“The term asthma is not appropriate for the bronchial narrowing
which results solely from widespread bronchial infection, e.g., acute or
chronic bronchitis; from destructive diseases of the lung, e.g., pulmonary
emphysema; or from cardiovascular disorders. Asthma, as here defined,
may occur in vascular diseases, but in these instances the airway obstruc.
tion is not causally related to these diseases.”

In rare instances, allergy to tobacco products has been ascribed a causa-
tive role in asthma (99, 105, 168, 169, 189). Support for this association
comes largely from the presence of skin test reactions to tobacco products
and passive transfer tests (168, 169).

In the “Tokyo-Yokohama Asthma” studies, a severe asthma-like disease,
presumed to be caused by air pollution, affected cigarette smokers predomi-
nantly (155). The absence of smoking data on unaffected members of the
same population leaves the question of an additive effect of cigarette smoking
unanswered. One study suggests that non-smokers may have a slightly
greater prevalence of asthma than smokers; the possibility of bias due to
self-selection of the base population could not, however, be excluded in this
study (84).

Apart from the exceptions noted above, it is clear that cigarette smoking
is of no importance as a cause of asthma. A hypothetical contraindication
to cigarette smoking can be postulated for asthmatics on the basis of the
physiologic alterations induced in the tracheobronchial tree by tobacco
smoke. Nonetheless, substantiation of worsening from cigarette smoking
in asthmatics has not been reported frequently. A cause-and-effect relation-
ship between cigarette smoking and asthma, as defined above, is not
supported by evidence available.

RELATION OF SMOKING AND INFECTIOUS DISEASES

The category, influenza and pneumonia (ISC 480-493), contributed to the
excess mortality of smokers observed in six of seven prospective studies
(Chapter 8, Tables 19 and 26). Details sufficient to warrant conclusions
about the nature of this association are not presented in these studies, nor
has the apparent association been evaluated further by careful epidemiologi-
cal research.

Studies adequate for examination of this association are available for only
two categories of infectious diseases, upper respiratory viral illness and

tuberculosis (301. Experiments on transmission of common colds failed
to demonstrate increased susceptibility in volunteers with a history of ciga-
rette smoking (50). Moreover, common colds were detected among 5,500

employees over a 2-year period with approximately the same frequency in
smokers and non-smokers (110). Ina study of illness in a group of families
under close observation for several years, the frequency and severity of
common respiratory diseases, such as the common cold, rhinitis, laryngitis,
acute bronchitis, and nonbacterial pharyngitis, were the same in cigarette
smokers and non-smokers (21). Similar results were obtained by ques-
tionnaires in an analysis of the frequency of common colds in a group of
college graduates followed over a 20-year period (85).

276.
A number of studies have suggested a substantial relationship between
smoking and pulmonary tuberculosis (55, 124, 133, 175). The possibility
that the relationship is not a direct one needs further careful examination.
Certain social factors, important to epidemiological assessment in tubercu-
losis, have not been considered in detail in these studies. Of particular
interest in this regard is a study (29) in which both cigarette and alcohol
consumption were found to be in excess in tuberculosis patients as compared
to the matched controls. The number of cigarettes consumed in the two
groups was the same, however, at each level of alcohol intake. Matching by
cigarette consumption failed to weaken the association between alcohol con-
sumption and tuberculosis (29). Thus, the relationship between tubercu-
losis and smoking in this study was only an indirect one: the association
was found to occur between smoking and alcohol consumption and between
alcohol consumption and tuberculosis, rather than between smoking and
tuberculosis.

Thus the association between smoking and the infectious diseases is con-
fined at present to a single cause-of-death category: Influenza and pneumonia
contribute to the excess deaths in cigarette smokers, but the data are insuffi-
cient to evaluate this observation. In the limited number of studies avail-
able, cigarette smoking has not been shown to contribute to the incidence or
severity of either naturally acquired or experimentally induced upper respir-
atory viral infections.

Curonic BRONCHOPULMONARY DISEASES

Mortality for certain respiratory diseases (bronchitis, bronchiectasis,
chronic pulmonary fibrosis, chronic interstitial pneumonia, and emphysema)
increased in the decade 1949-1959 (48) and continues to show an upward
trend (132, 141). In 1955, cancer of the lung was certified as the under-
lying cause of death in 27,133 persons and chronic bronchopulmonary dis-
eases in 11,480 persons. A tabulation of all diagnoses, both contributing
as well as underlying causes of death, however, showed that cancer of the
lung was entered upon a total of 28,123 death certificates, whereas the chronic
bronchopulmonary diseases were certified as contributing to 32,041 deaths
(47), The possibility that mortality data, as presently recorded, may under-
estimate the role of chronic bronchopulmonary diseases through incorrect
listing by the physician as contributory rather than the principal cause has
also been suggested (115).

Social security records in 1960 show that chronic bronchopulmonary dis-
eases, particularly emphysema, ranked high among the conditions for which
disability benefits were allowed to male workers 50 years of age or older
in the United States (186).

Chronic bronchitis and emphysema are the chronic bronchopulmonary
diseases of greatest public health importance in the United States. They
contribute to the excess mortality of cigarette smokers, but there is little
information about the effects of smoking on the other chronic broncho-
pulmonary diseases. The scope of the subsequent remarks is limited there-
fore to the possible relationship of smoking to chronic bronchitis and

277
emphysema. Since descriptions of both were published long before ciga.
rette smoking became commonplace (13, 14, 114), it seems reasonable to
suggest at the outset that cigarette smoking alone is not the only cause of
chronic bronchitis and emphysema.

Chronic Bronchitis and Emphysema
DEFINITIONS

Many definitions of chronic bronchitis and emphysema have been sug.
gested. For the purposes of this report the definitions proposed by the
American Thoracic Society (4) will be used:

“Chronic bronchitis is a clinical disorder characterized by excessive
mucous secretion in the bronchial tree. It is manifested by chronic
or recurrent productive cough. Arbitrarily, these manifestations should
be present on most days for a minimum of three months in the year and
for not less than two successive years. Many diseases of the lung, e.g..
tuberculosis, abscess, and of the bronchial tree, e.g., tumors, bronchiec-
tasis, as well as certain cardiac diseases, may cause identical symptoms:
furthermore, patients with chronic bronchitis may have other pulmonary
or cardiac diseases as well. Thus, the diagnosis of chronic bronchitis
can be made only by excluding these other bronchopulmonary or
cardiac disorders as the sole cause for the symptoms.”

This definition and classification of chronic bronchitis later considers
complications, listing three: infection, airway obstruction, and pulmonary
emphysema:

“Emphysema is an anatomic alteration of the lung characterized by
an abnormal enlargement of the air space distal to the terminal, non-
respiratory bronchiole, accompanied by destructive changes of the
alveolar walls.”

DIAGNOSIS

The diagnosis of chronic bronchitis is based essentially on descriptions
of clinical manifestations and is achieved by exclusion. Recollection and
interpretation on the part of the subject are necessary. There is no simple
sensitive pulmonary function test that will indicate which person has chronic
bronchitis.

A clinical diagnosis of emphysema, based on the clinical syndrome and
certain changes in pulmonary function, is even less exact. The clinical
features usually encountered in emphysema tend to be very similar to those
found in chronic bronchitis. Most of the symptoms and signs and many
of the physiological changes usually thought to indicate the presence of
emphysema may result from airway obstruction due to bronchitis (66, 180).
There is no completely satisfactory method of detecting emphysema by
pulmonary function testing and no pulmonary function test is specific for
the detection of pathologic lesions of emphysema (52). The clinical detec-
tion of emphysema is therefore not a simple matter, especially in the presence
of chronic bronchitis.

278
The following, adapted from the American Thoracic Society’s statement
(4), epitomizes the situation for emphysema:

Clinicopathologie correlations have demonstrated that certain per-
sons who have this morphologic alteration at autopsy have symptoms of
pulmonary insufficiency during life and die of this disease. Others show-
ing qualitatively similar pathologic findings had no respiratory symp-
toms during life and died of unrelated causes. In some persons, em-
physema may be strongly suggested by the patient’s symptoms and its
existence predicted on clinical grounds with considerable accuracy.
On the other hand, clinical manifestations identical with those of patients
with emphysema may occur in persons who are not found to have this
disease at autopsy but who have some other lung disease. Emphysema
may exist without any clinical manifestations, and its clinical and func-
tional alterations are not unique but occur in other pathologic conditions.

RELATIONSHIP BETWEEN CHRONIC BRONCHITIS AND
EMPHYSEMA

Chronic bronchitis and emphysema frequently coexist, although one can
be present without the other. A clinical continuum appears to extend from
bronchitis at one end, through a mixture of the two conditions in the major-
ity of cases, to emphysema at the other end (123).

An alternative method of assessing the relationship is by study of patho-
logical change. A close relationship is found between chronic bronchitis
and emphysema on purely morphologic grounds. Although emphysema
occurred more frequently in patients with chronic bronchitis than could be
accounted for by chance, the two conditions also occurred independently
of one another (183).

