TaBLeE 1.—Deaths from selected disease categories, United States, 1962

 

 

  
   
 

 

 

 

Cause of death* Total Males Females

Degenerative and arteriosclerotic heart. disease, including coronary
disease (420, 422)___ 0.22. o. eee eee --- 577, 918 348, 604 229, 314
Hypertensive heart disease (440-3)_.____.. - 62, 176 26, 654 35, 522
Cancer of lung (162-3). __1.22.2 we - - 41, 376 35, 312 6, OR4
Cirrhosis of liver (581)_........_.__._._-.-.---.---- eee 21, 824 14, 329 7,495
Bronchitis and emphysema (502, 527.1)..-.-.._..__- a 15, 104 12, 937 2, 167
Stomach and duodenal ulcers (540-1) __ 12, 228 8, R36, 3, 292
Cancer of bladder (181). ___ . 8, 081 5, S76 2, 506
Cancer of oral cavity (140-8). - i, 481 4, 920 1, 561
Cancer of csophagms (150) ___- 5, ORS 3, 973 115
Cancer of larynx (161). 2,417 2, 172 245
All ahove causes. _.....2..22--.-222--- eee eee eee 752, 693 463, 312 289, 381
Allother causes. .._2-2 2220222. e seen 1, 004, 027 531, 477 472, 550
All causes... 2.2222 222202222 eee 1, 756, 720 994, 729 761, 93]

 

 

 

 

“International Statistical Classification numbers in parentheses.

Nearly 70 million people in the United States consume tobacco regularly.
Cigarette consumption in the United States has increased markedly since the
turn of the Century, when per capita consumption was less than 50 cigarettes
a year. Since 1910, when cigarette consumption per person (15 years and
older) was 138, it rose to 1,365 in 1930, to 1,828 in 1940, to 3,322 in 1950,
and to a peak of 3,986 in 1961. The 1955 Current Population Survey
showed that 68 percent of the male population and 32.4 percent of the female
population 18 years of age and over were regular smokers of cigarettes.

In contrast with this sharp increase in cigarette smoking, per capita use
of tobacco in other forms has gone down. Per capita consumption of cigars
declined from 117 in 1920 to 55 in 1962. Consumption of pipe tobacco,
which reached a peak of 2% lbs. per person in 1910, fell to a little more
than half a pound per person in 1962. Use of chewing tobacco has declined
from about four pounds per person in 1900 to half a pound in 1962.

The background for the Committee’s study thus included much general
information and findings from previous investigations which associated the
increase in cigarette smoking with increased deaths in a number of major
disease categories. It was in this setting that the Committee began its work
to assess the nature and magnitude of the health hazard attributable to
smoking.

Kinps OF EvIpENCE

In order to judge whether smoking and other tobacco uses are injurious
to health or related to specific diseases, the Committee evaluated three main
kinds of scientific evidence:

1. Animal experiments.—In numerous studies, animals have been exposed
to tobacco smoke and tars, and to the various chemical compounds they con-
tain. Seven of these compounds (polycyclic aromatic compounds) have been
established as cancer-producing (carginogenic). Other substances in tobacco
and smoke, though not carcinogenic themselves, promote cancer production
or lower the threshold to a known carcinogen. Several toxic or irritant gases
contained in tobacco smoke produce experimentally the kinds of non-can-
cerous damage seen in the tissues and cells of heavy smokers. This includes

26
suppression of ciliary action that normally cleanses the trachea and bronchi,
damage to the lung air sacs, and to mucous glands and goblet cells which
produce mucus.

2. Clinical and autopsy studies.—Observations of thousands of patients
and autopsy studies of smokers and non-smokers show that many kinds of
damage to body functions and to organs, cells, and tissues occur more fre-
quently and severely in smokers. Three kinds of cellular changes—loss of
ciliated cells, thickening (more than two layers of basal cells), and presence
of atypical cells—are much more common in the lining layer (epithelium)
of the trachea and bronchi of cigarette smokers than of non-smokers. Some
of the advanced lesions seen in the bronchi of cigarette smokers are probably
premalignant. Cellular changes regularly found at autopsy in patients with
chronic bronchitis are more often present in the bronchi of smokers than
non-smokers. Pathological changes in the air sacs and other functional tissue
of the lung (parenchyma) have a remarkably close association with past
history of cigarette smoking.

3. Population studies —Another kind of evidence regarding an association
between smoking and disease comes from epidemiological studies,

In retrospective studies, the smoking histories of persons with a specified
disease (for example, lung cancer) are compared with those of appropriate
control groups without the disease. For lung cancer alone, 29 such retrospec-
tive studies have been made in recent years. Despite many variations in de-
sign and method, all but one (which dealt with females) showed that pro-
Portionately more cigarette smokers are found among the lung cancer patients
than in the control populations without lung cancer.

Extensive retrospective studies of the prevalence of specific symptoms and
signs—chronic cough, sputum production, breathlessness, chest illness, and
decreased lung function—consistently show that these occur more often in
cigarette smokers than in non-smokers. Some of these signs and symptoms
are the clinical expressions of chronic bronchitis, and some are associated
more with emphysema; in general, they increase with amount of smoking and
decrease after cessation of smoking.

Another type of epidemiological evidence on the relation of smoking and
mortality comes from seven prospective studies which have been conducted
since 1951. In these studies, large numbers of men answered questions
about their smoking or non-smoking habits. Death certificates have been
obtained for those who died since entering the studies, permitting total death
Tates and death rates by cause to be computed for smokers of various types
as well as for non-smokers. The prospective studies thus add several im-
Portant dimensions to information on the smoking-health problem. Their
data permit direct comparisons of the death rates of smokers and non-
smokers, both overall and for individual causes of death, and indicate the
Strength of the association between smoking and specific diseases.

