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        ..--
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26


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27


(63)

(64)

(65)

(66)

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28


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29


CHAPTER 2

       Nonneoplastic
Bronchopulmonaw Diseases


Page
35

Introduction____________________________----------------
Epidemiological Studies

COPD Mortality and n4orbidity--- -- ________ __-_- ______
  Filter Cigarettes---------------------------------
Pulmonary FuncGon----------------------------_
Occupational Hazards

   Byssinosis----------- _____-__--__--__-__________
   Exposure to Asbestos-_--------------------------
   Exposure to Coal Dust'---------------------------
   Miscellaneous Exposures-------_-----~-----------
Air Pollution..-_- _______ -------______--___-___ _______
.iutopsyStudies ____ ~_----------~-_-_-- __-___-_______-__-
Experimental and Histopathological Studies
Histopathological Studies-------------------------~----
Pulmonary Function ___________ --------------_- ____ --
Pulmonary Clearance__--_----------------------------
Phagocytosis _________ -----_---_-_-_----- ~~~~-~~-~~~~
Bacterial and Mycological Stu.dies----------------------
The Surjactant System_-___-_-_-----------__--___- __-_
*;llmmary of Recent Nonneoplast'ic Bronchopulmonary Find-
ings-_---_________--------------~~-----~-------------
Kf e erences _______________ -__----------------- __________

36
37
38

39
41
41
43
44
45

48
50
51
53
54
55

55
56

List of Figures

FiWre 1 .-Age-st.andardized percentage of chronic sputum
I)rcduction in males by amount smoked and type of
+!arette- _ _ __ _ ___ _ ___ ___ _ ___ _ _ _ _ ___ _ ___ _ __ _ __ _ __ _ - ---
I&re 2.-Age-standardized percentage distribution of whole
Iung sections of males with moderate to far-advanced emphy-
<ema (score 3-g) by smoking category- _ - _ - _ _ _ _ __ - - - - - ----
%lre S.-Prevalence of emphysema in adult males at autopsy
`?srnoking categor\-Mm ________ ~---..---__~ ------ ~----~~~

38

47

48

33


List of Tables

Page

Table l.-Percent prevalence of byssinosis for men by index of
severity and smoking habits (numbers in parenthesis indicate
number of cases in exposure risk group) _ - _ _ _ _ _ - _ _ - - _ - - _ _
Table 2.-Degrees of emphysema in current smokers and in
nonsmokers according to age groups- _ - _ - - _ _ - _ _ - _ _ - - _ _ - _ _

40

46

34


Introduction

The term chronic obstruct,ive bronchopulmonary disease (COPD) )
as used within this report, refers to chronic bronchitis and pulmonary
emphysema. The following is a brief summary of the major relation-
ships between smoking and nonneoplastic bronchopulmonary disease
which have been presented in previous reports of the hea1t.h conse-
quences of smoking (91, *9$. 93,94,95,%).

Epidemiological and clinical studies have established cigarette
smoking as the most important cause of COPD in the United States.
Cigarette smokers have higher death rates from pulmonary em-
physema and chronic bronchitis and more frequently have impaired
pulmonary function and symptoms of pulmonary disease than non-
smokers. Respiratory infections are more prevalent and more severe
among cigarette smokers, particularly heavy smokers, than among
nonsmokers. Cigarette smokers appear to develop postoperative pul-
monary complications more frequently than nonsmokers. The risk
of developing or dying from COPD among pipe or cigar smokers is
higher than that of nonsmokers, but it is clearly lower than that
among cigarette smokers. Ex-smokers have lower death rates from
COPD than do continuing smokers. Cessation of smoking is associated
with improved ventilatory  function and decreased pulmonary
symptom prevalence. Young cigarette smokers of high school age
have impaired ventilatorg function compared to nonsmoking peers.

For most of the United States population, cigarette smoking is a
much greater factor in the development of COPD than air pollution
or occupational exposure. Cigarette smoking may, however? act con-
jointly with atmospheric pollution or occupational exposure to pro-
duce greater mortality and morbidity from COPD than would occur
from on0 exposure factor alone.

A genetic error, homozygous alpha,-antitrypsin deficiency, present
in approximately 1 in 3,600 people in the United States, has been as-
sociated with the early development of severe panacinar emphysema.
Available evidence does not permit a firm conclusion about the nature
of the interaction between smoking and this condition.
Autopsy studies have demonstrated that smokers who die of diseases
other than COPD have histologic changes characteristic of COPD
more frequently than do nonsmokers.

                                                    35
405-028 %73---4


Experiments in both animals and humans have demonstrated that
the inhalation of cigarette smoke is associated with acute and chronic
changes in vent,ilatory function and pulmonary histology. Cigarette
smoking exerts an adverse e.flect on the pulmonary clearance mec.h-
anisms including ciliary and macrophage funct,ion.
The effect of cigarette smoking on nonneoplastic bronchopulmonaq
disease has been examined in detail in a number of recently published
epidemiological. pathological, and experimental studies.

