimulatory effect from
64:350
of thoron
64:145 .
tobacco smoke, and bronchogenic carci-
noma
67:129
tobacco smoke, and epidermoid carci-
noma
67:129
tobacco smoke, and papilloma formation
67:129
summary of previous findings on
75:4
Inorganic compounds
64:141
Insecticides
64:61, 145
aldrin as
64:62
arsenic as
64:61
chlordane as
64:62, 145
DDT as
64:62, 145
Diazinon as
64:62
dieldrin as
64:62
Dylox as
64:62
Endosulfan as
64:62
endrin as
64:62
Guthion as
64:62
heptachlor as
64:62, 145
lead arsenate as
64:61
malathion as
64:62, 145
parathion as
64:62, 145
paris green as
64:61
Sevin as
64:62
TDE as
64:62, 145
Insoluble particles
clearance mechanisms
64:267
Insufflation
application of carcinogens by
64:166

Insurance policyholders
breathlessness in
64:287
Intelligence quotient
64:370
Intermittent claudication
decrease in exercise time after exposure
to CO
75:28
effects of coffee drinking and cigarette
smoking
75:20
smokers vs. nonsmokers ~
72:22, 26
~ smoking and
73:21
smoking as a major risk factor
74:14-16
International Cooperative Study
interaction of smoking and other risk
factors in CHD
73:9 .
International Statistical Classification of
Diseases, Injuries, and Causes of
Death
64:10)
Intestinal neoplasms
64:103
Intestinal tone,
tobacco effect on

64:355
Intratracheal injections
application of carcinogens by
64:166
Involuntary smoking
see Passive smoking
Ionized radiation
neoplasm induction by
64:142, 143
threshold levels in

64:143.
Ireland

acute effect of cigarette smoke on hu-
man pulmonary function in
74:168

CHD mortality and morbidity in
71:96

CHD mortality and morbidity in, smok-
ers and nonsmokers in
71:94

lung neoplasms in, methods of retrospec-
tive study of smoking in
71:328

maternal smoking and infant weight in

71:399 .
methods used in study of smoking and

human pregnancy
71:394, 396

Northern, mortality rates from COPD
71:144

occupational exposure and smoking rela-
tionships to COPD in

71:218
relationship of lung neoplasms to smok-
ing, air pollution and residence in

71:218
serum lipid differences in smokers vs.

nonsmokers in
71:99

165
smoking and nicotine effects on human
peripheral vascular system
71:133
smoking relationship to thrombosis in
71:130
Iron oxide
64:166
Irritants
tissue tolerance to
64:353
Ischemia
64:319
Ischemic heart disease
see Coronary disease
Isomethy!nicotinium ion
structure of
64:72
Isoparaffins
64:51
Isoprene
64:52
Isoprenoids
64:49, 51
structural formula of
64:49
Isopropyl oil
lung neoplasm risk from
64:193
Israel
cigarette smoke effects on animal em-
bryos in
71:343
mortality rates from COPD in
71:140
Isuprel
aerosol
64:292, 293
italy
human experimental data on smoking
and pregnancy
71:409
prohibition of advertising in
64:8
serum lipid differences
in smokers vs. nonsmokers in
71:100
tracheobronchial tree changes in smokers
and nonsmokers in
71:263

Japan
bladder neoplasms in, methods and re-
sults in retrospective studies of smok-

ing
71:382, 384
CHD mortality
64:320
CHD mortality and morbidity in
71:96
cigarette smoke effects on human fetal
lung tissue in
71:343
esophageal neoplasms in retrospective
studies of tobacco use in
71:378

166

kidney and bladder neoplasms of smok-
ers in
71:295
lung neoplasms, mortality of smokers
and nonsmokers in
71:243
lung neoplasms, retrospective smoking
study, methods of
71:326, 328
mortality ratios, esophageal neoplasms in
71:291
mortality ratios, kidney neoplasms,
smokers vs. nonsmokers
73:77
mortality ratios, pancreatic neoplasms in
cigarette smokers
71:298
neoplasm risk in
64:127
relationship of lung neoplasms to smok-
ing, air pollution, and residence in
71:255
“Tokyo-Yokohama asthma”
64:276
Jena
autopsy records in
64:150
Jews
esophageal neoplasms in, in women
64:135
gastric neoplasms in
64:135
increased smoking among, in women
64:363
Job changing
smoker prevelance of
64:363
Johns Hopkins student study
64:384
Joint Tuberculosis Society of Great Britain
64:6

Keratin
oversecretion of, in stomatitis nicotina
64:271
Keratosis, senile
64:203
Keto-acids
64:53
Ketoamide
structure of
64:72
Ketones
64:52
Khat
64:349
Kidney neoplasms
epidermoid, associated with cigarette
smoking
69:60
mortality rates in U.S.
71:296
mortality ratios in
64:148, 149
mortality ratios, Japanese men and wo-
men, smokers vs. nonsmokers
73:77
mortality trends in
64:137, 149
relationship of tobacco use and
71:13, 299
in smokers and nonsmokers
71:238, 294-295
smoking and
69:60, 64; 73:77, 78
see also Urogenital neoplasms
Korea
relation of human pulmonary histology
and smoking in
71:255
tracheobronchial tree changes in smokers
and nonsmokers of
71:259
Kreyberg classification
comparison with World Health Oxganiza-
tion classification
64:174
in lang neoplasms
64:35, 159, 173
Kreyberg study
lung neoplasms and smoking
69:55-56

Labeling
of tobacco products
64:8
Laboratory techniques
for induction of experimental neoplasms
69:63-64
Laborers
coronary incidence in
64:321
Lactate metabolism
effect of smoking, in patients with an-
gina pectoris
73:13
Lactation
effect of maternal smoking
73:138-141
effect of maternal smoking, summary of
findings
73:141
epidemiological studies
73:138
experimental studies
73:138, 139
Lactones
carcinogenicity of
64:145
suspected carcinogenic agents in ciga-
rette smoke
71:265
Laparotomy
postoperative pulmonary complications
following, in smokers vs. nonsmokers
71:174
Laryngeal neoplasms
64:37, 205-212, 233, 234; 71:12,
237-239, 281

alcohol consumption in
64:210

development in hamsters following ciga-
rette smoke inhalation
71:239

development in smokers
71:12, 281

dose effect in
64:210, 234

effect of cessation of smoking on
67:149

epidemiological studies
72:68

extrinsic origin of
64:211, 212

incidence in males and females, by age
68:101, 102

incidence of secondary primary, in
smokers vs. nonsmokers
75:50

income class gradients in
64:134

inhalation effects in
64:209

inhalation patterns and,
73:193

intrinsic origin of
64:211, 212

mortality rates
64:37, 133, 135, 210; 71:277

mortality rates, by age
67:149

mortality rates, by age for men
67:148

mortality rates, by amount smoked
67:149

mortality rates, by smoking classification
67:147, 149

mortality rates, for women
64:134; 67:153

mortality rates, in smokers vs. nonsmok-
ers
71:237-238

mortality rates, in United States by age
67:148

mortality rates, in United States by sex
67:148

mortality ratios
64:113, 148, 149; 71:277-279

mortality ratios, and smoking
67:33-35, 148-149

mortality ratios, by age
67:149

mortality ratios, by age for men
67:148

mortality ratios, by amount smoked
67:149

mortality ratios, by smoking classifica-
tion
67:149

mortality ratios, cigar smokers vs. non-
smokers
67:35

mortality ratios for pipe, cigar, and
cigarette smokers vs. nonsmokers
73:193, 196, 197

mortality ratios in, in females
64:132

167
mortality ratios in, in males
64:130, 132

mortality ratios in, in smokers
64:149

mortality ratios in, Japanese male smok-
ers vs. nonsmokers
73:76, 77

mortality ratios, pipe smokers vs. non-
smokers
67:35

mortality trends in
64:137

in nonwhites
64:209

recurrent, incidence in smokers vs. ex-
smokers
73:71, 74-77

relationship of tobacco use and develop-
ment of
71:354-357

relative risk for cigar, pipe, and cigarette
smokers
72:67; 73:76, 77, 197-199

relative risk ratios from tobacco use
71:277, 358

tetrospective studies of
64:205-209

tisk ratios in
64:209

in Seventh Day Adventists
64:209

smokers vs. nonsmokers
69:58-59

smoking in etiology of
64:32, 188, 189; 72:4, 67, 68

summary of previous findings on rela
tionship to smoking
68:89, 90; 74:57

summary of retrospective studies
73:198, 199

susceptibility to
64:189

in Sweden, retrospective study of
64:205, 207

vitamin deficiency in
64:212

in women
64:234

Laryngitis

reversibility of

64:275
Larynx

atypical nuclei in cells of smokers
69:58-59

effect of cessation of smoking on
69:59

epithelial changes in, classification of
71:281, 283

epithelial changes in, smoke induced
64:275

hamster, C-14 labeled particulate deposi-
tion in
71:281-282

histological changes in cigar, pipe, ciga-
tette smokers vs. nonsmokers
73:197

premalignant changes in, and smoking
69:5, 55

168

see also Vocal cords
Laws
PL 89-92, requirements for smoking
hazards literature review
71:7
PL 91-222, requirements for smoking
hazards literature review
71:7
Lead arsenate
64:61
Leaf constituents
hydroxy-coumarin as
64:145
Leather workers
bladder neoplasm prevalence in
64:222, 224
Leukemia
and cigarette smoke
67:148
and tobacco tars
67:148
Leukocytes
effects of cigarette smoke on, in guinea
pigs
75:77, 78
Leukoplakia
64:233
experimentally induced, in rabbits
64:203
oral neoplasm development in smokers
and
72:68, 69
as precancerous lesion,
64:142
prevalence in tobacco chewing coal
miners
73:75
reverse smoking and,
73:76
smoking and betel nut chewing
69:58
smoking in etiology of
72:68, 69

_ see also Stomatitis nicotina
Licorice

64:62
Life expectancy

U.S.males, by cigarette consumption

68:9, 10
Lip neoplasms

chewing tobacco in
64:202

cigarette smoking in etiology of
73:190, 191

cigar smoking in etiology of
73:190, 191

mortality rates in United States
67:145

pipe smoking in etiology of
64:32, 37, 188, 197, 204; 67:35,
145; 71:289; 72:4; 73:190, 191

relative risk in pipe, cigar, and cigarette
smokers vs. nonsmokers
73:190, 191

retrospective studies of, by type of
smoking
64:201

snuff in
64:202
summary of retrospective studies
73:192
tobacco use relation to
64:233; 71:361, 362, 365, 367
see also Mouth neoplasms; Oral neo-
plasms
Lipoproteins
infiltration in arterial walls, carbon mon-
oxide effects on
71:63
in smokers vs. nonsmokers
71:99-102
Liquid paraffins
64:51
Liver
nicotine effects on
64:342
Liver cirrhosis
64:103, 342
and alcoho! consumption
67:40
mortality rates, and smoking
67:39, 184-185
mortality rates, by age
67:184
mortality rates, by amount smoked
67:184
mortality rates, by sex
67:184
mortality ratios, by age
67:184
mortality ratios, by daily amount smok-
ed

67:184
mortality ratios, by sex
67:184
mortality ratios, by smoking classifica-
tion for men
67:184
rates among cigarette smokers
71:5
and smoking
67:39, 184-185
Lobeline
as antitobacco agent
64:70, 354
Local anesthetics
64:354
London
mortality from smog
64:295
London Transport Executive
cough and smoking among male em-
ployees of
64:281, 286
Longevity
64:99
constitutional differences in
64:112
Longshoremen
coronary death rates in
64:323
pulmonary function in
64:292
Tespiratory conditions in
64:289
Los Angeles County General Hospital Study
64:173

Luminescence
techniques of, use in determining aro-
matic hydrocarbons in urine
71:297
Lung diseases
infections, and smoking, role in tung
neoplasm development
74:47, 48
in rabbits, similar to emphysema
69:41
in women
64:289
see also Bronchitis; Bronchitis, chronic;
Emphysema; Respiratory symptoms;
Respiratory tract diseases
Lung function
see Pulmonary function; Respiratory
function tests
Lung neoplasms
64:143, 144, 167
air pollution in etiology of
67:140; 68:98, 99; 71:11; 73:72
amount smoked in
64:105, 155, 175
anaplastic
64:159, 160
in animals
68:93
asbestos exposure and smoking as risk
factors
74:41-43; 75:49
in asbestos workers, by smoking habit
67:143
benzo(a)pyrene induction of

64:147

and blood cholesterol levels in male
smokers
69:57

causality
64:30, 31, 37

cigarette smoking in
64:31, 149, 175-196, 231; 71:11

and cigar smoking
67:34, 138-140

classification of, in smokers vs. non-
smokers
67:140-141

classification systems compared
64:174

decrease in risk of for ex-smokers
69:57; 75:43

detection of by sputum analysis of
smokers
69:58

development in dogs following cigarette
smoke inhalation
71:239

and development of chronic bronchitis
75:49

early smoking factor in
64:158

effect of air pollution and smoking
75:44, 47

effect of cessation of smoking on
67:15-17, 34, 139-140

effect of sex on development
711

environmental and atmospheric factors
71:252-255

169
epidemiological methods
64:175-189

epidemiological studies
69:55-58; 72:60-65; 73:68-72;
74:37, 38; 75:44

epidermoid, in male smokers
69:57

epithelial change in
64:168, 170, 172

etiology of
64:8; 72:59, 60

excessive smoking in
64:7

experimental
67:35, 144-145; 74:43-52

experimental induction by cigarette
smoke
67:144

experimental induction by radioactive
substances
67:128

experimental induction by tobacco
smoke constituents
67:145

ex-smoker risk in
64:158

filtering of tobacco
68:97

foreign-born mortality rate in
64:134

genetic factors and
64:167, 190, 191, 192, 193

genetic factors and smoking as risk fac-
tors

74:37 oo .
group characteristics of tobacco use in

smokers and nonsmokers
71:240, 244, 329-333
groupings
71::246-334
in heavy smokers
64:151, 196, 230, 232
histology of
64:159, 160, 167-173 ; 67:140-144
histology of, and smoking
71:246-249; 74:38, 39, 44-46
in human beings and laboratory animals
67:145
immunologic response to benzo(a)pyr-
ene-induced tumor, in animals
74:48, 49
incidence by smoking classification
67:34
incidence in British males by amount
smoked

72:62 :
incidence in cigar and/or pipe smokers

vs. nonsmokers
74:39, 40
incidence in cigar smokers
68:95, 96
incidence in Czechoslovakian males by
amount smoked
72:61
incidence in Jewish vs. non-Jewish wom-
en
72:63, 64
incidence in male smokers
69:4

170

incidence in Norway
69:55-56

incidence in pipe smokers
68:95

incidence in smokers vs. nonsmokers in
India
74:37, 38

incidence in smokers vs. nonsmokers in
Jersey, Channel Isles
73:70

incidence in smokers vs. nonsmokers in
LaPlata, Argentina
73:70

incidence in smokers vs. nonsmokers in
Philadelphia
73:70

incidence in uranium miners
72:64, 65

incidence in women
68:97; 69:4, 57

incidence in women smokers vs. non-
smokers
74:39, 40

income class gradients in
64:134

increased mortality from
64:25, 26, 128, 135, 136, 139, 140,
141, 185, 220, 231, 232

increase in mortality of female smokers
75:47

inhalation patterns and
73:203

Kreyberg classification of
64:35, 159, 173, 174

Kreyberg study
69:55-56

in men, smoking as cause
67:33, 131

microscopic determination of
64:140

mortality from chromium compounds
71:257-258

mortality rates
64:36, 105, 133, 134, 135, 138, 139,
140, 141, 176; 67:8, 34, 140; 68:68;

69:57 |

mortality rates, age-specific
64:36

mortality rates, by age
67:132-137; 68:94-99

mortality rates, by amount smoked
64:105, 175; 67:134-140

mortality rates by cigarette consump-
tion, by country

64:176 . .
mortality rates, by degree of inhalation

67:134-136

mortality rates, by sex
67:134, 140; 68:94-99

mortality rates, by smoking charac-
teristics
67:131-140

mortality rates, by smoking classification
67:34, 138-140

mortality rates, by smoking history
67:134-137

mortality rates, effect of cessation of
smoking on
67:4, 15, 34, 139
mortality rates expected in U.S. in 1970
74:237, 239

mortality rates, for men
64:132, 175, 176; 67:132, 134-135,
137, 139-140; 74:43

mortality rates, for women
64:132, 135, 175; 67:34:35,
133-134, 136, 153

mortality rates in asbestos workers,
smokers vs. nonsmokers
73:73

mortality rates in Britain
64:195

mortality rates in British physicians vs.
general population
67:16-17; 73:70

mortality rates in, errors in measurement
of
64:140

mortality rates in, occupational differ-
ences in
64:95

mortality rates in, sex differences in
64:177, 178, 179

mortality rates in smelter workers ex-
posed to arsenic
71:257

mortality rates in smokers
64:29, 162

mortality rates in smokers and nonsmok-
ers
71:240-243

mortality rates in smokers in Norway
and Finland
71:245-246

mortality rates in Sweden
64:176

mortality rates in United States
67:34; 71:239

mortality rates, smoking and
67:3, 10, 34

mortality rates, smoking duration and
64:36, 175; 71:240, 244

mortality ratios
64:103, 113, 148, 149, 162, 175

mortality ratios, by amount smoked
67:134-140

mortality ratios, by degree of inhalation
67:134-136

mortality ratios, by sex
67:134, 140

mortality ratios, by smoking charac-
teristics
64:164; 67:134-136

mortality ratios, by smoking classifica-
tion
67:138-140

mortality ratios, by smoking history
67:134-137

mortality ratios for cigar, pipe, and
cigarette smokers vs. nonsmokers
73:203-205

mortality ratios for women
67:34-35, 136, 153

mortality ratios in Japanese by amount
smoked and age started smoking
73:69

mortality ratios in Japanese males by
amount smoked
72:61

mortality ratios in Japanese women
72:63

mortality ratios in, variables affecting
64:163

mortality studies of, limitations of
64:163

multiple primary, autopsy findings
67:141-142

multiple primary, in smokers
67:35

mustard gas in
64:195, 196

nonrespondent rates, in surveys of
64:151

oat-cell, in male smokers
69:57

observed mortality in
64:118

occupational exposures
64:193, 194; 71:12

occupational exposures and smoking
73:67

particle deposition in bronchi and site of
74:44, 45

Philadelphia Pulmonary Neoplasm Re-
search Project histopathologic study
74:38

pipe and cigar smoking in
64:31, 37, 192, 196, 233

pipe smoking
67:34, 138-140

and polonium
67:128

prevalence in females
64:37

prevalence in males
64:35, 37

prevalence in males and females by
tumor type
71:246, 250

prevalence in smokers vs. nonsmokers in
Czechoslovakia
73:70

prevalence of, age factors in
64:177, 178, 179

prevalence of, in smokers
64:151

prevalence ratios in
64:182, 184, 185

previous respiratory history in

64:195, 196

prospective study in Czechoslovakian
males
72:61

prospective study in Japanese adults
72:4, 60, 61; 73:68, 69

race as a factor, smokers vs. nonsmokers
73:70

radioactive induction of
64:172

reduction in number using filter-type
cigarettes
71:275

relationship of asbestos and smoking to
71:257

17]
relationship of chronic bronchitis and
smoking to
72:62

relative risk in cigar, pipe, and cigarette
smokers vs. nonsmokers
73:203, 206-208

relative risk in ex-smokers by length of
cessation and previous duration of
habit
72:62-64

relative risk in ex-smokers vs. continuing
smokers
73:72

relative risk in pipe/cigar smokers
73:67, 68

retrospective studies of
64:150-165, 230, 231

retrospective study methods for smoking
relationships
71:240, 323-328

risk ratios in
64:160, 183, 184, 185, 187, 188

risk reduction with filter vs. nonfilter
cigarettes
74:40, 41

role of aryl hydrocarbon hydroxylase
activity and polyaromatic hydro-
carbons in
74:49-52

role of pulmonary infections and smok-
ing in etiology of
74:47, 48

and selenium in cigarettes
67:128

in Seventh Day Adventists
64:322

sex ratios in
64:133

sex ratio statistic
74:40

smoke inhalation in, urban-rural differ-
ences in
64:133, 186, 194, 195

and smokers
69:4-5

of smokers, in Rhodesia
69:57

smoking in etiology of
67:32-34, 141-144; 71:3, 237, 276;
72:4, 5,59, 60; 73:67

and smoking in men
67:34

and smoking in women
67:10, 34; 71:246, 251

summary of previous findings
75:3, 5-8

summary of previous findings on rela-
tionship to smoking
68:89, 90; 74:35-37

summary of recent findings
75:43

summary of retrospective studies
73:206-208

types implicated in smoking
71:237

typing of
64:35, 159, 173, 174, 175

172

and ulcers, relation to smoking
69:57

in uranium miners by smoking habit
67:143

World Health Organization classification
of
64:173, 174

Xenon-133 washout technique for detec-
tion of
74:43, 44

see also Respiratory tract neoplasms; and
specific histological types

Lungs

alveolar tissue, effect of smoking on
64:274, 275; 67:30

arterioles, effect of pipe/cigar smoking
vs. Cigarette smoking on
73:217

bactericidal activity, effect of nitrogen
dioxide on, in mice
74:103

compliance
64:292

effect of cigarette smoke in laboratory
animals
67:106

effect of cigarette smoke on tissue
64:274; 71:343-345

effect of nitrogen dioxide
64:266; 69:41

hamster, C-14 labeled particulates depo-
sition in
71:281-282

histology of pipe/cigar smokers vs. ciga-
rette smokers
73:217

histopathological differences in smokers
vs. nonsmokers
73:48, 49

hygiene
64:267, 268

injury
64:270

lesions
64:73, 295

parenchyma
64:27, 35, 167, 263, 264, 272, 301

parenchyma, effect of smoking on
67:144

pathological changes in emphysema pa-
tients by smoking history and sex
67:105

pathological effects of smoking on
64:165-172; 69:5

physiology, new animal model for test-
ing of
74:102

polonium-210 levels, smokers vs. non-
smokers
67:128

scars and susceptibility to carcinogens
69:64

see also Respiratory system

Lymphosarcoma

and cigarette smoke
67:148

and tobacco tars
67:148
Lysozyme
secretion by rabbit pulmonary alveolar
macrophages
69:42

Macrophages, alveolar
decrease in pinocytosis, in smokers vs.
nonsmokers
75:76
effect of cigarette smoke on
67:110; 69:42; 71:165; 73:52, 53:
74:50
effect of nitrogen dioxide
73:54
effect of tobacco smoke
72:47, 48
lysozyme secretion in rabbits
69:42
and pathogenesis of chronic bronchopul-
monary disease
64:43
reduction of enzymes in smokers
69:42-43
Tesponse to migration inhibition factor
or antigens, in smokers vs. nonsmok-
ers
75:76, 77
in sputum specimens of smokers vs.
nonsmokers
72:48
Macrophages, peritoneal
effect of nicotine on, in mice
74:105
Macrophages, pulmonary
effect of cigarette smoke extract, in
sheep lungs
74:105
effect of cigarette smoke, in guinea pigs
75:77, 78
effect of cigarette smoke, in rabbits
74:104, 105
effect of smoking
72:3, 4, 47-48:73:55
morphologic differences in smokers vs.
nonsmokers
72:4, 47-48
summary of recent findings
75:78
Mainstream smoke
see Smoke streams
Malathion
64:62, 145
Malaya
betel nut-tobacco chewing in
64:203
Mammals
effect of cigarette smoke tars on cells
71:343
nicotine metabolism in
64:71, 72,73, 74
Marihuana
64:349
Marital status
bladder neoplasms and
64:224
smoking prevalence by
64:364

Masculinity
64:383, 384, 385
smoking behavior association with
64:372, 373
Massachusetts General Hospital
64:141, 174
Mass spectrometry
64:51
Maternal-fetal exchange
effect of nicotine
72:88
polycyclic hydrocarbons and
73:119
see also Smoking, maternal
Maternal smoking
see Smoking, maternal
Maximum breathing capacity
64:290
Mayo Clinic
64:322
Mean expiratory flow rate
64:290
Measurement errors
in smoking studies