Each of these three lines of evidence was evaluated and then con-
sidered together in drawing conclusions. The Committee was aware that
the mere establishment of a statistical association between the use of tobacco
and a disease is not enough. The causal significance of the use of tobacco

in relation to the disease is the crucial question. For such judgments all three

27
lines of evidence are essential, as discussed in more detail on pages 26~27
of this Chapter, and in Chapter 3.

The experimental, clinical, and pathological evidence, as well as data
from population studies, is highlighted in Section B of this Chapter, which
in turn refers the reader to specific places in Part II of the Report where
this evidence is presented in detail.

In the paragraphs which follow, the Committee has chosen to summarize
the results of the seven prospective population studies which, as noted above,
constitute only one type of evidence. They illustrate the nature and potential
magnitude of the smoking-health problem, and bring out a number of factors
which are involved.

EvIpENCE FrRoM THE COMBINED RESULTS OF PROSPECTIVE
STUDIES

The Committee examined the seven prospective studies separately as well
as their combined results. Considerable weight was attached to the con-
sistency of findings among the several studies. However, to simplify presen-
tation, only the combined results are highlighted here.

Of the 1,123,000 men who entered the seven prospective studies and who
provided usable histories of smoking habits (and other characteristics such
as age), 37,391 men died during the subsequent months or years of the
studies. No analyses of data for females from prospective studies are
presently available.

To permit ready comparison of the mortality experience of smokers and
non-smokers, two concepts are widely used in the studies—excess deaths of
smokers compared with non-smokers, and mortality ratio. After adjustments
for differences in age and the number of cigarette smokers and non-smokers,
an expected number of deaths of smokers is derived on the basis of deaths
among non-smokers. Excess deaths are thus the number of actual (observed)
deaths among smokers in excess of the number expected. The mortality
ratio, for which the method of computation is described in Chapter 8,
measures the relative death rates of smokers and non-smokers. If the age-
adjusted death rates are the same, the mortality ratio will be 1.0; if the death
rates of smokers are double those of non-smokers, the mortality ratio will
be 2.0. (Expressed as a percentage, this example would be equivalent to a
100 percent increase. ).

Table 2 presents the accumulated and combined data on 14 disease cate-
gories for which the mortality ratio of cigarette smokers to non-smokers was
1.5 or greater.

The mortality ratio for male cigarette smokers compared with non-smokers,
for all causes of death taken together, is 1.68, representing a total death rate
nearly 70 percent higher than for non-smokers. (This ratio includes death
rates for diseases not listed in the table as well as for the 14 disease categories
shown. }

In the combined results from the seven studies, the mortality ratio of cig-
arette smokers over non-smokers was particularly high for a number of
diseases: cancer of the lung (10.8), bronchitis and emphysema (6.1), can-

28
TaBLE 2.'—Expected and observed deaths for smokers of cigarettes only and
mortality ratios in seven prospective studies

 

 

 
 
 
  
 
 
  
 
  

Underlying cause of death Expected | Observed | Mortality
deaths deaths ratio

Cancer of lung (162-3) ?._..- 12-12 eee ene nee 170.3 1, 833 10.8
Hronchitis and emphysema (502, 521.1) 89.5 546 6.1
Cancer of larynx (161)___. 14.0 75 5.4
Oral cancer (140-8) ..-.... 37.0 152 4.1
Cancer of esophagus (150) __ 33.7 3 3.4
Stomach and duodenal! ulcers (540, 541)_- 105.1 294 2.8
Other circulatory diseases (451-68)_.-...-..------..-----22- 2. = 254.0 649 2.6
Cirrhosis of liver (581) .. .._--_..--------2--2 2 eee eee eee - 169. 2 379 2.2
Cancer of bladder (181). ..._.--_. 2-2 eee eee ee - 11L.6 216 1.9
Coronary artery discase (420)_......---.---0- 22 eee eee eee - 6, 430. 7 11,177 1.7
Other heart diseases (421-2, 430-4) 526.0 BAR 17
Hypertensive heart (440-3). Ano, 2 631 15
General arteriosclerosis (450 210.7 310 1.5
Cancer of kidney (180)......_. 79.0 429 1.5
All canses 4 15, 653. 9 23, 223 1, 68

 

 

 

 

 

' Abridged from Table 26, Chapter 8, Mortality.
‘International Statistical Classification numbers in parentheses.
‘Includes all other causes of death as well as those listed above.

cer of the larynx (5.4), oral cancer (4.1), cancer of the esophagus (3.4),
peptic ulcer (2.8), and the group of other circulatory diseases (2.6). For
coronary artery disease the mortality ratio was 1.7.

Expressed in percentage-form, this is equivalent to a statement that for
coronary artery disease, the leading cause of death in this country, the death
rate is 70 percent higher for cigarette smokers. For chronic bronchitis and
emphysema, which are among the leading causes of severe disability, the
death rate for cigarette smokers is 500 percent higher than for non-smokers.
For lung cancer, the most frequent site of cancer in men, the death rate is
nearly 1,000 percent higher.

Other Findings of the Prospective Studies

In general, the greater the number of cigarettes smoked daily, the higher
the death rate. For men who smoke fewer than 10 cigarettes a day, accord-
'ng to the seven prospective studies, the death rate from all causes is about
40 percent higher than for non-smokers. For those who smoke from 10 to

9 cigarettes a day, it is about 70 percent higher than for non-smokers; for
those who smoke 20 to 39 a day, 90 percent higher; and for those who smoke
40 or more, it is 120 percent higher.

Cigarette smokers who stopped smoking before enrolling in the seven stud-
ies have a death rate about 40 percent higher than non-smokers, as against

0 percent higher for current cigarette smokers. Men who began smoking

fore age 20 have a substantially higher death rate than those who began
ter ape 25, Compared with non-smokers, the mortality risk of cigarette
smokers, after adjustments for differences in age, increases with duration of
smoking (number of years), and is higher in those who stopped after age 55
than for those who stopped at an earlier age.