COPD Xortality and Morbidity

Reid (70) reported that age-adjusted mortalit,y rates from chronic
nonspecific lung disease (ICD 502, 526, 527) among British citizens
varied with migration patttarns. British males living in the United
Kingdom had a death rate of 125 per 100,000. whereas migrants to the
IJnited States experienced a mortality rate of only 24 per 100,000,
which is similar to the mortality rate from chronic nonspecific lung
disease found in the T-3. population. The possibility that this varia-
tion was due to significant differences in diagnostic criteria was in
part ruled out by the finding that. standardized morbidity surveys
of bot.h populations demonstrated differences in morbidity rat,es that
were similar to the observed differences in mortality rates. The prev-
alence of respiratory symptoms increased in proportion to the num-
ber of cigarettes smoked per day. Cigarette smoking and air pollu-
tion were identified as the major factors contributing to the real excess
in bronchitis morbidity experienced by the British in the United
Kingdom.


Romania. Both areas were free of air pollution. The prevalence of
chronic bronchitis was higher in t,he mountains than in the. lowlands,
and although a definite association between chronic bronchitis and
smoking was found in both areas, smoking pat.terns could not com-
pletely account for the, difierences observed.

Several papers have been recently published (24, 2.5. X. J7.5.5. 100)
comparing respiratory symptoms. such as cough and sputum produc-
tion, among smokers and nonsmokers in different populations. In each
study. respiratory symptoms and disease were more common among
cigarette smokers than nonsmokers. Most of these studies (24, n)C, 37,
100) demonstrated a dose-response relationship be.t.ween smoking and
symptoms for the amount smoked as measured by the number of ciga-
rettes smoked per (lay, the lifetime number of cigarettes, or the degree
of inhalation.

The sl)ont,ane.ous development of a pneumothorax with the resultant
collapse of a lung is often produced by rupture of nn en~l~l~,vsematous
bleb on t.he 1)Ieural surface. Fonrnirr and Zivy (,`I) reviewed 81 cases
of spontaneous pneumothorax. The smoking habits of these patients
were cornp:JJwl with those. of matched controls. Spontancons pnemlo-
thorax after the, age of "5, was strongly associated with cigarette
smoking. Zivy (101) further characterized -IO of these cases.

FILTER CIGARETTES

The effect of smoking plain and filtered cigarettes on the. prevalence
of sputum production was examined by Rimington (71). A total of
10,414 volunteers aged -0) and older were studied by questionnaire and
chest X-ray. Of this group, 3,&G smoked filter cigarettes and 2.393
smoked nonfilter cigarettes. The rate of persistent daily SpUtLJJll pro-
duction was 31.9 peivent in filter cigarette smokers and 37.2 per-
cent in smokers of nonfilter cigarettes. The. difference is significant
(P<O.OOl). Although there was an increase in sput.um production
with the amount smoked in both groups, t.he difference between filter
and nonfilter smokers was maint,ained irrespective of the amount
smoked (fig. 1). The author observed, `While there is 110 doubt that
smokers of any t.ype of cigarette are liable to develop chronic bronchi-
tic symptoms such as persistent phlegm, it seems likely t.hat t,hose
plain cigarette smokers who are unable to stop smoking cigaret&s
~0u1d suffer less if the.y smoked filter brands of comparable size."

The eflect of smoking modified cigarettes on respiratory symptoms
and ventilatory capacity was examined by Freedman, et al. (22). Six
hundred men between the ages of 25 and 54 ~vho smoked at least 10
cigarettes a day and had symptoms of chronic bronchitis were divided
iJlt0 three equal g1.011ps matched by age, pulmonary function. cigarette
consumpt.ion, and cough frequency. The individuals were ljrovided

37


Figure l.-Age-standardized percentage of chronic sputum production in males
     by amount smoked and type of cigarette.

60

0 Filter cigarette smokers
_a Non.filter cigarette smokers

47.2
r7 / I

41.6 r/n

Number of

19.7

-

volunteers   4,976
Number with
sputum      836
          1 Non-

382  259   1,095  878   1,568 1,256

97   75    304  304    571  513
<lO       lo-19      >19

        smokers cigarettes/day cigarettes/day cigarettes/day
1 Includes ex.smokers and non-cigarette smokers.
SOURCE: Rimington, J. (71).

with test cigarettes "A"' " B," or "C." *411 t,he test cigarettes contained
1.65 mg. of nicotine. "A" delivered 22 mg. of tar, and "B" and "C"
17 mg. of tar. In addition. "C" had approximately a 50 percent reduc-
tion in the vapor phase constituents. Those provided with cigarette "C"
increased the average number of cigarettes smoked by about 10 per-
cent, There consumption eventually leveled off. 14fter 4 months, men
smoking cigarette "(1" began to have lower average cough frequency
scores than t,he others. Significant changes did not, OCCUI' in sputum
production or pulmonary function. The authors observed that, "* * *
modification of the composition of cigarettes and their filters can re-
duce smokers' cough, an important and early symptom of bronchitis."