Three of the possible reasons why chronic bronchitis and emphysema are
found in association more often than would be expected by chance are the
presence of a common cause and causation each by the other. The protective
mechanisms for the upper respiratory tract are cilia and a mucous sheath,
and the lower respiratory tract mechanisms involve macrophages, the
lymphatic system, and possibly the fluid lining of the alveoli. Although not
yet proved, failure of the protective mechanisms of the upper respiratory
tract might be expected to lead to chronic bronchitis and failure of the pro-
tective mechanisms for the lower respiratory tract to emphysema. On this
hypothetical basis, a common cause would not seem unlikely; noxious en-
vironmental agents in gaseous or aerosol form would be likely to affect upper
and lower respiratory tracts simultaneously, perhaps with potentiation of
the injury in the lower tract by particles. Several ways in which chronic
bronchitis might cause or aggravate emphysema have been suggested, such
as through trauma resulting from pressure changes induced in the thorax by
cough (138) and by airway obstruction (114). Clinical evidence of bron-
chitis preceded clinical evidence of emphysema in over 50 percent of cases in
one continuing study (137). Others suggest that emphvsema may be a cause
of chronic bronchitis (53). It seems likely that a common cause, causation
of emphysema by chronic bronchitis, and causation of chronic bronchitis
by emphysema are all operating mechanisms, with varying importance in
different populations and different individuals (123).

279
Evidence Relating Smoking to Chronic Bronchitis and Emphysema

Experimental and pathological evidence bearing on the possible rela-
tionship of smoking to chronic bronchitis and emphysema has been pre-
sented in an earlier section of this chapter. Epidemiological and clinical
evidence relating smoking to these diseases will be considered here.

EPIDEMIOLOGICAL EVIDENCE

Chronic bronchitis and emphysema probably represent disorders of multi-
ple causality. Such problems are particularly suited for analysis by the
epidemiological method, especially with regard to the identification of causes
and the disentanglement of their relations (140). Two types of studies,
prevalence studies and prospective studies, will be considered.

PREVALENCE STUDIES.—The most important epidemiological evidence
available relating smoking to non-neoplastic respiratory diseases is found in
the prevalence studies which concern the number of cases in a population at
one point intime. The definitions and criteria for diagnosis of chronic bron-
chitis and emphysema are not ideal for the purposes of these epidemiological
surveys. The absence of standardized diagnostic methods in chronic bron-
chitis and the non-specificity of clinical diagnostic criteria for emphysema
have resulted in the use of prevalence of symptoms and signs of the respira-
tory diseases under study as a basis for the surveys.

Studies of the prevalence of chronic bronchitis and emphysema in the
United Kingdom and in the United States over the last decade have developed
highly reliable epidemiological methods. Because of the nature of the diseases
in question, these surveys present results by the prevalence of specific symp-
toms and signs, or combinations, rather than diagnostic labels of disease en-
tities. Various levels or grades of severity of the symptoms or signs are
defined and the data are obtained and handled in a standardized manner,
permitting comparisons between different populations and communities;
thus it becomes feasible to evaluate whether smoking is associated with cer-
tain signs or symptoms to a greater extent than with other findings.

(1.) Smoking and Respiratory Symptoms—(a.) Chronic Cough—The
common phrase “smoker’s cough” suggests that this symptom is popularly be-
lieved to be associated with smoking. Several workers have investigated the
relationship between smoking and cough; Table 1 lists surveys that tabulate
the frequency of cough in smokers as compared with non-smokers. Several
different types of populations have been surveyed; the purpose of presenting
the findings together is to demonstrate the variation found among the differ-
ent populations.

The 1,456 mill workers studied by Balchum et al. (16) constituted the ran-
dom sample of those who volunteered for chest X-rays and pulmonary func-
tion tests. Of 1,198 smokers, 23.3 percent reported cough; of the 253 non-
smokers, 10.2 percent reported cough. When the percentage of smokers re-
porting cough is considered in each of several categories described by pack-
years of smoking experience, a gradient was found for those reporting cough,
ranging from 11 percent of those who smoked less than one pack-year of
cigarettes up to 50 percent of the subjects with 60 or more pack-years of
smoking experience.

280
TABLE 1.—Summary of reports on the prevalence of cough in relation to

 

 

 

 

 

 

 

  

smoking
Number of subjects | Percent with cough
Refer- - | a a
Author lYear: ence ; :
| _ Smokers, Non- j Smokers Non-
: ; smokers : Smokers
Balchum (16) 1,198 23 23.2; 10.2
Boucot._._.-- (25) 5, 331 | 806 31.5 8.0
Bower. __ (28) 76 | 49 27.6 4.1
Densen.___._.-__---- 222 (44) 2, 530 514 21.2 78
Fletcher:
London Transport (87) 272 30 20.6 0
(67) 166 10 18.7 0
(68) 157 51 54.8 98
(148) 142 VW 32.1 0
(148) 132 24 18.9 R.3
(176) 1, 292 496 6.4: 16
(120) | &3 52 6.0 0

 

 

 

Boucot and others (25) considered the relationship in older men of smok-
ing and chronic cough in a self-selected population 45 vears of age and older.
Chronic cough was defined as cough existing for months or years. Again. a
considerably higher percentage of the smokers reported cough. and a clear-
cut gradient was established according to amount of smoking.

Bower (26) studied 172 men and women employed in a bank. This study
is one of the few which included men and women working under similar con-
ditions. Eighteen percent of 95 men and 17 percent of 77 women admitted
to cough “more or less every day.” Of the smokers, 27.6 percent admitted
to daily cough (12 of 42 men, 9 of 34 women), whereas 4.1 percent of non-
smokers admitted to this symptom (0 of 13 men, 2 of 36 women).

Densen and others (44) presented findings in transit and postal employees.
Persistent cough was reported by 21.2 percent of 2.530 smokers and 7.8 per-
cent of 514 non-smokers.

Fletcher and Tinker (67) studied male workers aged 30 to 59 in the
British General Post Office and in the London Transport Executive. In the
G.P.O., 18.7 percent of 166 smokers reported cough during the whole of the
day in the winter, compared with none of 10 non-smokers. Among smokers
of the L.T.E., 20.6 percent of 272 admitted to a comparable cough pattern
whereas none of 30 non-smokers described such a cough pattern.

Flick and Paton (68) in a study of patients excluding those with cardiac
and respiratory disorders, found 55 percent of 157 smokers admitted to
habitual cough compared with 10 percent of 51 non-smokers. After the
first hundred patients, the admission to the study was weighted in the older
age groups. The questioning was not as standardized as in some of the more
Tecent surveys.

Olsen and Gilson (148), in their study comparing findings in population
samples in Britain with those in Denmark, found cough in 32.1 percent of
162 British smokers and in 18.9 percent of 132 Danish smokers; the cor-
responding figures for non-smokers was 0 percent of 11 and 8 percent of 24.

Schoetilin (173) studied a group of veterans in a domiciliary and medi-
cal-care center, mostly in the age group 45 to 74. The results for cough
(“constantly present for two years or more”) are presented in terms of

281
years of smoking, although the original figures were not published and
are not included in Table 1. By recalculation, it appears that of those who
smoked more than 10 years, 43.9 percent of 2,153 subjects had cough
whereas 18.0 percent of 718 who had smoked less than 10 years had cough.

In the population samples quoted thus far, the percentage of smokers
admitting io cough ranged from 17.3 percent to 55 percent, whereas the
range for non-smokers was 0 percent to 13.0 percent.

Two other studies show a considerably lower prevalence of cough both
among smokers and non-smokers in two unusual types of population. Short
and others (176) reported the frequency with which unselected policyholders
admitted to cough on periodic health examination, a time when they would
be expected to minimize their symptoms. Of 1,292 smokers, 6.4 percent
admitted to cough whereas 1.6 percent of non-smokers admitted to cough.
In a study of a parachute brigade, Liebeschuetz (120) found 6.0 percent
of 83 smokers and none of 52 non-smokers admitted to cough. The study
of members of this unit with particularly high fitness standards was con-
ducted at the time of discharge.

Hammond (82) has presented the frequency of cough in smokers and has
compared this with the frequency of cough among non-smokers. The
subjects were asked to state whether they had a cough at the time of the
questionnaire. They were also asked the question: “Have you had a cough
over a period of many years?” They also were asked to estimate its severity
as slight, moderate, or severe. The analysis of complaints has been reported
so far for 43,068 questionnaires, 18,697 for men and 24,371 for women.
For each age group and for both sexes, cough was significantly more common
among those who smoked cigarettes. The percentage with cough (and the
percentage with more than a slight cough) increased rapidly with the num-
her of cigarettes per day in both sexes and in all four age groups. Except
for ex-smokers, the relationship between “chronic cough” and smoking habit
was very much the same as the relationship between “‘present cough” and
smoking habits. The proportion of male smokers with the complaint of
cough was almost three times as great as might have been expected on the
basis of cough prevalence among non-smokers. For women, the ratio of
observed-to-expected smokers with the complaint of cough was 2.5 to 1.
The ratio of observed-to-expected numbers complaining of cough “more
severe than slight” was 4.09 for males and 2.74 for females. The difference
in frequency of the complaint of cough or of cough “more severe than slight”
between smokers and non-smokers is statistically significant at the 0.001
level. The study sample was not a random sample of the population, but it
provides information about the relationship between smoking and various
complaints for larger numbers of subjects than does any other study. The
results again make it clear that a larger proportion of cigarette smokers are
aware of cough than are non-smokers.