In two studies which recorded the degree of inhalation, the mortality ratio
°r a given amount of smoking was greater for inhalers than for non-inhalers.

€ ratio of the death rates of smokers to that of non-smokers is highest

all

29
at the earlier ages (40-50) represented in these studies, and declines with
increasing age.

Possible relationships of death rates and other forms of tobacco use were
also investigated in the seven studies. The death rates for men smoking
less than 5 cigars a day are about the same as for non-smokers. For men
smoking more than 5 cigars daily, death rates are slightly higher. There
is some indication that these higher death rates occur primarily in men
who have been smoking more than 30 years and who inhale the smoke to
some degree. The death rates for pipe smokers are little if at all higher
than for non-smokers, even for men who smoke 10 or more pipefuls a day
and for men who have smoked pipes more than 30 years.

Excess Mortality

Several of the reports previously published on the prospective studies
included a table showing the distribution of the excess number of deaths
of cigarette smokers among the principal causes of death. The hazard must
be measured not only by the mortality ratio of deaths in smokers and non-
smokers, but also by the importance of a particular disease as a cause of
death.

In all seven studies, coronary artery disease is the chief contributor to
the excess number of deaths of cigarette smokers over non-smokers, with
lung cancer uniformly in second place. For all seven studies combined,
coronary artery disease (with a mortality ratio of 1.7) accounts for 45 per-
cent of the excess deaths among cigarette smokers, whereas lung cancer
(with a ratio of 10.8) accounts for 16 percent.

Some of the other categories of diseases that contribute to the higher death
rates for cigarette smokers over non-smokers are diseases of the heart and
blood vessels, other than coronary artery disease, 14 percent; cancer sites
other than lung, 8 percent; and chronic bronchitis and emphysema, 4 percent.

Since these diseases as a group are responsible for more than 85 percent
of the higher death rate among cigarette smokers, they are of particular
interest to public health authorities and the medical profession.

ASSOCIATIONS AND CAUSALITY

The array of information from the prospective and retrospective studies of
smokers and non-smokers clearly establishes an association between cigarette
smoking and substantially higher death rates. The mortality ratios in Table
2 provide an approximate index of the relative strength of this association,
for all causes of death and for 14 disease categories.

In this inquiry the epidemiologic method was used extensively in the
assessment of causal factors in the relationship of smoking to health among
human beings upon whom direct experimentation could not be imposed.
Clinical, pathological, and experimental evidence was thoroughly considered
and often served to suggest an hypothesis or confirm or contradict other
findings. When coupled with the other data, results from the epidemiologic

30
studies can provide the basis upon which judgments of causality may be
made.

It is recognized that no simple cause-and-effect relationship is likely to exist
between a complex product like tobacco smoke and a specific disease in the
variable human organism. It is also recognized that often the coexistence of
several factors is required for the occurrence of a disease, and that one of the
factors may play a determinant role; that is, without it, the other factors
(such as genetic susceptibility) seldom lead to the occurrence of the disease.

THE EFFECTS OF SMOKING: PRINCIPAL FINDINGS

Cigarette smoking is associated with a 70 percent increase in the age-
specific death rates of males, and to a lesser extent with increased death
rates of females. The total number of excess deaths causally related to
cigarette smoking in the U.S. population cannot be accurately estimated.
In view of the continuing and mounting evidence from many sources, it
is the judgment of the Committee that cigarette smoking contributes sub-
stantially to mortality from certain specific diseases and to the overall death
Tate.

Lung Cancer

Cigarette smoking is causally related to lung cancer in men; the magni-
tude of the effect of cigarette smoking far outweighs all other factors. The
data for women, though less extensive, point in the same direction.

The risk of developing lung cancer increases with duration of smoking
and the number of cigarettes smoked per day, and is diminished by dis-
continuing smoking. In comparison with non-smokers, average male
smokers of cigarettes have approximately a 9- to 10-fold risk of developing
lung cancer and heavy smokers at least a 20-fold risk.

The risk of developing cancer of the lung for the combined group of pipe
smokers, cigar smokers, and pipe and cigar smokers is greater than for
non-smokers, but much less than for cigarette smokers.

Cigarette smoking is much more important than occupational exposures
in the causation of lung cancer in the general population.

Chronic Bronchitis and Emphysema

Cigarette smoking is the most important of the causes of chronic bronchi-
tis in the United States, and increases the risk of dying from chronic bron-
chitis and emphysema. A relationship exists between cigarette smoking and
emphysema but it has not been established that the relationship is causal.
Studies demonstrate that fatalities from this disease are infrequent among
non-smokers.

For the bulk of the population of the United States, the relative importance
of cigarette smoking as a cause of chronic broncho-pulmonary disease is
much greater than atmospheric pollution or occupational exposures.

714-422 O-64—4 31
Cardiovascular Diseases

It is established that male cigarette smokers have a higher death rate
from coronary artery disease than non-smoking males. Although the
causative role of cigarette smoking in deaths from coronary disease is not
proven, the Committee considers it more prudent from the public health
viewpoint to assume that the established association has causative meaning
than to suspend judgment until no uncertainty remains.

Although a causal relationship has not been established, higher mortality
of cigarette smokers is associated with many other cardiovascular diseases,
including miscellaneous circulatory diseases, other heart diseases, hyper-
tensive heart disease, and general arteriosclerosis.

Other Cancer Sites

Pipe smoking appears to be causally related to lip cancer. Cigarette
smoking is a significant factor in the causation of cancer of the larynx.
The evidence supports the belief that an association exists between tobacco
use and cancer of the esophagus, and between cigarette smoking and cancer
of the urinary bladder in men, but the data are not adequate to decide
whether these relationships are causal. Data on an association between
smoking and cancer of the stomach are contradictory and incomplete.

Tue Topacco Hapit AND NICOTINE

The habitual use of tobacco is related primarily to psychological and
social drives, reinforced and perpetuated by the pharmacological actions
of nicotine.