PULMONARY FKTNCTION

Results of studies of pulmonary function and smoking from several
countries, including India (65) ' Turkey (2)) Germany (7,34,38), and
Great Britian (4.1) indicate that cigarette smokers have diminished
average pulmonary function compared to nonsmokers. The various
measures of pulmonary function used included vital capacity, expira-
tory reserve volume. residual volume. residual functional capacity,
maximum voluntary ventilation, forced expiratory volume in I second!
and peak cxpiratorg flow rate.


Other studies in which both pulmonary function and respiratory
symptoms are c0nsidere.d (27, .N. 36: -/. .a
               `3 -9. 69) have again confirmed
that smoking is associated with an increase in pulmonary symptoms
and a decrease in pulmonary function.
Rx-smokers experience a decrease in t.he prevalence of respiratory
symptoms and an improvement in pulmonary function compared to
continuing smokers. These effects have been noted in several recent
studies (36, flw? 43).
Ulmer (87) conducted a survey of respiratory symptoms in a ran-
dom sample of 2>-1-13 individuals between the ages of 10 and 70 years in
I>uisburg, Germany. The prevalence of c.hronic bronchitis as measured
Iq cough and/or sputum produc,tion in the morning or throughout the
day increased with advancing age and with increasing cigarette con-
sumption ( P < 0.001).

Latime,r, et al. (JR) st,udied the ventilatory patterns and pulmonary
complications of 46 patients following elective upper abdominal sur-
gery. Factors that favored the development of postoperative macro-
iit&ctasis included smoking, obesity. and prolonged anest.hesia.
Teculescu and Stanescu (84) examined several measures of pulmo-
nary func.tion in 44 asymptomatic young men bet,ween the ages of 18
and 29 in Romania. So significant differences were found between the
smokers and nonsmokers. This may have been due to t.he selection of
:Isymptomatic subjects for examination and relatively insensitive meas-
ures of early airway obstruct,ion.

Occupationa Wa.saro?s

BYSSINOSIS

Ryssinosis is a respiratory disease found in cotton, flax, and hemp
\vorkers. The earliest manifestations of t'his disease are shortness of
breath, cough, and chest tightness. Initially, symptoms occur only
QIWI reexposure to cott,on dust at, the beginning of the work week.
In more advanced form, byssinosis is associated with permanent and
`lecasionally severe airway obstruction, which mav force the \vorker
to change his occupation 731). Abnormalities i11 &monary function
tc'stS reflect the severity of tile symptoms; however, chest films Of
`Qnkers with bvssinosis reveal 110 characteristic findings. McKerrow
            Y
~(1 Schilling (54) first suggested t.hat. bvssinosis ma,y occur more
il'qurntly among smokerti than noiismokrrs. &\-era1 relatively recent
`trldies hare clarified the relationship between smoking and byssinosis.
l~C)l~liuys, et al. (8) found 61 cases of byssinosis in 214 male workers
`I1 the carding and spinning rooms of a cotton mill. The prevalence of

39


byssinosis symptons was higher among cigarette smokers than in
nonsmokers (P<O.OZ) .

Szymczykiewicz, et, al. (8.2) found a higher prevalence of chronic
nonspecific pulmonary symptoms among smokers than nonsmokers
in a study of 3J6'7 cotton mill workers in Poland.

An examination of 500 cotton textile workers by Schrag and Gullett
(75) disclosed 63 individuals with byssinosis; 57 percent (36 workers)
of those with bvssinosis smoked more than a pack of cigarettes a day,
whereas only 34 percent (152 workers) of those without. by&no&s
smoked this amount (P<O.OOl) .

Merc.hant., et al. (C58) conducted a study of byssinosis in a yanl
mill in North Carolina: 25 employees with byssinosis were identified
in a population of 441 workers. A scale of 0 to 3 (based on 9 weighted
questions concerning cough, breathlessness, and chest tightness on
Monday mornings) was used to indicate the degree of severity of
byssinosis among the working population. The effect, of cigarette
smoking on this byssinosis index is apparent (table 1). Among the
employees with high exposure to cotton dust, no nonsmokers had a
byssinosis index rating orer 1, but nearly 18 percent of those currently
smoking had ratings of 2 or 3. The effect of smoking alone on the
byssinosis index is significant (P<O.Ol). Also, the interaction `between
current smoking and current. exposure-risk on the byssinosis index is
highly significant (P<O.O05). Women in this study were exposed to
lower levels of respirable cotton dust, and among them no age, smok-
ing, or exposure-risk effects were demonstrated. Smoking among
males also had a significant effect on the bronchitis index (P<O.O02).
Spiromet,ry results on 134 males and 100 females were categorized by
sex, age. and smoking history. -1mong men, the greatest impairment

TABLE l.-Percent prevalence of byssinosis for men by index of severi.ty
and smoking h.abits (numbers in parentheses indicate number of caSeS
in exposure-risk group)

                  Percentage of subject
Index rating  ~~ ---- _____------- __--
(see text)     Never smoked  Curren~ts~mokers    Ex-smokers
            m                      (21)

Total.---~~---.-~~..~~-     100         100         100

Source: Merchant, J. A., et al. (68)

40


\vas observed among the smokers who worked in the high exposure-
risk areas. The mean FEY 1 for 66 men in this category was only 76
percent of predicted, and their FVC was 90 percent of predicted.
Sonsmoking men in both the high- and low-exposure areas had better
pulmonary function than their smoking coworkers.