64:97, 111
Men
arteriosclerosis obliterans in
64:326

bladder neoplasms in
64:219, 222, 224, 255

breathlessness in
64:286, 287

bronchitis prevalence in
64:289

chest illness in
64:288

chronic cough in
64:281, 282, 285

college students, smoking patterns in
64:369

coronary diseases in
64:321, 322, 327

cough and sputum prevalence in
64:284

epithelial change in
64:170, 173

forced expiratory volume in
64:290, 291

increased lung neoplasm prevalence in
64:192

irreversible obstructive lung disease in
64:288, 289

laryngeal neoplasms
64:212

lung neoplasms in
64:183, 186

lung neoplasms in, by amount smoked
64:155

lung neoplasms in. cigarette smoking in
relation to
64:31, 37

lung neoplasms in, early smoking in
64:158

lung neoplasms in, prevalence of
64:231

lung neoplasms in, prevalence of, in
Seventh Day Adventists
64:363
mortality rates in
64:28, 85
mortality ratios in
64:28
mortality trends in
64:133, 135, 192
neoplasm mortality in, by site
64:132
neoplasm mortality rates in
64:135, 137, 175, 176
neoplasm mortality ratios in
64:130, 132, 175
nonsmokers, U.S. incidence of, by age
64:178
oral neoplasms
64:202, 204
risk ratios in
64:161
risk ratios in, in bladder neoplasms
64:222
single, mortality trends in
64:101
smokers, U.S. incidence of, by age
64:178
smoking and respiratory symptoms in
64:286
smoking habits of
64:231
smoking patterns in
64:177, 178, 179
smoking prevalence in
64:363
sputum production in
64:283
Menopause
and cardiovascular disease, in women
smokers vs. nonsmokers
74:10, 19
coronary death rates following
64:321
1,8-p-Menthadiene
64:51
Menthol
64:62
Mesenchymal tumors
classification of
64:174
Mesotheliomas
classification of

64:174
Metal mine workers

pulmonary function in

64:299
Metals

as carcinogens
64:166, 167, 189, 193, 194, 230,

232
Metal-working trades
neoplasm risks in
64:134
Metaplasia
64:170
anaplasia, lung neoplasms and
64:172
as precancerous change
64: 166
squamous, experimentally induced in
lungs by cigarette smoke
67:144

174

squamous, in stomatitis nicotina
64271
squamous, nickel carbonyl in
64:166
Methacrolein
as suspected contributor to health haz-
ards of smoking
72:145
Methane
in tobacco smoke
64:60
Methanol
64:60
Methoxy-coumarin
64:145
Methyl! alcohol
as suspected contributor to health haz-
ards of smoking
72:145
6-Methylanthranthrene
carcinogenicity, as component of ciga-
rette smoke
72:66
Methy] chloride
64:60
3-Methylcholanthrene
64:166
effects during pregnancy in laboratory
animals
73:117
20-Methy Icholanthrene
64:203-228
Methyl ethyl ketone
" 64:52, 60
Methylglycerol
64:62
N-methyinicotinamide
urinary excretion, effect of smoking
67:156, 71:297
Methy1 nitrite
64:60
Methyl protoanemonin
carcinogenicity of
64:145
Metrazol

treatment of depression with
64:352
Metropolitan Life Insurance Company
64:344

Mice

bladder neoplasms in, induction by
tryptophan metabolites
71:296 .

embryo, lethal effects of nicotine on
71:411

esophageal epithelium of, alcoholic ben-
zo(a)pyrene penetrability of
71:292

esophageal epithelium of, oil-dissolved
benzo(a)pyrene penetrability of
71:292

genetic variation in

64:167

induction of bladder neoplasms in
64:219, 223

induction of bronchitis in
64:272

induction of epidermoid neoplasms in
64:166
induction of hepatomas in
64:145

induction of oral neoplasms in
64:202

induction of neoplasms in
64:143, 144, 146

induction of pulmonary adenomas in

64:143, 144

induction of skin neoplasms in
64:143

induction of squamous cell carcinoma in
64:228

inhibition of phagocytic clearance in
64:269

irritation in, by formaldehyde
64:260

lung neoplasm incidence in, from chro-
mium oxide dust exposure
71:258
lungs of, effects of cigarette smoke on
64:165; 71:159, 343, 344
pulmonary carcinoma induction in, fol-
lowing asbestos dust inhalation
“71:257
pulmonary changes from chronic nitro-
gen oxide inhaltion
71:161, 220
pulmonary clearance in, cigarette smoke
effects on
71:170
resistance to pneumonia bacteria follow-
ing cigarette inhalation
7L:173
respiratory tract of, cigarette smoke in-
halation effect on
71:268-269, 349-353
skin painting of, smoke condensates ef-
fects on
71:267, 337-342
spontaneous neoplasms in
64:165
Spontaneous pulmonary adenomas in
64:165
Migrants
lung neoplasm rates in
64:194
Migration
lung neoplasm risks in
64:195
Migration inhibition factor
effects on alveolar macrophages, in
smokers vs. nonsmokers
75:76, 77
Mill workers
breathlessness in
64:286
chronic cough in
64:280
chronic respiratory disease in
64:289, 299
Mineral oil
carcinogenicity of
64:147, 148, 229
Miners
forced expiratory flow rates in
64:290
forced expiratory volume in
64:293, 294

impairment of pulmonary function in
64:299
mucous gland hyperplasia in
64:271
respiratory symptoms in
64:298, 299
Minnesota Multiphasic Personality Inven-
tory
64:366
Mitochondria
effect of tobacco smoke on, in rat liver
74:104
Molders
neoplasm risk in
64:134
Mollusks
ciliary function in, effect of cigarette
smoke on
71:223
Monkeys
atherogenic effects of carbon monoxide
and hypoxia
71:64
ciliary function in, effect of cigarette
smoke on
71:222
fetal bronchial tubes of, effects of ciga-
rette smoke on
71:345
thesus, development of bladder neo-
plasms from 2-naphthylamine
71:296
squirrel, nitrogen oxide effects on resist-
ance to pneumococcus
71:173
Monoamine 0 xidase inhibitors
effect on rabbits receiving nicotine
69:27
Monohydric alcohols
64:52
Morbidity
bladder neoplasms, and smoking
67:155
bronchitis, and smoking
67:3, 30, 96-99
bronchitis, in smoking discordant twin
pairs
67:102-103
chronic bronchopulmonary diseases
72:39-41; 73:36-39
coronary diseases, smokers vs. non-

smokers
67:53-54

emphysema, and cigar smoking
67:97

emphysema, and pipe smoking
67:97

emphysema, and smoking
67:3, 30, 96-99

lung neoplasms, and smoking
67:3

peptic ukers, and smoking
67:40

respiratory diseases, smokers vs. non-
smokers among college students
67:98

respiratory symptoms
75:62, 63

175
and smoking
67:6, 19

and smoking in college students
67:98

and smoking in 45-64 age group
67:24

studies of
64:127, 133, 293, 294

Morbidity rates

bronchitis, by age and smoking history
67 :96-98

bronchitis, by sex and smoking history
67:96-98

coronary disease, smokers vs. nonsmok-
ers by age
67:54

emphysema, by age and smoking history
67:96-98

emphysema, by sex and smoking history
67:96-98

smokers vs. ex-smokers
67:15

smokers vs. nonsmokers, by age
67:19-24

smokers vs. nonsmokers, by amount
smoked
67:19-24

smokers vs. nonsmokers, by sex
67:19-24

smokers vs. nonsmokers, by smoking
history
67:19-24

Morbidity ratios

angina pectoris, by smoking habit in
males
68:20

angina pectoris, smokers vs. nonsmokers,
67:59

coronary diseases
69:19

coronary diseases, smokers vs. nonsmok-
ers
67:59; 71:21-22, 24, 30-35

coronary diseases, smokers vs. nonsmok-
ers and lung function
67:56

coronary diseases, smokers vs. nonsmok-
ers by age
67:54

coronary diseases, smokers vs. non-
smokers by blood cholesterol jevels
67:55

coronary diseases, smokers vs. nonsmok-
ers by blood pressure values
67:55

coronary diseases, smokers vs. nonsmok-
ers by personality characteristics
67:57

coronary diseases, smokers with predis-
posing factors
71:24

coronary diseases, smoking and
71:32-35, 37, 39

coronary diseases, smoking habit in
males
68:17, 18

coronary diseases, retrospective studies
71:40, 93-97

176

in Danish twins, smoking effects on
71:49-51

development of COPD in smokers vs.
nonsmokers
71:145, 195-205

myocardial infarction, by risk factors in
males
68:23

myocardial infarction, smokers vs. non-
smokers
67:59

myocardial infarction, smokers vs. non-
smokers by physical activity
67:56

Mortality rates

64:25, 27, 30, 35, 36, 37, 84, 101, 162.
301
by age
67:9-10, 12-13, 23
by age, and smoking history
67:10; 68:6
by age, for men
67:9, 10
by age, for women
67:23
age started smoking and
64:29, 111
alcoholism, relation to smoking
67:10
amount smoked and
64:111; 67:9, 23
aortic aneurysm, for men by amount
smoked

69:16
arteriosclerosis

64:25, 321; 67:28
bladder neoplasms, by amount smoked.

67:155

bladder neoplasms, by sex
67:154

bladder neoplasms, by smoking classifi- -
cation
67:155

bladder neoplasms, effect of cessation of _
smoking on
67:155

bladder neoplasms, for men by age
67:154

bladder neoplasms, in United States
67:154

from bladder neoplasms in U.S. for 1967
71:293

bronchitis
64:25, 297; 67:8, 90-91; 68:66-68

bronchitis, and smoking
67:3, 90-96

bronchitis, effect of cessation of smok-
ing on
67:94, 96

from bronchopulmonary disease
74:141-145

cardiovascular diseases
69:17

cerebrovascular diseases, and athletic ac-
tivity
67:68

cerebrovascular diseases, and coronary.
disease history
67:68
cerebrovascular diseases, and parental
death history
67:68

cerebrovascular diseases, and smoking
67:68

cerebrovascular diseases, by age
67:66; 75:31

cerebrovascular diseases, by sex
67:66; 75:31

cerebrovascular diseases, smokers vs.
nonsmokers
71:66-67, 68-70

cerebrovascular diseases, smoking classi-
fication
67:66; 75:31

in chronic bronchopulmonary disease
64:301; 72:38, 39; 73:36-39

in chronic bronchopulmonary disease,
cigar/pipe smokers vs. cigarette smok-
ers and nonsmokers
73:216, 217

cigar smokers vs. nonsmokers
67:3

in cigar smoking
64:30; 67:7

compared rates for cigarette vs. pipe/ci-
gar ex-smokers
73:172, 173

Connecticut data on
64:132

coronary diseases
64:25, 320, 321; 67:8, 25-28, 47;
71:21; 75:14

coronary diseases, among physicians
68:17

coronary diseases, and age
67:47, 50-51; 69:13-14; 74:6; 75:14

coronary diseases, by amount smoked
67:51; 69:12-13, 17

coronary diseases, by blood cholesterol
69:17

coronary diseases, by blood pressure
69:14, 17

coronary diseases, by relative weight
69:14

coronary diseases, by sex
67:47, 50; 69:13-14

coronary diseases, by smoking habit
67:51; 69:14

coronary diseases, effect of cessation of
smoking on
67:25, 28, 47-49, 50

coronary diseases in Japanese men and
women by cigarette consumption and
age started smoking
73:7,8

coronary diseases in middle-aged men in
seven countries
74:6

coronary diseases in survivors of myo-
cardial infarction, smokers vs. non-
smokers
74:46

coronary diseases, male smokers vs. ex-
smokers by age
67:49

coronary diseases, paired combinations
of high risk characteristics in

coronary diseases, retrospective studies
71-40 93.97
coronary diseases, smokers vs. ex-

smokers
67:9; 69:15

coronary diseases, smokers vs. ex-smok-
ers by amount smoked
67:49

coronary diseases, smokers vs. ex-smok-
ers by smoking history
67:51

coronary diseases, smokers vs. nonsmok-
ers
69:12-13, 15-17; 74:24, 26-29;
74:3-4

coronary diseases, smoking and
67:10, 27, 65-66

in Danish twins, smoking effects on
71:51

differences in rates, defined
68:7

digestive tract neoplasms, by amount
smoked
67:147

digestive tract neoplasms, by smoking
classification
67:147

duration of smoking in
64:29, 36

early smoking and, excess in, in smokers
64:29, 30, 35, 36, 84, 111, 162, 301

emphysema
64:25; 67:34, 8, 90-91; 68:66-68

emphysema, effect of cessation of smok-
ing on
67:7, 24, 29

esophageal neoplasms
67:150, 153; 68:102; 71:289

esophageal neoplasms, by age
67:150

esophageal neoplasms, by amount smok-
ed
67:150

esophageal neoplasms, by smoking classi-
fication
67:150

esophageal neoplasms, for men by age
67:150 |

esophageal neoplasms, for women
67:153

esophageal neoplasms in Japanese males
by smoking and drinking characteris-
tics
72:71

in former smokers, relation to CHD
71:46, 4748

in heavy smokers
64:36, 107, 111, 163

-nhalation patterns and
64:111; 68:5

from kidney neoplasms in U.S. for 1967
71:296

in laryngeal neoplasms
64:205; 67 :153;68:101, 102

laryngeal neoplasms, by age
67:148-149

laryngeal neoplasms, by amount smoked
67:149

177
laryngeal neoplasms, by sex
67:148

laryngeal neoplasms, by smoking classi-
fication
67:149

laryngeal neoplasms, for women
67:148

from laryngeal neoplasms, in Japanese
smokers vs, nonsmokers
68:102

lip neoplasms, in United States
67:145

liver cirrhosis, and smoking
67:40, 184

liver cirrhosis, by age
67:184

liver cirrhosis, by amount smoked
67:184

liver cirrhosis, by sex
67:184

liver cirrhosis, for men
67:184

lung neoplasms
64:25, 29; 67:8, 153; 68:68, 94-99,
69:57

lung neoplasms, and smoking
67:3

lung neoplasms, by age
67:34, 134-137, 140

lung neoplasms, by amount smoked
67:137, 140

lung neoplasms, by birth cohorts
67:131-133

lung neoplasms, by sex
67:134, 137, 140

lung neoplasms, by smoking characteris-
tics
67:134-136, 140

lung neoplasms, by smoking classifica-
tion
67:136, 140

lung neoplasms, by smoking exposure
67:34

lung neoplasms, by smoking habit
67:136, 140)

lung neoplasms, by smoking history
67:134-137

lung neoplasms, cigar smokers
67:34, 140

lung neoplasms, effect of cessation of
smoking on
67:34, 140

lung neoplasms, effect of reduction of
smoking on
67:4

from lung neoplasms expected in 1970
71:237, 239

lung neoplasms, ex-smokers
67:140

Jung neoplasms, for men
67:34, 131, 133-137, 139-140

from lung neoplasms for 1939 vs. 1967
in U.S,
71:239

lung neoplasms, for women
67:132-133, 136, 153; 75:47

lung neoplasms in Japanese women
72:63

178

from lung neoplasms in smelter workers
exposed to arsenic
71.257

lung neoplasms, pipe smokers
67:140

lung neoplasms, reduction in, British
physicians
67:15

male-female ratios in
64:133

mouth neoplasms, by age and amount
smoked
67:146

mouth neoplasms, by smoking classifica-
tion
67:146

mouth neoplasms, for women
67:153

mouth neoplasms, in United States
67:145-146

from myocardial infarction
75:14

neoplasms
64:128, 129, 130, 131, 132, 136,
137, 138, 139

neoplasms, by site, in women
64:132

neoplasms, increase in
64:127, 136

neoplasms, in Japanese smokers vs. non-
smokers
68:17

in nonwhites
64:218

occupations
64:134; 67:11

from oral neoplasms in 1967
71:285

overall rates for cigar smokers vs. pipe
smokers
73:179, 180

overall rates for pipe/cigar smokers and
dose-response relationships
73:180-189

overall rates for pipe/cigar smokers vs.
nonsmokers
73:179, 180

overall rates from cancer in pipe and
cigar smokers
73:189

pancreatic neoplasms
68:103; 72:74

pancreatic neoplasms by age

67:158-159
pancreatic neoplasms, by amount smok-

e
67:159
pancreatic neoplasms, by sex
67:153, 158, 159
pancreatic neoplasms, by smoking classi-
fication
67:159
paralysis agitans
67:8
peptic ulcer
67:40, 181-182; 71:423
peptic ulcer, by age
67:18]
peptic ulcer, for men
67:181-182
peptic ulcer, smokers vs. ex-smokers
7:181
pharyngeal neoplasms
67:153

pharyngeal neoplasms, by smoking classi-
fication ,
67:35

pharyngeal neoplasms, for women
67:153

in pipe smokers
64:30; 68:6

Pipe smokers vs. nonsmokers
67:10

Poisson distribution of
64:117, 118

reduction in, effect of cessation of smok-
ing
67:16

from renal neoplasms in males, by age,
type and smoking habit
68:105, 106

respiratory tract neoplasms, and smoking
67:5-7, 9-10, 147

rural vs. urban
64:133;67:11

in selected diseases
64:26

by sex
67:12-13

of smokers, non- and ex-smokers
68:5-8, 69

smokers vs. ex-smokers
67:9, 15

smokers vs. ex-smokers, by smoking his-
tory
67:9

smokers vs. nonsmokers
67:8-9, 19; 71:3

and smoking
67:5-9; 69:3

by smoking history
67:9-10, 23

stomach neoplasms, by age
67:157-158

stomach neoplasms, by amount smoked
67:157-158

stomach neoplasms, by smoking classi-
fication
67:157-158

stomach neoplasms, effect of cessation
of smoking

67:157-158
stroke

69:17

stroke, by age
67:67; 69:12-13

stroke, by amount smoked
67:67; 69:12-13

stroke, by sex
69:12-13

stroke, smokers vs. ex-smokers
69:15

stroke, smokers vs. nonsmokers
69:12-13, 15

in Swedish twins, smokers vs. nonsmok-
ers
71:51

studies of
64.100

study of Chicago Peoples Gas Light and
Coke Co. employees
69:16-17
summary of previous findings
75:3-8, 13
summary of previous findings on rela-
tionship to smoking
68:5-10
trends
64:135, 140
urinary tract neoplasms, by age
67:154
urinary tract neoplasms, by amount
smoked
67:154
urinary tract neoplasms, by smoking
classification
67:154
urogenital neoplasms, by age
67:154
U.S. male veterans from CHD
71:26, 38
in veterans
64:88, 293
in women
64:133
in women smokers
67:7,9;68:6, 8,9

Mortality ratios

64:36, 84, 99, 101, 118, 119; 69:12-13
18
after cessation of smoking
64:29, 111
age etfects on
64:36, 87
alcohol consumption and
64:112
by amount smoked
67:150, 153
aortic aneurysm, for men by amount
smoked
69:16
behavioral factors in
64:101
bladder neoplasms
67:36, 154
bronchitis
64:28, 29, 293; 67:90, 94
cerebrovascular diseases, by age
67:66
cerebrovascular diseases, by sex
67:66
cerebrovascular diseases, by smoking
classification
67:66
in cigarette smokers
64:28, 29, 35
in coronary diseases
64:29, 184
coronary diseases, associated with other
complicating diseases
67:52

,

coronary diseases, by age
67:25-26, 49, 51-52; 69:12-13, 18
coronary diseases, by amount smoked
67:49

coronary diseases, by blood pressure

status
67:52

179
coronary diseases, by sex
67:49; 69:12-13
coronary diseases, by smoking habit
67:51-52
coronary diseases, by smoking history
67:25-26
coronary diseases, by sociocultural mo-
bility status
67:57
coronary diseases, for men by age
67:48
coronary diseases, for men by amount
smoked
67:48
coronary diseases, smokers vs. ex-smok-
ers
69:15
coronary diseases, smokers vs. nonsmokers
69:12-13, 15
coronary diseases, with high risk charac-
teristics, estimated
74:25
daily cigarette consumption and
64:89
definition of
64:28, 117; 67:11; 68:6
duration of smoking in
64:111
educational level factors in
64:112
in emphysema
64:28, 29
esophageal neoplasms, by age
67:150
esophageal neoplasms, prospective and
retrospective studies
71:289-291
in ex-smokers
64:104
genetic factors in
64:36, 112,113
in influenza, in smokers
64:276
inhalation effects on
64:36, 91,92
interna! consistency of
64:130
laryngeal neoplasms
67:353 71:277-279
laryngeal neoplasms, by age
67:149
laryngeal neoplasms, by amount smoked
67:149
laryngeal neoplasms, by smoking classi-
fication
67:149
laryngeal neoplasms, cigar smokers vs.
nonsmokers .
67:35
laryngeal neoplasms, for men by age
67:148-149
laryngeal neoplasms, for women
67:153
laryngeal neoplasms, pipe smokers vs.
nonsmokers
67:35
liver cirrhosis
64:342;67:184

180

liver cirrhosis, by age
67:184
liver cirrhosis, by sex
67:184
liver cirrhosis, by smoking classification
67:184
liver cirrhosis, for men
67:184
liver cirrhosis, for men by amount smok-
ed
67:184
longevity and
64:99, 100
lung neoplasms and
64:28, 29, 133, 163, 164, 175-189
lung neoplasms, by age
67:134-140
lung neoplasms, by amount smoked
67:135, 137-140
lung neoplasms, by sex
67:135, 137-140
lung neoplasms, by smoking characteris-
tics
67:134-136
lung neoplasms, by smoking classifica-
tion
67:139-149
lung neoplasms, cigar smokers
67:140
lung neoplasms, for men
67:34, 134-135, 137-139
lung neoplasms, for women
67:34, 153
lung neoplasms, in Japanese males by
amount smoked
72:61
lung neoplasms, in males by cigarette
smoking duration
71:240, 244
lung neoplasms in smokers in Norway
and Finland ,
71:246
lung neoplasms, pipe smokers
67:140
measurement limitations of
64:98
mouth neoplasms
67:35 .
mouth neoplasms, by age and amount
smoked
67:146
mouth neoplasms, by smoking classifica-
tion
67:146
mouth neoplasms, cigar smokers vs. non-
smokers
67:35, 146
mouth neoplasms, for women
67:153
mouth neoplasms, pipe smokers vs. non-
smokers
67:35, 146
neoplasms. by site
64:149 ©
in occasional smokers
64:163
occupational exposure and
64:112
pancreatic neoplasms, by sex
67:158
pancreatic neoplasms, for men by age
67:159
pancreatic neoplasms, for men by
amount smoked
67:159
pancreatic neoplasms, for men by smok-
ing classification
67:159
pancreatic neoplasms, for women
67:153
from pancreatic neoplasms in smokers
and nonsmokers
71:289-299
peptic ulcer, for men by age
67:181
from peptic ulcer in smokers and non-
smokers
71:424
peptic ulcer, smokers vs, ex-smokers by
age
67:181
pharyngeal neoplasms
67:35
pharyngeal neoplasms, by age and
amount smoked
67:146
pharyngeal neoplasms, by smoking class-
ification
67:146
pharyngeal neoplasms, cigar smokers vs.
nonsmokers
67:35
pharyngeal neoplasms, for women
67:153
pharyngeal neoplasms, pipe smokers vs.
nonsmokers
67:35
pharyngeal neoplasms, smokers vs. non-
smokers
67:3
in pipe and cigar smokers by age and
inhalation
73:184, 187
previous respiratory history and
64:112
psychological factors in
64:101
sampling in
64:95, 98,99
smokers vs. nonsmokers, from lung neo-
plasms
71:240-243
stability of
64:117
stomach neoplasms, by age
67:157
stomach neoplasms, by amount smoked
67:157
stomach neoplasms, by smoking classi-
fication
67:157
stroke, by age
69:12-13
stroke, by amount smoked
69:12-13

stroke, by sex
69:12-13

stroke, for men
67:67

stroke, for men by amount smoked
67:67

stroke, smokers vs. ex-smokers
69:15

stroke, , smokers vs. nonsmokers
69:12-13, 15

thrombosis, by age
67:36

thrombosis, by smoking history
67:26

underestimation of

64:111
urban-rural differences in
64:99
urinary tract neoplasms, by age
67:154
urinary tract neoplasms, by smoking
classification
67:154
urogenital neoplasms, by amount smoked
67:154
in white population
64:132
Motor vehicle exhaust
hydrocarbons as
64:296
Mouth
retention of tar in
64:264
Mouth epithelium
histopathological change in
64:271
keratinization of
64:203
smoking effect on
64:275
Mouth neoplasms
and cigar smoking by age
67:146
and cigar smoking in men
67:146
experimental induction by pipe tobacco
smoke
67:147-148
frequency in smokers and nonsmokers
74:238
mottality rates, by age
67:146
mortality rates, by amount smoked
67:146
mortality rates, by smoking classification
67:146-147
mortality rates, for women
67:153
mortality rates in United States
67:145
mortality ratios
67:35
mortality ratios, by smoking classifica-
tion
67:35, 146
mortality ratios, cigar smokers, men, by
age
67:146

