EPA-650/1-74-007
August 1974
Environmental Health Effects Research Series
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EPA-650/1-74-007
EPIDEMIOLOGY
OF
CHRONIC RESPIRATORY DISEASE:
A LITERATURE REVIEW
by
Dr. I.T.T. Higgins
Department of Epidemiology
School of Public Health
University of Michigan
Ann Arbor, Michigan 48104
Contract No. PH-86-68-142
Program Element No . 1AA005
ROAP No. 21BLE
Human Studies Laboratory
National Environmental Research Center
Research Triangle Park, N.C. 27711
Prepared for
OFFICE OF RESEARCH AND DEVELOPMENT
ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
August 1974
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This report has been reviewed by the Office of Research and Development, Environmen-
tal Protection Agency, and approved for publication. Approval does not signify that the
contents necessarily reflect the views and policies of the Environmental Protection Agency,
nor does mention of trade names or commercial products constitute endorsement or rec-
ommendation for use.
Publication No. EPA-650/1-74-007
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ACKNOWLEDGMENTS
It is a pleasure to acknowledge the help of Mrs. Susan Bilakos, Mrs. Mary Martin,
Miss Kay Good, Mrs. Florence Bramley, and Mrs. Mary Oh, Assistants in Research, all
of whom worked on this Contract.
I. am also indebted to Dr. George W. Comstock, Dr. John C. Gilson, Dr. Millicent W.
Higgins, Professor Walter W. Holland, Dr. Irving Kass, Dr. William S. Lainhart, and
Dr. Frank W. Mount, who read and criticized the manuscript and made many helpful sug-
gestions; to Dr. Robert G. Loudon for bibliographic and other help; and to Medlars per-
sonnel at the National Library of Medicine for the initial printout of the literature.
Many of the abstracts were collected while I was working, especially with Dr. R.G.
Loudon , on an annotated bibliography of respiratory disease surveys as a member of
the Ad Hoc Committee of the American Thoracic Society
I am particularly grateful to my secretary. Mrs. Anne Tenerelli, for bringing so much
order out of chaos, for her remarkable patience and tolerance, and for her impeccable
typing .
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CONTENTS
Page
LIST OF TABLES vii
ABSTRACT
INTRODUCTION 1
HISTORICAL BACKGROUND 1
DEFINITIONS 2
Ciba Conference Recommendations 2
American Thoracic Society Recommendations 4
SCOPE OF PROBLEM 6
DISTRIBUTION OF CHRONIC RESPIRATORY DISEASE 11
TEMPORAL EFFECTS 11
Secular Trends 11
Seasonal Variations 14
SPATIAL EFFECTS 14
International Differences 14
Intranational Differences 15
Urban-Rural Differences 16
SOCIOECONOMIC EFFECTS 16
METHODOLOGY FOR EPIDEMIOLOGICAL STUDIES OF CHRONIC
RESPIRATORY DISEASE 19
DIAGNOSIS AND INVESTIGATION 19
Standardized Questionnaires 19
Self-administered Questionnaires 19
Cough and Sputum Tests 20
Lung Function Tests 20
Chest Radiographs 21
Morphological Changes 22
Measurement Reproducibility 22
STUDY POPULATIONS 23
FACTORS IN THE ETIOLOGY OF CHRONIC RESPIRATORY DISEASE. ... 31
AGE, SEX, AND RACE 31
Mortality and Morbidity Rates 31
Lung Function Levels 33
GENETICS AND PHYSIOLOGY 34
Heredity 34
Familial Aggregation 35
Disease among Twins 35
Familial Emphysema 35
Mucoviscidosis 35
Alpha^-antitrypsin Deficiency 35
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Page
Blood Groups and Secretory Function 36
AIR POLLUTION 36
Acute Episodes 36
Variation in Mortality, Morbidity, and Lung Function with Time 38
Geographical Differences 40