EXPOSCRE TO ASBESTOS

Langlands, et al. ($5) surveyed respiratory symptoms, pulmonary
function, and radiological findings among 252 asbestos insulat,ion
workers in Belfast, Ireland. Respiratory symptoms of cough, sputum
production, and wheezing were ~nr~c*h rno~~ frtqu(wt in smokers. Of the
tests for pulmonary function, the peak flow rate and forced expiratory
volume at 1 second were most impaired in cigarette smokers. Although
little difference was reported in the S-ray- findings of smokers and
nonsmokers, smokers of more than 25 cigarettes a day had a go-percent
reduction in pulmonary function as measured by these tests.
Lung funct.ion and ~~ulrnona~~ symptoms in 1,015 chrrsotile asbestos
mine and mill workers in Quebec were studied by Becklake, et al. (6)
and McDonald, et al. (S.?) . -in analysis of respiratory symptoms indi-
cated that. shortness of breath was more closely related to dust ex-
posure than to smoking. However, cough, wheezing, and sputum
production were much more frequent in smokers than nonsmokers.
Pulmonary function was hssessed by measuring lung volumes, flow
rates, and diffusing capacity. The best pulmonary function was found
in nonsmokers with low dust, exposure while smokers wit.11 high dust
exposure had lower pulmonary function values.

In a survey of 201 asbestos workers, Regan, et al. (67) investigated
the relative power of 16 clinical, radiological, and pulmonary function
variables including smoking for diffcrentiatinp between asbest,osis and
chronic obstructive airway disease. Cigarette smoking was not a char-
acteristic that, could be used to separate these conditions.

EXPOSCRE TO COAL DUST

The spectrum of pulmonary reactions to coal dust was reviewed in
a volume edited by Key, et al. (No). Hunter (33) noted that coal miners
who smoked experienced a higher prevalence of respiratory symptoms
(col;gh, sputum p reduction, breathlessness, and wheezing) and de-
veloped them earlier than nonsmoking miners. Their pulmonary func-
tion tests also t,ended to show greater impairment than those of
*lonsmokers. Lainhart, and Morgan ($4) reported that' coal miners
llad an increase in persistent productive cough with increasing years
of exposure to coal dust. This effect was magnified by cigarette smok-
iV independent of age or wars of underground ~vork In an autopsy

41


study, Naeye (62) observed more right ventricular hypertrophy and a
hig1le.r emphysema intlcx in smoking miners than in nonsmoking min-
ers. In commenting on the et.iolopy of pulmonary re.act,ions in coal min.
crs. T,ee (+@I) felt that snloking in coal miners probably facilitated the
development of bronchitis and emphysema, rather than participating
in the genesis of the characteristic lesion of coal workers! pneumo.
coniosis.

The prevalence of chronic bronchitis in 3,012 ex-coal miners and
9,361 nonminers of sinlilar age and social class was examined by Lowe
and Khosla (51). All were employed at the time of the investigation
in two steel works in South Wales. The es-miners had substantially
more chronic bronchitis and more impaired ventilatory capacit.y than
t,he nonminers irrespective of age and smoking habits. The prevalence
of chronic bronchitis was 24.9 percent in smoking ex-miners and 12.0
percent in nonsmoking ex-miners. The prevalence was 18.6 percent and
7.7 percent in smoking and nonsmoking nonminers, respectively. In
this study, smoking appeared to be a more important factor for the
development of chronic bronchitis than coal mining or age.
Haber, et al. (20) studied cigarette smoking, dust inhalation, and
sputum production as factors in the etiology of chronic bronchitis
among 479 coal miners and 166 farmers in Hungary. In both the
miners and the farmers. there was a significantly higher proportion
of chronic bronchitis cases among smokers than among nonsmokers,
and the proportion of bronchitics increased with the number of
cigarettes smoked. Cigarette smoking was found to be a more im-
portant factor in the etiology of bronchitis than dust inhalation.
Lapp. et' al. (46) examined changes in several measures of ventila-
tory capacity in 93 coal miners and $2 nonminers before and after
a work shift. Follo\vinp the shift. small but significant decrease,s in
vent.ilat0r.v capacity owurr~d anion g the nline.rs (P<O.O:i). while
significant increases in veutilatory capacity occurred among the non-
miners (P<().O;i). I)ccrenses in pulmonary function tests were related
to the dust exposure of the nliners: howc~\-er. the greatest decreases
in pulmonary flinction occ~*rirretl aniong the smokers.
Senton. et al. (76) exaniined several measures of ~mlnionary func-
tion in 214 coal \vorkers who had radiologic evidence of CWP with
lung opacities that r;inged in size from Icss than I.3 mm. to 3 mm. in
diameter. They found no significant diflcrence in pulmonary function
between the lOti snloliels and 112 nonsmokers \vith coal lvorkers
pne~lnlocnniosis. Similar resl1lts were rcportcd by I,yons. et al. (52).
H.vperinflation of the lungs in coal miners was st uditd by Morgan.
et al. ((;I). Residual \olur~ws, total lung capacities. and chest X-rays
of 1.4-5.i working I'ennsylv;~nia coal miners were csainined. The rcla-
t ionship bet wcen radiograpl~ic evidence of coal workers' lmeumoconi-
osis anal lung \-olun~es was investigated. The residual volume in-