Social stimulation appears to play a major role in a young person’s early
and first experiments with smoking. No scientific evidence supports the
popular hypothesis that smoking among adolescents is an expression of
rebellion against authority. Individual stress appears to be associated more
with fluctuations in the amount of smoking than with the prevalence of smok-
ing. The overwhelming evidence indicates that smoking—its beginning,
habituation, and occasional discontinuation—is to a very large extent psy-
chologically and socially determined.

Nicotine is rapidly changed in the body to relatively inactive substances
with low toxicity. The chronic toxicity of small doses of nicotine is low
in experimental animals. These two facts, when taken in conjunction with
the low mortality ratios of pipe and cigar smokers, indicate that the chronic
toxicity of nicotine in quantities absorbed from smoking and other methods
of tobacco use is very low and probably does not represent an important
health hazard.

The significant beneficial effects of smoking occur primarily in the area
of mental health, and the habit originates in a search for contentment. Since
no means of measuring the quantity of these benefits is apparent, the Com-
mittee finds no basis for a judgment which would weigh benefits against
hazards of smoking as it may apply to the general population.

32
THE CoMMITTEE’S JUDGMENT IN BRIEF

On the basis of prolonged study and evaluation of many lines of converging
evidence, the Committee makes the following judgment:

Cigarette smoking is a health hazard of sufficient importance in
the United States to warrant appropriate remedial action.

B. COMMENTS AND DETAILED CONCLUSIONS
(A Guide to Part II of the Report)

All conclusions formally adopted by the Committee are presented at the
end of this section in bold-faced type for convenience of reference. In the
interest of conciseness, the documentation and most of the discussion are
omitted from this condensation. Together with the tables of contents which
appear at the beginning of each chapter in Part II, it is intended as a guide
to the Report.

CHEMISTRY AND CARCINOGENICITY OF TOBACCO AND TOBACCO
SMOKE

Condensates of tobacco smoke are carcinogenic when tested by application
to the skin of mice and rabbits and by subcutaneous injection in rats (Chap-
ter 9, pp. 143-145). Bronchogenic carcinoma has not been produced by the
application of tobacco extracts, smoke, or condensates to the lung or the
tracheobronchial tree of experimental animals with the possible exception
of dogs (Chapter 9, p. 165).

Bronchogenic carcinoma has been produced in laboratory animals by the
administration of polycyclic aromatic hydrocarbons, certain metals, radio-
active substances, and viruses. The histopathologic characteristics of the
tumors produced are similar to those observed in man and are predominantly
of the squamous variety (Chapter 9, pp. 166-167).

Seven polycyclic hydrocarbon compounds isolated from cigarette smoke
have been established to be carcinogenic in laboratory animals. The results
of a number of assays for carcinogenicity of tobacco smoke tars present a
puzzling anomaly: the total tar from cigarettes has many times the carcino-
genic potency of benzo(a)pyrene present in the tar. The other carcinogens
known to be present in tobacco smoke are, with the exception of dibenzo(a,i)
pyrene, much less potent than benzo(a) pyrene and they are present in smaller
amounts. Apparently, therefore, the whole is greater than the sum of the
known parts. This discrepancy may possibly be due to the presence of
cocarcinogens in tobacco smoke, and/or damage to mucus production and
ciliary transport mechanism (Chapter 6, p. 61, Chapter 9, p. 144 and Chap-
ter 10, pp. 267-269) .

ere is abundant evidence that cancer of the skin can be induced in man
by industrial exposure to soots, coal tar, pitch, and mineral oils. All of these

33
contain various polycyclic aromatic hydrocarbons proven to be carcinogenic
in many species of animals. Some of these hydrocarbons are also present
in tobacco smoke. It is reasonable to assume that these can be carcinogenic
for man also (Chapter 9, pp. 146-148).

Genetic factors play a significant role in the development of pulmonary
adenomas in mice. It is possible that genetic factors can influence the smok-
ing habit and the response in man to carcinogens in smoke. However, there
is no evidence that they have played an appreciable role in the great increase
of lung cancer in man since the beginning of this century (Chapter 9, p. 190).

Components of the gas phase of cigarette smoke have been shown to pro-
duce various undesirable effects on test animals or organs. One of these
effects is suppression of ciliary transport activity, an important cleansing
function in the trachea and bronchi (Chapter 6, p. 61 and Chapter 10, pp.
267-270).

CHARACTERIZATION OF THE Tosacco Hasit

The habitual use of tobacco is related primarily to psychological and
social drives, reinforced and perpetuated by the pharmacological actions
of nicotine on the central nervous system. Nicotine-free tobacco or other
plant materials do not satisfy the needs of those who acquire the tobacco
habit (Chapter 13, p. 354).

The tobacco habit should be characterized as an habituation rather than
an addiction. Discontinuation of smoking, although possessing the difficul-
ties attendant upon extinction of any conditioned reflex, is accomplished best
by reinforcing factors which interrupt the psychogenic drives. Nicotine
substitutes or supplementary medications have not been proven to be of

major benefit in breaking the habit (Chapter 13, p. 354).

PATHOLOGY AND MorpnoLocy

Several types of epithelial changes are much more common in the trachea
and bronchi of cigarette smokers, with or without lung cancer, than of non-
smokers and of patients without lung cancer. These epithelial changes are
(a) loss of cilia, (b) basal cell hyperplasia, and (c) appearance of atypical
cells with irregular hyperchromatic nuclei. The degree of each of the
epithelial changes in general increases with the number of cigarettes smoked.
Extensive atypical changes have been seen most frequently in men who smoked
two or more packs of cigarettes a day.