181
mortality ratios, for men by age
67:146
mortality ratios, for pipe smokers
67:35, 146
and smoking
67:35, 145-147
smoking induced
71:12
and tobacco use
67:145
in women, smokers vs. nonsmokers
67:153
see also Gingival neoplasms; Lip neo-
plasms; Oral neoplasms; Palatal neo-
plasms; Salivary gland neoplasms;
Tongue neoplasms
Mucociliary transport
effect of smoking
74:101, 102
Mucopolysaccharides
function as surfactants in lung tissue
71:172
Mucous celis
hyperplasia in
64:272
hypertrophy of
64:271
increase in number of
64:269
Mucous glands
abnormalities, in smokers vs. nonsmok-
ers
74:97
morphological changes in
64:35, 268, 271
Mucous membranes
effect of cigarette smoke on
67:140
effect of smoking on
67:144
irritation of
64:73
smoking and neoplasms of

69:58
Mucus

alterations in
64:268
reduction of, by smoke
64:270
secretion
64:268, 269, 270
Muscles, skeletal
curariform action of nicotine in
64:69
Mussels
ciliary function in, effects of cigarette
smoke on
71:221, 222
Mustard gas
64:195, 196
Mutation rate
hypothesized variation in

64:192
Myocardial infarct

64-320, 323

acute, and smoking effects on blood
circulation in coronary disease pa-
tients
67:62

182

cholesterol levels and relapse rate
68:23

coffee drinking, smoking and
74:8- 75:19, 20

coronary thrombosis and
64:321

damage to rabbits after exposure to
carbon monoxide
75:29

in Danish twins
71:51

epidemiological study in Goteborg, Swe-
den
72:14, 15, 16

etiology of
69:27-28

etiology of, smoking as
64:325

fatal, incidence of, and smoking
67:59

in German, Japanese, and Norwegian
smokers vs. nonsmokers
68:18, 19

incidence in European vs. American men
73:9

incidence in male smokers vs. nonsmok-
ers
68:18, 19, 23

incidence in men in Yugoslavia
73:9

incidence in men with and without
ventricular premature beats
74:10

incidence in miners in Sardinia
73:10

incidence in Minnesota men by age and
smoking habit
72:14, 15

incidence in pipe and cigar smokers
73:215

and incidence of coronary disease
67:53

incidence rates and smoking
69:21-22; 72:15

morbidity ratios, for smokers vs. non-
smokers
67:56, 59

mortality, in smokers vs. nonsmokers
75:14

nonfatal, morbidity ratios, smokers vs.
nonsmokers
67:59

prevalence in current vs. ex-smokers
74:8

prevalence in farmers
64:323

prevalence in smoking vs. nonsmoking
men in Czechoslovakia
73:10

recurrence in smokers vs. nonsmokers, in
Buenos Aires
74:9

and smoking
69:4, 18; 73:19

and smoking in India
74:8

summary of previous findings
75:4, 13
in Swedish women smokers vs. nonsmok-
ers
75:14

see also Coronary diseases

Myocardium

arteriole wall, effects of filtered cigar-
ettes in dogs
72:20

arteriole wall thickness in smokers vs.
nonsmokers
72:2,19

arteriole wall thickness in smoking and
nonsmoking dogs
72:2, 20

effect of catecholamines on
67:60

effect of cigarette smoking on
67:60; 69:11; 71:5, 8

effect of nicotine on
67:60

effect of nicotine on catecholamine re-
lease from
67:60

effect of nicotine on, clinical and exper-
“imental studies
67:26

effects of hydrogen cyanide in smoke on
71:62

oxygen consumption in nicotine stimu-
lated
71:59

oxygen demand of, nicotine effects
71:38

see also Heart

Myosmine

structural formula of

64:49

2-Naphthy lamine
development of bladder carcinomas and
papillomas in dogs, hamsters, and
monkeys
71:296,
suspected bladder carcinogen in tobacco
smoke
71:265
Naphtols
64:54
Nas (tobacco and ashes)
and oral neoplasms in the USSR
69:58
Nasopharyngeal neoplasms
in smokers vs. nonsmokers, in Taiwan
75:50
National Cancer Institute
64:7
Biometry Branch
64:137, 138, 139
National Center for Health Statistics
64:13
survey of U.S. smoking habits by
71:5-6
survey on relationship of smoking and

incidence of respiratory disease
71:173

National Clearinghouse for Smoking and
Health
responsibilities
71:7
survey of smoking, 1970
71:6
National Cooperative Pooling Project
mortality statistics from coronary dis-
ease
71:21-22
National Heart Institute
64:7
National Institutes of Health
64:13
National Library of Medicine
64:13, 14
assistance in literature review on smok-
ing
71:7
National Safety Council
64:344
National Tuberculosis Association
64:8
National Vital Statistics Division
64:134
Natural gas
respiratory tract carcinoma in workers
exposed to
71:256
Neonates
effect of maternal smoking on
67:39, 185-187
tats, LD 50, nicotine determination
71:412
see also Birth weight; Infant mortality;
Smoking, maternal
Neoplasms
adenomatous, induction in mice by ciga-
tette smoke inhalation
71:350
age-adjusted incidence of
64:183
benign, in mice
64:165
classification of, by World Health Or-
ganization
64:173
death statistics in, validation of
64:101
development in smoking dogs, per-
centages of
71:274
experimental, bronchogenic carcinoma
69:63-64
experimental, epidermoid carcinoma
69:64
experimental, induction by tobacco
smoke
67:35
female mortality trends in
64:129, 131, 132, 133, 135, 137
induction of
64:33, 143, 146, 147, 148, 166
mammalian, cigarette smoke effect on
71:343
mortality rates in alcoholics
73:71

183
mortality rates in, international statistics
of
64:129, 130, 131
mortality rates in Japan
68:17
mortality ratios in, by site
64:137, 148, 149
mortality trends in
64:135, 137
occupational factors in
64:147
prevalence of, smokers vs. nonsmokers
69:56
recurrent primary, incidence in smokers
vs. nonsmokers
73:71, 74
by sex
69:56
sex ratios in, in mortality
64:132, 133
by site
64:127, 133, 134, 148, 149, 188,
189, 191, 197, 211
smoke constituents in, as promoters
64:26, 229
smoking and
72:4, 5, 59-75
summary of previous findings on rela-
tionship to smoking
68:89, 90; 73:67, 68; 75:3-8
summary of recent findings on relation-
ship to smoking
73:88; 74:58, 59; 75:43, 54
by type of tumor and smoking history
69:56
typing of
64:35
virus induction of
64:142, 166
see also Cancer registries; and specific
neoplasm terms, e.g., Lung neoplasms
Nephritis
64:103
Netherlands
cigarette smoke inhalation effects on
mice respiratory tract in
71:349
lung neoplasms, methods of retro-
spective study of smoking in
71:323
serum lipid difference, in smokers vs.
nonsmokers of
71:101
Neuroticism
64:365, 366, 367
New Haven Study
64:186
Newton, Massachusetts study
64:368, 369, 370
New York City
myocardial infarctions in cigar and pipe
smokers in
71:32, 38-39
New York State
cancer registry in
64:127, 129
neoplasm statistics in
64:135

184

New Zealand
coronary death rate in
64:320
human experimental data on smoking
and pregnancy
71:408-409
Nickel
anaplastic changes from
64:166
carbonyl, as a cocarcinogen
69:62
chloride
64:55
cigarette content of, in ash and smoke
64:55, 167
compounds, suspected carcinogenic
agents in cigarette smoke
72:265; 72:145
metaplasia and
64:166
Nickel workers
64:193, 194, 232
Nicotine
64:49, 69-75
absorption of
64:73, 74, 349
acceleration of alpha rhythm by
64:70
administration of
64:349
antigenic properties
72:104
atherogenic effects of
71:120-122
carcinogenic effect of
64:144
in cigar, pipe, and cigarette smoke
73:177
clinical effects on offspring of smoking
mothers
73:140, 141
coronary heart disease and
74:13, 19
degradation of
64:74
dosage of
64:74, 352
in duodenal ulcer induction in cats
73:158, 159
effect as antidiuretic
64:69
effect as cerebral anoxia
64:70
effect as chronic toxicity
64:32, 73, 74
effect as convulsant
64:70
effect as curariform action
64:69
effect as depressor action
64:74
effect as digestive disturbance
64:74
effect as discharge pattern
64:70
effect as emetic
64:70
effect as nausea
64:71, 74
effect as paralysis of ganglia
64:317
effect as stimulation
64:69
effect as stimulation of ganglia
64:317
effect as tranquilization
64:350
effect as vasomotor activity
64:70, 74
effect during pregnancy
67:186-187
effect during pregnancy in laboratory
animais
72:88; 73:115, 116
effect in “arousal” action
64:70, 350
effect on adipose tissue, in rats
74:13
effect on apexcardiogram
72:21
effect on autonomic nervous system
67:60
effect on birth weight in rats
72:88
effect on blood circulation
60:61
effect on blood circulation in coronary
disease patients
67:61
effect on blood lipids
71:123-128
effect on blood pressure
64:70; 67:60; 71:36
effect on blood vessels
67:62
effect on bronchoconstrictor response in
laboratory animals
72:46
effect on cardiac rhythm of heart
71:36
effect on cardiovascular system
67:60; 71:56-58, 107-118
effect on gardiovascular system in dogs
73:17
effect on catecholamine release
67:60; 71:36, 119; 75:29
effect on cats
64:70
effect on chemoreceptor activity
64:69
effect on chemoreflex induction
64:318
effect on chlorpromazine inhibition
64:70
effect on ciliary activity
64:268
effect on colon
64:71
effect on dogs
64:70
effect on fetus in laboratory animals
72:88
effect on gastric secretion
72:97

effect on gastric secretion in cats
73:158, 159

effect on gastric secretion in rats
733159

effect on gastrointestinal secretion in
dogs
72:6

effect on habituation
64:349-354

effect on heart blood flow in dogs
73:17

effect on heart function
67:60

effect on heart rate
67:60; 71:36

effect on hypercholesterolemic rabbits
69:27

effect on immune response in man
72:109

effect on lactation in laboratory animals
73:138, 139

effect on lactation in smokers vs. non-
smokers
73:139, 140

effect on lipid biosynthesis in aorta in
dogs
73:17

effect on lipid metabolism in rabbits
72:21

effect on liver
64:342

effect on microcirculation in atrium in
cats
73:17

effect on monkeys
64:70

effect on mucus secretion
64:268, 269

effect on myocardium
67:26, 60

effect on myocardium oxygen demand
71:38

effect on myometrial strips in gravidic
women
71:408

effect on nicotine-sensitive cells
64:69

effect on novice smoker
64:70

effect on pancreatic secretions in animals
73:161, 162

effect on peripheral vascular system
71:72, 75, 133-134; 72:25, 26

effect on peritoneal macrophages, in
mice
74:105

effect on pinocytosis, in mouse perito-
neal macrophages
74:105

effect on pipe/cigar smoke inhalation
73:183, 184

effect on pregnancy
71:411-414

effect on pregnant laboratory animals
67:187-188

effect on pregnant rats
69:80

185
effect on rabbits
64:70
effect on rat and mouse fetus, site of
action
73:121
effect on respiration, clinical experi-
mental studies
67:26
effect on respiratory system
64:70
effect on respiratory tract in rats
74:104
effect on supraopticohypophyseal sys-
tem
64:69
effect on sympathetic ganglia cells
64:69
effect on systolic pressure rise
64:74
effect on vascular resistance in dogs
67:60
effect, tolerance to
64:353, 354
effect, toxicity from
64:74
effect, tremors from
64:70
effect, unpredictability of
64:69
excretion, by passive smokers
75:97
experimental studies
72:21; 73:16, 17
hypoxia and
72:21
induction of necrosis in arterial] walls
71:63
as most likely contributor to health
hazards of smoking
72:8, 143
neurogenic effects of
74:57
N-oxides, presence in tobacco smoke
69:62
oxidized, in vitro ciliostatic effects
69:42
as potentiator of duodenal ulcers in
animals
73:161-163
pyrolysis of
64:59
secretion, effect of cigar, pipe and ciga-
rette smoke in dogs
73:216
structural formula of
64:49
substitutes for
64:34, 354
suppression of immunoglobulin — re-
sponse, in cell cultures
75:77
systemic toxicity of
64:71, 73
tissue storage of
64:71
toleration of
64:352, 353, 354

186

toxicity of
64:32, 71, 73, 74, 352, 353, 354

see also Nicotine content; Nicotine me-
tabolism; Nicotine pharmacology

Nicotine content

in blood, new assay methods
73:15, 23

and cigarette smoke
72:21

and cigarette smoke and tumorigenicity
67:34

effects of room size, amount of tobacco
burned and ventilation
75:91-94, 97

in little cigars compared to cigarettes and
cigars
73:223-226, 228

in milk of laboratory animals
73:138, 139

in milk of smoking mothers
73:139

smoker awareness of
64:349

and tar content, and tumorigenicity of
cigarette smoke
67:15

and tar content, of cigarette smoke as
measurement of dosage

Nicotine metabolism
64:31, 71,72
metabolites
69:61-62
metabolites, excretion of
64:71, 72
pathways of, in mammals
64:72
see also Cotinine

Nicotine pharmacology
64:32, 69, 70, 71, 72, 317, 318, 319,
320, 349
effect of acetylcholine on

67:60
effect of adrenalectomy on

67:60
effect of tetraethylammonium chloride
on
67:60
Nine-State Study
expected deaths in
64:109
mortality ratios in
64:109, 149
observed deaths in
64:109
Nitrates
in tobacco smoke
67:128
Nitric oxide
exposure to
64:266
as probable contributor to health haz-
ards of smoking
72:144
Nitrogen
gas phase. cigarette smoke
64:60
Nitrogen bases
64:54
Nitrogen dioxide
64:60, 266
ciliastatic effect of
64:268
effect on AHH activity
74:52
effect on alveolar wall cells in guinea pigs
73:50
effect on bacterial retention in hamsters
73:54
effect on bactericidal activity in mouse
lung
74:103
effect on pulmonary physiology, in ani-
mals
74:102-103
effect on pulmonary physiology, in mon-
keys
74:103
effects on rats’ lungs
69:41; 72:46, 47; 73:49, 50
in emphysema etiology
72:46
obliterative fibrosis from
64:266
as probable contributor to health haz-
ards of smoking
72:144
pulmonary changes in rodents chroni-
cally inhaling
71:161, 220
pulmonary edema from
64:266
toxic action of
64 :295
Nitrogen oxides
64:296, 297
as air pollutants in cigarette smoke
74:124, 125
in cigarette smoke
64:296, 297
effects on resistance of squirrel monkeys
to pneumococcus
71:173
pharmacology of
64:266
smoke content of
64:266
Nitroglycerine
effect on blood circulation in coronary
disease patients
67:61-62
effect on blood circulation in normal
individuals
67:61-62
4-Nitroquinoline 1-oxide
alcoholic solution of, development of
papillomas in mice drinking
71:292
Nitrosamines
effect on lactating hamsters
73:139
role in respiratory tract carcinogenesis,
in animals
74:47
N-nitrosamines
69:62

carcinogenicity
67:127
carcinogenicity in cigarette smoke
71:264-266
determination in cigarette and tobacco
smoke condenstate
73:87, 88
esophageal neoplasms induced in animals
by
71:292
in tobacco smoke
67:127
N-nitrosoanabasine
69:62
N-Nitrosoheptamethyleneimine
incidence of lung neoplasms, in rats
75:49
N-nitrosonornicotine
in tobacco
69:62; 75748, 49
Nonrespondents
age adjusted death rates in
64:114
magnitude of, in surveys
64:97
mortality ratios in
64:116
proportion of smokers in
64:114
Nonresponse bias
64:96, 104, 115
Nonsmokers
age-adjusted mortality in
64:100
by age and sex, U.S.
64:178
airway resistance in
64:292, 293
allergic and irritative reactions to ciga-
rette smoke
72:128, 129
allergic skin reactions in
64:319
allergic symptoms in, from tobacco
smoke exposure
72:110,111
bladder neoplasm risk in
64:222
bladder neoplasms in
64:223
body weight of
64:384, 385
carboxyhemoglobin effects on oxygen
uptake
71:61
carboxyhemoglobin levels in
72:125
chronic cough prevalence in
64:299, 302
coronary diseases rate in
64:322, 323
emphysema in
64:297
epithelial changes in
64:170, 173, 189
epithelial changes in, females
64:170

187
extroversion in
64 :366
forced expiratory volume in
64:290, 291
hemoglobin concentration in
64:319
1.Q. measurement of
64:370
liver cirrhosis in
64:342
lung neoplasms in
64:118, 184, 191, 193, 230, 232
morphology of
64:385, 386
mortality rates in
64:100, 102,117,118
mortality ratios in
64:163, 202, 301
occupational factors in
64:187
oral neoplasms
64:202
passive smoking and
72:121-125
as percent of population
64:114
pneumoconiosis in
64:298
psychosomatic disorders in
64:367
respiratory conditions in
64:289
tisk ratios in
64:222, 223, 230, 232
urban-rural mortality in
64:186, 194
US., by age
64:178
see also Smokers vs. nonsmokers
Norepinephrine
64:318
effects of nicotine

75:29
Nornicotine

69:62
structural formula
64:49
North Dakota studies

64:323
Norway

coronary death rates in
64:320

incidence rates of lung neoplasms
69:55-56

tung neoplasms in, for pipe smokers
71:244

lung neoplasms mortality in, relationship
to tobacco use
64.176; 71:245-—246

neoplasm risk in
64:127

tracheobronchial tree changes in smokers
and nonsmokers of

71:259
Nose

effect of smoking
64:275
Nose neoplasms
64:193

188

mortality rates, by amount smoked
67:147
mortality rates, by smoking classification
67:147
Noxious gases
exposure magnitude of
64:296, 297
in respiratory diseases
64:279
Nutritional deficiency
64:341

Oat cell carcinoma
see Carcinoma, oat cell
Obesity
64:38, 321, 355
coronary diseases mortality and
64:321; 71:43
relationship to smoking and CHD
71:43-45
relationship to smoking in peripheral
arteriosclerosis
71:72
as risk factor for CHD
72:16; 73:9
Occupational diseases
asbestosis
73:41
asbestosis, in asbestos workers, in Singa-
pore
74:95
bronchitis
72:42
bronchitis and respiratory tract irrita-
tion, in rubber industry workers
74:96
bronchitis, in cement and rubber in-
dustry workers
74:95, 96
bronchitis, in wool and cotton textile
workers
74:93, 94
byssinosis
73:39, 41
byssinosis, in cotton and wool textile
workers
74:93, 94
byssinosis in cotton millworkers
75:68
chronic obstructive pulmonary disease
72:3, 42-44
chronic obstructive pulmonary disease,
in autoworkers
74:80
chronic obstructive pulmonary disease,
in firemen
75:68
coal workers’ pneumoconiosis
73:42
lung neoplasms in uranium miners
75:47
pneumoconiosis
72:42-44
pulmonary fibrosis
72:44
and risk of neoplasms
75:43

smoking and
72:3, 4244 ;74:93-96; 75 :68-70

see also Occupational factors; Occupa-
tional hazards; Occupations

Occupational factors

64:224
chronic bronchitis and
64:298, 299, 300, 302
coronary disease and
64:321, 322; 73:5,7
lung neoplasms and
64:95, 187,193, 194, 232
mortality and
64:112, 134
smoking prevalence and
64:362, 363
see also Occupational diseases; Occupa-
tional hazards; Occupations

Occupational hazards

64:100, 101, 232

air pollution exposure in Boston police-
men
74:82, 83

asbestos exposure
67:35; 73:41

asbestos exposure and smoking as factors
in tung neoplasm development
74:41-43; 75:49

in bladder neoplasms
64:222

bladder neoplasms, and smoking
73:78

carboxyhemoglobin levels in workers ex-
posed to exhaust gases
75:21

coal dust exposure
73:4143

from coal tar
64:147

cotton, flax, and hemp dust exposure
73:39-41

dust exposure
73:43, 44

exposure to chemicals, fumes, sprays and
dusts, in smokers vs. nonsmokers, by
Tace and sex
75:69, 70

exposure to 100% pure oxygen
73:43

higher reporting of exposure to, by
smokers vs. nonsmokers
75:68

in lung neoplasms
64:232

myocardial infarction as
64 :323

nitrogen dioxide in
64:266

pancreatic neoplasms and
73:77

pulmonary disease from
64:266, 298, 299, 300, 302

radiation exposure in uranium miners
73:72

risk ratios in
64:31, 134

rubber industry fumes and smoking
74:96

smoking and
72:3, 4, 42-44; 73:39-44

smoking as additive risk for COPD
73:55

textile dust exposure and smoking
74:93-96

uranium exposure
67:35

see also Occupational diseases; Occupa-
tional factors; Occupations

Occupations

asbestos workers, lung neoplasm morbid-
ity
67:143

asbestos workers, lung neoplasm mortal-
ity and smoking
71:257

asbestos workers, respiratory tract car-
cinoma
71:256

bank employees, smoking and COPD
71:198

coal miners, impaired pulmonary func-
tion in smoking
71:163

coal miners, respiratory tract carcinoma
71:256

coal miners, smoking and COPD
71:153, 197, 218-219

coal miners, smoking and ventilatory
function
71:207

flax mill workers, smoking and COPD
71:199

government employees, blood pressure
differences in smokers vs. nonsmok-
ers
71:99

longshoremen, mortality from smoking-
related cerebrovascular disease
71:70

longshoremen, mortality rates from CHD

in
71:28

longshoremen, smoking and COPD
71:28

longshoremen, smoking and ventilatory
function
71:208

medical students, serum lipid differences
in smokers vs. nonsmokers
71:98

medical students, smoking and nicotine
effects on blood lipid levels
71:124

medical students, smoking and thrombo-
sis relationships
71:130

medical students, smoking and ventila-
tory function
71:209-210

mortality rates, smokers vs. nonsmokers
by
67:11

nickel workers, lung neoplasms in
71:256

189
physicians, bladder and kidney neo-
plasms in smoking
71:293, 294

physicians, cessation of smoking effect
on COPD

71:142

physicians, COPD mortality rates
71:149

physicians, decline in cigarette smoking
rates
71:48

physicians, mortality from smoking-
telated cerebrovascular disease
71:68

physicians, mortality rates from CHD
71:26

physicians, mortality ratios from esoph-
ageal neoplasms
71:290

physicians, mortality ratios from peptic
ulcer in smoking and nonsmoking
71:424

physicians, pulmonary function foliow-
ing cessation of smoking
71:149

physicians, smoking and ventilatory
function
71:209-210, 213

plant workers, occupational exposure
and smoking relationships to COPD
71:153, 218, 219

plant workers, smoking and COPD

71:198
plant workers, smoking and ventilatory

function
71:206-208

post office workers, blood pressure dif-
ferences in smokers vs. nonsmokers
71:104

post office workers, smokers and ventila-
tory function

71:209
post office workers, smoking and coPpD

71:200, 202

prisoners, serum lipid differences in
smokers vs. nonsmokers
71:100

prisoners, smoking and nicotine effects
on peripheral vascular system
71:133

railroad employees, mortality and mor-
bidity, CHD and smoking
71:28, 34,97

and respiratory symptoms by smoking
habit
67:97

smelter workers, Jung neoplasm mortal-
ity from arsenic exposure
71:257

smoking habit for
67:143

soldiers, smoking and COPD
71197

steel workers, COPD development from
dust exposure

71:153
students, carbon monoxide effects on

blood lipids
71.129

190

students, infectious respiratory disease in
smokers vs. nonsmokers
71:228-229

students, mortality from smoking-related
cerebrovascular disease
71:68

students, mortality rates from CHD
71:28

students, smoking and COPD
71:201

students, smoking and nicotine effects
on blood lipid level
71:125

students, smoking and thrombosis rela-
tionships
71:130

students, smoking and ventilatory func-
tion
74:211

telephone company employees, smoking
and COPD
71:200

textile workers, occupational exposure
and smoking relationship to COPD
71:218-219

transportation workers, air pollution re-
lationship to COPD
71:198, 202

transportation workers, smoking and
COPD
71:198, 202

transportation workers, smoking and
ventilatory function
71:207, 212

uranium miners, tung neoplasms in
smokers and nonsmokers
71:256

uranium miners, lung neoplasms morbid-
ity by smoking habit for
67:143

utility company employees, CHD mor-
bidity in smoking
71:30

veterans, bladder and kidney neoplasms
in smoking
71:294-295

see also Occupational diseases; Occupa-
tional factors; Occupational hazards

Office of Science and Technology

64:8

Oleic acid

suspected carcinogenic agent in cigarette
smoke
742266

Olive oil

penetrability of benzo(a)pyrene in mice
esophageal epithelium
71:292

Opium

64:349

_ Optic nerve

atrophy, and cyanide in tobacco smoke
67:183

sensitivity, amblyopia from
64:341

Oral diseases, non-neoplastic

smoking and
69:5-6, 85-87; 72:6
Oral hygiene
relationship to smoking and noncancer-
ous oral disease
69:85-86
smoking and
72:6
Oral mucosa
64:203
effect of carcinogens in laboratory ani-
mals
72:70
effect of cigarette smoke
72:6, 69
effect of reverse smoking
72:69
effect of tobacco/bidi smoking and
chewing
72:69
Oral neoplasms
64:37, 196-204, 233
alcohol consumption and smoking in
etiology of
73:193; 74-53-55
amount smoked in
64:233
cigar smoking in
64:189
epidemiologic studies
64:196-202; 74:53-55
estimated incidence in U.S. for 1970
71:284
experimental induction of
64:233
incidence of secondary primary, in
smokers vs. nonsmokers
75:50
income gradients in
64:134
inhalation patterns and
73:191
mortality rates in
64:37, 133; 71:285
mortality rates in, in females
64:131, 132
mortality rates in, in foreign born
64:134
mortality rates in, in Irish
64:135
mortality rates in, in males,
64:130, 132
mortality rates in Japanese male smokers
vs. nonsmokers
73:74
mortality ratios for pipe, cigar, and
cigarette smokers vs. nonsmokers
73:191-193
mortality ratios in
64:113, 202
mortality ratios in, in cigarette smokers
64:149
mortality trends in
64:137
neoplasm site by tobacco use in
64:197
pipe smoking in
64:37, 150, 189; 72:67
prevalence of, decline in
64:204

recurrent, incidence in smokers vs. ex-
smokers
73:71, 74-75
relationship of tobacco use
71:285, 289, 361-367
relative risk in tobacco smokers and
chewers
72:70
relative risk of development in pipe,
Cigar, and cigarette smokers vs. non-
smokers
73-191, 194, 195
retrospective studies of
64:198, 199, 200, 201
reverse smoking in
64:203, 204; 73:76
risk gradients in, by amount smoked
64:233
tisk ratios in, in females
64:134
smoking induced increase in
64:197
smoking in etiology of
64:204; 69:58; 71:289; 72:4, 67-70;
73:74-76
snuff in
64-233
summary of previous findings on rela-
tionship to smoking
74:52, 53
summary of retrospective studies
73:194, 195
and tobacco chewing
69:58
urban-rural factors in
64:133
in waiters
64:134
see also Gingival neoplasms; Mouth neo-
plasms; Oropharyngeal neoplasms
Oral ulceration
reverse smoking in
64:203
Organ cultures
cigarette smoke effects on cell growth
and reproduction in
71:267, 343-345
Oropharyngeal neoplasms
64:201
frequency in smokers and nonsmokers
71:238
Oxidoreductases
reduction of, in smokers’ alveolar macro-
phages
69:42-43
Oxygen
in cardiac function
64:318
debt, effect of smoking
73:246, 247
debt, exercise performance and
73:246, 247
myocardial consumption of, following
nicotine stimulation
71:58, 75
in smoke
64:60