In each of the surveys. smoking was found to be associated with the
symptom of cough defined in a variety of ways. The studied populations
varied considerably—from hospital patients, workers in dusty trades and
clean offices. urban and rural population samples to members of a parachute
brigade. Despite the diversity of these groups, it is surprising to note the
consistency of the difference between smokers and non-smokers in regard

282
to cough. In each of the surveys, a larger proportion of the subjects ad-
mitting to cough were smokers and about twice the proportion of smokers
admitted to cough as non-smokers.

(b.) Sputum.—Table 2 lists surveys in which the frequency of sputum pro-
duction has been tabulated separately for smokers and non-smokers in preva-
lence surveys. Most of the studies were considered in the section on cough
and in Table 1. It is interesting that in most of these studies non-smokers
report sputum production more frequently than cough.

TaBLE 2.—Summary of reports on the prevalence of sputum in relation to

 

 

 

 

 

 

 

  
 
 

 

 

 

smoking
|
Number of subjects j Percent with
sputum
Author Year| Refer- ae ee ee
' ence ;
| Smokers | Non- Smokers} Non-
smokers smokers
Balchum (16) 1, 198 253 30,4 11.1
Bower. (26) 76 49 34.2 20.4
Densen_ (44)} 2,530 514 21.9 13.8
Ferris: |
Males_- (61) 340 125 140.3 113.8
Females (61) 209 379 119.8 19.4
Fletcher :
London Transport._._._.__-_.._.._._...___. 1961 (67) 272 30 16.9 | 7.0
Post Office - ~-| 1961 (67) 166 10 | 18.7 | 10.0
Plick. 12.2 t lo. ee 1959 (68) 156 | 49 fL7 24.5
Olsen: ' :
United Kingdom______....22---.22.. 1960 (148) 162 | M1 27.2 0
Denmark_.___...2-0.22222.-----..--- eee 1960 (148) 132 | 24 W.4 R83

 

) Percentages standardized for age.

Ferris and Anderson (61) studied a sample of the population of a town;
their results are presented as percentages, standardized for age. The sample
sizes were 542 males and 695 females. Among males 40.3 percent of smokers
and 13.8 percent of non-smokers admitted to sputum production with the
corresponding figures for females being 19.8 percent for smokers and 9.4
percent for non-smokers.

Thus, sputum production in each of the diverse populations was found
associated with smoking and a consistent difference between smokers and
non-smokers was present in regard to sputum production.

{c.) Cough and Sputum.—The closely associated symptoms of cough and
sputum have been combined in the results of a number of epidemiologic sur-
veys. Table 3 shows the prevalence of cough and sputum in smokers and
in non-smokers among samples studied.

Of particular interest is the series of comparisons made by Higgins and
his colleagues (88, 90, 92, 93, 95), on samples drawn from contrasting pop-
ulations, selected for their different backgrounds. Lapse rates were low,
and a high degree of uniformity was achieved in the collection of informa-
tion. In the disparate groups studied—including male and female subjects,
older and younger, and varying in degree of dust exposure and exposure to
tural or urban environment—the consistent direction and extent of the dif.
ference between prevalence rates in smokers and non-smokers demonstrates
a strong relationship between smoking and productive cough in a variety
of different situations, and the predominance of smoking as a determinant
of these symptoms.

283
TABLE 3._-Summary of reports on the prevalence of cough and sputum in
relation to smoking

eee el | | o
i Number of subjects | Percent with court;

 

 

 

 

 

 

 

 

 

  

 

i : : and sput
Author | Year| Refer- __ mes tam
| ence | —
| Smokers | Non- | Smokers | Non-
| smokers ) smokers
ee | =|
Higgins: | |
Males. .----------e ener __..1 1957; (88) 222 28 23.9 1y
Pomals.. owls vceceeceeeceeereeecsressont 1957 | (88) 93 176 17.2 it
Higgins: | . ”
Males _..------------- 200 (93) 75 | 6 24.0 0
Females... .--------------00000077 (93) | 20 64 30.0 3 I
Higgins
Males .....-----------c0eeo (90) 315 33 29.8 61
Hiegins:
Males, 25-34 (92) 282 56 29.1 | na
Males, 55-f4 (92) 293 29 44.7 3
Payne:
Males... -.---------- 00000077 - 1962 (153) 1, 400 364 11.0 lo
Females... .----------- _.| 1962 | (153) 888 1, 468 6.0 La
phillips. .-------------- 1956 | (156) 823 451 51.0 ay
ead:
ReneS. (eee eee eee rece eseeecsserrrste 1961 | (159) 9 46 23.1 44
Females. ..-------------00 (159) 43 81 18.6 44
Liebeschuetz 7.2 0

1961 |
1959 | (120) | 3 | 52

 

The percentages of symptoms noted by Oswald and Medvei (150) are
unusually high because occasional cough or sputum is included, in addi-
tion to more frequent or persistent symptoms. The results are not shown
in Table 3, which considers only smoking and cough with sputum, among
males, 63.7 percent of 2,617 smokers and 47.7 percent of 985 non-smokers
in Oswald and Medvei’s study had cough or sputum. Among females, 63.2
percent of 970 smokers and 47.7 percent of 1,272 non-smokers admitted to
either or both of these symptoms.

Payne and Kjelsberg (153) presented data on respiratory symptoms,
lung function, and smoking habits in the adult population of Tecumseh,
Michigan, where a comprehensive epidemiological study is being made of
the entire community. Cough and sputum were graded in severity as Grade
I or Grade II, the latter being defined as both cough and phlegm, of which
at least one was present throughout the day for three months in the year
or longer. The prevalence of Grade II symptoms is noted in Table 3. Dur-
ing an interview period continued for 18 months, authors were able to
show that the prevalence of symptoms did not vary significantly with the
season of the year. Cough and sputum at the Grade II level were admitted
to by 11 percent of 1,400 cigarette-smoking males, and 2 percent of 364 non-
smoking males. The corresponding figures for females were 6 percent of
888 smokers and 2 percent of 1,468 non-smokers. These Grade II symptoms
increased in prevalence with advancing age in men, and in women up to 49
years. It is interesting to note that lesser degrees of cough and sputum,
classed as Grade I symptoms, showed little change in frequency after 19
years of age in either sex. In both sexes, Grade I symptoms of cough and
sputum were considerably more prevalent among smokers than among non-
smokers—45 percent of 1,400 smokers and 19 percent of 364 non-smokers

among the males, and 29 percent of 888 smokers and 17 percent of 1,468 non-
smokers among the females.

284.
Phillips and his associates (156) studied two groups: one of male em-
ployees in a steel-making plant, examined as part of an industrial hygiene
program, and containing sub-groups with different types of industrial ex-
posure, and a second group consisting of 300 patients in a Veterans Ad-
ministration Hospital who were chosen at random, except for exclusion of
cases of specific pulmonary diseases such as tuberculosis or tumor and
cases of congestive heart failure. Chronic cough was defined as daily cough
with sputum for a period of one year or more. Various possible environ-
mental factors—geographic area, air pollution, specific work environment.
and smoking—were considered. Fifty-one percent of 823 cigarette smokers
were recorded as having cough, and 2 percent of 451 non-smokers. In a
tabulation of chronic cough by age in decades, for cigarette smokers and
non-smokers, it was shown that the increasing prevalence of chronic cough
with age was much greater in the cigarette-smoking group.

Read and Selby (159) in a mixed group of 302 subjects, some of them
clinic patients, some patients’ friends, and some hospital staff. found that
male smokers admitted to cough or sputum ten times as often as did male
non-smokers, and to cough and sputum five times as often. In their female
subjects the ratios for these categories were eight to one and four to one.

Liebeschuetz (120) in his study of parachute brigade members found,
as might be expected, a much lower proportion of subjects with cough and
sputum; these do not include subjects previously noted in Table 1 as having
cough alone.

Considering these surveys as a group, it appears that the presence of
cough, sputum, or the two symptoms combined, is consistently more frequent
among smokers than non-smokers, in a variety of samples drawn from
populations differing so widely in other respects that this association may
he taken to be a general one.