Women cigarette smokers, in general, have the same epithelial changes as
men smokers. However, at given levels of cigarette use, women appear to
show fewer atypical cells than do men. Older men smokers have more atypical
cells than younger men smokers. Men who smoke either pipes or cigars
have more epithelial changes than non-smokers, but have fewer changes than
cigarette smokers consuming approximately the same amount of tobacco.
Male ex-cigarette smokers have less hyperplasia and fewer atypical cells
than current cigarette smokers.

It may be concluded, on the basis of human and experimental evidence,
that some of the advanced epithelial hyperplastic lesions with many atypical

34
cells, as seen in the bronchi of cigarette smokers, are probably premalignant
(Chapter 9, pp. 167-173).

Typing of Tumors.—Squamous and oval-cell carcinomas (Group I of
Kreyberg’s classification) comprise the predominant types associated with
the increase of lung cancer in the male population. In several studies,
adenocarcinomas (Group II) have also shown a definite increase, although
to a much lesser degree. The histological typing of lung cancer is reliable,
but the use of the ratio of histological types as an index of the magnitude of
increase in lung cancer is of limited value (Chapter 9, pp. 173-175).

Functional and Pathological Changes.—Cigarette smoke produces signif-
icant funtional alterations in the trachea, bronchus, and Jung. Like several
other agents, cigarette smoke can reduce or abolish ciliary motility in experi-
mental animals. Postmortem examination of bronchi from smokers shows
a decrease in the number of ciliated cells, shortening of the remaining cilia,
and changes in goblet cells and mucous glands. The implication of these
morphological observations is that functional impairment would result.

In animal experiments, cigarette smoke appears to affect the physical
characteristics of the lung-lining layer and to impair alveolar (air sac)
stability. Alveolar phagocytes ingest tobacco smoke components and assist
in their removal from the lung. This phagocytic clearance mechanism
breaks down under the stress of protracted high-level exposure to cigarette
smoke, and smoke components accumulate in the lungs of experimental
animals (Chapter 10, pp. 269-270).

The chronic effects of cigarette smoking upon pulmonary function are
manifested mainly by a reduction in ventilatory function as measured by
the forced expiratory volume (Chapter 10, pp. 289-292).

Histopathological alterations occur as a result of tobacco smoke exposure
n the tracheobronchial tree and in the lung parenchyma of man. Changes
‘egularly found in chronic bronchitis—increase in the number of goblet
vells, and hypertrophy and hyperplasia of bronchial mucous glands—are
nore often present in the bronchi of smokers than non-smokers. Cigarette
smoke produces significant functional alterations in the upper and lower
urways to the lungs. Such alterations could be expected to interfere with
he cleansing mechanisms of the lung.

Pathological changes in pulmonary parenchyma, such as rupture of
Iveolar septa (partitions of the air sacs) and fibrosis, have a remarkably
‘lose association with past history of cigarette smoking. These latter changes
‘annot be related with certainty to emphysema or other recognized diseases
't the present time (Chapter 10, pp. 270-275).

MorTALITY

The death rate for smokers of cigarettes only, who were smoking at the
ime of entry into the particular prospective study, is about 70 percent higher
han that for non-smokers. The death rates increase with the amount smoked.
*or groups of men smoking less than 10, 10-19, 20-39, and 40 cigarettes
ind over per day, respectively, the death rates are about 40 percent, 70 per-

35
cent, 90 percent, and 120 percent higher than for non-smokers. The ratio of
the death rates of smokers to non-smokers is highest at the earlier ages (40-
50) represented in these studies, and declines with increasing age. The same
effect appears to hold for the ratio of the death rate of heavy smokers to that
of light smokers. In the studies that provided this information, the mortality
ratio of cigarette smokers to non-smokers was substantially higher for men
who started to smoke under age 20 than for men who started after age 25,
The mortality ratio was increased as the number of years of smoking in.
creased. In two studies which recorded the degree of inhalation, the mor.
tality ratio for a given amount of smoking was greater for inhalers than for
non-inhalers. Cigarette smokers who had stopped smoking prior to enroll.
ment in the study had mortality ratios about 1.4 as against 1.7 for current
cigarette smokers. The mortality ratio of ex-cigarette smokers increased
with the number of years of smoking and was higher for those who stopped
after age 55 than for those who stopped at an earlier age (Chapter 8, p. 93),

The biases from non-response and from errors of measurement that are
difficult to avoid in mass studies may have resulted in some over-estimation
of the true mortality ratios for the complete populations. In our judgment,
however, such biases can account for only a part of the elevation in mortality
ratios found for cigarette smokers (Chapter 8, p- 96).

Death rates of cigar smokers are about the same as those of non-smokers
for men smoking less than five cigars daily. For men smoking five or more
cigars daily, death rates were slightly higher (9 percent to 27 percent) than
for non-smokers in the four studies that gave this information. There is some
indication that this higher death rate occurs primarily in men who have been
smoking for more than 30 years and in men who stated that they inhaled the
smoke to some degree. Death rates for current pipe smokers were little if at
all higher than for non-smokers, even with men smoking 10 or more pipefuls
per day and with men who had smoked pipes for more than 30 years. Ex.
cigar and ex-pipe smokers, on the other hand, showed higher death rates than
both non-smokers and current pipe or cigar smokers in four out of five
studies (Chapter 8, p. 94). The explanation is not clear but may be that
a substantial number of such smokers stopped because of illness.

Mortality by Cause of Death—lIn the combined results from the seven
prospective studies, the mortality ratio of cigarette smokers was particularly
high for a number of diseases. There is a further group of diseases, including
some of the most important chronic diseases, for which the mortality ratio
for cigarette smokers lay between 1.2 and 2.0. The explanation of the
moderate elevations in mortality ratios in this large group of causes is not
clear. Part may be due to the sources of bias previously mentioned or to
some constitutional and genetic difference between cigarette smokers and
non-smokers. There is also the possibility that cigarette smoking has some
general debilitating effect, although no medical evidence that clearly supports
this hypothesis can be cited (Chapter 8, p. 105).