191
tension, smokers vs. nonsmokers
72:22
transport in body, carbon monoxide
effects
71:60, 75
uptake in nonsmokers with specific
carboxyhemoglobin levels
71:61, 75
Ozone
ciliastasis from
64:268
irritation action of
64:295
Ozonized gasoline
64:166

Pachyderma oralis
64:203
Palatal mucosa
64:275
Palatal neoplasms
64:204
see also Mouth neoplasms; Oral neo-
plasms
Palate
hamster, C-14 labeled smoke particulates
deposition in
71:281-282
smoking and stomatitis nicotina
69:87
Pancreatic neoplasms
incidence in cigar/pipe and cigarette
smokers vs, nonsmokers
74:55, 56
mortality rates, by age
67:158-159
mortality rates, by amount smoked
67:159
mortality rates, by sex
67:158
mortality rates, by smoking classification
67:159 ,
mortality rates, for women
67:153
mortality rates in United States
72:74
mortality ratios, by age
67:158-159
mortality ratios, by age and amount
smoked
67:159
mortality ratios, by sex
67:158
mortality ratios, for men by smoking
classification
67:159
mortality ratios, for women
67:153
mortality ratios in Japanese male and
female smokers
72:74
occupational exposure and
73:77
relationship of smoking to mortality
from
71:298-299

192

relative risk in men by number of ciga-
rettes smoked
74:55
smoking and,
67:36, 158-159; 69:60-61; 71:13,
238, 298-299; 72:5, 68, 74; 73:77
summary of previous findings on rela-
tionship to smoking
74:55
Pancreatic secretions
bicarbonate content, effect of smoking
73:159, 160
effect of nicotine in animals
73:161, 162
Papain
pulmonary effects on rats exposed to
cigarette smoke with
71:163
Paper chromatography
64:51, 57
Papillomas
64:142, 165
development in mice drinking alcoholic
benzopyrene
71:292
formation following skin painting with
smoke tars
71:337-339, 341
induction in hamsters exposed to ben-
zo(a)pyrene
71:346-347
induction of
64:142, 143, 144, 203, 223
transformation of
64:144
Papillomas, benign
64:142
origin of,
64:165
tar induced, in mice
64:223
Paraffin
64:147
Paralysis
of ganglionic nerve celis
64:69
Paralysis agitans
mortality rates, smokers vs. nonsmokers
67:8
Parasorbic acid lactone
64:145
Parathion
62:145
Parents
incidence of penumonia and bronchitis
in children of smokers
75:105, 106
influence
64:369, 370
prevalence of respiratory symptoms in
children of smokers
75:102, 103
smokers cough and phlegm production,
and respiratory symptoms in children
75:103
see also Smoking, parental
Paris green
64:61
Particulate matter
and lung neoplasm development
74:44, 45
pollution levels in four U.S. locations
75:65, 66
Particulate phase, cigarette smoke
64:51-60, 263, 264, 265
carcinogenic accelerators in
72:5, 65
effect on pulmonary and cardiac struc-
ture and function
727:78
harmful constituents in
72:143
Particulate phase, tobacco smoke
composition of
64:51
deposition sites of
64:264, 265
gravitational settling of
64:264
measurement of
64:263
removal of
64:264
respiratory damage from
64:279
retention of
64:264, 300
water content of
64:51
Passive smokers
pathologic studies
75:99
summary of previous findings
75:87, 88
summary of recent findings
75:107, 108
Passive smoking
CO, nicotine, benzo(a)pyrene, acrolein
and acetaldehyde levels
75 :90-95
effect on cardiovascular function in dogs
73:14
effect on children
72:129,
effect on respiratory tract in laboratory
animals
72:129, 130
effects of carboxyhemoglobin levels, in
persons with angina pectoris
75:95,97
effects of carboxyhemogiobin levels on
CO absorption
75:95, 96
effects of CO in tobacco smoke on
psychomotor performance
75:99-101
effects of exposure to cigarette smoke,
in passive smokers
75:99
effects of tobacco smoke constituents
75 88-98
effects on bus and plane passengers
75:102
excretion of nicotine

75:97

exposure to cigarette smoke, and devel-
opment of eye and throat irritations
75:99, 100

incidence of pneumonia and bronchitis
in children of parental smokers
75:105, 106

maternal smoking, and development of
bronchitis and pneumonia in infants

75:103, 104

in neoplasm induction in laboratory ani-
mals
72:130

parental cough and phlegm production,
and respiratory symptoms in children
75:103
Pathophysiologica! studies
alveolar macrophages and smoking
75:76, 77
effects of cigarette smoke on leukocytes,
in guinea pigs
75:77, 78
effects of cigarette smoke on pulmonary
macrophages, in guinea pigs
75:77, 78
effects of smoking on tracheal mucus
velocity, in dogs
75:78
suppression of immunoglobulin response
by nicotine or water soluble fraction
of cigarette
75:77
Patulin
64:145
Peak Flow Meter
64:290
Pearl’s hypothesis
64:105
Peer group status
64:372, 373
Penicillic acid
64:145
Penis
skin neoplasms of
64:147
Pentacy clic compounds
64:54
Pentolinium
blockage of nicotine cardiac stimulation
by
71:57
Peoples Gas Company Study
epidemiologic study of smoking and
CHD
74:6,7
Peoples Gas Light and Coke Co.
study of CHD, serum cholesterol and
smoking relationships
71:43
Peptic ulcer
64:337-340
antacid efficacy and healing of, effects
of cigarette smoking on
71:423
cessation of smoking as therapy for
67:182
cigarette smoking in

64:39

193
clinical studies
73:155-157

development in smokers
71:43

and diet
67:182

duodenal, and smoking
67:39

epidemiological studies
73:155-157

gastric, morbidity, and smoking
67:40, 182

gastric, mortality, and smoking
67:40, 181-182

gastric secretion in smokers vs. nonsmok-
ers
73:157, 158

incidence rates, smokers vs. nonsmokers,
by sex
67:182

increased mortality in Japanese smokers
vs. nonsmokers
73:155, 156

increased prevalence in male smokers
72:97

and lung neoplasms, relation to smoking
69:57

morbidity, and smoking
67:40, 181

mortality rates
67:40; 71:423

mortality rates, by amount smoked
67:182

mortality rates, by smoking classification
67:182

mortality rates, smokers vs. ex-smokers
67:181

mortality ratios, for men by age
67:181

mortality ratios from
64:339, 340

mortality ratios from, in smokers and
nonsmokers
71:424

mortality ratios from, smokers vs. ex-
smokers by age
67:181

mortality ratios in Japanese adults by
age started smoking
73:155, 156

mortality ratios in male cigar and pipe
smokers
73:222

predisposing factors
73:157

recurrence in smokers vs. nonsmokers
73.157

retrospective and cross section study
methods for smoking relationship to
71:425427

smoking and
67:22, 39-40, 181-182; 72:5, 6, 97,
98, 73:155

smoking as cause in dogs
72:26

Perception

of health hazards, and smoking behavior
67.191

194

1,8,9 -Perinaphthoxanthene
64:54
Perinatal studies
effect of materna! smoking on mortality,
summary of findings
73:134, 135
maternal smoking and
72:83-88
Periodontal diseases
smoking and
69:85-86; 72:6
smoking and, in Ceylon
69-85-86
smoking and, in Norwegian Army re-
cruits
69:85
Peristalsis
64:71
Peroxides
suspected carcinogenic agent in cigarette
smoke
71:265
Personality characteristics
64:365-368
and coronary disease
64:321;67:57
coronary disease morbidity ratios, smok-
ers vs. nonsmokers by
67:57
drug use and
64-353
relationship to CHD and smoking
71:48-49, 105-106
in smokers
64:326, 365-368
and smoking habit
67:57, 188-192
and smoking habit in college students
67:189
Pesticides
64:61, 62, 145
content in cigarette smoke
74:265, 266
pH
pipe/cigar smoke inhalation and
73:183
of smoke in cigarettes, cigars, and little
cigars
73:223, 224, 228
Phagocytosis
64:35, 267, 269, 270, 300
effect of cigarette smoke in laboratory
animals
73:53, 54
effect of cigarette smoke in rabbits
72:109
effect of tobacco smoke
72:47-48
pulmonary alveolar, in smokers vs. non-
smokers
71:165
Pharyngeal fungi
smokers vs. nonsmokers in South Africa
73:54
Pharyngeal neoplasms
64:201, 202
frequency in smokers vs. nonsmokers
71:238
incidence of secondary primary, smokers
vs. nonsmokers
75:50

mortality rates, by smoking classification
67:35, 146-147

mortality rates, cigar smokers vs. non-
smokers
67:146

mortality rates, for men by amount
smoked
67:147

mortality rates, for women
67:153

mortality rates, pipe smokers vs. non-
smokers
67:146

mortality ratios
67:35

mortality ratios, by smoking classifica-
tion
67:146

mortality ratios, for cigar smokers
67:35

mortality ratios, for cigar smokers by age
67:146

mortality ratios, for men by age
67:146

mortality ratios, for men by amount
smoked
67:146-147

mortality ratios, for pipe smokers
67:35

mortality ratios, for pipe smokers by age
67:146

recurrent, incidence in smokers vs. ex-
smokers
73:74, 75

relationship to tobacco use
71:362-364, 366

retrospective studies of, by type of
smoking
64:200, 201

smoking in etiology of
67:35, 145,147

Phenols

64:49, 54, 58, 59, 61, 62, 145, 267

in cigar, pipe, and cigarette smoke
73:177

ciliatoxic agents
67:108

cocarcinogens
67:131

as probable contributors to health haz-
ards of smoking
72:144

suspected carcinogenic agent of cigarette
smoke
71:266

in tobacco smoke
67:129

tumor promoting agents
67:129

Phenotypes

partially deficient heterozygote, in
COPD etiology
75:73, 74

Phenylmethyloxadiazole (PMO)
protection against adverse effects of ciga-
rette smoke in animals
73:49, 53
Philadelphia Pulmonary Neoplasm Research
Project
jung neoplasm histopathologic studies
and
74:38
Phlebitis
64:103
Phiegm production
by occupation and smoking habit
67:97
by parental smokers, and development
of respiratory symptoms in children
75:103
by parental smokers, and incidence of
pneumonia and bronchitis in children
75:105, 106
by smoking habit and sex
67:98
Phospholipids
function as surfactants in lung tissue
712172
smokers vs. nonsmokers
71:99-100, 102
Physical activity
64:322
as a factor in coronary heart disease
73:4,5
myocardial infarct morbidity ratios, for
smokers vs. nonsmokers by level of
67:56
occupational, and smoking habit
67:56
relationship to myocardial infarction,
smokers vs. nonsmokers
71:44
and risk of cerebrovascular accident
67:68
smoking and, relationship to CHD
71:41, 43, 44
Physique
smokers
64:383-387
Phy tadiene
64:51
Phytol
structural formula of
64:52
Picoline
64:59
Pigmentation
induction of
64:146
Pigments
64:272
in lungs of emphysematous patients
64:273

Pinocytosis
decrease in alveolar macrophages, in
smokers vs. nonsmokers
75:76
effect of nicotine, in mouse peritoneal
macrophages
74:105

195
Piperidine, nitroso-
suspected carcinogenic properties in ciga-
rette smoke from
71:265
Pipe smoke
see Smoke, pipe
Pipe smokers
see Smokers, cigar and pipe; Smokers,
pipe
Pipe smoking
see Smoking, pipe
Pipe tobacco
see Tobacco, pipe
Pitch
64.147, 229
skin neoplasms from
64:33
Placebos
ginseng root as
64:355
nicotine-free cigarettes as

64:70

Placenta
ability to hydroxylate benzo(a)pyrene in
smoking mothers
71:407
morphology

64:343
Platelets

see Blood platelets
Plethysmogram
abnormalities, in smokers vs. nonsmok-
ers
73:22
Pleura! neoplasms
mesothetiomas, classification of
64:174
Plumbers
neoplasm risks in
64:134
Pneumoconiosis
64:269, 290, 298
in coal miners
72:42-44
in coal miners, smokers vs. nonsmokers
73:42
smokers vs. nonsmokers
72:42-44
Pneumonia
64:277, 294, 302
epithelial changes in
64:170
incidence in children of smokers
75:105, 106
maternal smoking, and development in
infants
75.103
mortality ratios in
64:276
neoplastic-like pathology in
64:195
in passive smokers, summary of recent
findings
75 :108
phenol induction of
64:267
Pneumothorax, spontaneous
smoking and
73:37

196

Poisson distribution
in mortality rates
64:117, 118, 119
Poland
bladder neoplasms, in, methods and re-
sults in retrospective studies of smok-
ing and
71:382, 383
CHD mortality and morbidity in,
71:96
esophageal neoplasms in Polish-born
64:135
esophageal neoplasms in, retrospective
studies of tobacco use with
64:214; 71:378
gastric neoplasms in Polish-born
64:135
laryngeal neoplasms in, retrospective
studies of tobacco use with
64:205, 208; 71:357
lung neoplasms, in males
64:135
oral neoplasms in, retrospective studies
of tobacco use with
64:200, 201; 71:364
serum lipid differences in smokers vs.
nonsmokers in
71:100, 102
smoking and nicotine effects on human
blood levels in
71:124
smoking relationship to thrombosis in
71:131
Polonium 210
64:145
carcinogenicity
67:128
in cigarette smoke
67:128
levels in lung tissue, smokers vs. non-
smokers
67:128
and lung neoplasms
67:128
suspected carcinogenic agent in cigarette
smoke
71:265-267, 335-336
in tobacco leaf
67:128
as tumor initiator
67:128
Polyoma virus
64:166
Polyphenols
64:54
Population studies
British physicians, mortality and smok-
ing (Doll and Hill Study)
67:5, 17, 52, 93, 139, 155, 182-186
bronchitis and smoking
69:37
Canadian pensioners smoking and health
study
67:5, 48, 93, 138, 154, 159
U.S. population, mortality and smoking
(Hammond)
67:5, 13, 49-54, 66, 69, 94, 135-137,
146-158, 181-189
U.S. veterans, mortality and smoking
(Dorn)
67:5, 13, 48-49, 67-69, 92, 137-139,
146-159, 181-184
Portland student study
64 368
Postal employees
breathlessness in
64 :286
chronic cough in
64:281
Post-operative complications
in duodenal ulcer removal, smokers vs.
nonsmokers
73:157
incidence in bronchitic and nonbron-
chitic smokers vs. nonsmokers
74:92
pulmonary, smokers vs. nonsmokers
74:174-175; 72:38
smoking, obesity, anesthesia and
73:39
Potassium
64:55
Potassium-40
64:145
present in tobacco leaf
71:266
Preeclampsia
maternal smoking and
69:79; 72:84; 73:142
in smoking vs. nonsmoking women
71:404, 407; 73:142
Pregnancy
carboxyhemoblobin levels in fetuses
75:26, 27
carboxyhemoglobin levels of smokers in
69:80
effect of blood pressure and smoking
habits on
69:77-78
effect of nicotine on, in rats
69:80
effect of smoking during
64:343; 67:185-187; 69:4-5, 77-81;
71:4, 13, 82-87, 389, 397-399, 415;
73:103-142
effect of smoking during, and develop-
ment of bronchitis and pneumonia in
infants
7§:103, 104
effect of smoking during, in Hungary
69:79
effect of smoking during, in Ireland
69:79
effect of smoking during, in Scotland
69:79
effect of smoking during, in Venezuela
69:79
effect of tobacco smoke, nicotine, and
carbon monoxide in laboratory ani-
mals
73:114-118
effects of nicotine on uterus during
67:187
human, methods used in smoking study
of
71:391-396

nicotine effects on myometrial strips in
71:408
and previous smoking habits, effect on
infant birth weight
73:112-114
summary of previous findings
75:5,6
timing of influence of smoking on birth
weight
73:120,121
unsuccessful, smoking effects on
74:13
see also Maternal fetal exchange;
Smoking, maternal
Premalignant lesions
in bronchi
64:27
in epithelial tissue
64:231
in oral cavity
64:142
Prematurity
and maternal smoking
64:343; 67:185-186; 69:77, 79;
71:390, 400-403; 72:5, 83-87;
73:112
and maternal smoking, among Negroes
69:78
Presbyterian Hospital Study
64:141, 174
Pressure-volume work loops
64:292
Prevalence studies
64:301
in bronchopulmonary disease
64 :280-293
pulmonary function tests in
64:280
sputum production in
64:383
Printing ink
64:193
Professional workers
smoking incidence of
64:187
Promoting agents
64:26, 142, 146, 229
ethyl alcohol as
64:217
urethan as
64:142
Propane
64:60
beta-Propiolactone
64:145
Propionaldehyde
64:52
Propionic acid
ciliatoxic agent
67:108
in tobacco smoke
67:108
Propylene
64:60
Prospective mortaity studies
age adjustments in
64:84

197
alcohol in
64:99, 101

by American Cancer Society
64:81, 96, 101

by Best, Josie, and Walker
64:81

British doctors study as
64:97, 102,109

California occupational study as
64:95, 106

Canadian study as
64:91, 92, 94

cause of death in
64:109

certification validity in
64:109, 110

city population size in
64:99

comparison of
64:83

by Dorn
64:81

by Dunn, Buell, and Breslow
64:81

by Dunn, Linden, and Breslow
64:81

educational level in
64:100, 101

exercise in
64:101

in ex-smokers
64:93

fried foods in
64 :100

genetic longevity in
64:99

by Hammond
64:81

by Hammond and Horn
64:81

infectious diseases in
64:276

inhalation practices in
64:99

limitations in
64:94.95, 96, 111, 163

mate death rates in
64:28

maternal smoking in
64:343

mortality ratios in
64:84, 118

nonresponse bias in
64:96, 97, 104

occupational exposure in
64:100, 101

previous disease in
64:100, 101

religious factors in
64:99, 101

smoking data in
64:82

socioeconomic factors in
64:96

tranquilizers in
64.100

twenty five-state study as
64:103, 104

198

type of smokers in
64:82

usable responses in
64:96

USS. veterans study as
64:91, 94, 96, 97, 103

variables affecting
64:84

weaknesses of
64:96

Prospective studies

64:27, 28, 30, 81-116, 293, 294, 322,

323

64:36
by Doll and Hill
64:81
esophageal neoplasms
64:217
excess deaths in
64:28
in gastric neoplasms
64:227
methodology of
64:81
methodology of, in peptic ulcer
64.338, 339
morphology correlations in
64:385, 386
neoplasms
64:231
neoplasms by site
64:149
reliability of
64:180
Prostatic neoplasms
64:135, 136
mortality rates in
64:131
mortality ratios in
64:148, 149
Protestants
smoking prevalence in
64.364
Protozoa
ciliary function in, effect of cigarette
smoke on
71:165, 224
Pseudoephedrine

64:349
Psychoanalytic theory

64:367
Psychomotor performance
effects of CO in tobacco smoke
75:99-101
in passive smokers, summary of recent
findings

75.108
Psychosocial factors
in cardiovascular disease
64:327
smoking habit
67:39, 188-192
Psychosomatic disorders
in heavy smokers
64:367
Psychotherapy
cure of tobacco habit by
64:354
Public Health Service
64:6, 13, 127, 342
1967 study of, starting point for new
studies
71:4
review of medical literature on smoking
hazards
71:7
Public transportation
effects of passive smoking on bus and
plane passengers
75:102
Puerto Rico
esophageal neoplasms in, retrospective
studies of tobacco use with
71:378
relationship of tobacco use and neo-
plasms of oral cavity in
71:367
Puffmeter ratios
64:291, 292
Pulmonary alveoli
changes in rates after exposure to nitro-
~ gen dioxide
69:41
effect of smoking on
64:274, 275; 67:30, 107
epithelium
64:165
epithelium, experimentally induced
changes in
64:272
fluid lining, smoking effects on
64:269, 270
tupture, in pipe/cigar smokers vs. ciga-
rette smokers and nonsmokers
73:217
septa, rupture of
64:35, 274, 275, 301
septa, thickening of
64:275
stability, cigarette smoke in
64:35, 300
Pulmonary clearance
effect of heavy smoking
73:52,53
effect of nitrogen dioxide, in rats
74:103
effect of smoking
72:3,47; 73:55; 74:101, 102
effect of sulfur dioxide on
64:295
mechanical vs. bactericidal clearance in
guinea pigs
73:53
mechanism, in smokers vs. nonsmokers
73:52, 53
in monozygotic vs. dizygotic twins
73:51
particle deposition in smokers vs. non-
smokers
73:53
in smokers, ex-smokers, and nonsmokers
with and without pulmonary disease
74:100, 101
see also Pulmonary function
Pulmonary diseases
see Lung diseases

Pulmonary edema
nitrogen dioxide in
64:266
Pulmonary embolism
64:103
Pulmonary emphysema
See Emphysema
Pulmonary fibrosis
64:35, 301
in asbestos textile workers
72:44
autopsy studies, smokers vs. nonsmokers
75:74-76
chronic
64 277-294
in heavy smokers
64:274
in moderate smokers
64:274
obliterating
64:266
in pipe/cigar smokers vs. cigarette smok-
ers and nonsmokers
73:217
smokers vs. nonsmokers
71:161
smoking and
67:107; 72:44
Pulmonary function
64:35
abnormalities, and rheumatoid arthritis
in smokers vs. nonsmokers
74:92, 93
abnormalities, during viral illness, in
smokers vs. nonsmokers
75:63
in asymptomatic young men in Romania
73:39
before and after smoking one non-filter
cigarette
74:99
of Boston policemen, smokers vs. non-
smokers
74:82, 83
closing volume abnormalities as indicator
of small airways disease