42


creased with radiographic category, obstruction to air flow, and
cigarette smoking. Each of these factors had a separate and additive
effect that resulted in an increased residual volume.

Ulmer (86) examined a random sample of t)he working population
in the Ruhr area of West GermanJ. Measurements were made of the
total lung capacity, airway resistance, and arterial oxygen satura-
tion. All coal miners had larger total lung capacities than workers
wit,hout dust exposure. Smokers had significantly larger volumes than
nonsmokers (PCO.05).

Lapp! et al. ($7) examined pulmonary hemodynamics in 47 asymp-
t,omatic coal miners. They were divided into t.wo groups depending
upon the absence or presence of airway obstruction. Pulmonar?; hyper-
tension was more frequent in the group with obstruction. Thr group
of 23 men (mean age 51 years) without airway obstruction. had an
average cigarette consumption of 17 pack-years per miner. whereas
the group of 21 men (mean age 56 Sears) with airway obstruction
averaged 31 pack-Fears per miner.

From t.he work of several investigators it can be concluded that,
cigarette smoking is an important factor in the development of re-
spiratory disease other than pneumoconiosis, among coal miners (a9.
MO, 46, ~$7~ 51, 61, 86). There is no consensus in recent publications on
what role cigarette smoking may play in the development of coal
workers' pneumoconiosis (40, 61, 76).

MISCELLANEOUS EXPOSURE~~

The effect of cigarette smoking on pulmonary function in jet fighter
pilots and crew- members was r~xamine(l by Ijrowning (I,). -It. high
altitudes, loo-percent oxygen is delivered under low pressure to the
aircrew members in order to maintain adequate blood oxygen levels.
The vital capacity was acutely conlpromised in flight on the loo-per-
cent oxygen mixture. This was cspccially t.rue under high G (gravity)
condit,ions. Smokers had a significant, inflight, VO~UIIW loss that, was
three and one-half times that noted among the nonsmokers untlc~
these conditions (P<O.OFi). Recovery of normal vital capacit.y follow-
ing flight was also delayed in the smokers.

Gregory (28) reviewed 840 casrs of chonic bronchitis that, occurred
among the employees of the Shr&ld steclworks in England. Smoking
NLY associated with a high prt~valrnce of chronic bronchitis, but of
part,icular interest. was the etfcct of cigarette smoking on disability.
The interval between th<b onset of chronic bronchit.is and disabilit,y
from t.his diseas(l was significantly less (P<W2) for those smoking
more than 20 cigarettes a day than for nonsmokers and for those
smoking less than this amount ( P<o.o~).

Ratawi (5) examined the prtlvalencc of several diseases including

43


respiratory illnesses in 4,643 employees in Egypt, comprising a 5.3
percent sample of 92,000 employees in 17 major industries. Respira-
tory illnesses occurred more frequently in all segments of the cotton
industry, as well as leather, printinlg, and glass industries; 40 percent
of all employees were smokers, and they experienced higher rates of
respiratory symptoms and illnesses than nonsmokers. Smokers with
occupational exposure to dust were particularly affected.

The effect of cigarette smoking and occupational exposure to dust
on the prevalence of chronic bronchitis was examined by Golli ($3')
in Romania. There were 2,942 individuals examined of whom 142 were
employed in dusty occupations. Chronic bronchitis was present in 24.6
percent of the 457 smokers and 4.4 percent of the 2,343 nonsmokers
(P<O.OOl). Increasing age, cilgarette smoking, and occupational ex-
posure to dust each independently contributed to an increased prev-
alence of chronic bronchitis.

Recent studies in metal casting, plaster, coke, baking, agricultural,
and chemical industries have documented a higher incidence of respir-
atory symptoms and/or diminished pulmonary function among ciga-
rette smoking workers than nonsmoking workers (&,64,89,97,99).