In all seven studies, coronary artery disease is the chief contributor to the
excess number of deaths of cigarette smokers over non-smokers, with lung
cancer uniformly in second place (Chapter 8, p. 108).

36
For cigar and pipe smokers combined, there was a suggestion of high
mortality ratios for cancers of the mouth, esophagus, larynx and lung, and
for stomach and duodenal ulcers. These ratios are, however, based on small
numbers of deaths (Chapter 8, p. 107).

CANCER BY SITE

Lung Cancer

Cigarette smoking is causally related to lung cancer in men; the
magnitude of the effect of cigarette smoking far outweighs all other
factors. The data for women, though less extensive, point in the
same direction.

The risk of developing lung cancer increases with duration of
smoking and the number of cigarettes smoked per day, and is
diminished by discontinuing smoking.

The risk of developing cancer of the lung for the combined group
of pipe smokers, cigar smokers, and pipe and cigar smokers, is
greater than for non-smokers, but much less than for cigarette
smokers. The data are insufficient to warrant a conclusion for
each group individually (Chapter 9, p. 196).

Oral Cancer

The causal relationship of the smoking of pipes to the develop-
ment of cancer of the lip appears to be established.

Although there are suggestions of relationships between cancer
of other specific sites of the oral cavity and the several forms of
tobacco use, their causal implications cannot at present be stated

(Chapter 9, pp. 204-205).

Cancer of the Larynx

Evaluation of the evidence leads to the judgment that cigarette
smoking is a significant factor in the causation of laryngeal cancer
in the male (Chapter 9, p. 212).

Cancer of the Esophagus

The evidence on the tobacco-esophageal cancer relationship sup-
ports the belief that an association exists. However, the data are
a adequate to decide whether the relationship is causal (Chapter

2p. 218).

Cancer of the Urinary Bladder

Available data suggest an association between cigarette smoking
and urinary bladder cancer in the male but are not sufficient to
support a judgment on the causal significance of this association

(Chapter 9, p. 225).

37
Stomach Cancer

No relationship has been established between tobacco use and
stomach cancer (Chapter 9, p. 229).

Non-NEopuastic RESPIRATORY DIsEASES, PARTICULARLY CHRONIC
BRONCHITIS AND PuLMonary EMPHYSEMA

Cigarette smoking is the most important of the causes of chronic
bronchitis in the United States, and increases the risk of dying from
chronic bronchitis.

A relationship exists between pulmonary emphysema and cig-
arette smoking but it has not been established that the relationship
iscausal. The smoking of cigarettes is associated with an increased
risk of dying from pulmonary emphysema.

For the bulk of the population of the United States, the impor.
tance of cigarette smoking as a cause of chronic bronchopulmonary
disease is much greater than that of atmospheric pollution or
occupational exposures.

Cough, sputum production, or the two combined are consistently
more frequent among cigarette smokers than among non-smokers,

Cigarette smoking is associated with a reduction in ventilatory
function. Among males, cigarette smokers have a greater preva-
lence of breathlessness than non-smokers.

Cigarette smoking does not appear to cause asthma.

Although death certification shows that cigarette smokers have
a moderately increased risk of death from influenza and pneumonia,
an association of cigarette smoking and infectious diseases is not

otherwise substantiated (Chapter 10, p- 302).

CARDIOVASCULAR DISEASE

Smoking and nicotine administration cause acute cardiovascular effects
similar to those induced by stimulation of the autonomic nervous system,
but these effects do not account well for the observed association between
cigarette smoking and coronary disease. It is established that male cigarette
smokers have a higher death rate from coronary disease than non-smoking
males. The association of smoking with other cardiovascular disorders is
less well established. If cigarette smoking actually caused the higher death
rate from coronary disease, it would on this account be responsible for
many deaths of middle-aged and elderly males in the United States. Other
factors such as high blood pressure, high serum cholesterol, and excessive
obesity are also known to be associated with an unusually high death rate
from coronary disease. The causative role of these factors in coronary
disease, though not proven, is suspected strongly enough to be a major
reason for taking countermeasures against them. It is also more prudent to
assume that the established association between cigarette smoking and coro-

38
nary disease has causative meaning than to suspend judgment until no un-
certainty remains (Chapter 11, p. 327).

Male cigarette smokers have a higher death rate from coronary
artery disease than non-smoking males, but it is not clear that the
association has causal significance.

OTHER ConDITIONS

Peptic Ulcer

Epidemiological studies indicate an association between cigarette
smoking and peptic ulcer which is greater for gastric than for
duodenal ulcer (Chapter 12, p. 340).

Tobacco Amblyopia

Tobacco amblyopia (dimness of vision unexplained by an or-
ganic lesion) has been related to pipe and cigar smoking by clini-
cal impressions. The association has not been substantiated by
epidemiological or experimental studies (Chapter 12, p. 342).

Cirrhosis of the Liver

Increased mortality of smokers from cirrhosis of the liver has
been shown in the prospective studies. The data are not sufficient
to support a direct or causal association (Chapter 12, p. 342).

Maternal Smoking and Infant Birth W. eight

Women who smoke cigarettes during pregnancy tend to have
babies of lower birth weight.

Information is lacking on the mechanism by which this decrease
in birth weight is produced.

It is not known whether this decrease in birth weight has any

influence on the biological fitness of the newborn (Chapter 12,
p. 343),

Smoking and Accidents

Smoking is associated with accidental deaths from fires in the
home,

No conclusive information is available on the effects of smoking
on traffic accidents (Chapter 12, p. 345).

MorpPHotocicaL ConstTiTUTION OF SMOKERS

_ The available evidence suggests the existence of some morpholog-
leal differences between smokers and non-smokers, but is too
meager to permit a conclusion (Chapter 15, p. 387).