75:71, 72

in coal miners, smokers vs. nonsmokers
73:42, 43

in coal miners vs. nonminers
73:42

decline in forced expiratory volume, in
smokers by race
75:72

diffusing capacity, smokers vs. nonsmok-
ers in Berlin, New Hampshire
73:50, 51

effect of asbestos exposure and smoking
73:41

effect of cigarette smoke, in monkeys
74:102

effect of coal dust exposure and smoking
73:41-43

effect of dust exposure and smoking
74:95

effect of exercise performance and
smoking
74:99

199
effect of isoproterenol in smokers, non-
smokers and bronchitics
74:99, 100

effect of lung hyperinflation in coal
miners
73:42, 43

effect of nitrogen dioxide, in animals
74:102, 103

effect of smoking
69:5, 42; 72:37, 38; 74:80

effect on exercise performance in smok-
ers vs. nonsmokers
73.246, 247

in ex-smokers
73:39

of insurance company employees, smok-
ers vs. nonsmokers
74:80, 81

in jet fighter pilots, smokers vs. non-
smokers
73:43

of male and female smokers, in New
Guinea
74:81, 82

of male executives, smokers vs. non-
smokers
74:81

in males from industrial town in Eng-
land, smokers vs. nonsmokers
68:69

of pipe and cigarette smokers, ex-smok-
ers, and nonsmokers
74:99

in pipe/cigar smokers vs. nonsmokers
73:217, 221

prevalence of deficient heterozygote
phenotypes, in smokers vs. nonsmok-
ers
75:74

pulmonary hypertension and
73:43

respiratory flow resistance
64:266

small airways disease, smoking, and
74-84-87; 75:71, 72

in smokers vs. nonsmokers
67:99-101; 72:40; 73:55; 74:80-82

in smokers vs. nonsmokers in Berlin,
New Hampshire
73:50, 51

in smokers vs. nonsmokers, under 30
years of age
73:50

smoking and
73:38, 39

summary of recent findings
75:78

tests
64:278, 292

volume tests
64:292

in young smokers
67:110-111

see also Pulmonary clearance; Respira-
tory function tests

Pulmonary heart disease

COPD and

72:24

200

smoking as cause
72:24, 27
Pulmonary surfactant
effect of smoke
67:110; 72:48
effect of smoking
69:42; 73:55
Pyelitis
64:224
Pyrene
64:59, 147
in cigar, pipe, and cigarette smoke
73:178
Pyridine
64:54, 59
as suspected contributor to health haz-
ards of smoking
72.145
3-Pyridylacetic acid
64:72
gamma- (3-Pyridyl)-gamma-methylamino
butyric acid

64:71, 72
gamma- (3-Pyridyt)-gamma-oxo-butyric
acid
64:72
Pyrolysis

64:50, 53, 59, 62
Pyrrolidine, nitroso-
suspected carcinogenic properties in ciga-
rette smoke from
71:265
Pyruvic acid
64:53

Quassia
64:354

Quinine
64:354

Quinoline
64:54

Rabbits

atherogenic effects of carbon monoxide
and hypoxia
71:64

atherogenic effects of nicotine
71:120-122

blood lipids in, smoking and nicotine
effects on
71:127

cardiovascular function in, smoking and
nicotine effects
71:108, 109

cholesterol fed, carbon monoxide effects
on
71:65-66

ciliary function in, cigarette smoke ef-
fect on
71:221-222

ciliastasis in
64:268

coronary blood flow in
64:318
leukoplakia in
64:233
neoplasm induction in
64:143, 146, 202, 203
offspring, nicotine and smoke effects on
birth weight
71:407
offspring, smoking effects on stillbirth
and mortality
71:411
pregnant, tritium-labeled nicotine effects
in
71:413
pulmonary changes in cigarette smoking
71:159
pulmonary clearance in, cigarette smoke
effect on
71:164, 170, 171
pulmonary damage in
64:266
skin painting, smoke condensate effects
on
71:267, 338
smoke deposition in
64:265
Race
64:224, 363, 364
asa factor in coronary heart disease
73:4, 5,23
as a factor in perinatal mortality in
smoking vs. nonsmoking mothers
73:129-132
asa factor in stillbirth rates
73:124, 125
Radiation exposure
smoking and, as cause of respiratory
cancers
73:72
smoking and, in uranium miners
72:64, 65
Radioactive carbon
64:166
Radioactive cerium
64:166
Radioactive particles
in tobacco leaf, tobacco smoke, and
smokers” lungs
73:72
Radioactive substances
epidermoid neoplasms from

blood lipids in, nicotine and smoke
effects
71:128

carcinoma induction in

64165
ciliary function in, cigarette smoke on

71:221, 222

clearance mechanisms in
64:269

epidermoid lung neoplasm induction in
64:66

hepatoma induction in
64:145

LDsg nicotine determination in female
4-412

lung neoplasms, from intrabronchial im-
planting of chromium compounds
71:258

lung neoplasms, from nickel carbonyl
and dust inhalation
71:256

lungs, cigarette smoke effects on sur-
factant activity
71:172, 225

mucous cell increase in
64:269

neoplasm induction in
64:143

offspring, nicotine and smoke effects on
birth weight
71:407

pregnant, aromatic compound stimula-
tion of placental BP-hydroxylase ac-
tivity
71:414

pregnant, fetal wastage and neonatal
death in nicotine and smoking
71:411

pulmonary carcinoma induction follow-
ing asbestos dust inhalation
71:257

pulmonary changes from chronic nitro-
gen dioxide inhalation
71:161, 220

pulmonary damage in
64:269

respiratory tract, cigarette smoke inhala-
tion effects
71:268, 349, 353

sarcoma induction in

64:166, 230 64:266
as tracers skin painting, smoke condensates effect
64:265 71:267, 340
Radioactivity tobacco allergy in
64:145, 166, 193, 230 64:319
Radionuclides trachea, cigarette smoke effects on
64:193 71:343
Radium tracheal ligation, cigarette smoke and
64.145 papain effects on
Radon 71:163
inhalation tracheobronchial tree, cigarette smoke
64:145 effects on
Rats Readi 71 oes. 346-349
. : eading ability
alveolar lining changes in in children of smoking mothers
64:269, 270 71:407
atherosclerosis in, nicotine induced Rectal neoplasms
64:319; 74:120, 121 64:103
Registrar General of England and Wales
64:134
Relative risk ratios
amount smoked in
64:161
Cornfield method in
64:160
measure of
64:183
Religion
64:244
cure of tobacco habit
64:354
in prospective studies
64:99, 101
and smoking habit
67:54, 97
smoking prevalence by
64:364
Reserpine
nicotine cardiac stimulation blockage by
71:57
Residues
64:145
Resorcinol
64:54
Respiration
effect of nicotine, clinical and experi-
mental studies
67:26
trate
64:266
Respiratory function tests
64:289-293, 297
body height effect on
64:290
effect of smoking
72:45

in ex-smokers
67:100

smokers
71:146-147, 206-214

smokers vs. nonsmokers by sex
67:99

smokers vs. nonsmokers, twins
67:103

of smokers with mild bronchitis
69:39

by smoking history
67:100

using radioactive xenon
69:39

and young smokers
67:100-101

see also Pulmonary function, Respira-
tory system

Respiratory symptoms

68:69, 70.71

effect of air pollution and smoking
74:90, 91

effect of air pollution exposure levels in
telephone workers
75:67

effect of asbestos exposure in smokers
vs. nonsmokers
73:4)

effect of cigarette smoke
68:73, 74

202

pipe/cigar smokers and cigarette smokers

vs. nonsmokers
* 72:3, 40

prevalence in cement and rubber indus-
try workers, smokers vs. nonsmokers
74:95, 96

prevalence in children of parental smok-
ers
75:102, 103

prevalence in Duisburg, Germany, by age
and cigarette consumption
73:39

prevalence in ex-smokers
73:39

prevalence in pipe and cigar smokers
73:217, 220, 221

prevalence in smokers vs. nonsmokers
73:55

prevalence in smokers vs. nonsmokers in
Bordeaux, France
73:36

in school children
67:69, 70, 71

in smokers vs. nonsmokers
68:66, 67, 71; 75:62, 63

in smokers vs. nonsmokers by amount
smoked
73:37

summary of previous findings
75:5

summary of previous findings on rela-
tionship to passive smoking
75:88

summary of recent findings
75:78

in women
64:286

Respiratory system

acute effect of cigarette smoke on hu-
man pulmonary function
71:163, 166-169

animal, cigarette smoke instillation or
implantation effects on
71:268, 346-348

animal, effect of cigarette smoke inhala-
tion on
71:268-269, 349-353

defense mechanisms in
64:267, 268

effect of cigarette and cigar smoke on
bronchial reactivity
7£:164

effect of cigarette smoke on human
ciliary function
71:165, 221-224

effect of cigarette smoke on human
pulmonary clearance
71:164, 170

effect of smoking on
67:14]

glossary of terms used in testing
71:215

histological changes in smokers
64:270-274; 71:154-157

improvements in function following
smoking cessation
74:148, 149
irritation, prevalence in rubber industry
workers, smokers vs. nonsmokers
74:96

pathological changes in cigarette smokers
FLATS

postoperative complication in, of smok-
ers vs. nonsmokers
71:174-176, 230

pulmonary alveolar phagocytosis in
smokers vs. nonsmokers
71:165

pulmonary infarction in dogs inhaling
cigarette smoke
71:271

surface tension of, effect of cigarette
smoke on
71:172, 225

surfactant activity of, in smokers vs.
nonsmokers
71:172, 225

surfactants in, definition
71:172

see also Bronchi; Lungs

Respiratory tract diseases

64: 263-302

by amount smoked
67:97

chronic, definition
64:288

chronic, epidemiology
64:297, 298

cigarette smoking and
64:276

clinical evidence of
64:294

definition of
64:289

epidemiology of
64:297, 298

etiology of
64:302

infections, in emphysema development
67:111

infections, prevalence in smokers
71:10, 176

infections, smoking and
67:29; 71:172, 226-229; 72:3, 38

non-influenzal, in smokers vs. nonsmok-
ers
72:48

pathological and cytological changes in,
of smokers vs. nonsmokers
71:258-263

role of constitutional factors in
67:102-104

tole of heredity factors in
67:102-104

tural vs. urban dwellers
67:97

smokers vs. nonsmokers, by age
67:100

smokers vs. nonsmokers, by occupation
67:97

by smoking characteristics
67:97-98

by smoking classification
67:97-98

in smoking-discordant twin pairs
67:102-104

twin studies
67:102-104

ventilatory function in, smokers vs. non-
smokers
71:175

see also Lung diseases

Respiratory tract neoplasms

carcinogenesis induction in animals
74:46, 47

by country, in females
64:131

experimental induction of
69:63-64

mortality rates
67:147

mortality trends in
64:136

and smoking
67:10

and smoking classification
67.147

see also Lung neoplasms

Respondents
age-adjusted death rates in
64:114
mortality ratios in
64:116

Restricted activity days
by age, sex, and smoking history
67:19-21
definition of
67:19
Reticulosarcoma
and cigarette smoke
67:148
and tobacco tars
67:148
Retinal sensitivity
to tobacco
64:341
Retinoblastoma
64:191
Retrospective studies
64:27, 28-31, 150-157, 160, 161, 198,
199
association of diseases in
64:160, 161
control groups in
64:181
definition of
64:27
inhalation patterns in
64:159
laryngeal neoplasms
64:233, 234
lung neoplasms, and smoking, methods
71:323-328
lung neoplasms, duration of smoking in
64:158
maternal smoking
64:343
methods
64:152, 153, 154, 198, 199, 200
mortality studies
64:150

203
peptic ulcer
64:337
reliability of
64:180
risk ratios in
64.160, 161
smoking characteristics in
64:156
Reverse smoking
64:203, 204
effect on oral mucosa
72:6, 69, 70
heat effects in
64:204
leukoplakia and
73:76
nicotine stomatitis and
72:6. 69, 70
oral neoplasms and
73:76
Rhesus monkeys
64:166
Rheumatic heart disease
mortality from
64:103, 325
Rhinitis
64:275
Rhodesia
methods used in retrospective studies of
smoking in relation to lung neo-
plasms
71.328
Risk factors
in coronary heart disease
72:16-18
Risk ratios
calculation of
64:183, 230
on cessation of smoking, in lung neo-
plasms
64:187, 188
consistency of
64:182, 183
by lifetime cigarette consumption
64:161
in lung neoplasms
64:187, 188
RNA
binding of polycyclic hydrocarbons to
73:86, 87
synthesis, effect of cigarette smoke on
69:62, 63
Rodents
carcinogenesis tests in
64:142
ozone effect on
64:142
Roswell Park Memorial Institute
64:174, 219
Rubber
carcinogenic activity of
64:147
Rubidium-84
tracing capillary flow in coronary blood
flow
71:59
Rum
64:62

204

Running
effect of smoking
73:243, 244
Rural areas
64:99
lung neoplasm incidence in, in Switzer
land
71:244
relationships of lung neoplasm to smok.
ing, air pollution, and
714:252-255
smokers in
64:99, 364
Rural populations
lung neoplasms in, suspected etiology o;
increased .
71:276
Rural vs. urban populations
bladder neoplasm prevalence
64:225
mortality rates
67:11
smoking and
67:97
Russia
atherogenic effects of nicotine on rabbits

in
71:120
atherosclerosis autopsy studies in
71:54
cigarette tar effects on rat  tracheo-
bronchial tree in
71:348
gastric neoplasms, in Russian-born
64:135
gastric neoplasms in Russian Jews
64:135
Rutin
structural formula of
64:54

Saliva
64:203
interference in action of carcinogens on
oral cavity
74:288
Salivary gland neoplasms
64:134
see also Mouth neoplasms; Oral neo-
plasms
Salivary glands
64:271
Sample selection
bias resulting from
64:180, 181
Sarcomas
anaplastic, tar induction of
64:223
classification of
64:174
formation following animal skin painting
with smoke condensates
71:338, 340
induction in rats by cigarette smoke
injection
71:346-347
induction of
64:144, 176
subcutaneous
64:143
Saslow Psychosomatic Screening Inventory
64:367
Saturated fats
64:322
Scholastic achievement
64:370, 372
School children
smoking and respiratory systems in
68:69, 70, 71
School grade level
smoking prevalence by
64:361, 362
Scotland
Tespiratory symptoms in miners of
64:288, 298
Scotoma
64:341
Scottish Home and Health Department
Standing Medical Advisory Committee
64:304
Scrotal neoplasms
64:147
Secondary infections
64:272
Sedation
smoking effect as
64:350
Sedatives
withdrawal treatment with
64:352
Selection bias
in health studies
64:180, 181
Selenium
carcinogenicity
67:128
in cigarette smoke
67:128
potential respiratory carcinogenesis
68:92
Senile keratosis
64:203 ’
Sensory drives
64:354
Seven Countries Study
epidemiologic study of smoking and
CHD
74:6
Seventh Day Adventists
coronary disease incidence in
64:322
laryngeal neoplasm prevalence in
64:209
lung neoplasm prevalence in
64:155
Sex
acute diseases in smokers and non-
smokers by
67:22
ages of cigarette smokers by
71:6
bed days by, and smoking history
67:20-21

bladder neoplasm mortality rates in
United States by
67:154

bronchitis, prevalence rates by
67:96

cerebrovascular disease mortality rates,
by age and
67:66

cerebrovascular disease mortality rates,
by smoking classification and
67:66

cerebrovascular disease mortality ratios,
by age and
67:66

cerebrovascular disease mortality ratios,
by smoking classification and
67:66

chronic diseases in smokers and non-
smokers by
67:22

coronary disease incidence rates and
smoking history by
69:21-22, 24

coronary disease mortality rates, by
67:25, 47, 50, 56; 69:13, 17

coronary disease mortality ratios, by
67:49; 69:13

cough and smoking habit by
67:98

effect of, in alpha-l-antitrypsin defi-
ciency emphysema
71:151

effect of, in lung neoplasms and tobacco
use
71:244, 329-333

effect of, in mortality in cigarette smok-
ers
71:276

sffect of, on laryngeal neoplasm inci-
dence development
71:277

emphysema mortality rates
67:91

esophageal neoplasm mortality rates
67:150

laryngeal neoplasm mortality rates
67:148

liver cirrhosis mortality rates, by
67:184

liver cisrhosis mortality ratios, by
67:184

lung neoplasm development by
Fhe1l

lung neoplasm mortality rates by
67:34, 134, 140; 71:252

lung neoplasm mortality ratios by
67:33, 134, 140

mortality by, and smoking history
67:23

mortality rates of cigarette smokers by
71:3

pancreatic neoplasm mortality rates, by
67:158

pancreatic neoplasm mortality ratios, by
67:158

peptic ulcer morbidity rates, by
67:182

205
ratio, effect of maternal smoking on
73:135, 136
ratio, in lung neoplasm mortality
74:40, 46
ratio, in lung neoplasm mortality in
Norway and Finland
71:245-246
restricted activity days by, and smoking
history
67:20-21
and smoking habit
67:4
stroke mortality rates by
69:13, 17
stroke mortality ratios by
69:13
tumor prevalence among smokers by
69:56
Sex differentials
64:133
in jung cancer
64:185, 186
in smoking prevalence
64:363
Sheep
pregnant, nicotine injection and smoke
inhalation effects on
71:444
Sheet metal workers
neoplasm risks in
64:134
Sheidon somatotyping method
64:383
Shoe repairers
bladder neoplasms in
64:222, 224
Side stream smoke
see Smoke streams
Silica
64:271
Silver nitrate
64:354
Single-breath tests
smokers vs. nonsmokers
73:5)
Sinusitis
64:275
in smokers and nonsmokers
67:22
Sitosterols
64:52
Skin
benzo(a)pyrene effect on
64:146
effect of tobacco extracts
72:105-107
reactions of, tobacco induced
64:319
tests of
64:143
tobacco antigens and
72:7, 104. 105
Skin neoplasms
64:143, 144
carcinogenic induction of
64:229
carcinoma in situ
64.172

206

experimentally induced by cigarette
smoke
67:144
mineral oil induction of
64:229
ultraviolet radiation induction of
64:144
Skin testing
for reactions to tobacco
72:105-107
Smog
64:295
Smoke, cigar
benzo(a)pyrene content of
64:58
chemical constituents in
73:177-179
cilioto xicity
73:218
effect of curing methods
73:218, 219
effect of pH on inhalation of
73.183
little, pH, compared to cigarette and
cigar smoke
73:224, 228
tumorigenic activity in laboratory ani-
mals
73:210-214
see also Smoke, tobacco

Smoke, cigarette

64:50-62

alteration of coronary blood flow
71:58

aromatic hydrocarbons in
67 127-128

benzo(a)pyrene content of
64:58

and bronchoconstriction in animals

68:72

bronchogenic carcinoma induction in
dogs inhaling
71:269, 270
butylmethylnitrosamine in
67:128
cadmium levels in
FA:1S4
carbon monoxide levels in
71:59
carcinogenic content of
75:48
carcinogenicity
67:15, 34, 144; 72:65, 66
carcinogenicity of components to ani-
mals
71:12, 277
cause of death in dogs from inhalation
74:271
chemical constituents in, compared to
pipe/cigar smoke
73:177, 178
ciliary activity
67:107-108, 140; 68:71, 72; 69:42
ciliary depression by
64:61, 265, 267, 268, 270
ciliary inhibition
71:267
ciliatoxic effect, mechanism of action
67:107

cocarcinogenic effect on respiratory
tract in rabbits
72:67

cocarcinogens in
64:144

composition of
64:50-60

and decrease in pulmonary macrophages,
in guinea pigs
75:77, 78

deposition patterns of
64:265

effect of curing methods
73:218, 219

effect of nickel on induction of lung aryl
hydroxylase
71:256-257

effect on adenosine triphosphatase
67:108

effect on alveolar macrophages
69:42

effect on apexcardiogram
72:21

effect on bacterial retention in hamsters
73:54

effect on breathing in guinea pigs
72:46

effect on bronchial epithelium
67:107, 144-145

effect on bronchial epithelium in dogs
69:40; 73:49

effect on bronchial mucosa
67:30, 104-107, 144-145

effect on DNA and RNA synthesis
69:62-63

effect on Dunaliella bioculata
69:42

effect on influenza virus in mice
68:70, 71

effect on lung AHH-activity
74:50, 51

effect on lungs
67:106

effect on lung surface tension in dogs
72:48

effect on nasociliary mucosa in donkeys
72:47

effect on oxidative enzymes
67:108

effect on phagocytosis in laboratory
animals
73:53, 54

effect on phagocytosis in rabbits
72:109

effect on pulmonary clearance

* 73:51-53

effect on pulmonary macrophage func-
tion, in rabbits ’
74:104

effect on pulmonary physiology, in ani-
mals
74:102

effect on pulmonary surfactant
67:110; 69:42

effect on rat and mouse fetus, site of
action
73:121

effect on respiratory tract, in rats
74:104

effect on tissue cultures
69:42; 71:267, 343-345

effect on tracheobronchial clearance, in
donkeys
75:78

effect on vascular resistance
67:61

effect on ventricular fibrillation thresh-
old in dogs
73:13, 14

endrin in
64:62

epidermoid neoplasms from
64:144

experimental induction of bronchial neo-
plasms
67:144-145

experimental induction of lung neo-
plasms by
67:144-145

experimental induction of tracheal neo-
plasms by
67:144-145

experimental studies in dogs
73:13, 14

experimental studies in laboratory ani-
mals
72:21

exposure magnitude to
64:296, 297, 298

extract, effect on pulmonary macro-
phages, in sheep lungs
74:105

formaldehyde gas in
64:266

gaseous deposition of
64:265

harmful constituents of
72:8, 141-146

heterocyclic nitrogen compounds in
67:127

high tar, risks in
71:11

inhalation by dogs, lung neoplasm de-
velopment
71:268-269, 272-274

inhalation effects on animal respiratory
tract
71:268-269, 349, 353

inhalation effects on hamster larynx
71:281, 284

inhalation methods
69:62

inhalation of, and coronary disease
67:54

inhalation of, effect on blood pressure
67:54

and leukemia
67:148

listing of identified or suspected tumori-
genic agents
71:264-267

and lymphosarcoma
67:148

metallic constituents of
64:55

207
naphthylamine content, and bladder
carcinogenesis
68:105
2-naphthy lamine identified in
71:265
negative ions in
64:268
neoplastic changes in animals inhaling
71:238-239
nickel carbonyl in
69:62
nickel in
64:167
nicotine content in
67:34
nitrosamines in
67:127-128
nonvolatile condensates of
64:50
phenols in
64:54, 267; 67:127-128
polonium-210 in
67:128
positive ions in
64:268
pyrolysis reactions in
64:50
radioactivity of
64:145
reduction of adverse effects in animals
by phenylmethyloxadiazole (PMO)
73:49, 53
and reticulosarcoma
67:148
selenium in
67:128
skin neoplasm induction by
67:144
and sulphur dioxide, effect on glands in
laboratory animals
73:49
suppression of immunoglobulin re-
sponse, in cell cultures
75:77
TDE content of
64:62
tobacco amblyopia relationship to
cyanide metabolism in
71:435-436
see also Smoke, tobacco

Smoke condensates
see Tars, cigarettes; Tars, tobacco
Smoke, pipe
benzo(a)pyrene in
64:58
carcinogenicity
67:147-148
chemical constituents in
73:177, 178
ciliotoxicity of
73:218
effect of pH on inhalation of
73:183

mouth neoplasms experimentally in-

duced by
67:147-148

208

tumorigenic activity in laboratory anj-
mals
73:210-214

see also Smoke, tobacco

Smokers

airway resistance in
64:292, 293
alcoho! consumption by
64:385
allergic reactions in
64:319
angina pectoris in
64:325
arteriosclerosis in
69:26
behavioral variables in
64:112
bladder neoplasms in
64:131, 132, 219, 222, 223, 224,
225
body weight of
64:326, 384, 385
breathlessness in
64:27, 286, 287
bronchitis prevalence in
64:289
cholesterol levels in
64:326, 385
chronic cough in
64:27, 280, 281, 282, 283, 299, 302
ciliary effects in
64:27, 34, 35, 61, 168, 169, 170,
172, 173, 267
constitutional differences in
64:112, 326
coronary disease in
64:322-325
current, mortality rates in
64:95
current, mortality ratios in
64:93
current, neoplasm risk in
64:158
current, pulmonary fibrosis in
64:274
epithelial changes in
64:165, 167-173, 189, 263-275
forced expiratory flow rate in
64:290, 291
heavy, risk ratios in
64:161, 213, 232
heavy, urban-rural mortality in
64:186, 194
hemoglobin levels in
64:319
hereditary factors in
64:385
1.Q. measurements in
64:370
laryngeal neoplasms in
64.131, 132, 133, 209, 211
lung function in
64:27
lung neoplasms in
64.118, 131, 132, 133, 149-196, 232
morphologic constitution of
64:383-387
mortality rates in, from gastric neo-
plasms
64:132
mortality rates in
64:99, 117, 118, 162, 209, 322, 323
mortality rates in, from laryngeal neo-
plasms

64:211
nonrespondents among

64:114

occupational asbestos exposure and car-

cinogenesis
67:35
occupational uranium exposure and car-
cinogenesis
67:35
oral neoplasnis in
64:131, 132, 133, 202, 204
as percentage of population