TaBLe 4.—Summary of reports on the prevalence of breathlessness in relation

 

 

 

 
 
 

 

 

to smoking
Number of Percent with
subjects hreathlessness
Author Year| Refer-
ence
Smokers Non- Smokers Non-
smokers smokers
Balehum__.... .._-.--- 2222. -2---2eeee------- 1962 (16) 1, 198 253 14.5 9.8
Densen.._ 222.222 eee nee een eee 1963 (44) 2, 530 514 25.3 16.9
Fletcher:
London Transport..___.._.......---.------- 1961 (67) 272 30 8.5 0
Post Office....--..222 222 lett e eee eee 1961 (67) 166 10 9.0 10.0
Higgins:
(88) 222 28 19.8 71
Fen (88) 93 176 9.7 19.9
igegins:
Males ____ .-| 1958 (93) 75 6 | 29.3 33.3
Females | 1958 (93) 20 64 20.0 45.3
Higgins:
Males... 2-822 1959 (90) 315 33 31.7 18.2
Higgins:
Males, 25-34... 28-8 1959 (92) 282 56 9.9 fi
ales, 55-64-___20. 82882 1959 (92) 293 29 42.7 17.2
(153) 1, 400 364 24.0 12.1
(153) 888 1, 468 2.1! 29.0
(176) 1, 292 496 15} 48

 

 

 

 

 

 

285
Some of these surveys are limited in one respect, and some in another.
The degree to which bias has been avoided varies; several of the surveys
quoted are open to criticism in this regard. but in others considerable pains
have been taken to avoid any possibility of suggesting a relationship which
may not truly exist. It would be wrong to extrapolate from, say, a hospital
population to the general public, but the groups surveyed vary enough that
the evidence demonstrates clearly that cigarette smokers more often report
symptoms of cough. sputum, or both. than do non-smokers.

(d.) Breathlessness.—Table 4 summarizes the prevalence of breathlessness
as reported in surveys of various populations.

Balchum and others (16) in their survey of mill workers, reported a
greater prevalence of breathlessness among the smokers in their sample.
Tabulation of the frequency of this complaint by pack-years of smoking
experience showed a less smooth gradient than for prevalence of cough and
sputum.

Densen and others (44), who studied respiratory symptoms in transit
workers and postmen in New York City. found that 25.3 percent of 2,530
smokers and 16.9 percent of 514 non-smokers admitted to breathlessness of
Grade {I or worse (indicated by positive answers to specific questions on the
questionnaire).

Fletcher and Tinker (67), in a study of Transport Executive employees
and Post Office employees, had only one non-smoker out of 40 complain of
breathlessness. and 38 smokers out of 438. These figures are for workers
complaining of dyspnea (a positive answer to the question, “Do you have
to walk slower than most people on the level?” or “Do you have to stop
after a mile or so on the level at your own pace?”’).

In the four studies by Higgins listed in the table, the difference in
prevalence of breathlessness between smokers and non-smokers is more
variable. In his study (88) in the agricultural district of the Vale of
Glamorgan, the author presents prevalence figures for the various symptoms
among females in two age groups, those under age 45, and those over age
45. His reason for doing so is the considerable difference in frequency of
the smoking habit between women in these two age-groups. In both the
age groups of females, the prevalence of breathlessness is greater among the
non-smokers, but the difference is not statistically significant. Female
smokers in the over 45 age groups have rather more cough and sputum and
wheeze than the non-smokers, but apparently have less breathlessness. In
his study in Annandale (93) the prevalence of breathlessness among all men
and all women studied was greater in the non-smokers than in the smokers.
although the numbers of non-smoking men and of smoking women were
small. When males aged 55 to 64 are considered, from the three surveys
(90), breathlessness is more prevalent among the smokers, and the same
thing applies to the two different age groups of males studied in Staveley (921.

Payne and Kjelsberg (153), in their survey of a total community, have
stated that among the men, cigarette smokers were affected more often with
breathlessness at all ages. Among the women, cigarette-smokers had a higher
prevalence of breathlessness than non-smokers below the age of 40, and above
this age the non-smokers had a higher prevalence. Considering all ages
together. twice the proportion of male smokers admitted shortness of breath

286
compared to non-smoking males: the prevalence of shortness of breath among
females was the same for smokers and non-smokers.

Short et al. (176), ina study of answers to a questionnaire on routine medi-
cal examination for insurance purposes, obtained a larger percentage of com-
plaints of breathlessness among smokers than among non-smokers.

Hammond (82) also presents figures for the frequency with which breath-
lessness was noted in answer to a questionnaire by 18,697 men and 24,371
women. The relationship between breathlessness and smoking is less clear
than the relationship between cough and smoking. A significantly greater
proportion of complaints of breathlessness was encountered among male
and female cigarette smokers, both for total complaint of breathlessness and
complaint of breathlessness “more severe than slight.” The ratio of ob-
served-to-expected complaints of breathlessness among male smokers was
1.97 for the total number with this complaint, and 2.62 for those complain-
ing of breathlessness more severe than slight. The ratios for females were
1.36 and 1.49. A consideration of the frequency of complaints of shortness
of breath in smokers and in non-smokers, by age group and by sex, shows
that the excess of breathlessness among cigarette smokers is greater and more
consistent for men than for women. The older age groups of women show
only a slight excess.

Thus, the relationship between smoking and the symptom of breathless-
ness is less general than the relationship between smoking and cough or
sputum, which is found in all age-sex groups in a variety of different pop-
ulations. For males the association is clear; male cigarette smokers com-
plain of breathlessness more often than do non-smokers, particularly in the
older age groups. Females present a less uniform pattern. In several sur-
veys, females show a higher prevalence of breathlessness in non-smokers
than in smokers, particularly in the older age-groups. The reasons for this
sex difference have not been explained.

(e.) Smoking and Chest Illness.—The percentage of smokers and non-
smokers who reported chest illness in the three years prior to the interview

TABLE 5.—Summary of reports on history of chest illness in the past 3 years
in relation to smoking

 

i Number of subjects Percent with chest

 

 

 

ness
Author Year| Refer- _ __ oe
ence
' Smokers | Non- Smokers Non-
smokers | smokers
Fletcher: ye — —_ of fe ot
Tondon Transport __. _.___........._...... 1961 | (67) 272 30 9.2 4.3
Post Office...) i961 | (67) 166 10 33.7 20.0
Nigeins: i | | | |
pales once 1957 | (88) 209 | wi oid! Boi
lige: +2222 eee 1957 (88) 93 | 176 | 15.1 | 13.1
LAS:
| i |
; ales 1958 (93)! 75 | 7 16.0 | 0
ligeles wee eee eee 1958, (93) 20 4; 10.0 10.9
ns: | i
iglales... wee eee 1959; «| 315 33 BBs 3.0
INS: |
Males, 26-3400 1959 | (92): 282 56 | x nA
pegtales, BeB4 ' 1959 ; 203 | 29 | 7.3 64
ayne: : i ! |
pales wee eee ee eee , 1962) (153) 1,400 | R64 | 10° 91
emales 20 1962 (153) RSS) 1 46S 16.0 | 10
oe ee

714-499 O-64—20 287
date is presented in Table 5. For men, the prevalence was consistently higher
among smokers, and in one study (93), the association of smoking and chest
illness was apparent for the younger (25-34) as well as the older males (55_
64). For female smokers and non-smokers, the prevalence of chest illness
was about the same.

(f.) Combinations of Symptoms.—A number of prevalence studies (7, 54,
61, 62, 77, 150) have reported results, either totally or in part, under diag.
nostic headings which cannot be translated into single symptoms. The
symptom combinations and the names applied to them varied; some of the
studies gave the percentages of smokers and non-smokers with “any” signs

or symptoms rather than specified combinations. The results are presented
in Table 6.

TABLE 6.—Summary of reports on the prevalence of combinations of certain
symptoms in relation to smoking

 

 

 

   

t
: Number of Percent with
| subjects symptoms
Author | Year | Refer-
ence
| Smokers | Non- | Smokers| Non-
| smokers smokers
|
Ashford ._.-.______-__---2 2 - eee n-ee 1961 (7) 3, 214 677 21.7 10.3
Edwards. __....22.2.22 222222222 eee eee eee 1959 (54) 7719 524 29.4 19.5
Ferris:
Males ____.-..-.-0- 2-0-2 ae een eee (61) 340 125 124.9 '7.3
Females. -- (61) 209 379 117.5 '9.4
Ferris:
Males ... (62) 54 20 42.6 15.0
Females. _. (62) 10 60 20.0 10.0
Goldsmith __......-.-----.------------2------ (77) 1, 238 744 43.0 314
Oswald:
Males .. ._....------------- 2-22 - ene eee eee 1955 (150) 2,617 [ 985 16.1 9.7
Females. .-_.......-------.----------------- 1955 (150) 970 1, 272 15.4 9.1

 

 

 

 

 

1Percentages standardized for age.

Ashford and his colleagues (7) found twice the proportion of “respira-
tory symptoms” among Scottish coal mine workers who smoked than among
those who did not smoke. ‘“‘Respiratory symptoms” were regarded as pres-
ent in those who have cough or sputum all day for more than three months per
year and walk slower than others on the level, or wheeze, or if the weather
affects their chest. or if they have had a chest illness in the last three years.
Those who had wheeze and who claimed the weather affected their chest
were also classed under “respiratory symptoms.”