39
PsycHo-SociaL ASPECTS OF SMOKING

A clear cut smoker’s personality has not emerged from the results so far
published. While smokers differ from non-smokers in a variety of charac.
teristics, none of the studies has shown a single variable which is found solely
in one group and is completely absent in another. Nor has any single varia-
ble been verified in a sufficiently large proportion of smokers and in suff.
ciently few non-smokers to consider it an “essential” aspect of smoking.

The overwhelming evidence points to the conclusion that smok-
ing—its beginning, habituation, and occasional discontinuation—is
to a large extent psychologically and socially determined. This
does not rule out physiological factors, especially in respect to
habituation, nor the existence of predisposing constitutional or
hereditary factors (Chapter 14, p- 377).
PART II

 

Evidence of the
Relation Between Smoking
and Health
uhapter 5

 

Consumption of
Tobacco Products in
the United States
List of Tables

Page

TaBLeE 1. Tobacco products: Consumption per capita, 15 years
and over, United States, 1900-1962 ....... 45

TaBLe 2. Filter tip cigarettes: estimated output and percentage
distribution. . 2... 2... ee 46
 

Chapter 5

 

CONSUMPTION OF TOBACCO PRODUCTS
IN THE UNITED STATES

The U.S. Department of Agriculture estimates that the total number of
persons in the United States, including overseas members of the Armed
Forces, who consume tobacco on a regular basis is close to 70 million (1).

Consumption of tobacco products per capita. 15 years and over, has risen
from 7.42 pounds in 1900 to 10.85 pounds in 1962. Cigarette consumption
increased steadily from 1910. when the per capita consumption was 138
cigarettes, to the 1962 figure of 3,958. Per capita cigar consumption re-
mained steady at slightly over 100 in the first two decades of the century,
but started to decrease in 1921. The figure for 1920 is 117, and for 1962
itis 55. Per capita consumption of pipe tobacco remained steady until the
mid-1940’s. In 1945 the figure was 1.59 pounds, but in 1962 it was just
over half a pound (0.56). Consumption of chewing tobacco showed a de-
cline during about the same period, from 1.09 pounds per capita in 1945

to 0.50 in 1962. Consumption of snuff has shown very little change (2)
(Table 1).

TaBLe 1.—Consumption of tobacco products per person aged 15 years and
over in the United States for selected years, 1900-1962

 

 

 

 

 

 

|
. All tobacco, | Cigarettes, Cigars, Pipe tobacco, Chewing
Yeur pounds number number \ pounds tobacco, Snuff, pounds
| pounds
|
I
7.42 49 | 1 1.63 4.10 0. 32
8. 59 138 113 2. 58 3.99 - 50
8.66 611 117 1.96 3.06 - 0
8. 88 1, 365 72 1.87 1.0 46
8.91 1, 828 56 2.05 1.00 . 38
11.59 3, 322 50 . 94 78 . 36
10. 97 3, 888 57 . 59 -51 29
11.15 3, 986 56 . 59 | - 51 27
10. 85 3, 958 55 . 56 . 50 - 26

 

 

Source: Department of Agriculture, Economie Research Service.

Starting in 1950, production of filter tip cigarettes began to rise. Un-
official estimates for 1950 show that only about half of one percent of ciga-
rettes produced were filter tip. In 1952, unofficial estimates show 1.3 per-
cent of cigarettes produced were filter tips. In 1956 the ficure had reached
27.6 percent. From 1958 on, official estimates, based on figures reported
to the Department of Agriculture by the industry, show a continuous in-
Crease from 45.3 percent filter tip cigarettes produced in 1958 to 54.6 percent
Produced in 1962 (3) (Table 2).

45
TABLE 2.—Estimated output of filter-tip cigarettes and percentage of total
cigarette production, United States, 1950-1962

 

 

Filter-tip Percent of Filter-tip Percent of
Year cigarettes total Year cigarettes total
(billions) (billions)
2.2 0.6 168. 3 38.0
3.0 0.7 213.0 45.3
5.6 1.3 238.8 48.7
12.4 2.9 258.0 50.9
36.9 9.2 277.1 52.5
77.0 18.7 292. 5 54.6
116.9 27.6

 

 

 

 

 

 

*Data from 1958 through 1962 are official estimates from Census of Manufacturers.
Source: U.S. Department of Agriculture, Economic Research Service.

REFERENCES

1, U.S. Department of Agriculture. Special report to the Surgeon General’s
Advisory Committee on Smoking and Health.

2. U.S. Department of Agriculture. Economic Research Service. Tobacco
products. Consumption per capita. 15 years and over, United States,
1900-62.

3. U.S. Department of Agriculture. Economic Research Service. The
tobacco situation. March 1962, March 1963, September 1963.
Chapter 6

 

Chemical and Physical
Characteristics of Tobacco

and Tobacco Smoke

714-429 0-645
Contents

Page
CHEMISTRY OF TOBACCO... ............ 49
COMPOSITION OF CIGARETTE SMOKE........ 50

COMPOUNDS OF THE PARTICULATE PHASE OTHER
THAN HIGHER POLYCYCLICS..........2.. 5]
Aliphatic and Alicyclic Hydrocarbons... ... 2... 51
Terpenes and Isoprenoid Hydrocarbon... ....... 51
Aleohols and Esters . . 2... 1... eee ee ee 59
Sterols . . 6 1 ee ee ee ee 59
Aldehydes and Ketones. . . . . 2... ee ee ee ee 59
Acids . 6 6 ee ee 53
Phenols and Polyphenols... . . 1... 2.1 ee ee 54
Alkaloids, Nitrogen Bases, and Heterocyclics . . . . .. . 54
Amino Acids... 1. 6 6 ee ee ee ee 54
Inorganic Components... . . - 2. ee eee ee 55
Noncarcinogenic Aromatic Hydrocarbons. . ...... . 53