64:114
personality

64:39, 326, 365, 368
physical characteristics of
64:326
population of
64:45
psychological factors in
64:112
reduction of life expectancy
69:3
respiratory conditions in
64:289
risk ratios in
64:160, 161, 222, 223, 232
risk ratios in, in bladder neoplasms
64:222
risk ratios in, in lung neoplasms
64:161
serum cholesterol in
64:326
smoking patterns in
64:177, 178, 179
somatotype classification of
64 :383, 385
sputum analysis of
6939-40, 57-58
sputum production in
64:27, 283-286
urban-rural differences in
64:99, 101
U.S. incidence of
64:178, 179
see also Passive smokers; Smokers, cigar;
Smokers, cigar and pipe; Smokers,
cigarette; Smokers, pipe

Smokers, cigar

amblyopia in
64:341, 342

atypical nuclei in male esophageal epi-
thelium
71:379

bladder neoplasm mortality in
64:219, 222, 223, 224, 235

bladder neoplasms in
71::293-294

body weight of
64:384

carboxyhemoglobin levels in
72:21-23

cell rows and atypical cells in vocal cords

of

71:280, 359-360
coal miners as

64:299
COPD morbidity in

71:146, 197-198, 201-202, 204-205
coronary deaths in

64:323 i.
decreased neoplasm risk in

64:37
duodenal ulcers in
64:37
duration of smoking in
64:36
effects of smoke on bronchial reactivity
71:164
epithelial lesions in
64:170, 173, 189
esophageal neoplasm mortality ratios in
71:290
esophageal neoplasms in
64.213, 217, 218, 234
fibrosis in
64:291
forced expiratory volume in
64:291
gastric ulcers in
64:37
gingival neoplasms in
64:202
inhalation practices in
64:36, 92, 188
kidney neoplasms in
71:294-295
lack of risk in CVD
71:67
laryngeal neoplasm induction in
71:12, 354-357
laryngeal neoplasms in
64:37, 192, 205, 209, 211, 212;
71:281
lip neoplasms in
64:197, 202, 230, 240
lung neoplasms in
64:37, 150, 155, 159, 163, 170, 173,
175, 188, 1
lung neoplasms, incidence in rural Swit-
zerland
71:244
lung neoplasms, mortality in
71:11, 240-243
morphological constitution of
64:385, 386
mortality rates in
64:30, 36
mortality ratios from COPD in
74:142-143, 145
mortality ratios from pancreatic neo-
plasms in
71:298
mortality ratios from peptic ulcer in
71:424
mortality ratios in
64:86, 87, 107, 112, 163
myocardial arteriole wall thickness in
72:19
myocardial infarction in
71:32, 38-39

209
oral neoplasms in
64:37, 189, 192, 202
pharyngeal neoplasms in

64:202 :
relationship of neoplasms of oral cavity

with

71:12, 361-365. 367-371

relationship to infectious respiratory dis-
eases

71:227
relative risk in esophageal neoplasm de-

velopment

72:68
relative risk in laryngeal neoplasm de-

velopment

72:67
relative risk in tung neoplasms develop-

ment
71:276; 73:67, 68
respiratory diseases in
64:274, 289
risk of CHD
risk of COPD
71:10
risk ratios in
64:31, 37, 231, 233
tongue neoplasms in
64:189, 202
U:S. trends in number of
64:26, 45
see also Smokers, cigar and pipe
Smokers, cigar and pipe
causes of death in
64:107
expected death rate in
64:107
gastric neoplasm mortality in
64:288
gastric ulcer in
64:113
incidence of atypical nuclei in larynx
69:59
incidence of coronary heart disease
69:21, 24
incidence of gingivitis
69:86
incidence of stomatitis nicotina
69:87
liver cirrhosis in
64:113
lung neoplasms in
64:113
mortality ratios in
64:107
observed deaths in
64:107
oral neoplasms in
64:113
thickness of vocal cords
69:60
see also Smokers, cigar; Smokers, pipe
Smokers, cigarette
air pollution effects on
64:194, 195, 276, 295-298, 301, 302
arterial occlusions in
71:73
atherosclerosis in aortic and coronary
arteries
71:52-56

210

atypical nuclei in male esophageal epi-
thelium
71:379-380

bladder neoplasms in
71:293-295

bladder neoplasms mortality in
64:32, 37, 219, 234

bronchitis in
64:102, 103, 301

cell rows and atypical cells in vocal cords
°
71:280, 359-360

cessation of smoking, effects on COPD
morbidity
74:146, 197, 199, 203-204

cessation of smoking, lowers lung neo-
plasm rate in
Till

changes in ventilatory function and pul
monary histology
T1:175

comparative risk for lung neoplasms
71:237

coronary diseases in
64:322

coronary diseases in, AHA pooling pro-
ject
71:28, 30, 39

coronary diseases risk by
71:8, 23-25

coronary mortality in
64:324

decline in, British physicians
71:48

development of altered ventilatory func-
tion in young
71:10

development of esophageal neoplasms
71:12, 293

development of laryngeal neoplasms
71:12

development of oral neoplasms
71:12

development of second primary oral
neoplasms in continuing
71:287

effect of filters on emphysema develop-
ment
71:162

effect on cardiovascular system
71:56-58, 107-118

effects of inhalation on bronchial reac-
tivity
74:164

effects on uterine activity in gravidic
women
71:408

emphysema in
64:277-294

emphysema mortality in
64:102, 103

epithelial changes in
64:170, 173, 189

esophageal neoplasms in
64:102, 103, 188, 212, 213

esophageal neoplasms, mortality ratios in
71:290-29 1
excess mortality in
64:108
expected mortality in
64:108
forced expiratory volume in
64:291
histology and smoking relationship of
tung neoplasms in
71:246-249
hypertension in
64:325
infant birth weight
71:397-399
inhalation effects on human pulmonary
function
71:163, 166-169
inhalation patterns in
64:159
kidney neoplasms in
64:102; 71:294-196
laryngeal neoplasm induction in
71:354-357
laryngeal neoplasm mortality in
64:32, 188, 205, 212, 234
lung neoplasms, etiology
71:239
lung neoplasms in
64:31, 37, 149-196, 229-233
lung neoplasms, mortality in
71:240-243-244
mortality from cerebrovascular disease
71:67-70
mortality from neoplasms, by site
64:149
mortality rates affected by sex
71:3
mortality rates in
64:35, 102, 106, 108, 109, 110, 115,
162, 194, 3
mortality ratios
64:90, 93, 102, 103
mortality ratios from COPD
71:142-144
mortality ratios from pancreatic neo-
plasms in
71:298
mortality ratios from peptic ulcers in
71:424
nonrespondents, mortality in
64:115
oral neoplasms, mortality in
64:102, 103, 131, 132, 196-205, 233
otolaryngological symptoms in
64:275
peptic ulcer
71:427
Peptic ulcer in, smoke effects on antacid
therapy
71:423
percent of population as
64:26
percent of women of childbearing age
71:389
pharyngeal neoplasms in
64:103, 202
possible processes for increased mor-
tality in
71:4-5

postoperative pulmonary complications
in
71:174, 230

pulmonary surfactant activity in
71:172, 225

relationship in coronary and lower limb
arteriosclerosis
71:72

relationship of asbestos in lung neoplasm
mortality
71:257

Telationship to infectious Tespiratory dis-
eases
71:172, 226-229

relationship to laryngeal neoplasm devel-
opment in
71:281

relationship to lip or oral cavity neo-
plasms
71:361-370

relationship to lung neoplasms
71:275, 276

relationship with bladder neoplasms in
men
71:299

relationship with dust on COPD develop-
ment
74:153

tisk gradients in, from bladder neoplasms
64:223

risk gradients in, from esophageal neo-
plasms
64:234

risk gradients in, from laryngeal neo-
plasms
64:37, 211, 234

risk gradients in, from lung neoplasms
6431, 37, 184, 185, 230

risk of COPD in
71:140

stomach ulcers in
64:103

survey by age and sex
71:6

survey of U.S.
7TL:6

see also Smokers

Smokers, pipe

amblyopia in
64:39, 341, 342
amount smoked, in mortality ratios
64:86, 87
atypical muclei in male esophageal epi-
thelium
71:379
bladder neoplasms in
64:219, 222, 223, 235; 71:293-294
body weight in
64:384
carboxyhemoglobin levels in
72:21
cell rows and atypical cells in vocal cords
of
71:280, 359-360
COPD morbidity in
71:146, 197-198, 201-205
coronary mortality in
64:323

211
development of chronic bronchopul-
monary disease
71:10
development of esophageal neoplasms
71:13, 293
development of lung neoplasms
7WsAl
development of oral neoplasms
71:12
duodenal ulcers in
64:37
epithelial changes in
64:170, 173, 189
esophageal neoplasms in
64:37, 212, 217, 218, 234
esophageal neoplasms, mortality ratios
71:290
extroversion in
64:366
fibrosis in
64:274
forced expiratory volume in
64:291
gastric ulcers in
64:37, 337
gingival neoplasms in
64:202
inhalation by
64:92, 188
kidney neoplasms in
71:294-295
lack of risk in CVD
71:67
lar yngeal neoplasms in
64:37, 192, 209, 211, 212
laryngeal neoplasms, induction
71:12, 354-357
lip neoplasms in
64:32, 37, 188, 197, 204
lung neoplasms in
64:31, 37, 196, 233
lung neoplasms, incidence in Norway
74:244
lung neoplasms, incidence in rural Swit-
-zerland
71:244
lung neoplasms, mortality in
71:324-327
morphology of
64:385, 386
mortality rates
64:30, 36, 74, 194, 202, 222, 223
mortality rates from COPD
71:142-143, 145
mortality ratios
64:90, 91, 162
mortality ratios from pancreatic neo-
plasms
74.298
mortality ratios from peptic ulcer
71:424
myocardial arteriole wall thickness in
72:19
myocardial infarction in
71:32, 38-39
neoplasm location in
64:197

212

oral changes in
64:302

oral neoplasms and
64:37, 150, 189, 192, 202; 72:67

peptic ulcer in
71:427

pharyngeal neoplasms in
64:202

psychosomatic disorders in
64:367

relationship to infectious respiratory dis.
eases
71:227

relationship to laryngeal neoplasm devel.
opment
74:281

relationship to lip neoplasms
71:289

relationship to oral cavity neoplasms
71:361-364, 367

relative risk in esophageal neoplasm de-
velopment
72:68

relative risk in laryngeal neoplasm devel.
opment
71:67

relative risk in lung neoplasm devetop-
ment
71:276; 73:67, 68

respiratory diseases in
64:289, 299

risk of CHD
71:8

risk ratios in, from neoplasms
64:31, 37, 196, 209, 211, 231, 233,
235

tongue neoplasms
64:188, 189, 202

see also Smokers, cigar and pipe

Smokers vs. ex-smokers

atypical nuclei in larynx
69:59

coronary disease mortality rates, for men
by age
67:49

coronary disease mortality rates, for
men, by years stopped smoking
67:49; 69:15

coronary disease mortality rates, for
men, compared to nonsmokers
69:15

coronary disease mortality rates for men,
compared to nonsmokers
69:15

lung neoplasm mortality rates
67:34, 137, 139

morbidity rates
67:15

mortality rates
67:9, 15

peptic ulcer mortality rates by age
67:181

peptic ulcer mortality ratios by age
67:181

stroke mortality for men, compared to
nonsmokers
69:15
thickness of vocal cords
69:60

Smokers vs. nonsmokers

abortions, still births, and neonatal death
71:390, 405-406

acute diseases in
67:22

o-aminophenols in urine of
69:64

angina pectoris morbidity ratios
67:59

aortic aneurysm mortality
69:16

arteriosclerosis
67:22; 72:19

arteriosclerosis, mortality rates
67:26

attitudes
67:190-191

atypical nuclei in larynx
69:59

bladder neoplasms in
71:293-295, 381-384

bladder neoplasms, mortality rates, by
age
67:154, 155

blood cholesterol levels, twin studies
67:55

blood factors of mothers and infants
69:80

body constitution
67:99

breathlessness in
67:29, 286

bronchitis mortality rates
67:8, 29, 90-92

carboxyhemoglobin levels
67-100; 72;21-23

cardiopulmonary function, in young
male
67:100

cell rows and atypical cells in vocal cords
of
71:280, 359-360

cerebrovascular diseases
72:25

cerebrovascular diseases mortality rates
67:66; 71:67-70

cerebrovascular diseases mortality ratios
67:66

chronic diseases in
67:22

coronary disease incidence
69:18, 20-22

coronary disease incidence and behavior
type
69:24

coronary disease incidence rates, by age
67:54, 65

coronary disease morbidity ratios
67:59; 71:24

coronary disease morbidity ratios, and
blood pressure status
67:55

coronary disease morbidity ratios, and
lung function
67:56

coronary disease morbidity ratios, by age
67:54

coronary disease morbidity ratios, by
blood cholesterol levels
67:55

coronary disease morbidity ratios, by
personality characteristics
67:57

coronary disease morbidity tatios, by
sociocultural mobility status
67:57

coronary disease mortality
67:47; 71:21-22, 24, 26-29

coronary disease mortality, by age
67:50; 69:13

coronary disease mortality, by amount
smoked
67:51; 69:13

coronary disease mortality, by sex
67:50; 69:13; 71:28-31

coronary disease mortality, by smoking
history
67:51

coronary disease mortality, for men
67:27

coronary disease mortality, for women
67:28

coronary disease mortality, in Swedish
twins
TL:S1

coronary disease mortality ratios
67:8

coronary disease mortality ratios, by age
67:49, 52; 69:13

coronary disease mortality ratios, by
amount smoked
67:47-49; 69:13

coronary disease mortality ratios, by
blood pressure status
67:52

coronary disease mortality ratios, by sex
67:49; 69:13

cough in
67:29

Curschmann’s spirals in sputum of
69:39-40

development of COPD in
71:141, 145, 195-205

differences in emphysema types in
71.154, 156

digestive tract neoplasm mortality rates
67:147

emphysema mortality rates
67:8

emphysema mortality ratios
67:90-92

esophageal epithelial cells with atypical
nuclei in
71:292

esophageal neoplasm mortality rates, for
men by age
67:150

esophageal neoplasm mortality ratios
67:35, 150-151; 71:290-291

excretion of trytophan metabolites in

71:297 ;
frequency of esophageal neoplasms in
71:238

213
frequency of kidney neoplasms in
71:238

frequency of mouth and pharyngeal neo-
plasms in
71:238

frequency of urinary bladder neoplasms
in
71:238

group characteristics in lung neoplasms
and smoking in
71:240, 244, 329-333

3-hydroxyanthranilic acid urinary excre-
tion in
67:156

3-hydroxykynurenine urinary excretion
in
67:156

incidence of edentulism
69:87

incidence of gingivitis
69:86

incidence of periodontal disease
69-85-86

incidence of preeclampsia among preg-
nant women
69:79

laryngeal neoplasm mortality rates
67:148; 71:237-238

laryngeal neoplasm mortality ratios
67:35; 71:278-279

laryngeal neoplasms in, relationship to
tobacco use
71:354-357

lung fibrosis development in
71:161

lung neoplasm mortality in uranium
miners
71:256

lung neoplasm mortality rates
67:8, 34, 47

lung neoplasm mortality rates, by age
67:132-138, 140

lung neoplasm mortality rates, by sex
67.136, 140

jung neoplasm mortality rates, for men
by age
67:131-132, 134-135, 137-140

lung neoplasm mortality rates, for men
by amount smoked
67 :134-135, 137-140

lung neoplasm mortality rates, for men
by smoking characteristics
67:134-135, 139

lung neoplasm mortality rates, for men
by smoking history
67:134-135, 137-140

lung neoplasm mortality rates, for wom-

en
7:1:240-243

lung neoplasm mortality ratios, by age
67:134-140

lung neoplasm mortality ratios, by sex
67:136, 140

lung neoplasm mortality ratios, by smok-
ing classification
67:139

214

lung neoplasm mortality ratios, for men
by age
67:134-135, 137-140

lung neoplasm mortality ratios, for men
by amount smoked
67:134-135, 137-140

lung neoplasm mortality ratios, for men
by smoking characteristics
67:134-135

jung neoplasm mortality ratios, for men
by smoking history
67:134-135, 137, 139

lung neoplasm mortality ratios, for wom-

en
67:34, 136

lung neoplasm occurrence in asbestos
workers
67:143

lung neoplasm occurrence in uranium
workers
67:143

N-methylnicotinamide urinary excretion
67:156

morbidity rates, in United States
67:3,5

mortality rates
71:3

mortality rates, by age
67:79-10

mortality rates, by occupation
67:11

mortality rates, for Canadian pensioners
67:10

mortality rates, for men by age
67:12-13

mortality rates, for U.S. veterans by age
67:12-13

mortality rates, for women by age
67:12-13, 21

mortality ratios, by age and sex
67:12-13

mortality ratios, for U.S. veterans by age
67:12-13

mortality ratios from pancreatic neo-
plasms in
71:298

mortality ratios, in United States
67:8

mortality ratios of COPD in
71:142-144

mouth neoplasm mortality rates
67:146

mouth neoplasm mortality ratios
67:35, 146

mucous gland abnormalities in
74:97

myocardial infarction morbidity ratios
67:59

myocardial infarction morbidity ratios,
by physical activity levels
67:56

myocardial infarction relationships to
physical activity
71:44

oral diseases and
72:6
pancreatic neoplasm mortality rates, by
age
67:158-159

pancreatic neoplasm mortality rates, by
amount smoked
67:159

pancreatic neoplasm mortality rates, by
sex
67:158-159

pancreatic neoplasm mortality rates, by
smoking classification
67:159

paralysis agitans mortality rates
67:8

pathological and cytological changes in
respiratory tract of
71:258-263

peptic ulcer in, comelated amounts of
tobacco use
71:427-428

peptic ulcer morbidity rates, by sex
67:182

peptic ulcer mortality rates, for men, by
age
67:181

peptic ulcer mortality ratios, for men, by
age
67:181

pharyngeal neoplasm mortality rates
67:146

pharyngeal neoplasm mortality ratios
67:35, 146

postoperative hypoxemia in
71:174-230

postoperative pulmonary complications
in
71:174-175, 230

postural hypoxemia mechanism in
symptomatic
71:147

prevalence of neoplasms, by type of
tumor, sex and
69:56

pulmonary alveolar phagocytosis in
71:165

relation between CHD and serum choles-
terol level
71:43

relationship to infectious respiratory dis-
ease
71:172, 226-229

respiratory symptoms
72:40

respiratory symptoms by age
67:29, 100

respiratory symptoms by occupation
67:97

respiratory tract neoplasm mortality
tates
67:147

serum lipids in
71:41, 98-102

small airways abnormalities in
74:97, 98

stomach neoplasm mortality rates
67:157-158

stroke mortality, by age
69:13

stroke mortality, by amount smoked

69:13

stroke mortality, by sex
69:13

stroke mortality, compared to ex-
smokers
69:15

stroke mortality ratios, by age
69:13

stroke mortality ratios, by amount
smoked
69:13

stroke mortality ratios, by sex
69:13

surfactant activity in lungs of
71:172, 225

thickness of myocardial arteriole walls
72:19

thickness of vocal cords
69:60

tracheal neoplasm mortality rates
67.147

type of tung neoplasms in male and
female
71:250

urinary excretion of tryptophan metab-
olites
69:64

urinary tract neoplasm mortality rates,
by age
67:154

see also Smokers vs. nonsmokers, cigar;
Smokers vs. nonsmokers, pipe

Smokers vs. nonsmokers, cigar

esophageal neoplasm mortality ratios
67:35-36

laryngeal neoplasm mortality ratios
67:35

mortality rates
67:8

and mouth neoplasm mortality ratios
67:35

and pharyngeal neoplasm mortality
tatios
67:35

Smokers vs. nonsmokers, pipe

esophageal neoplasm mortality ratios
67:35

laryngeal neoplasm mortality ratios
67:35, 149

mortality rates
67:8

mortality rates for Canadian pensioners
67:10

mouth neoplasm mortality rates
67:35

pharyngeal neoplasm mortality ratios
67:35

Smoke streams

aluminum in
64:55. 61. 62
arsenic in
64:55
benzo(a) pyrene content
72:123
beryllium in
64:55
chromium in
64:55
CO levels in mainstream cigar smoke
75:90

constituents of tobacco smoke
75:88-98

definition of
64:50

effect on nonsmokers
72:122, 123

Guthion in
64:62

nickel in
64:55

potassium in
64:55

Sevin in
64:62

sodium in
64:55

summary of previous findings
75:87, 88

tar and nicotine content

72:123

Smoke, tobacco

64:26, 33, 34, 5062, 69-75,
142-146, 167, 168, 263-267
acenapthene in
64:55
air cured and tumorigenicity
68:91
as air pollutant
72:7, 121, 122
alkylbenzene in
64:55
allergic and irritative components, effect
on nonsmokers
72:2, 128, 129
antigenic properties
72:104
aromatic hydrocarbons in
64:55; 67:127; 69:61
arsenic in
64:55. 61
benz(a)anthracene in
67:127
benzene in
64:55
benzo(b)fluoranthene in
67:127
benzo(j)fluoranthene in
67:127
benzo(k)fluoranthene in
67:127
benzo(a)pyrene in
67:127
benzo(e)pyrene in
67:127
beryllium in
64:55
bladder carcinogens in
69:64
and bronchogenic carcinoma
67:129-130
carcinogenic heterocyclics in
64:54
carcinogenic hydrocarbons in
64:55
carcinogenicity
64:143, 145; 68:90. 91; 69:62

216

chromium as
64:55
chronic toxicity of
64:73
chrysene in
67:127
clearance mechanism for
64:267, 269
cocarcinogens in
69:61
composition of
64:50-62, 263, 264
constituents of
64:51
constituents of, and bladder neoplasm
carcinogenesis
67:156
constituents of, effect on bronchial mu-
cosa
67:144-145
constituents of, lung neoplasms induced
by
67:144
cyanide in, and vitamin B-12 deficiency,
in tobacco amblyopia ,
67:40
deposition of
64:263-267
dibenz(a,j)acridine in
67:127
effect during pregnancy in laboratory
animals
73:114, 115
effect of constituents on passive smokers
75 :88-98
effect on air pollution in aircraft
73:45
effect on bronchial epithelium
67:129
effect on macrophages
72:47
effect on mitochondrial function, in rat
liver
74:104
effect on nonsmokers, in aircraft
73:45
effect on stillbirth rate in laboratory
animals
73:125
and epidermoid carcinoma
67:129-130
exposure
64:272
filtration of, effect on bronchoconstric-
tor response in smokers
72:45
heterocyclic nitrogen compounds in
67:127
indeno(1,2,3-c,d) pyrene in
67:127
irritants in
72:109, 110
leukoplakia from
64:233
liver effect of
64:342
and lung neoplasms in animals
68:93
nicotine content of
68:91
nicotine-N-oxides in
69:62
Nitrates in
67:128
N-nitrosamines in
67:127
organ toxicity of
64:73
papilloma formation in tracheobronchial
mucosa
67:129-130
pH of, effect of leaf constituents
73:224
polonium-210 content, and carcino-
genesis
68:92
polycyclic aromatic compounds
64:26, 144
potassium
64:55
potential source of N-nitrosamines
68:91
pyrolytic temperature effect in
64:50
retention of
64263-267
summary of previous findings on rela-
tionship to passive smoking
75:87, 88
summary of recent findings
75:108
systemic toxicity of
64:73
tar content of
68:91
in tobacco amblyopia etiology
67:40
toluene
64:55
toxicity of
64:73
tumorigenic activity
68:90, 91; 73:210-214
tumor-promoting agents in, and neo-
plasm pathogenesis
67:35
and vitamin B deficiency in tobacco
amblyopia
67:40
see also Smoke, cigar; Smoke, cigarette;
Smoke, pipe