Edwards and others (54) presented the percentage of smokers and non-
smokers with bronchitis. according to clinical assessment by one of 11
general practitioners cooperating in the survey. No attempt to standardize
the diagnosis was reported. Of 779 smokers, 29.1 percent had “bronchitis”
compared with 19.5 percent of 524 non-smokers.

Ferris and Anderson (61\ presented the prevalence of “irreversible ob-
structive lung disease,” which was defined as the report that wheezing or
whistling in the chest occurred most days and nights, that the subject had
to stop for breath when walking at his own pace on the level, or had a forced
expiratory volume in the first second of expiration (F.E.V. 1.0) of less than
60 percent of the total forced expiratory volume. According to this defi-
nition, male smokers showed a 24.9 percent prevalence of irreversible

288
obstructive lung disease, compared with 7.3 percent of male non-smokers.
The corresponding percentages for females were 17.5 percent and 9.4 per-
cent. These percentages were age-standardized.

In a study conducted in a flax mill, Ferris, et al (62) presented the prev-
alence of “chronic respiratory disease,” defined as productive couch on
four days of the week, for three months of the year, for three successive
years; or wheezing in the chest most days and nights; or breathlessness, of
Grade HI or more, in the winter; or asthma diagnosed by the physician at
the time of the survey; or F.E.V. 1.0 less than 60 percent of forced vital
capacity. Under this definition, 42.6 percent of 54 male smokers and 15.0
percent of 20 male non-smokers had “chronic respiratory disease.” For
females, the figures were 10.0 percent of 10 smokers and 10.0 percent of 60
non-smokers.

Goldsmith and others (77). in their study of longshoremen. classified the
subject as having a “respiratory condition” if he had ever had asthma or
bronchitis, or currently was “troubled by constant coughing.” With this
definition, 43.0 percent of 1,238 moderate or heavy smokers had a respira-
tory condition, compared with 31.4 percent of 744 non-smokers.

Oswald and Medvei (150), defining “bronchitis” as disability from acute
exacerbations of chest symptoms, or breathlessness, or both, found a prev-
alence of 16.1 percent among 2,617 male smokers, and of 9.7 percent among
985 non-smokers. In their female subjects, 15.4 percent of 970 smokers
compared with 9.1 percent of 1,272 non-smokers had “bronchitis.”

Although these various combinations of symptoms are not comparable.
the consistency and extent of the differences between prevalence of symp-
tom combinations in smokers and non-smokers are striking.

(g.) Relationship between Symptoms or Signs and Amount Smoked.—In
several surveys, smoking categories were based on the daily consumption or
total lifetime consumption (16, 61, 67, 82. 90, 153). In the majority. the
Prevalence of cough and sputum increased with amount smoked. A recent
study (82) showed that those who smoked cigarettes of low nicotine content
tended to cough less than those who smoked cigarettes of high nicotine con-
tent. Other symptoms and measurements of pulmonary function show a less
clear relationship between prevalence and amount smoked.

(h.) Relationship between Symptoms and Signs and Method of Smoking —
The numbers of pipe and cigar smokers in many prevalence studies are so
smal] that conclusions about the effects of these methods of smoking are not
teliable, but they all tend to show that pipe and cigar smokers are likely to be
intermediate between non-smokers and cigarette smokers in prevalence of
Symptoms and signs.

(i) Ventilatory Function.—Pulmonary tests and the method of presenting
results, though varying widely, are important features of the prevalence
Surveys,

In the study by Ashford and others (7) of 4,014 coal miners, the forced
*xpiratory volume in the first second of expiration (F.E.V. 1.0) of non-
Smokers was slightly higher than that of the smokers. and a small but sta-
Ustically significant difference was found even after correction for differ-
rnces attributable to physique. No consistent relationship was reported

‘tween the amount smoked and the average F.E.V. 1.0.

289
Balchum and others (16) reported that 19.3 percent of 1,194 smok

ers
and 7.8 percent of 243 non-smokers had an “abnormal” test, an FEY, 10
f less than 70 percent. When the “abnormal” test was |
of less tha percen 1 the compared with
the number of pack-years of cigarettes smoked, a steady increase jn yj,
proportion of men with decreased F.E.V. 1.0 was found with increasin,,
pack-years. .

Ferris and Anderson (61) showed a progressive decrease in the meay,
F.E.V. 1.0 in successive age groups for male smokers, male non-smokers,
and female non-smokers. In males, there was also a regular decrease in
F.E.V. 1.0 within each age group with increase in the number of Cigarettes
currently smoked. In females, there was little difference in the F.E.V. |
between smokers and non-smokers except in one age group. The peak
expiratory flow rate showed a decrease with age and a decrease within th.
age groups with cigarette smoking.

Chivers (36) showed that smoking, age. and height were correlated sig.
nificantly with the expiratory flow rate. The older and shorter men had
greater impairment associated with smoking.

Flick and Paton (68) demonstrated a distinct decline, beginning at abow
40 years of age, in expiratory flow rate among smokers, but no apparen;
change among non-smokers until 70 years of age.

Fletcher and Tinker (67), measuring expiratory flow rates by the Peak
Flow Meter, found one group of smokers, but not another, had lower value.
than the non-smokers. Ina later paper (58), Fairbairn, Fletcher and Tinker
reported that the Peak Flow Meter appeared to be a less satisfactory screen.
ing test than the forced expiratory volume.

Franklin and Lowell (73), in a study of 1,000 apparently healthy factor
workers, found the mean expiratory flow rate during the third quarter af
maximal forced expiration to be approximately 20 percent less in “heavy
smokers” than in “light smokers.” “Heavy smokers” were defined as those
who had smoked 30 pack-years or more, and “light smokers” less than 10
pack-years.

Higgins (88) showed a decrease in F.E.V. 0.75 among smokers of 15
grams or more of tobacco per day. compared with non-smokers and with
those who smoked less than 15 grams a day. For this test, there was no
significant difference between non-smokers and the lighter smoking group.
Peak flow measurements indicated a difference between heavy and light
smokers, and also between non-smokers and light smokers. In each 10-year
age group over 45, the peak flow was lower in smokers than in non-smokers.
but the numbers were small. These differences are not explained by differ-
ences in age, social class, or occupation. The difference between smokers
and non-smokers in peak flow measurement was not seen in tests of women.

Higgins (90) summarized the difference in F.E.V. 0.75 in a variety of
different samples of the population. Tabulations for 16 different groups
included miners and ex-miners in varying pneumoconiosis categories and
non-miners in the same district, and agricultural workers in two different
areas in Britain. In the 13 groups in which comparisons were feasible.
non-smokers recorded a higher F.E.V. 0.75 than the smokers. The small
over-all difference in means was recorded (as indirect Maximum Breathing
Capacity) as 50 liters per minute, which was significant at the one percent

290
level. By pooling subjects with different occupations in the older age
groups, differences between light and heavy smokers were apparent, though
not statistically significant. Higgins commented on a strong trend in the
prevalence of persistent cough and sputum, with amount of tobacco smoked,
without a significant trend in ventilatory capacity. His possible explanation
of the difference is that smokers are more likely to give up smoking or re-
duce the amount smoked, once their lung efficiency becomes impaired. than
they are when their only symptoms are cough and sputum.

In their study of miners and foundry workers in Staveley (92), Higgins
and his colleagues showed a decrease in the F.E.V. 0.75 in smokers. Non-
smokers, light smokers, and heavy smokers (15 grams per day and over)
tanked in that order for decreasing F.E.V. 0.75, both in men aged 25 to 3-1
and in those aged 55 to 64. The difference between the non-smokers and
the light smokers was smaller than the difference between the light and the
heavy smokers in the younger age group; in the older age group the dif-
ference was larger between non-smokers and light smokers.

Olsen and Gilson (148) measured the F.E.V. 0.75 in a sample of a pop-
ulation in Denmark for comparison with British population samples. Cig-
arette smokers had a lower mean F.E.V. 0.75 than cigar smokers or pipe
smokers who in turn had a higher mean than non-smokers, but these differ-
ences were not statistically significant. If non-smokers, cigar smokers, and
pipe smokers are grouped together, non-cigarette smokers had a significantly
higher mean F.E.V. 0.75 than the cigarette smokers.

Payne and Kjelsberg (153), who presented mean values of F.E.V. 1.0 for
men and women by age group and by smoking category, found a lower mean
value for cigarette smokers than for non-smokers in each age group of men
over 19. In the 16-to-19 age group. cigarette smokers had a slightly higher
mean value than non-smokers. A comparison of the mean values by age group
for non-smokers and for cigarette smokers shows a decline with advancing
years in both, but more rapid in the cigarette smokers. Women also show a
decline of F.E.V. 1.0 with advancing years. but this is no more marked and no
more rapid in the cigarette smokers than in the non-smokers. The reduction
in F.E.V. 1.0 in cigarette smokers amounted to 7 percent and 3 percent of
the mean values in non-smoking men and women respectively when values
adjusted to the over-all mean age of 40 years were compared.