Reichel and Elmer (68,88) examined the effect of air pollution on
the prevalence of respiratory disease among 8,162 men and women in
West Germany. The three areas chosen for study had widely different
atmospheric levels of sulphur oxides and particulate matter. The fre-
quencies of cough and sputum production were the same within the
nonsmoking groups in all three areas. No differences were found in
pulmonary function or arterial blood gases between subjects of the
three districts. Smokers in each are,a had a higher prevalence of res-
piratory symptoms than nonsmokers. The authors concluded, "There
is no doubt that the influence of air pollution is less important than
that of age, sex, and smoking habits."

Tsunet.oshi, et al. (85) examined the prevalence of chronic bron-
chitis in Osaka, Japan. The independent contributions of age, smoking
habits, and air pollution were e.xaminkd. In male cigarette smokers
using more than a pack a day, chronic bronchitis was three to four
times more prevalent than in nonsmokers. In female smokers using
half a pack or more a day, chronic bronchitis was five to six times
more prevalent than in nonsmokers. The standardized prevalence of
chronic bronchit.is increased with the degree of air pollution, particu-
larly sulphur dioxide pollution, but not with increasing levels of
suspended particulate matter.

44


The Federal ,1viation Administ,ration, I)epartment of Transporta-
tion, and the Sational Inst.it.ute for Occupational Safety and Healt,h
jointly conducted a study of the lrvels of c.ertain combustion byprod-
ucts of tobacco on milit.ary and civilian ;tir(araft. I~roduced by pas-
sengers' smoking and also askecl the 1)assenprrs for their subjective
reaction to tobacco smoke (XI). I,e\-els of carbon mo~~ositle, particu-
late, matter, polycyclic hyclrocai~l~ona~ ammonia. and ozone were meas-
ured on 20 military and eight domestic flipht.s. On all aircraft the
measured level of each substanw was 11rw11 ion-PI. thall r~c~co~l~mr~~ltlt~d
ofcnpational and en\.i~r~nnlcntnl air quality stantlards. This was prob-
ably the result of the efficient \-cntilntioll systcnrs wcluirrd on all air-
waft (20 exchanges of cabin air each IIoiIr).
More than 60 lwrcent of the ~mk5~~1Ip1s rrporttd that tlwy w'rc
IJothered by tobacco smoke ant1 su,qystcd tllat corrt,cti\-1% act ion such
as segregation of smokcars and nonsmoktbrs 1~ taktlll. 3101~ tllan 70 per-
rent. of t.he nonsmokers who had a history of respiratory conditions
we annoyed bv tobacco s~nolct~. `1'11~1 disconlfort attributetl to tobacco
Sllloke in spite of the etlicient wnt ilation srstchni might haw wflwtcd
crowded seat.ing conditions or tlrying of the respiratory membranes
\rhich results from the very low humidity found on most aircraft..

Autopsy Studies

dnerbach, et al. (4) studied the relationship b&Keen age', smoking
habits, and emphysematous changes in \I-hole lung sections obtained at
aatopsv from 1,448 males and X88 fenlales. ,\ total of 7.324 sections
1 IIm. ;,hick were graded on a scale of 0 to 9 according to the severity of
(`mphvsema. So distinction was matlc betwwn centrilobular and pan-
lob&r emphysema. Tile IIwII were clwssifietl t)y ape, tyl)r of smoking
`pipe, cigar, or c,igarettr). and amount of cigarcttc smoking. Smoking
habits were ascertained bv interviews with relatives. Within each of
the six smoking catrporieL+ the nwan degree of emphysema increased
aith age. Adju&ing the data for age rc\-paled that. the I~P:I~ dcprw of
"~Qhvsema was lowest, among 1m11 who
Pipe or cigar smokcrj, and highest   never smokctl, was higher in
                             anIon g rrg111n I' ciga rettc snlokers.
-1 dose-rwponsc rc~lationship was found for the number of cigarett.es
smoked per day alIt1 the se\-eritv of c~ml~hyma. Table 2 and figure 2
stKnv these r~rlationshil~s.
Fingerland. et al. (29) investigatrd the prevalence of various patho-
logical contlitions including rI111~lIyse1Im and cllronic bronchitis in an
aLitol)sy population conlprisinp alI lwrsons owr thtx apcl of 20 who
"alllp to autops)- OYCI- R 2-yw1~ lwriotl at thcb Institute of I':~tlrologicaI
-\llatomv in (`z~~choslo\.aI;i;l : 76.7 Iiiulvs iIIl(l .i7:`, f<`Illill(`S \vel'(' inclutl~d

45


in the study. Smoking histories mere obtained from patients before
death, medical records, or relatives. The smokers were divided into
three groups based upon the number of cigarettes smoked during their
lifetime J 26 percent of the male nonsmokers showed some evidence of
emphysema, whereas 70 percent. of male smokers of more than 500,00r~
lifetime cigarettes showed these changes (fig. 3). Similar relationships
were demonstrated for chronic bronchitis.