Smoking

and absenteeism
67:19

and adenocarcinoma
67:140-143

and air pollution
64:295-298

and air pollution, effect on pulmonary
function and COPD prevalence
74:82, 83

and alcohol consumption, in esophageal
neoplasm formation
67:152

and alveolar bone loss
69:85-87

and alveolar cell carcinoma
67:142

and angina pectoris
69:18

and anoxia

67:183
and aortic aneurysm

67:183
and arrhythmia
69:4
and arteriosclerosis
67:28; 69:4, 5
and asbestos exposure, as factors in lung
neoplasm development
74:41 43
association with other risk factors in
CHD
68:21; 74:6, 7,17
and asthma
67:29
and atherogenesis
67:66
and basal cell hyperplasia
67:30
and bed days
67: 20-22
and behavior type
69:20, 24
and bladder neoplasms
67:33, 36; 69:60; 72:68, 72-74
and bladder neoplasms in men
67:153
and bronchitis
69:4; 74:79
and bronchitis morbidity
67:6, 94,99
and bronchitis mortality
67:3, 29, 90-92
in bronchitis pathogenesis
67:29-31, 96, 108; 69:37-40
and carboxyhemoglobin levels in smok-
ers
67:183
and cardiovascular diseases
67:3, 25-28, 47-69; 69:3-5
as cause of fires
67:187-188
as cause of traffic accidents
67:187-188
and cerebrovascular diseases
67:27, 66
and cerebrovascular diseases by age
67:68
and cerebrovascular thrombosis
67:27, 68
cigarette sales and CHD mortality rate
68:16
and coffee drinking, in myocardial in-
farction etiology
74:8
and COPD etiology
73:35, 36
and coronary disease
69:3-5, 20
and coronary disease, age as factor
74:6
in coronary disease etiology
67:26, 54

217
and coronary disease incidence rates
67:54; 68:27

and coronary disease, in women
74:9,10

and coronary disease mortality
67:10. 26-67

in coronary disease patients
67:26, 28

in coronary disease patients, effect on
blood pressure
67:61

in coronary disease patients, effect on
heart function
67:61

in coronary disease patients, etfect on
heart rate
67:61

and coronary thrombosis mortality for
men
67:26

and diet
67:66

and digestive tract neoplasms mortality
67:30

duration of,
64:29, 31,37, 187, 188

duration of. and lung neoplasm increase
64:31, 37, 158, 161, 163, 170, 187,
188

duration of habit and incidence of CHD
68:17

effect of abstinence in excercise per-
formance
73:241, 242, 246, 247

effect on bladder neoplasm morbidity
67:155

effect on blood cholesteroi levels
67:55, 56

effect on blood circulation
67:26, 60-61; 69:11

effect on blood circulation, and arterio-
sclerosis pathogenesis
67:61-62

effect on blood circulation, and coro-
nary disease pathogenesis
67:62

effect on blood coagulation
67:64

effect on blood lipids
68:31.73:11, 12

effect on blood platelets
67:64; 69:27-28; 74:18, 19

effect on blood pressure
67:54, 60

effect on blood vessels
67-111

effect on bronchial epithelium
67:104-106, 144

effect on cardiac lactate metabolism
73:13

effect on cardiovascular system
67:26, 60; 72:6, 13.14

effect on coronary vessels
67:65

effect on esophageal sphincter
72:97, 98

effect on esophageal tissue
67:30, 150-153

218

effect on free fatty acids
69:27

effect on gastric acidity
67:182

effect on gastrointestinal secretions in
dogs
72:6

effect on heart function
67:60

effect on heart rate
67:60

effect on hemoglobin oxygen affinity
69:29

effect on larynx and true vocal cords
69:59-60

effect on leg blood mean-flow capacity
73:22

effect on Jeukocytes in guinea pigs
72:46

effect on lung function
67:29, 55;69:5

effect on lungs
67:104, 140-143

effect on lungs in dogs
72:46

effect on mortality rates from eso-
phageal neoplasms in Japanese males
72:71

effect on mucous membranes
67:144

effect on myocardium
67:60

effect on neoplasm recurrence at site of
primary
72:69

effect on oxygen tension in arteriat
blood
72:45

effect on pentagastrin-stimulated gastric
secretion
72:97

effect on peripheral circulatory system
72:25, 26

effect on plasma nicotine levels
73:15-17

effect on precapillary sphincters
73:22

effect on pulmonary clearance
72:47

effect on respiratory tract
67:141

effect on thrombus formation
69:27-28

effect on thrombus formation in coro-
nary disease patients
67:26

effect on tryptophan metabolism
67:36, 156

effect on vascular resistance
67:60

effect on ventilation/perfusion relation-
ships of lung
69:39

etfect on vision
67:183

electrocardiogram patterns from
64:319
and emphysema morbidity
67:3, 6, 94, 99

and emphysema mortality
67:3, 29, 90-92

in emphysema pathogenesis
67:29-31, 96, 104, 106; 69:37-38

and epidermoid carcinoma
67:35, 140-143

and esophageal neoplasms
67:33, 149, 150-151

and fertility history
69:79-80

genetic factors in
64:190, 385

and gingivitis
69:85-86

health hazards of. similarities of ciga-
rettes with little cigars
73:224, 225

heartburn and
72:97, 98

histopathologic changes from
64:300

inhalation of cigarette smoke as measure
of exposure to
67:15

interaction with other risk factors in
CHD
73:4-11

and intermittent claudication
74:14-16

and kidney neoplasms
69:60

in laryngeal neoplasm etiology
67:3, 148;69:55

in laryngeal neoplasm etiology in men
67:33

and liver cirrhosis morbidity
67:39

and liver cirrhosis mortality
67:10, 36

and lung neoplasms
64:175-196; 69:4, 55-58

and lung neoplasms ctiology
67:33-34, 140-144

and lung neoplasms incidence
68:94-99

and lung neoplasms, in men
69:57

and lung neoplasms, in women
67:10; 69:67

and lung neoplasms morbidity
67:3, 142

and lung neoplasms mortality
67:3, 10, 34

and lung neoplasms, retrospective studies
of, by smoking characteristics
64:156

aS a major risk factor in peripheral
vascular disease
74:14-16

and morbidity by age
67:24

and morbidity in United States
67:6,19

and mortality
69:3

and mortality, British men
67:10

and mortality, British physicians
67:5

mortality, follow-up study
67:8

mortality from esophageal neoplasms
68:102

and mortality in United States
67:5

and mortality rates by sex
67:7

and mortality, U.S. veterans
67:5

and mouth neoplasms
67:145

and myocardial infarction
69:4, 18

and myocardial infarction incidence
rates
67:57

and noncancerous oral diseases
69:5-6, 85-87

and oat cell carcinoma
67:140-141

and obesity
67:66

and oral neoplasms
69:58

and oral neoplasms incidence
68:99, 100

and pancreatic neoplasms
67:36, 159: 69:60-61

patterns
64: 368, 369

and peptic ulcer
67:39; 72:6, 97, 98

and peptic ulcer morbidity
67:39-40, 181-182

and peptic ulcer mortality
67:39-40, 180-182

pleasure
64:350

population studies
67:8-11

and premalignant changes in larynx
69:5

prevalence of
64:363, 364

prevalence of, in nonwhites

64:363, 364 .
prevalence of in U.S. and Great Britain

73:173, 174
psychoanalytic explanation of
64:367
and pulmonary fibrosis
67:107; 72:44

rate
64:98

reduction of among British physicians,
and reduced mortality
67:15

reduction of, effect on lung neoplasm
mortality
67:4

relation to blood cholestero! and lung
neoplasms
69:57
relation to lung neoplasms and stomach
ulcers
69:57
and respiratory tract infections
67:10
and restricted activity
67:19
status, errors of measurement in
64:111
and stomach neoplasms
67:29, 36, 158
and stroke
67:27
and thrombosis
67:111
tobacco amblyopia and
72:6
trends for U.S. men, for years 1955,
1966, and 1970
74:40
and tryptophan metabolites in urine
67:36
type, esophageal neoplasms and
64:32, 33
type, mortality ratios by
64:90
type, neoplasm sites by
64:188
type, oral neoplasm sites by
64:197
type, retrospective neoplasm studies
64:201
typology
67:189-191
and undifferentiated carcinoma
67:140-143
vasoconstrictive effects in normal sub-
jects
74:16
wish- for-adult-status as reason for
64:371
withdrawal methods and
64:352
in young people, effect on lung function
67:110
in young people, effect on respiratory
tract
67:31
See also Reverse smoking; Passive smok-
ing; Smoking, bidi; Smoking, cigar;
Smoking, pipe
Smoking, bid
64:211
esophageal neoplasms from
64:213
in neoplasm etiology in Bombay, India
72:69
Smoking characteristics
bronchitis prevalence rates in men and
74:79
COPD prevalence rates in Yugoslavia and
74:79
dosage score and
67:14-15
and incidence rates of lung neoplasms
for men
69:56

we
i)
Q

and incidence rates of hung neoplasms
for women
69:56

and lung neoplasm mortality rates
69:57

lung neoplasm mortality rates, for men

by
67:134-135, 139

lung neoplasm mortality rates,
women by
67:136

lung neoplasm mortality ratios, for men
by
67:139

lung neoplasm mortality ratios, for
women by
67:136

patients with lung or bladder neoplasms
68:104

tor

Smoking, cigar

autopsy studies, in smokers with emphy-
sema, fibrosis, or thickening of arte-
rioles or arteries
75:75

and bronchitis morbidity
67:94, 99

and bronchitis mortality
67:30, 94

CO levels in mainstream smoke
75:90

effect on blood lipids
68:31

effect on mortality and morbidity com-
pared to cigarette smoking
73:171-173

and emphysema morbidity
67:94

and emphysema mortality
67:30, 94

in esophageal neoplasm development
73:197, 200-202

gastrointestinal disorders and
73:222

health consequences of
73:179

histological effects on bronchial epithe-
lium
73:203, 204, 209

histological effects on esophagus
73:200

histological effects on larynx
73:197

histological effects on lungs
73:217

incidence of CHD
68:27

incidence of lung neoplasms in Switzer-
land
68:95, 96

inhalation patterns and
73:184-189

in laryngeal neoplasm development
73:197-199

in lung neoplasm development
73:203-206; 74:39, 40

and lung neoplasm mortality
67:34, 138-140
and lung neoplasm mortality ratios
67:138-140; 73:203-205

and mortality
67:7

mortality from esophageal neoplasms
68:102

mortality, in smokers vs. nonsmokers
68:5

mortality ratios from cardiovascular dis-
eases and
73:215, 216

mortality ratios from COPD and
73:217, 219

mortality ratios from esophageal neo-
plasms and
73:197, 200

mortality ratios from laryngeal neo-
plasms and
73,193, 196, 197

mortality ratios from oral neoplasms and
73:191, 193

oral neoplasm development and
73:193-195

overall mortality rates by amount
smoked
73 :180-182

overall mortality rates from neoplasms
73:189

prevalence in Great Britain
73:173, 174

prevalence in United States
73:173, 174

relationship to neoplasms
75:43, 44

summary of previous findings on effects
75:4, 13

and tobacco amblyopia
67:39

see also Smoking

Smoking classification

bladder neoplasms mortality rates by
67:155

bronchitis mortality by
67:30

bronchitis respiratory symptoms by
67:98

cerebrovascular disease mortality rates
by age and sex
67:66

cerebrovascular disease mortality ratios
by age and sex
67:66

cough by
67:97

digestive tract mortality rates by
67:147

emphysema mortality by
67:30

esophageal neoplasms mortality rates by
67:50

esophageal neoplasms mortality ratios by
67:150

laryngeal neoplasms mortality rates by
67:147-149

laryngeal neoplasms mortality ratios by
67:149

liver cirrhosis mortality rates in men
67:184

liver cirrhosis mortality ratios for men
67:184

lung neoplasms morbidity by
67:33, 143

lung neoplasms mortality rates by
67:34, 137, 139-140, 143

lung neoplasms mortality ratios by
67:137, 139-140

mortality rates by
67:8

mouth neoplasm morbidity by
67:32

mouth neoplasm mortality by
67:35, 146

pancreatic neoplasms mortality rates for
men by
67:159

pancreatic neoplasms mortality rates for
US. veterans by
67:159

pancreatic neoplasms mortality ratios for
men by
67:159

peptic ulcer mortality rates for men by
67:182

pharyngeal neoplasms mortality by
67:35, 146

respiratory tract neoplasms mortality
rates by
67:147

stomach neoplasms mortality rates by
67:157-158

stomach neoplasms mortality ratios by
67:157

tracheal neoplasms mortality rates by
67:147

urinary tract neoplasms mortality rates
by
67:154

urinary tract neoplasms mortality ratios

by
67:154

Smoking habit

64:366

appetitite reduction by
64:71, 355

behavioral research
67188:192

beneficial effects of
64:32, 355

and body constitution
67:54

British physicians
67:9-10

and cognition
67:189-191

compulsive nature of
64:352

and cultural characteristics
67:54

demographic factors in
64:361-365

and heredity
67:53-54

intelligence factors in
64:370

measurement of
64:98

221

 

 

 
modification of
64:375, 376
mortality rates associated with
64:27
nausea from
64:71
neuroticism and
64:367
and occupational physical activity
67:56
oral hypothesis of
64:367, 363
and perception
67:189-191
and personality characteristics
67:57
psychological determinants in
64:40, 350
psychosocial aspects of
67:39, 188-192
reasons for
67:189
and religion
67:54
social determinants in
64:361-374
and socioeconomics
67:54
see also Tobacco habit
Smoking history
aortic aneurysm mortality rates by
69:16
aortic aneurysm mortality ratios by
69:16
and bronchitis prevalence rates
67:96
and chronic diseases
67:22
and coronary disease incidence rates
69:21-24
and coronary disease mortality rates
67:25-26; 69:13-14, 17
and coronary disease mortality rates, for
ex-smokers
67:51
coronary disease mortality ratios
69:13, 15,18
incidence of atypical nuclei in larynx by
69:59
and laryngeal neoplasms
67:35
and lung neoplasm morbidity
67:33
and lung neoplasm mortality rates
67:34, 135-137, 139-140
and lung neoplasm mortality rates for
ex-smokers
67:137, 139
and mortality
67:7-9
and respiratory disease morbidity
67:98
and respiratory function tests
67:100
and stroke
67:68
and stroke mortality rates
69:13, 17

222

and stroke mortality ratios
69:13,15

Smoking machines

64:45

Smoking, maternal

and abortion
69:77-79, 7E:13; 72:5, 84, 85; 73:123, 124
carboxyhemoglobin levels .
69:80
carcinogenic effects on fetus
72:88
congenital malformations and
73:136, 137
and development of bronchitis and pneu-
monia in infants
75:103, 104
effect during pregnancy
67:185-186; 72:5, 83-87.
73:103-142
effect on birth weight
67:39-40, 185; 69:5, 77-78, 80:
72:5, 83-87; 73:103-114, 119-122
effect on body height of children
72:88
effect on fetal growth rate
72:5, 83-87
effect on fetal morbidity
67:186
effect on fetal mortality
67:185; 69:77-78; 73:124, 125
effect on gestation duration
73:103-106
effect on infant mortality
67:185; 69:77-78; 72:84-87
effect on infants growth rate
69:78
effect on lactation
73:138-141
effect on neonatal carboxyhemoglobin
levels
73:118, 119
effect on neonate
67:39-40, 185
effect on neoplasm development in off-
spring
72:87, 88
effect on placental ability to hydrox-
ylate benzo(a)pyrene

69:80 . .
effect on placental metabolizing activity
72:89
effect on pregnancy
69:4-5, 77-81
effect on pregnancy, in Ireland
69:79
effect on pregnancy, in Scotland
69:79
effect on pregnancy, in Venezuela

9:79
effect on sex ratio

73:135, 136
epidemiological studies of effects
69:77-80
preeclampsia and
69:79; 72:84; 73:142
pregnancy toxemias and
69:79
and prematurity
67:185; 69:77, 79
and prematurity, among Negroes
69:78

selective action on fetus of certain wom-
en vs. others
73:131

teratogenic effects
IADR

timing of influence on birth weight
73:120, 121

unwanted pregnancy and
72:84

see also Infant mortality; Neonates

Smoking, parental

effect on children
72:129

Smoking, paternal

effect on infant birth weight
73:110, 111

Smoking, pipe

and adenocarcinoma
67:143

autopsy studies, in smokers with emphy-
sema, fibrosis, or thickening of arte-
rioles or arteries
75:75

and bronchitis morbidity
67:94, 99

and bronchitis mortality
67:94, 99

effect on mortality and morbidity com-
pared to cigarette smoking
73:171-173

and emphysema morbidity
67:94

and emphysema mortality
67:34

and epidermoid carcinoma
67:143

in esophageal neoplasm development
73:197, 200-202

gastrointestinal disorders and
73:222

health consequences of
73:179

histological effects on bronchial epithel-
jum
73:203, 204, 209

histological effects on esophagus
73:200

histological effects on larynx
73:197

inhalation patterns and
73:184-189

in laryngeal neoplasm development
73:197-199

and lip neoplasms
67:35, 145

in lung neoplasm etiology
67:143; 74:39, 40

in lung neoplasm etiology by amount
smoked
73:203-206

and lung neoplasm mortality
67:34, 139-140

and hing neoplasm mortality ratios
67:139-140; 73 :203-205

and mortality
67:7

and mortality ratios
64:86, 87

mortality ratios from cardiovascular di-
seases and
73:215, 216

mortality ratios from COPD and
73:217, 219

mortality ratios from laryngeal neo-
plasms and
73:193, 196, 197, 200

mortality ratios from oral neoplasms
73:191, 193

and mouth neoplasms
67:33

oral neoplasms development and
73:193-195

overall mortality rates by amount smok-

ed
73:180-182

overall mortality rates from neoplasms
and
73:189

prevalence in Great Britain
73:173, 174

prevalence in United States
73:173, 174

pulmonary histological changes and
73:217

relationship to cancer
75:43, 44

sedation from
64:350

stomatitis nicotina from
64:271; 69:87

summary of previous findings on effects
on smokers
75:4, 13

and tobacco amblyopia
67:39

see also Smoking

Snuff

64:73, 349
effect on oral mucosa in hamsters
72:70
lip neoplasms from
64:202
oral lesions from
64:203
oral neoplasms
64:202, 233; 71:287, 361, 364-365
per capita consumption of, in U.S.
64:45

Social adjustments

in children of smoking mothers
71:407

Social stimulation

64:32

Socioeconomic level

smoking prevalence by
64:362

Socioeconomics

ir. COPD
71:152-153, 216-217
and smoking habit
67:54

Sodium

in main stream smoke
64:55

N
tr
Gd
Solanesol
64:52
pyrolysis of
64:53
structural formula of
64:53
Somatotypes
64:372, 383, 384, 385, 386
Soot
benzo(a)pyrene content of
64:148
neoplasm induction by
64:33, 147, 229
South Africa
coronary death rate in
64:320
esophageal neoplasms in, retrospective
studies of tobacco use
71:378
health surveys in
64:186
methods of retrospective studies of lung
neoplasms in
71:328
occupational exposure and smoking rela-
tionship to COPD in
72:219
serum lipid differences in smokers vs.
nonsmokers in
71:99
Specificity
as measure of statistical association
64:182-185, 204, 210, 225
Spirometric test
64:292
Sports
smokers’ participation in
64:372, 373
Spray exposure
in smokers vs. nonsmokers, by race and
sex
75:69, 70
Sputum
64:38, 282, 283-287, 301
effect of asbestos exposure in smokers
vs. nonsmokers
73:41
effect of filtered cigarettes
73:55
effect of modified cigarettes
73:37, 38
effect of plain vs. filtered cigarettes
73:37, 38
in males by amount smoked and type of
cigarette
73:37, 38
prevalence in pipe and cigar smokers
73:220, 221
in women

64:231
Squalene

64:51
Status striving
smoking and
64.372, 373
Stearic acid
suspected carcinogenic agent of cigarette
smoke
71:266

224

Steel workers
64:285, 299
Sterols
64:52
Stigmasterol
64:52
pyrolysis of
64:59
Stillbirths
abortions, and neonatal death and, in
smoking and non-smoking mothers
71:390, 405-406
effects of maternal smoking
71:415; 73:124, 125
rates in blacks vs. whites
73:124, 125
in smokers vs. nonsmokers
73:124, 125
see also Fetal death; Smoking, maternal
Stimulants
64:354
nicotine as
64:38, 69, 70, 71, 317-320, 349-350
Stockholm Prospective Study
epidemiologic study of smoking and
CHD
74:6
Stomach neoplasms
mortality rates
67:158
mortality rates, by age and amount
smoked
67:157-158
mortality rates, by age and daily tobacco
consumption
67:158
mortality rates, by smoking classification
67:157-158
mortality rates, effect of cessation of
smoking on
67:158
mortality ratios, by age and amount
smoked
67157-3158
mortality ratios, by smoking classifica-
tion
67:157
and smoking
67:36
and tobacco use
67:33

Stomatitis nicotina
64:275, 302
and pipe smoking
64:271; 69:87
reverse smoking and
72:6, 69, 70
symptoms of
64:271
see also Leukoptakia
Stramonium
64:354
Stress
64:373, 374
socioenvironmental, and coronary dis-
ease incidence

67:56
Stroke
mortality rates, by age
69:13
mortality rates, by age and sex
67:67
mortality rates, by amount smoked
69:13
mortality rates, by sex
69:13
mortality ratios, by amount smoked
69:13
mortality ratios, by sex
69:13
and smoking
67:27, 28; 72:24, 25
see also Cerebrovascular diseases
Strontium 90
64:146
Students, college
smoking patterns in
64:369
Students, high school
effect of smoking
72:40, 41
pulmonary function of smokers vs. non-
smokers
72:3
respiratory symptoms
72:40, 41
Study populations
representativeness of
64:94
Subcutaneous neoplasms
64:143, 144
Subglottis
64:271
Suburbs
coronary diseases in
64:322
Sugar
64:62
Sulfonamides
64:224
Sulfur dioxide
air pollution from
64:295
and cigarette smoke, effect on glands in
laboratory animals
73:49
ciliastatic effect of
64:268
mucus alteration of
64:268
pollution levels in four U.S. locations
75:65, 66
toxicity of

64:295
Sulfuric acid

carcinogen extraction by
64:147
Surfactant
see Pulmonary surfactant
Surgery
complications following, in smokers vs.
nonsmokers
74:92
Survey of Tobacco Smoking Patterns in the
United States
64:187

Sweden
acute effects of cigarette smoke on
human pulmonary function
71:168
blood pressure differences in smokers vs.
nonsmokers in
71:104
CHD mortality and morbidity in
71:97
COPD morbidity in smokers in
71:203, 205
coronary mortality rates in
64:320
effect of cigarette smoke on animals
ciliary function in
71:221-224
genetic studies of twins in, smoking
effects on
71:50, 99
laryngeal neoplasms in relationship to
tobacco use
71:356
lung neoplasm mortality rates in
64:176
relationship of tobacco use and lip neo-
plasms in
71:361
relationship of tobacco use and oral
cavity neoplasms
71:364
Tetrospective studies of esophageal neo-
plasms, by tobacco use
64:214; 71:378
retrospective studies, of oral neoplasms,
by type of smoking
64:198, 200, 201
retrospective study, of laryngeal neo-
plasms
64:205, 206
serum lipid differences in smokers vs.
nonsmokers of
71:99
smoking and nicotine effects on human
cardiovascular system
71:115
smoking and nicotine effects on human
peripheral vascular system
71:133
tracheobronchial tree changes in smokers
and nonsmokers in
71:263
Swimming
effect of smoking
73:242, 244
Switzerland
CHD morbidity and mortality in, smok-
ers vs. nonsmokers
71:95
cigarette smoke effects on mice lung and
kidney tissue in
71:344
cigarette smoke inhalation effects on
mice respiratory tract
71:351
lung neoplasm incidence in cigar and
pipe smokers of rural
71:244

225
jung neoplasm mortality rate in
64:176

lung neoplasms, methods of retrospec-
tive study of smoking in
71:325

serum lipid differences in smokers vs.
nonsmokers of
71:100

Tachycardia

development in dogs induced by nicotine
71:57

Tars, cigarette

carcinogenic effect on animal oral cav-
ities
71:288

carcinogenicity
67:34; 69:61; 71:11, 264, 265

carcinogenic properties on animal skin
71:337-342; 73:210-214

as cause of bladder neoplasms, in rats
74:58

content
64:50; 67:34; 68:91

effect of instillation or implantation in
animal tracheobronchial tree
71:346-348

effect on RNA
73:86

effect on tissue and organ cultures
71:343-344

as harmful component of cigarette
smoke
72:142, 143

and nicotine content of cigarette smoke,
and tumorigenicity
67:15, 34

and nicotine content of cigarette smoke,
as measurement of dosage
67:15

N-nitrosamines in
73:87, 88

reduction of
69:61

retention in mouth
69:62

role in experimental carcinogenesis
73:80-84

role in respiratory tract carcinogenesis,
in animals
74:47

summary of previous findings on effects

bladder neoplasms and
64:219, 223
buccal retention of
64:264
carcinogenicity
64:33, 143, 146, 147, 165, 192:
67:128; 69:61; 72:65, 66
clearance of
64:269
cocarcinogens in
67:131
condensation temperature of
64:50
definition
72:143
dosage score as function of
67:15
effect on respiratory symptoms and ven-
tilatory capacity
73:38
esophageal neoplasms and
64:212, 213, 218
fatty acids in
64:53
gastric neoplasms induced by
64:228
and leukemia
67:148
in little cigars, compared to cigarettes
and cigars
73:223-226, 228
and lymphosarcoma
67:148
mouth neoplasm experimentally induced

by
67:147-148
nonvolatile fraction of
64:50
pulmonary adenoma from
64:165
retention of, in mouth
64:264
and reticulosarcoma
67:148
sarcoma induction in rats following in-
stillation
71::346
skin neoplasm induction by
67:131; 71:238, 337-342:
73:210-214
sterol fraction of
64:52
see also Tars, cigarette