Read and Selby (159) measured peak flow rates in smokers with cough.
and in smokers with cough and sputum. To a statistically significant extent.
male smokers without cough or sputum showed a more rapid fall in peak flow
Tate with age than expected. Male smokers with cough showed a still more
tapid fall with age, and those with cough and sputum, the most rapid fall.
Amount smoked had no obvious effect. Results were similar for women.

Revotskie and his colleagues (165), who grouped smokers in Framingham
48 never smoked, light smoker, medium smoker, and heavy smoker, found
that the F.E.V. 1.0 measurements show a gradient from never smoked to
heavy smoker in the “normal” subjects, both for males and females; in the
other groups this gradient is not clear. The “Puffmeter” ratios tended in
the same direction, but in less clear-cut fashion than the F.E.V. 1.0
measurements.

29)
Goldsmith and others (77) showed that smokers, regardless of
smoked, have a slight diminution in the pulmonary function test resyl
in the absence of respiratory symptoms. The total vital capacity was much
less sensitive in this regard than the F.E.V. 1.0 or the “Puffmeter” readin
Longshoremen with “respiratory conditions,” and particularly those with
shortness of breath, had a more marked decrease in pulmonary function
Cough was associated with the greatest diminution of pulmonary function
measurement.

amount
ts, even

The relationship between cigarette smoking and abnormal results of pul.
monary function tests is more difficult to evaluate from the published surveys
than is the relationship between symptoms and cigarette smoking. Py.
monary function test results are influenced by several factors, among which
are age, physique, and perhaps occupation. When allowance is made fo,
these factors, there appears to be a clear difference in the ventilatory func.
tion between smokers and non-smokers.

In the majority of prevalence surveys, the subjects were not forbidden to smoke Prior
to pulmonary function testing, Since acute alterations due to smoking might be mis.
interpreted as due to a permanent abnormality, it is important to examine the magnitude
and significance of the acute effects of smoking on pulmonary function.

Bickerman and Barach (20) found no consistent alterations in vital capacity or in
maximum breathing capacity before and after their patients and normal subjects smoked
three cigarettes. Simonsson (177) found a smal] decrease in the F.E.V. 10 in 13 of
16 young subjects after smoking, and the difference for the group was statistically sig.
nificant. No significant change was found in the total capacity.

Several authors have studied more sensitive tests of airway resistance and lung com.
pliance. Eich, Gilbert and Auchincloss (56) made compliance and airway resistance
measurements, using an esophageal balloon technique, on a group of nine healthy adults,
five of whom had respiratory symptoms. No difference was detected after one cigarette.
In a group of emphysematous patients, a statistically significant increase in airflow re.
sistance was found, but without significant change in compliance.

Attinger and others (8) reported no statistically significant difference in expiratory
airflow resistance or compliance, but in a later study of subjects with pulmonary disease,
significant physiological changes—increased mechanical resistance and increased work of
breathing—were noted after smoking one or two cigarettes.

Motley and Kuzman (142) studied the lung volumes, spirometry, blood gas exchange.
and pulmonary compliance in 141] subjects, before and after smoking two cigarettes. Not
all of these measurements were made on all subjects. There was no significant change in
the mean values of vital capacity performed after smoking, some subjects showing a
decrease, and others an increase. Six of the normal subjects showed a decreased com-
pliance after smoking. In 33 subjects with cardiac or respiratory disease, 17 had a sig-
nificant decrease in compliance after smoking. The authors felt that a decrease in pul-
monary compliance was the only notable abnormality which followed smoking acutely.
Forced expiratory volume and airflow resistance studies were not included.

Miller (134a), who constructed pressure-volume work loops, demonstrated increased
airflow resistance and uneven ventilation, resulting in increased work of breathing.
This author concluded that inhalation of cigarette smoke gives rise to a significani
degree of uneven ventilation, which is responsible for the observed decrease in dynamic
compliance and increased elastic work of breathing.

Nadel and Comroe (146) showed a mean decrease of 31 percent in the ratio of airway
conductance to thoracic gas volume after inhalation of cigarette smoke, the changes being
highly significant statistically, and similar for smokers and non-smokers. Repeated test-
ing after smoking showed the response to Jast for from 10 to 80 minutes. Without inhala-
tion, no significant change in the conductance to thoracic gas volume ratio occurred.
Inhalation of Isuprel aerosol before smoking prevented the increase in airway resistance.
and when given after cigarette smoking it counteracted the increase.

292
Zamel, Youssef, and Prime (194) found that the smoking of one cigarette increased
airway resistance in smokers and non-smokers, and that the inhalation of Isuprel reduced
airway resistance in both groups. The authors comment that the difference in airway
resistance between non-smokers and cigarette smokers is apparent only when the actual
estimates of airway resistance are compared with predicted values based on lung volume,
because of a reciprocal relationship between airway resistance and lung volume. They
add that the experimental values for airway resistance in two groups of persons are not
comparable unless allowance is made for the volume of the lungs in each.

To sum up this point, the acute effects of cigarette smoking upon pulmonary function
are expressed mainly through increase in airway resistance, which is not severe enough to
produce clinically evident manifestations. The smoker is not immediately aware of any
increased difficulty in breathing nor are the pulmonary function tests used in surveys
sufficiently sensitive to detect the acute effects. The differences in results of pulmonary
function tests between smokers and non-smokers, therefore, are greater than can be
accounted for by acute effects from a recently smoked cigarette.

PRosPECTIVE STUDIES.—In six of seven prospective studies, chronic bron-
chitis and emphysema contribute markedly to the excess mortality among
cigarette smokers; in the remaining study the mortality ratio was increased
but to a lesser extent. In all these studies, mortality ratios for chronic
bronchitis and emphysema have been calculated (see Tables 19, 23, 26 in
Chapter 8, Mortality). Cigarette smokers in these studies died of chronic
bronchitis and emphysema 6.1 times more frequently than non-smokers.

In the large study of U.S. veterans (49) the observed number of deaths
among smokers attributed to chronic bronchitis was 26 whereas the expected
number based on deaths among non-smokers was 5.6, or a mortality ratio of
4.6. For emphysema, the observed number of deaths among smokers was
115, whereas the expected number was 8.8, or a mortality ratio of 13.1.

In a recent study (82), information is available on the first 22 months of
follow-up of 447,831 men between the ages of 35 and 89, of whom 11.612 have
died. The observed number of deaths attributed to emphysema in cigarette
smokers was 115 whereas the expected number was 15.4; the mortality ratio
was 7.47, For other pulmonary diseases the mortality ratio was 1.65, with
185 observed deaths in smokers as compared with 112.7 expected deaths. The
duration of follow-up is not yet sufficiently long to allow one to expect deaths
from chronic bronchopulmonary disease in persons who were not afflicted at
entry,

The paucity of published morbidity studies is striking. Very little is
known of the progression in population samples of symptoms or signs related
'o chronic bronchitis or emphysema, or found in smokers more frequently
than in non-smokers. And very little is known of the incidence rates of such
‘ymptoms and signs in the different categories of subjects constituting popu-
lation samples. This is unfortunate, as prospective studies of morbidity in
Population samples can best measure the possible health hazard of smoking.
“everal studies are under way, but some of the important information will
“oncern changes occurring over a period of five years or more.

The only study of this type reported so far is by Higgins and Oldham (94),
who measured the F.E.V. 0.75 in a five-year follow-up study on ventilatory
“apacity in a population sample in a mining district in Wales. In non-
miners this measurement fell more over the five years in smokers than in
"on-smokers, and within the smoking group there was an increasing fall
with amount of smoking. When the miners and ex-miners were considered.

293
the pattern was less clear. In three of the four groups, the F.E.V. 0.75 f
the smokers fell more than that of the non-smokers or ex-smokers; but th
fall was usually greater in the light than in the heavy smoking group. Th.
authors pointed out that when the original sample was selected, no follow-u,
was intended, and that the sample was not very suitable for this purpose,

Thus, morbidity data are insufficient at present to be of value in the
estimation of the possible health hazard of smoking. Prospective studies jn
populations followed over long periods offer the best opportunity for filling
the major gaps in knowledge about the relationships of smoking and chron
bronchopulmonary diseases.

CLINICAL EVIDENCE

Several studies concerned with individual patients rather than defined
populations form the basis for the clinical evidence.

A current and continuing study of an “emphysema registry” with entry
based on clinical and physiological evidence, has been reported (138). (Of
131 patients with diffuse pulmonary emphysema, 20 had findings at necropsy
of widespread alveolar destruction. Clinical differentiation was made into
three groups: a “bronchitic” group in whom a history of cough was present
years before onset of dyspnea on exertion, a “dyspneic” group in whom
cough and dyspnea occurred at about the same time or in whom dyspnea
occurred first, and an “asthmatic” group who gave a history of episodic
dyspnea or asthma for years before the onset of uninterrupted dyspnea.
When the sample of patients was adjusted for age and sex, 95 percent were
smokers as compared with an expected 80 percent based on smoking habits
of Americans. In a later report (137), the number of patients had in.
creased to 150; 99 percent of the “bronchitic” group, 98 percent of the
“dyspneic” group, and 79 percent of the “asthmatic” group were cigarette
smokers. Improvement occurred in 70 percent of the 60 patients who
stopped smoking, as compared with 1 percent of the 84 patients who con.
tinued smoking.