TABLE 2.-Degrees of emphysema in current 1 smokers and in nonsmokers
           accordi,ng to age groups

Age group and degree of
emphrsems (see text)

Subjects   Current       Packages smoked per day
who never  pipe or ---
smoked    cigar    <M    yi to 1     1 to 2    >2
regularly

-

<60:
  oto0.75--- -._-_-_   53     18     12      3      2       0
  1 to1.75_-- -.-____    2      11      4      9     24       5
  2to2.75--- -._.___    0      1      2     17    130      56
  3to3.75-_- -.--__ -    0      1      5     12     50      38
  4 to 4.75---__-----    0      0      0      4      8       7
  5 to 6.75----------    0      0      0      0      4       5
  7to9.00- __-.----_    0      0      0      0      3       1
    Totals---.._----   55     31     23     45     221     112

  Mean-.----..--_--     . 10    .83    1. 29    2. 37    2. 56    2. 86
  SD---w ____ ----__    .04    .13    .26    .16    .07     .lO

                                                         -
60 to 69:
   0 to 0.75----------   35     17      4      0      0       0
   1 to 1.75---mm-----    1      8       1      0      4       1
  2 to 2.75--------..    2      3      4      5     37      23
   3 to 3.75--_----_..    2      2      2      9     42      24
   4 to 4.75_--m-_m---    0      0      1      3     11       9
  5 to 6.75--_--_-._.    0      0      0      1      8       1
   7 to 9.00--_----.._    0      0      0      1      5       4

    Totalsmm..F.--mm_    40     30      12     19    107      62

   Mean---.__----_--     .39    .95    1. 90    3. 59    3. 39    3. 37
   SD---mm...--mm.m_     13     .16    .34    .35     .l.i     .20

70 or older:
  0 to 0.7.5mmm---  ~~.   68     21      2      0      0       0
   1 to 1.7.5mm_--mm...    4     28     10      8      2       2
   2 to 2.75--m--__._.    -
        ;      22      13     23     40       9
  3 to 3.75-------_-_          8      5     10     38      18
  4 to 4.75----------    0      2      1      7     11       7
   5 to 6.75-_._--mmm.    0      1      0      2      9       3
   7 to 9.00.-----.--.    0      0      0      1     12       5

    Totalsm--_...---   81     82     31     51     112      44

   hlean~.---~~~-----      50
  SD-----m_.------m   :39    1. 66    2. 15    2. 98    3. 68     3. 91
                             11      17     20     17     .27

1 Subjects who smoked regularly up to time of terminal illness.
Source: Auerbach, O., et al. (1).

46


Figure 2. -Age-standardized percentage distribution of whole lung sections of
     males with moderate to far-advanced emphysema (score 3-9) by
     smoking category.

   Number 6
     of    Never
    cases   smoked
       regularly
SOURCE: Auerbach, 0.. et al. (4).

14
Pipe
or
cigars

   64         323
   Cigarette smokers
<l pack/day   >l pack/day

Mitchell, et al. (6'0) conducted a study to determine the accuracy
of the recorded cause of death on deat.h certificates of adults; 578
autopsies were performed on patients 40 years of age and older at two
large hospitals in Colorado. In addition, 409 patienk with COPD were
enrolled in an emphysema registry. A autopsies were performed on the
56 patients who died during the st.udy period. Death certificates were
obtained from the State Health Department, and t,he recorded cause
of death was compared with the autopsy findings. In 211 of the 634
autopsies performed, the cause of death was found to be COP11 ; how-
ever, in only 160 of these cases (76 percent) was COPI) listed as the
cause of death on the death certificate; 3 ljercent, of death certificates
incorrectly listed emphvsema as a cause of death when this was not
supported bv autopsy e;,idence. The authors concluded their study by
suggesting ;* * * that national statist,& which arc based on non-
autopsv confirmed diagnoses. might, understate tlraths f ram chronic
bronchitis and `e.mphysema.' "

47


Figure 3 .-Prevalence of emphysema in adult males at autopsy by smokina
      category.

50

40

30

20

10

0

58.90

48.62

Number autopsies 145       164       236       60       109
Number w/
  emphysema 38        66       139       42        53

Non-    Number cigarettes smoked during life   ii-
smokers  <200,000 200,000-500,000 >500,000 smoh

SOURCE: Fingerland, A., et al. (19).