CARCINOGENIC HYDROCARBONS AND HETEROCY-
CLICS IN TOBACCO SMOKE ............. 55
COCARCINOGENS..... 2... ee ee eee ee 58
MECHANISM OF THE FORMATION OF CARCINOGENS . 59
THE GAS PHASE... ...- 2-2-0. 0 eee ee ee 60
EFFECTS ON CILIARY ACTIVITY. .......... 61
PESTICIDES AND ADDITIVES... .......... 61
SUMMARY... . 2... ee ee ee ee ee 62
REFERENCES... ... 2-022 0 eee ee ee 63

List of Tables

TasLe 1. Major classes of compounds in the particulate phase
of cigarette smoke .. .. 2... +e ee eee 51

Taste 2. Carcinogenic polycyclic compounds isolated from
cigarette smoke. 2 6. ee ee ee ee ee a6

Taste 3. Polycyclic hydrocarbons isolated from tobacco
smoke... 6. 6 ee ee ee ee ee 38
TaBLe 4. Some gases found in cigarette smoke... ... . 60

48
 

Chapter 6

 

Tobacco is an herb which man has smoked for over 300 years. The
plant was given the generic name Nicotiana after Jean Nicot, French ambas-
sador to Portugal, who in 1560 publicly extolled the virtue of tobacco as
a curative agent. The species Nicotiana tabacum is now the chief source
of smoking tobacco and is the only species cultivated in the United States.

CHEMISTRY OF TOBACCO

The tobacco leaf contains a complex mixture of chemical components:
cellulosic products, starches, proteins, sugars, alkaloids, pectic substances,
hydrocarbons, phenols, fatty acids, isoprenoids, sterols, and inorganic min-
erals. Many of the several hundred components isolated have been found to
occur also in other plants. Two groups of components are specific to tobacco
and have not as yet been isolated from other natural sources. One includes
the alkaloid nicotine and the related companion substances nornicotine,
myosmine, and anabasine. These nitrogen-containing substances are all

 

a oO ~ oO
} } oy — )
SS
Sy cH Sy H N Sy H
Nicotine Nornicotine Myosmine Anabasine

basic and hence extractable with acid. Seven members of a second group
of compounds fairly distinctive to tobacco have been isolated and charac-
terized (1962-63) by D. L. Roberts and R. L. Rowland(36). They are de-
scribed as isoprenoids, since the structures are divisible into units of isoprene,
the building principle of rubber, of the red pigment of the tomato, and
of the yellow pigment of the carrot, as illustrated in the following formulas:

MON CHs

Cc Cc
“EO
H c Cc Cc c Cc
CHs Ne Ng YNG YN”
OH | |
co Ne oO

HC

   

HC on ® |
Cc
Isoprenoid tobacco
component 4 Isoprene units

Although none of the 7 isoprenoid components of tobacco has been isolated
from another source, the hydrocarbon cembrene from a pine exudate has
the same 14-membered ring with the same complement of an isopropyl group
at GC: and methyl groups at Cs, Cs, and Cz (9).

49
COMPOSITION OF CIGARETTE SMOKE

Cigarette smoke is an heterogeneous mixture of gases, uncondensed vapors,
and liquid particulate matter (32). As it enters the mouth the smoke is q
concentrated aerosol with millions or billions of particles per cubic centimete;
(25, 30). The median size of the particles is about 0.5 micron (1). Fo,
purposes of investigating chemical composition and biological properties,
smoke is separated into a particulate phase and a gas phase, and the gas phase
is frequently subdivided into materials which condense at liquid-air tempera.
ture and those which do not. The large quantities of material required fo;
investigation of the chemical components are prepared on smoking machines
(25) in which large numbers of cigarettes are smoked simultaneously in q
fashion designed to simulate average smoking habits, and a yellow-brown
condensate known as tobacco tar is collected in traps cooled to the temperature
of dry ice (70° C.) or liquid nitrogen (—196° C.). The tar thus containg
all of the particulate phase of smoke as well as condensable components of the
gas phase. The amount of tar from the smoke of one cigarette is between
3 and 40 mg., the quantity varying according to the burning and condensing
conditions, the length of the cigarette, the use of a filter, porosity of paper,
content of tobacco, weight and kind of tobacco.

An important factor determining the composition of cigarette smoke is the
temperature in the burning zone. While air is being drawn through the
cigarette the temperature of the burning zone reaches approximately 884° (.
and when the cigarette is burning without air being drawn through it the
temperature is approximately 835° C. (42). The smoke generated during
puffing, when air is being drawn through the cigarette, is called main-stream
smoke; that generated when the cigarette is burning at rest is called side.
stream smoke. At the temperatures cited extensive pyrolytic reactions occur.
Some of the many constituents of tobacco are stable enough to distil un.
changed, but many others suffer extensive reactions involving oxidation,
dehydrogenation, cracking, rearrangement, and condensation. The large
number and variety of compounds in tobacco smoke tar is reminiscent of the
composition of the tar formed on carbonization of coal, which in many cases
is conducted at temperatures lower than those of a burning cigarette. It is
thus not surprising that some 500 different compounds have been identified
in either the particulate phase of cigarette smoke or in the gas phase.

In one study (50) regular cigarettes (70 mm. long, about 1 g. each) with.
out filter tips produced 17—10 mg. of tar per cigarette. In another investiga-
tion (43) 174,000 regular size American cigarettes afforded a total of 4 kg.
of tar, an average of 23 mg. per cigarette. In still another study (31) 34,000
70-mm. cigarettes were smoked mechanically on a constant puff-volume type
machine with which 35-ml. puffs, each of two seconds duration, were taken
at one minute intervals from each cigarette. Eight puffs were required to
smoke each cigarette to an average butt length of 30 mm. The smoke was
condensed in a series of three glass traps cooled in liquid air. The conden.
sate was rinsed out of the traps with ether, water, and hexane. The yield of
condensate nonvolatile at 25° C. and 25 mm. of mercury was 20.9 mg. per
cigarette.

20