Studies of series of patients by others (1, 125) have also noted the fre-
quent association of cigarette smoking with emphysema. A number oi
clinical studies indicate the frequent association of cigarette smoking in
chronic bronchitis (106. 117, 149). Fewer non-smokers were among the
bronchitis patients than in matched controls in two of the studies (117, 149).
Of interest is a comparison of 127 cases of chronic bronchitis with a similar
number of controls (75); no difference in smoking habits was found in
the men, and very little difference in the women.

On the basis of such studies, with varying diagnostic criteria, several
authors have concluded that cigarette smoking may be an etiologic factor
in chronic bronchitis and emphysema. Most but not all of the studies have
shown smoking to be a more common habit among the bronchitis or
emphysema patients than among the control groups. Such evidence can
do little more than provide a basis for hypothesis and indicate the effect
of continued smoking on established disease; it does not, of course, establish
or exclude a causal relationship.

294
Relationship of Smoking, Environmental Factors, and Chronic
Respiratory Disease

ATMOSPHERIC POLLUTION

Basis FOR INTERRELATIONSHIP AND RELATIVE MAGNITUDE OF ExPOSURE—
(1.} Experimental Evidence.—The threshold level below which chronic ex-
posure to a toxic agent fails to produce damage to the respiratory system has
not been established even for many of the known components of tohacco
smoke and atmospheric pollution. It is known, however, that the mechanism
by which inhaled substances produce an irritant response in the lung is not
asimple one. Physical, chemical. and biologic interaction may result from
multiple, simultaneous exposure to a wide variety of the components. Poten-
tiation of the irritative action of certain gases when inhaled together with an
aerosol of small particles has been demonstrated (5,113,152). A possible
example of potentiation may be found by contrast of two natural atmospheric
pollution disasters; the 1962 London smog episode had lower particulate
levels, approximately equivalent sulfur dioxide levels. and fewer deaths than
the 1952 London smog.

Innumerable components with potential biologic effects are present in
tobacco smoke and as atmopheric pollution; some components are common
to both, At present, information concerning the effects on the respiratory
system is available for relatively few of these components. In an earlier
chapter of this report (Chapter 6), the toxic actions of the particulate phase
and major gas constituents of cigarette smoke are discussed ; nitrogen dioxide,
and to a much lesser extent, formaldehyde, are the gas components capable of
producing pulmonary lesions related to respiratory disease of man. The
components which constitute pollutants in ambient air vary widely, largely
because of differences in source, meteorologic variables, and photochemical
interactions. The effects of some of the major gas constituents in air pollu-
tion upon the respiratory system are known and will be presented briefly.

Sulfur dioxide is rapidly absorbed into the lung but removed slowly, per-
sisting for one week after a single exposure (15). Interference with the
clearance mechanism is produced through effects upon the mucus, rather
than by inhibition of ciliary motility as seen with cigarette smoke.

Sulphur dioxide usually exerts its effects upon the upper bronchial tree but
intensive, protracted exposure may result in damage to the more distal air-
ways, In animals, short-term, high-level exposures result in increased air-
flow resistance, and hypersecretion of mucus has been suggested by changes
i the mucosa after moderately high, intermittent exposure of guinea pigs
for six weeks (162). Chronic low-level sulfur dioxide exposures have pro-
duced fibrotic bronchitis (86). Experimental human exposures confirm the
increased airflow resistance which may occur without symptoms; augmenta-
tion of the effects of sulfur dioxide in the presence of particulates also has
een observed in humans but it was less evident than in guinea pigs (72, 76,

).

Ozone produces irritant actions on the respiratory tract much deeper in
the lung than sulfur dioxide. Repeated irhalation of 1 ppm. produces chronic
bronchitis and bronchiolitis in rodents, especially rats, but no detectable ef-

295
fects are produced in dogs (179). Under conditions of acute exposure,
somewhat more than | ppm. of ozone produced increased airway resistance
and decreased diffusing capacity in man (76). It is not known whether
chronic low-level exposure to ozone produces lung damage in man.

The ingredients of motor vehicle exhausts most likely to have biologic
effects are aldehydes, hydrocarbons, oxides of nitrogen, and carbon monox.
ide. Guinea pigs exposed to ultra-violet irradiated exhaust gases have
enhanced susceptibility to infection and bronchospasm (2, 144). No data
are available on the long-term inhalation of low concentrations of irradiated
exhaust gases or photochemical smog and its effects on human pulmonary
tissues.

At present, it has not been demonstrated that other components common
in air pollution are associated with pulmonary lesions similar to those found
in the chronic respiratory diseases of man.

(2.) Relative Magnitude of the Exposure.—Estimates of the relative mag.
nitude of exposure to constituents common to both cigarette smoke and
atmospheric pollution are made diffcult by the complex nature of the char.
acteristics of the exposure, such as the relationship between concentration
and duration, and by the paucity of studies specifically designed to evaluate
this aspect. In general, levels are likely to be high, brief, and frequently
repeated in the discontinuous exposure to cigarette smoke; air pollutant
exposure may be considered to be relatively continuous but with wide varia-
tion in concentration and composition, particularly in the United States,

The relative magnitude of each type of exposure cannot be accurately
calculated at present. Insight may be gained, however, into the relative
magnitude of exposure to two components, carbon monoxide and the oxides
of nitrogen, common to cigarette smoke and atmospheric pollution. The
smoking of 30 cigarettes per day is estimated to provide a 20- to 25-fold greater
exposure to carbon monoxide than would be experienced in the ambient air
of Pasadena by non-smokers (76). The effect of smoking on carboxyhemo.
globin levels in man has been determined in studies utilizing carbon monox-
ide in air expired by cigarette smokers and non-smokers with similar high
level community atmospheric pollution exposure. The effect of cigarette
smoking on carboxyhemoglobin levels in man was more than five times
greater than the effect of atmospheric pollution, even when the studies were
performed in a relatively heavily polluted area (76).

The relative magnitude of exposure to the oxides of nitrogen may also
be estimated for cigarette smoking as compared with atmospheric pollution.
The average concentration of nitrogen oxides in ambient air is 0.3 ppm. in
the Fall quarter in downtown Los Angeles. The oxides of nitrogen present
in cigarette smoke vary from 145 to 665 ppm.: moreover. virtually complete
absorption occurs after inhalation (23). During periods of cigarette smok-
ing, therefore, a substantially greater exposure to nitrogen oxides would be
expected (76).

Since cigarette smoking is likely to occur on every day of the year and
periodically throughout the day and evening, and community air pollution
is likely to be relatively less common or persistent, the relative magnitude of
the effect of cigarette smoking for the bulk of the United States population
is certain to he greater than indicated above. The exact magnitude is per-

296
haps less important than the finding that it is substantially greater (76).
Thus, using exposure either to oxides of nitrogen or carbon monoxide as
an index, substantially greater exposure results from cigarette smoking than
from atmospheric pollution, even when studies are conducted in a highly
polluted atmosphere in the United States. Whereas estimates of exposure
to many other constituents of both types of pollution will be necessary
before the relative hazard can be calculated more fully, the experimental evi-
dence at present is consistent and indicates that cigarette smoking affords
the greater exposure for the bulk of the population of the United States.

EPIDEMIOLOGICAL EvIDENCE.—Most investigations of epidemiologic design
have not been directed toward determination of the relative importance,
or the combined effects, of cigarette smoking and atmospheric pollution in
chronic respiratory disease. Discernible effects of cigarette smoking, such
as cough and sputum production, have been observed and documented
in the presence or absence of atmospheric pollution. A detailed considera-
tion of the epidemiological data is available (76); only selected studies
will be considered here.

The prevalence of cough and sputum in the United States appears to be
determined much more by the amount and duration of cigarette smoking
than by atmospheric pollution. In comparable samples of cigarette smokers
in New York, Baltimore, Los Angeles, and San Francisco no major differ-
ences were found in the prevalence of cough and sputum (76, 101); it is
interesting that similar results were obtained comparing cigarette smokers
in London, England and Bergen, Norway (139). Atmospheric pollution
had little or no detectable effect on the prevalence of respiratory disease
among residents of a New Hampshire town: a substantially greater preva-
lence of chronic nonspecific respiratory disease was present, however, in
cigarette smokers than in non-smokers of similar age and sex (6,61). In
veterans paired by age and smoking history. the frequency of respiratory
symptoms and alterations in pulmonary function tests correlated well with
past cigarette smoking history; in contrast, study of these men during the
season in which Los Angeles atmospheric pollution was high did not result
in detectable response attributable to the atmospheric pollution (173). In
studies in areas with varying severity of atmospheric pollution, the effects
of cigarette smoking have been observed (16, 77, 165). Pulmonary em-
physema is relatively rare in a population of non-smokers who live mostly
in the areas of California with greatest atmospheric pollution (51).