Experimental and Histopathological Studies

Nistopatholoyical Studies

Studies in Man

Xaeye and Dellinger (63) esamined the small pulmonary art,eries
of 126 male cigarette smokers and 67 nonsmokers for quantitative
changes in collagen, elastic tissue, and circularly and longitudinallp
oriented smooth muscle. Thq fount1 a progressive increase in collagen

40


;,a(1 longitudinally oriented smooth muscle fibers and a progressive
,]rcrease in circularly oriented muscle fibers with age. These changes
\rere more advanced at each age in smokers than in nonsmokers
IP<O.Ol).
Sobonya and Kleinerman (78) quantified t,he smooth muscle and
~~nrcous glands in the bronchi of 13 male cigarette smokers and 11 male
rlonsmokers from Ohio who were 18 to 46 years old and had died of
nonrespiratory causes. The smokers averaged 24 pack-years of ex-
posure. Although the smokers had a Iiistory of more respiratory
symptoms and colds than the nonsmokers. no tliffercncc was found in
the percentages of smoot,h muscle or bronchial glands bet,ween smokers
and nonsmokers. Five of t,he 13 smokers showed evidence of squamous
netaplasia.
Ellefsen and Tos (17) determined the goblet cell density in tracheal
biopsies from 50 pat,ie.nts 1vit.h respiratory symptoms or disease. Goblet
wll density inweased with symptoms of tracheobronchitis and history
of exposure to dust. A slight increase was also noted in mean goblet
Tell density with increasing consumption of cigarettes from 136 in
symptomatic nonsmokers to 15-I in smokers of more than a pack a day.

Sudies in A\nimals

Syzganov, et al. (81) exposed 55 dogs to cigarette smoke inhaled
through tracheostomas for periods of up to a. year or longer. An addi-
tional 15 dogs served as nonsmoking controls. The smoking animals
developed bronchitis, bronchopneumonia, interst,it.ial pneumonia, and
hyperplasia of the, bronchial epithelium. Later histologic changes in-
cluded squamous metaplasia and papilloma formation not found in
controls.

The effect of sulphur dioxide (SO,) and cigarette smoke on the
a~ous glands of rats and the bronchial glands of lambs was studied
by Mamdesley-Thomas, et al. (57). There was a slight increase in the
goblet cell count of rats with the inhalation of SO, and cigarette smoke.
Exposure of lambs to cigarette smoke inhaled through a tracheostoma
resulted in hypertrophy of the bronchial glands.
Jones, et al. (&?) found that the addition of phenylmethyloxadiazole
(NO) to tobacco protects rats against some of the adverse effects of
exposure to cigarette smoke. Two groups of 13 Sprague-Dawley rats
ore exposed to 25 cigarettes a (lay. 4 days a week for 6 weeks. The
:`reUp exposed to cigarettes containing 1'310 showed less immediate
ctistrrss after esposurc and had a lower tmchtal goblet ccl1 count, less
tlnckening of the traclwal epitheIium, antI fewer cells in mitosis than
those exposed to the regular cigarettes.
The response of the rat lung to low levels of nitrogen dioxide (SO,),
i1 (!cnst,ituent, of cigarcttc smoke. was studied bv Strplwns. Evans. and

49


their associates (18, 80). Young male rat.s mere continuously exposed
to X0, at concentrations of 2 p.p.m. and 17 p.p.m. for 1 year. Animals
mere sacrificed after a short exposure and also at regular intervals Over
the 12-month period. ,1t the level of 17 p.p.m., destructive changes
occurred in the respiratory epitheliurli within 4 hours. These changes
included cell hypertrophy. loss of cilia. and increased mitotic, activity.
After 24 hours of exposure at this level some repair began. but cuboidal
cells replaced the normal respiratory epithclium. At 2 p.p.m. the acute
damage was less severe, and complete recovery occurred over a period
of several weeks.

Sherwin, et. al. (77) studied the effect of low doses of SO, on the
alveolar ~111 cells of the guinea pig. They founcl that continuous
exposure of 2 1~p.m. SO, produced a significant. increase (P<O.O5) in
the lactate dehydrogenase (I,I)EI ) index of the lower lobes of the lung.
suggesting that, the ultrathin type 1 (LT)Il positive) alveolar wall cells
were beinp replaced by relatively thick type :! cells resulting in a
physiologically sipnificant blood-gas barrier.

Ingram and O'Cain (3) studied dynamic compliance in nine smok-
ers and nine nonsmokers under the age of 30 who were in good health.
Both groups were identical with respect to airway resistances. lung
volumes. maximal expiratory fiow rates, and static compliance values.
Dynamic compliance fell more rapidly in the sniokcrs than in the non-
smokers above a frequenq- of 40 breaths a minute. `I'lw tlitYercncc was
statistically significant (P<O.OOOl). Isoproterenol produced no sig-
nificant increase in dynamic compliance in either the smokers or the
nonsmokers. In sis of the smokers who stoplw(l s111okinp. the dynamic
complianw CIII'VCS gr:~d~lnll~- :~~~~~IY~:I~~IL~YI tllcx \-illtles of the nonsmokers
over an H-week period. (`liaiipcs over tliis relatively loilg ~wriotl of time
indicate that the decrease in tlynarnic conll)li;~n(~c~ obscr\-cd in s~nokers
was more likely caused 1)~ inflamnlatory c*hanps or SOIW ot lwr mecha-
nism rather than miiscular cwiistriction in tlw I~t~oncliiolrs. Thr authors
concluded that peripheral :lil'\\-;ly :~l)l~ol~~n:~litic~s are rep~larl~ present
in yoiuig as)-mptomat ic smokers.

50