Taste bud reflexes

64:71

on smokers Taylor’s Manifest Anxiety Scale

75:5 64:367
see also Tars, tobacco TDE
Tars, tobacco 64:145
64:50 Tea
alkaloid content of 64:349
64:54 Tecumseh Study
anticarcinogens in 64:284
64:143, 144 incidence of CHD in cigarette smokers
application of, in carcinogenesis 68:19
64:165 jung function differences in smokers and
and bladder neoplasm carcinogenesis nonsmokers
67:156 74:81

226
Temperature effect
64:50
Ten-city mortality surveys
64:135
Tension
64:353
Teratogenesis
maternal smoking implications in
71:407
in mice embryos, nicotine effects on
71:411
Terpenes
64:51
Terpenoids
64:51, 52
as flavoring agents in cigarettes
64:52
from pyrolysis of solanesol
64:52
Tetraethylammonium chloride
blockage of nicotine cardiac stimulation
by
71:57
effect on nicotine pharmacology
67:60
Theobromine
64:352
Thiocyanate

64:266
Thorium

64:145
Thoron
64:145
Throat
effect of exposure to cigarette smoke, in
passive smokers
75:99
effect of smoking
64:275
Thromboangiitis obliterans
allergic skin reactions in
64:319
cessation of smoking, and remission
71:74
cessation of smoking in
64:326
definition
71:73
tobacco allergy and
7A
treatment of
64:326
Thrombogenesis
effects of smoking
68:32-43
Thrombophlebitis
oral contraceptives and
72:26
smoking and
72:26
Thrombosis
coronary
64:321
effect of epinephrine on
67:64
and emphysema
67:111
plasma and
69:27-28

smoking and
67:26, 64, 65, 111; 69:27-28; 71:66,
130-132; 72:23; 73:19; 74:18, 19
Thrombus formation
and smoking
68:32-43; 69:27-28; 75:32
Thumbsucking
64:367, 368
Tidal volume
acrolein effects on
64:266, 267
Tissue cultures
effect of cigarette smoke on
69:62-63; 71:267, 343-345
Tobacco
advertising, prohibition of
64:8
allergic reaction to
64:302
“angina”
64:319
antigenic properties of
64:319;72:104
antigens, in smokers vs. nonsmokers
72:107
anti-obesity effect of
64:355
arsenic content of
64:61, 62
arsenic spraying of
64:61
beneficial effects of
64:255, 355, 356
carcinogenicity of
64:143
chemical composition of
64:49, 50-60
cholesterol content
72:24
controversy over
64:5, 6,7
curing methods, and incidence of respira-
tory infections in rats
73:218, 219
denicotinized
64:34, 349
effect on immune responses
72:6, 107-109
flavoring in
64:52, 62
flue-cured vs. air-cured, effect on respira-
tory system in animals
73:217, 218
form used and relation to gingivitis
69:86
history of
64:5
humectants in
64:62
irritants
64:353
modification of taste of
64:354
and mouth neoplasms
67:145
in oral neoplasms

64:198, 199, 200, 201

227
and oral submucous fibrosis
69:58
pharmacologic, irritative, and allergic ef-
fects
72:7, 109-111
role in carcinogenesis
69:62
and stomach neoplasms
67:33, 158
see also Tobacco additives; Tobacco ex-
tracts; Tobacco leaf components; To-
bacco, pipe
Tobacco Act of 1842
64:62
Tobacco additives
64:62, 145
flavorings as
64:62
humectants as
64:62
prohibition of
64:62
see also Tobacco
Tobacco alkaloids
see Alkaloids, tobacco
Tobacco ambylopia
see Ambylopia, tobacco
Tobacco chewing
64:45, 211, 213, 349
decrease of
64:45, 211
gingival neoplasms from
64:202
laryngeal neoplasms from
64:212
leukoplakia and
73:75
lip neoplasms from
64:202; 71 :361-363, 365-366
oral neoplasms from
64:233; 69:58; 71:361-363,
365-366; 72:69
per capita consumption of chewing to-
bacco, U.S.
64:45
Tobacco consumption
64:5, 26, 29, 30, 35, 36, 45, 46, 85, 86,
87, 89, 155, 187, 188
bladder neoplasms, mortality rates by
67:155
bladder neoplasms, prevalence by
64:223
coronary diseases and
64:106, 323
coronary diseases, mortality rates by
64:324
cough and sputum prevalence by
64:289
epithelial cell changes by
64:231
errors of measurement of
64:111
esophageal neoplasm risk ratio by
64:213, 217
factors determining
64:163
forced expiratory volume by
64:289

228

gastric neoplasms mortality rate by
64:228; 67:158
laryngeal neoplasms risk ratios by
64:209
lung neoplasms mortality rates by
64:137, 186
lung neoplasms risk by
64:37, 196, 232
mortality rates by
64:29, 105, 106, 111, 139, 180, 324
mortality ratios by
64:85, 86, 105, 106
oral neoplasms gradients by
64:202, 233
per capita, U.S.
64:45 .
in pneumoconiosis
64:291, 298
relative risk ratios by
64:183
respiratory symptoms by
64:289
stress factors in
44:32, 373, 374
Tobacco extracts
64:143, 144
antigenic properties
72:104, 105
carcinogenesis from
64:143, 144, 165
effect on cell cultures
73:85, 86
effect on skin
72:105-107
irritants in
72:104, 105
thromboangiitis obliterans and
72:111
see also Tobacco
Tobacco habit
64:349-354
cure of
64:354
dependence on
64:350
nicotine in
64:32, 349
psychological drives in
64:32, 350, 351
see also Smoking habit
Tobacco Industry Research Committee
64:6
Tobacco Institute, Inc.
64:8
Tobacco leaf components
antigenic properties
72:104, 105
polonium-210 in
67:128
presence of potassium
71:266
see also Tobacco
Tobacco, pipe
definition and processing
73:176
decrease in consumption
64:45
per capita consumption, U.S.
64:45
see also Tobacco
Tobacco workers
coronary diseases in
64:322
health studies in
64:182
laryngeal neoplasms in tobacconists
64:205
Tokyo-Yokohama asthma
64:276
Toluene
64:55, 59
Tongue
hamster, C-14 labeled particulate deposi-
tion in
71:281-282
Tongue neoplasms
cigar smoking in
64:189, 202
pipe and cigar smoking in
64:202
pipe smoking in
64:188, 189
retrospective studies in, by type of
smoking
64:201
risk gradients in
64:233
see also Mouth neoplasms; Oral neo-
plasms
Tooth extraction
effect of smoking on healing of socket
69:87
Toxicity
birth rate reduction from
64:343
from nicotine
64:73
from sulfur dioxide
64:295
threshold levels in
64:295

Trachea

changes in, in smokers
64:167-172

hamster, C-14 labeled particulate deposi-
tion in
71:281-282

histopathology of
64:167-172, 271

mucus secretion in
64:268

mucus velocity, effects of smoking, in
dogs
75:78

Tracheal neoplasms

experimentally induced by cigarette
smoke
67:144

mortality rates, by amount smoked
67:147

mortality rates, by smoking classification
67:147

smoking and
73:71

Tracheobronchial tree
clearance, effects of cigarette smoke in
donkeys
75:78
epithelial changes in
64:167-172
function
64:35
histopathologic changes in
64:167-173, 270-274 passim
secondary infection in
64:272
Traffic
effect on air pollution in Boston
74:82, 83
Traffic accidents
64:39, 344, 345

Tranquilizers
64:100, 101, 354
nicotine as
64:350
Transit workers
breathlessness in
64:286
chronic cough in
64:281
Treadmill performance
cardiovascular parameters in smokers vs.
nonsmokers
73:243-245
effect of vitamin C
73:245
oxygen intake in smokers vs. nonsmok-
ers
73:245
Tricaprylin
64:143
Triglycerides
coronary disease relationship to
71:65; 73:8
smokers vs. nonsmokers
71:99-100, 102

Trout

hepatoma induction in

64:145
Tryptophan metabolism

alteration in urinary tract neoplasms by
smoking
71:13

alterations by smoking
71:297

carcinogenicity in mice bladders
71:296

disorders, and bladder neoplasms
67:36, 106

disorders, effect of cessation of smoking
on
67:156

effect of smoking on
67:36, 156

effect of smoking on, and bladder neo-
plasms
67:36

relation of excretion in smokers and
nonsmokers
71:297

bo
nw
Oo
Tryptophan metabolites
carcinogenic, and smoking
67:36
carcinogenic, in urine, and bladder neo-
plasms
67:36
excretion of, by smokers
69:64
intermediate, and bladder neoplasms
67:156
Tuberculosis
64:276, 302
alcoho! consumption in
64:277
cigarette consumption in
64:277
in smokers vs. nonsmokers
71:172, 226-228
smoking and
72:41
Tumors
see Neoplasms; and specific neoplasm
terms
Twenty-five State Study
expected deaths, in
64:110
lung neoplasm mortality in
64:118
mortality ratios in
64:110, 118, 149
observed deaths in
64:110
Twins
air pollution exposure levels and respira-
tory symptoms
75:67
air pollution vs. smoking in bronchitis
development in
67:109
air pollution vs. smoking in emphysema
development using
67:109
angina pectoris development in, smoking
effects on
71:50-51
blood cholesterol levels by smoking
habit in
67:55
constitutional factors in bronchitis devel-
opment in
67:109
constitutional factors in emphysema de-
velopment in
67:109
coronary disease incidence rates in, with
discordant smoking habits
67:103
cough incidence rates, smokers vs. non-
smokers by age and sex in
67:102
dizygotic, bronchitis morbidity prev-
alence rates for, with discordant
smoking habits
67:103
dizygotic, chronic cough in, with dis-
cordant smoking habits
67:103

230

genetic and environmental factors in
angina pectoris in
69:25

genetic studies of smoking effects on
71:49-52

monozygotic, angina pectoris incidence
rates in, by smoking habit
67:59

monozygotic, bronchitis morbidity prev-
alence rates for, with discordant
smoking habits
67:113

monozygotic, chronic cough in, with
discordant smoking habits
67:103, 113

monozygotic, respiratory symptoms in,
with discordant smoking habits
67:103, 113

morbidity rates by smoking habit in
67:103

mortality from CHD, in smokers vs,
nonsmokers
75:14, 15

neoplasm incidence in
64:190

predisposition to smoking in
64:326

role of heredity factors in respiratory
diseases in
67:102

role of respiratory tract diseases
67:20

smoking and coronary heart disease in
72:18

smoking effects on mortality and mor-
bidity in
7h:51

smoking habits of
64:190

Ultraviolet rays

absorption determination of
64:51

neoplasm induction by
64:144

Underachievement

64:372, 373

Unemployed

smoking in,
64:363

United Kingdom

bladder neoplasms in, methods in retro-
spective studies of smoking and
71:382-384

blood pressure differences in smokers vs.
nonsmokers in
71:103, 104

British Perinatal Mortality Survey
71:390, 395, 404, 415

cigarette smoke effects on animal ciliary
function in
71:221

cigarette smoke effects on human fetal
lung and mice trachea
71:344
cigarette smoke effects on human pul-
monary function
71:168, 169

cigarette smoke effects on mice respira-
tory tract
71:352

cigarette smoke implantation effects on
rat tracheobronchial tree in
71:346-347

comparison of abortions, stillbirths and
neonatal deaths in smoking and non-
smoking mothers
71:406

COPD morbidity in smokers in
71:195-197, 203, 204

human experimental data on smoking
and pregnancy in
71:408

kidney and bladder neoplasms in smok-
ers in
71:294

tung neoplasms mortality in males in
England and Wales
71:240

maternal smoking and infant weight in
71:397, 399

methods of retrospective study of lung
neoplasms and smoking in
71:324, 326

methods used in smoking study and
human pregnancy
71:391, 394-395

mortality from cerebrovascular disease
related to smoking in
71:68

mortality rates from COPD in, lack of
increase
71:140

mortality ratios from esophageal neo-
plasms in
71:290

mortality ratios from laryngeal neo-
plasms in
71:278

mortality ratios from peptic ulcer in
smokers and nonsmokers in
71:424

occupational exposure and smoking rela-
tionships to COPD in
71:218-219

peptic ulcer in, methods and results of
retrospective and cross section
studies of smoking and
71:425-428

physicians in, decline in cigarette smok-
ing rates
71:48

physicians in, mortality from lung neo-
plasms in smokers and nonsmokers
71:241

pulmonary function in, cigarette smoke
effects on
71:168

relationship of lung neoplasms to smok-
ing, air pollution, and residence in
71:253-254

relationship of smoking and tuberculosis
in
71:226

serum lipid differences in smokers vs.
nonsmokers in
71:101, 102

smoking and nicotine effects on anima!
cardiovascular function in
71:107

smoking and nicotine effects on human
blood lipids in
71:126

smoking and nicotine effects on human
cardiovascular system in
TEAIS

smoking relationships to thrombosis in
71:131

United States

acute effect of cigarette smoke on hu-
man pulmonary function in
71:166-167, 169

arteriosclerosis mortality in
64:321

atherosclerosis autopsy studies in
71:53-55

bladder neoplasms in, methods and
results in retrospective studies of
smoking and
71:381-384

blood pressure differences in smokers vs.
nonsmokers in
71::103-104

Bureau of the Census
64:177

CHD mortality and morbidity in smok-
ers vs, nonsmokers in
71:30-35, 37, 93-94

chewing tobacco consumption, decrease
in
64:45

chronic bronchitis studies in
64:271

cigarette consumption increase in
64:26, 45, 46, 185

cigarette smoke effects on animal ciliary
function in
74:221-224

cigarette smoke effects on animal tissues
in
71:343-345

cigarette smoke effects on pulmonary
surfactants and surface tension
71:172, 225

cigarette smoke implantation effects on
animal tracheobronchial tree
71:346-348

cigarette smoke inhalation effects on
animal respiratory tracts
71:349-350, 352, 354

comparison of abortions, stillbirth, and
neonatal death in smoking and non-
smoking mothers
71 :405-406

COPD development in
71:10

COPD morbidity in smokers
71:195, 196, 198-200, 201-202, 205
Department of Agriculture
64:15

Department of Commerce
64:15

esophageal neoplasms in, retrospective
studies of tobacco use
71:378

esophageal neoplasms mortality in, in
1967
71:289

Food and Drug Administration
64:8, 13, 15

human experimental data on smoking
and pregnancy in
71:391-395, 408-410

human pulmonary function following
cessation of smoking in
71:149

inhalation practices in, in smokers
64:177

kidney and bladder neoplasms in smok-
ers in
71:293-295

laryngeal neoplasms incidence in 1967
71:277

laryngeal neoplasms in, relationships to
tobacco use
71:278-279, 354-355

lung neoplasms mortality rates
64:176

lung neoplasms mortality rates in, smok-
ers and nonsmokers in
71:240-243

maternal smoking and infant weight
71:397-399

methods of retrospective study of lung
neoplasms and smoking in,
71:323-328

mortality from aortic aneurysm related
to smoking in
W171

mortality from cerebrovascular disease
related to smoking
71:68-70

mortality rates for bladder neoplasms in
1967
71:293

mortality rates for COPD
71:139-140

mortality rates for kidney neoplasms in
1967
71:296

mortality rates for lung neoplasms ex-
pected in 1970
71:237, 239

mortality rates for lung neoplasms in
1939 vs. 1967
71:239

mortality ratios for COPD
71:142-145

mortality ratios for esophageal neo-
plasms in
71:290-294

mortality ratios for laryngeal neoplasms
71:278-279

mortality ratios for pancreatic neoplasms
in smokers and nonsmokers in
71:298

232

mortality ratios for peptic ulcer in smok-
ers and nonsmokers in
71:424

neoplasm mortality increase in
64:229

nonsmokers in, by age and sex
64:178

occupational exposure and smoking rela-
tionships to COPD in
71:218-219

Office of Science and Technology
64:8

oral neoplasms incidence in, estimated
for 1970
71:284

peptic ulcer in, methods and results for
retrospective and cross section stud-
ies of smoking and
71:425, 426-428

peptic ulcer mortality in 1967 in
71:423

polonium-210 levels in lungs of smokers
in
71:335-336

Public Health Service
64:6, 13, 127, 343

relationship of human pulmonary his-
tology and smoking in
71:155-157

relationship of lung neoplasms to smok-
ing, air pollution, and residence in
71:253-254

relationship of smoking to infectious
respiratory diseases in
71:227-229

relationship of tobacco use and lip neo-
plasms
71:36 1-365, 367

relationship of tobacco use and neo-
plasms of oral cavity
71:361-365, 367

retrospective studies in, neoplasms
64:150-165, 197-202, 205-209

serum lipid differences in smokers vs.
nonsmokers in
71:98, 100, 101

smokers in, by age
64:177

smoking and nicotine effects on animal
cardiovascular function in
71:107-112

smoking and nicotine effects on human
blood lipids
71:123-126

smoking and nicotine effects on human
cardiovascular system
71:113-114, 116, 117-119

smoking and nicotine effects on human
catecholamine levels
71119

smoking and nicotine effects on human
peripheral vascular system
71:133-134

smoking relationship to thombosis in
71:130, 131

surveys of cigarette smoking in
71:6
tracheobronchial tree changes in smokers
and nonsmokers in
71:259-263
white males in, mortality rates in
64:95
white population in, mortality tatios in
64:132
United States veterans
64:109, 174
chronic cough in
64:281, 282, 285
expected deaths in
64:109
mortality rates in
64:88, 293
mortality ratios in
64:109, 149, 174
nonresponse rate in
64:113
observed deaths in
64:109
respiratory performance in
64:297
smoker mortality rates in
64:115
University of Minnesota Hospital
64:140
Unsaturated fats
64:322
Unsaturated fatty acids
64:53
Uranium miners
lung neoplasms in
64:193; 67:143; 71:256
Urban areas
contribution to lung neoplasm mortality
TAL
coronary disease incidence in
64:322
hung neoplasm rates in
64:186, 194, 195; 71:276
relationship of lung neoplasms, smoking,
air pollution to
71::252-255
smoking prevalence in
64:99, 101, 364
Urbanization
64:186, 232
Urban populations
lung neoplasms in, suspected etiology of
increased
71:276
Urban vs. rural populations
bladder neoplasm prevalence
64:225
mortality rates
67:11
smoking and
67:97
Urethan
neoplasm promotion by
64:142
neoplasms from
64:143, 144
pulmonary adenomas from
64:144
Urinary tract diseases
see Urogenital diseases

Urinary tract neoplasms
see Urogenital neoplasms
Urogenital diseases
64:224
Urogenital neoplasms
cigarette smoke condensate as cause, in
animals
74:58
excretion of tryptophan in smokers vs.
nonsmokers with
74:58
incidence in males and females by age
68:104
incidence in smokers vs. nonsmokers
74:58
mortality and smoking factors in bladder
neoplasms
68:104, 105
mortality rates, by age
67:154
mortality rates, by amount smoked
67:154
mortality rates, by smoking classification
67:154
mortality ratios, by age
67:154
mortality ratios, by amount smoked -
67:154
mortality ratios, by smoking classifica-
tion
67:154
smoking and
69:60, 64; 75:50
summary of previous findings on tela-
tionship to smoking
68:89, 90; 74:57
see also Bladder neoplasms; Kidney neo-
plasms
Uterus
cigarette smoking effects on, in preg-
nancy
71:408

Vanillin
64:62
Vascular diseases, occlusive
64:319
smoking and
73:21
Vascular diseases, periphera!
carboxyhemoglobin levels and

72:26

epidemiologic studies
74:14-16

experimental studies
74:16

nicotine and
72:25

smokers vs. nonsmokers
72:26

smoking as a risk factor
72:2, 25, 26, 56; 73:19-23; 74:14-16
Vascular reconstruction
effect of smoking
73:22, 23

233
Vascular resistance
effect of cigarette smoke on
67:61
effect of histamine on
67:61
effect of nicotine on
67:60
effect of smoking on
67:60
Vascular system
peripheral, smoking and nicotine effect
on
71:9, 72-73, 75, 133-134
Vasoconstriction
fetal weight reduction by
64:343
nicotine induction of
64:318
pulmonary, effects of cigarette smoking
68:75, 76
Vegetable fibers
64:59
Venezuela
maternal smoking and infant weight in
71:450
methods used in smoking study and
human pregnancy
71:445
Ventilation
effects on constitutents of tobacco
smoke
7§:90-95
Ventilatory function
64:35, 292, 300, 302
effect of exercise and smoking
73:244, 245
Ventricular fibrillation
64:321
death from, nicotine effects on
71:36
effect of cigarette smoke in dogs
73:13, 14
Ventricular hypertrophy
as a risk factor in CHD
73:8
Ventricular premature beats
effect of cigarette smoking
75:20
Veterans
see Canadian veterans study; United
States veterans
Viruses
as etiologic agent in cancer
64:166, 230
influenza, cigarette smoke effects on
resistance of mice with
FA:173
influenza, nitrogen oxide effects on
squirrel monkey resistance to
71:173
neoplasm induction by
64:142
Vision
carboxyhemoglobin etfect on
64:344
effect of carbon monoxide
72:126

effect of smoking on
67:183
Vitamin B complex
deficiency, and tobacco ambylopia
67:40, 183
Vitamin B 12
deficiency,
64:212
deficiency, potentiation of cyanide in
tobacco ambylopia
67:40, 183
in pregnant smokers vs. nonsmokers
73:119
Vitamin C
effect on treadmill performance in smok-
ers vs. nonsmokers
73:245
in milk of smoking mothers
73:141
in pregnant smokers vs. nonsmokers
73:119
Vitamin D
and nicotine, effect on hypercholes-
terolemic rabbits
69:27
Vocal cords
effect of smoking on thickness
69:59-60
hyperkeratosis in
64:271
see also Larynx

Waiters
esophageal neoplasms in
64:134
oral neoplasms in
64:134
Washington University study
64:174
Water
hardness, and smoking as risk factors in
CHD
73:9, 10
soluble fraction of cigarettes, suppres-
sion of immunoglobulin response
78:77
Welsh miners
64:293, 294
Western Collaborative Group Study
CHD risk factors, in smokers vs. non-
smokers
68:25, 26
incidence of myocardial infarction in
younger male smokers
68:21
White House Conference on Narcotics and
Drug Abuse
64:355
White Pekin duck
nature of phagocytized clearance prod-
ucts in
64:269
Whites
canter mortality in
64:135
esophageal neoplasms in
64:218
laryngeal neoplasm prevalence in
64:209
mortality rates
64:133
mortality ratios by sex
64:133
smoking patterns in
64:363, 364
Wire implantation
64:166
Withdrawal
clinics
67:191
methods
64:354
symptoms
64:352, 354
see also Cessation of smoking
Women
autopsy studies, in smokers vs. nonsmok-
ers with emphysema, fibrosis, or
thickening of arterioles or arteries
75:75
blood pressure and smoking habits dur-
ing pregnancy
69:77-78
CHD incidence in
74:9, 10
exposure to chemicals, fumes, sprays and
dusts, in smokers vs. nonsmokers
75:69, 70
hypertension, in cigarette smokers with
CHD
68:22
incidence of lung neoplasms
68:97; 74:39, 40; 75:43
incidence of lung neoplasms and smok-

ing
69:4, 57

increase in mortality from lung neo-
plasms
75:47

mortality from lung neoplasms
68:97

mortality, in smokers vs. nonsmokers
68:6, 8,9

mortality rates from lung neoplasms and
asbestos exposure
74:42, 43

mortality rates from lung neoplasms,
statistical sex ratio
74:40, 45

mortality rates, in smokers vs. nonsmok-
ers
74:9, 10

myocardial infarction in pre- vs. post-
menopausal
74:10

myocardial infarction, in Swedish smok-
ers vs. nonsmokers
75:14

secular trends of lung neoplasm develop-
ment in
74:40

sudden death rates in
74:9, 10

summary of previous findings on effects
of smoking
75:5-7

trends in neoplasm incidence rates for
selected sites in
74:41, 42

Working classes

64:362

Work-loss days

definition
67:19

and smoking
67:20-21

World Health Organization

64:350, 354
classification of lung neoplasms
64:173, 174

Xenon

radioactive, regional pulmonary function
using
— 74:147
washout technique for detection of lung
neoplasms
74:43, 44

+? U.S. GOVERNMENT PRINTING OFFICE: 1976— 648/297