In the United Kingdom, cigarette smoking and atmospheric pollution both
contribute to the development and progression of chronic bronchopulmonary
disease (28). Chronic bronchitis results in a mortality rate 30 to 40 times
higher in both sexes and at all ages than is seen in the United States. The
*xcess mortality remains even after removal of possible differences in clas-
sification and misinterpreted diagnosis (63). Moreover, differences in to-
acco consumption do not appear to be sufficiently large to account for the
*xcess mortality due to bronchitis in the United Kingdom.

In producing simple, uncomplicated bronchitis, cigarette smoking appears
0 have the same result in the two countries (63). Although recurrent chest
IIness and evidence of airway obstruction are more frequent in cigarette
mokers, the frequency of more advanced forms of chronic bronchitis does

297
not increase With increasingly heavy smoking (65). Atmospheric polly
tion in the United Kingdom exerts its effects primarily among chronic brow
chitics (117) almost all of whom are cigarette smokers (64); it also is a
major factor in the urban-rural differences in prevalence and mortality
(37, 65, 154, 160). When those findings are considered together with other
evidence documenting the role of atmospheric pollution in chronic bronchiti,
(28, 76, 161), it seems probable that atmospheric pollution and cigarett.
smoking in the United Kingdom are at least additive and possibly synergi..
tic in their deleterious effect on the respiratory tract. “

Thus the epidemiological evidence on the relationship of cigarette smuk.
ing, atmospheric pollution, and chronic respiratory disease clearly indicate.
that the dominant association in the United States is between cigarette
smoking and chronic respiratory disease. In the United Kingdom, disabling
respiratory conditions and death are more likely to occur among persons
who smoke cigarettes and are exposed frequently to atmospheric pollutant.
than in those exposed to either alone.

OCCUPATIONAL FACTORS

Occupational exposures provide other possible etiologic factors in the
production of chronic bronchitis and emphysema. There is little convincing
evidence on specific relationships. Nevertheless, epidemiological studic.
(reviewed in 123, 128) provide information on the relative importance of
cigarette smoking and occupational exposures in selected groups.

In a study of 4,014 Scottish coal miners (7), the prevalence of respiratory
symptoms among non-smokers was appreciably lower than among smokers
of the same age, and the ventilatory function of non-smokers in all age
groups was significantly higher than that of the smokers. Among smokers
of 50 years of age and above, the prevalence of pneumoconiosis tended to be
lowest among the men who smoked the most and highest among men who
smoked the least. However, the prevalence of pneumoconiosis was higher
in ex-smokers than among smokers and non-smokers, except in the oldest
age group, suggesting that men with pneumoconiosis tend to reduce their
tobacco consumption. The possibility that factors of selection eliminate
some persons with symptomatic pneumoconiosis from study groups should
also be considered in the evaluation of these studies.

In a sample of 1,317 men aged 40 to 65 who worked in a variety of non-
dusty and dusty environments, a greater prevalence of bronchitis (daily
cough for at least the preceding six months, productive of one teaspoon of
sputum per day) was found in moderate and heavy smokers (27). Between
the non-smokers and the heavy smokers, a significant difference was found
at all age levels, and also between non-smokers and moderate smokers excep!
in the oldest age group. Although effects from dust exposures could be
noted, it appeared that cigarette smoking was the dominant etiologic factor
in “chronic bronchitis” in this selected group.

Among alkaline dust workers it was found that the dusts in the working
environment did cause some increase in respiratory illness but the sig-
nificance of the dusts in the production of respiratory disability, either
functional or pathological, was not as important as the number of cigarettes

smoked daily (36).

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In a study of 1.274 steel workers, non-smokers had a comparatively low
incidence of chronic cough, regardless of their job classification or condi-
tions of work or residence. There was a direct relationship between chronic
cough and the number of cigarettes smoked daily in each occupational
category (156). Cigarette smoking was of greater importance in deter-
mining the prevalence of chronic cough than was the occupational exposure.

In a study of New England flax mill workers, 161 subjects were subjected
to a questionnaire and measurements of pulmonary function to determine
the presence of “chronic non-specific respiratory disease.” The prevalence
of such a syndrome. based on a certain combination of symptoms or signs.
was related to age, sex. smoking habits, years of exposure to dust, and
estimated inhaled quantity of dust. The effect of smoking “far out-shadows
any effect due to age or occupational exposure to dust” (62).

The studies by Higgins and his colleagues (87, 88. 89. 91. 921 show that
smoking and occupational exposure are both related to the prevalence of
chronic respiratory disease but do not allow quantitative assessment of their
relative importance in the populations defined. As this series of studies was
undertaken to demonstrate any effect from industrial exposure. and the popu-
lations surveyed were such that exposure to occupational dusts was more
varied than in the general population. the importance of the effect of smoking
in this group of studies on the production of respiratory symptoms is rather
convincing (123). The authors comment in one of the papers in this series:
“So important is the influence of tobacco smoking that it is essential to allow
for differences in smoking in comparable groups before drawing conclusions
about the importance of other factors.”

In a recent study of bituminous coal miners (103) , ex-smokers had pul-
monary function results and prevalence of respiratory symptoms comparable
to those of non-smokers; no impairment was attributed to pure pipe or cigar
smoking. Cigarette smokers had the most symptoms of respiratory disease
and, except for vital capacity, they had the lowest pulmonary function. The
authors comment: “. . . although smoking definitely impairs pulmonary
function, the impairment of pulmonary function by years worked under-
ground is clear and separate from the effect of smoking.”

In a study of 7,404 metal mine workers, aged 35 years and older, a com-
parison was made of the effects of 20 years’ aging and smoking on pulmonary
ventilation, as measured by the F.E.V. 1.0 in individuals without X-ray evi-
dence of silicosis. A decrease of 23 percent occurred with the process of
aging 20 years. For heavy smokers (those who smoked for 25 years or more
and now smoke more than 20 cigarettes a day), there was an additional de-
cline of 10 percent over that of aging alone. “The decline in pulmonary
function associated with heavy smoking was equivalent to the decline that
comes about by the process of aging 10 years. For the entire group of
metal mine workers, the reduction in pulmonary function associated with
smoking was equivalent to half the effect of heavy smoking, or about five
years of aging” (128).

The population at risk from occupational exposure is relatively small com-
pared to the population of cigarette smokers. Among occupational groups,
cigarette smoking is an important variable that must be considered in all

299
studies of chronic bronchopulmonary disease. In most studies, but not all,
the relative importance of cigarette smoking is greater than occupational ex.
posures in the production of symptoms and signs of chronic bronchitis or
emphysema.

SUMMARY

Tobacco smoke is a heterogenous mixture of a vast number of compounds,
several of which have the ability to produce damage to the tracheobronchial
tissues and lung parenchyma. Retention of inhaled cigarette smoke particles
in the respiratory system of man is about 80-90 percent complete with breath
holding of two-to-five seconds. Particles penetrate deeply into the respira.
tory tract and are deposited on the surface of the terminal bronchioles,
respiratory bronchioles, and pulmonary parenchyma. Little information is
available concerning the specific toxic properties of the particulate phase
components. Gas phase components probably have a diffuse though not
uniform pattern of distribution. It seems likely on the basis of the physical
characteristics of gas absorption and distribution, that a substantial portion
is retained along the upper bronchial tract. Certain of the gases known to
be present in cigarette smoke are capable of producing pulmonary damage
in experimental animals and man.

Cigarette smoke produces significant functional alterations in the upper
airways. Like several other agents, cigarette smoke can reduce or abolish
ciliary motility in experimental animals. Post-mortem 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 func.
tional impairment would result.

Cigarette smoke is also capable of interference with functions in the lower
airways. In animal experiments, cigarette smoke appears to affect the phy.
sical characteristics of the lung lining layer and to impair alveolar stability.
Alveolar phagocytes ingest tobacco smoke components and assist in their re-
moval from the lung. This phagocytic clearance mechanism decompensates
under the stress of protracted high-level exposure to cigarette smoke and to-
bacco smoke components accumulate in the pulmonary parenchyma of
experimental animals.

The acute effects of cigarette smoking result in an increase in airway re-
sistance but clinical expression of this change in pulmonary function is not
common. The chronic effects of cigarette smoking upon pulmonary func-
tion are manifested mainly by a reduction in ventilatory function as measured
by the forced expiratory volume.

Histopathological alterations occur as a result of tobacco smoke exposure
in the tracheobronchial tree and in the lung parenchyma of man. Changes
regularly found in chronic bronchitis—increase in the number of goblet
cells. and hypertrophy and hyperplasia of bronchial mucous glands—are more
often present in the bronchi of smokers than non-smokers. In experimental
animals, cigarette smoke consistently produces significant functional altera-

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