Disease among Homogeneous Occupational Groups 44
Disease among Children 44
Yokohama and New Orleans Asthma Studies 46
Dose-response Relationships 47
Miscellaneous Studies » 49
OCCUPATION 49
General Industrial Studies 49
Specific Occupational Studies 56
ALLERGIES 65
Reactivity to Common Allergens 65
Eosinophilia 67
Bronchial Hyper reactivity 67
SMOKING 68
Mortality Rates 68
Morbidity Rates 69
Lung Function Tests 71
Effects of Cessation of Smoking 72
INFECTIONS AND THERAPY 73
Bacterial (Bronchial) 73
Viral and Mycoplasmal 74
Chemotherapy 75
SOCIOECONOMIC STATUS 76
WEATHER AND CLIMATE 77
MISCELLANEOUS FACTORS 78
Poisonous Gas Exposure in World War I 78
Infection of Teeth and Sinuses 79
Postoperative Pulmonary Complications 79
FOLLOW-UP STUDIES OF CHRONIC RESPIRATORY DISEASE .... 79
RECOMMENDATIONS FOR FURTHER RESEARCH 83
ETIOLOGY OF RESPIRATORY DISEASE 83
DIFFERENTIATION OF CHRONIC RESPIRATORY DISEASE 84
FACTORS INVOLVED IN EXACERBATIONS OF DISEASE ....... 84
FACTORS INVOLVED IN DECLINE IN VENTILATORY
LUNG FUNCTION 84
INTERVENTION TO ALTER THE NATURAL DISEASE COURSE .... 85
CORRELATION OF CLINICAL AND PHYSIOLOGICAL CHANGES ... 85
SUMMARY
87
REFERENCES 91
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LIST OF TABLES
Table . Page
1 Disabling Respiratory Conditions among Men under 65 Years of
Age Granted Disability Awards by the Social Security Adminis-
tration, 1959-1962 6
2 Deaths and Percentage Distributions of Respiratory Disease:
United States and United Kingdom, 1967 7
3 Deaths and Death Rates for Diseases of the Respiratory System by
Color and Sex: United States and United Kingdom, 1967 8
4 Deaths for which Selected Diseases Were Coded as Underlying
and as Contributory Causes of Death: United States, 1965 9
5 Trends in Mortality from Major Chronic Respiratory Diseases
in the United States, 1940 through 1967 12
6 Bronchitis Mortality Rates by Sex for Selected Countries, 1962 ... 15
7 Mortality Rates for Diseases of the Respiratory System in the
United States, England, and Wales, 1962 15
8 Mortality Rates for Bronchitis and other Chronic Respiratory
Diseases by Sex for Selected Countries, 1967 16
9 Mortality Ratios by Occupation for Men Aged 20 through 64 in
the United States, 1950 17
10 Radiographic Criteria for Diagnosis of Emphysema 21
11 American Field Studies of the Prevalence of Bronchitis 24
12 British and Comparative Field Studies of the Prevalence of
Chronic Bronchitis 26
13 European Studies of the Prevalence of Chronic Obstructive
Lung Disease 29
14 Mortality Rates by Sex for Chronic Bronchitis and other Chronic
Respiratory Diseases in the United States, 1967 31
15 Regression Relationships of FEV on Age and Height 33
16 Main Types of Epidemiological Investigations of Effects
of Air Pollution on Health 37
17 Mean Annual Mortality Rates from Asthma, Bronchitis, or
Emphysema by Economic Status and Pollution Levels for White
Males Aged 50 to 69 Years in Buffalo, New York, 1959 to 1961 ... 43
18 Frequency by Pollution Levels of Lower Respiratory Tract
Infections in British Children 45
19 Particulate and Sulfur Dioxide Levels and Effects on Health 48
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Table Page
20 Standardized Mortality Ratios for Bronchitis in Men Aged
20 to 64 and Their Wives in England and Wales 50
21 Standardized Mortality Ratios Greater Than 150, by Occupation,
for Diseases of the Respiratory System Exclusive of Influenza
and Pneumonia in United States, 1950 51
22 Respiratory Disease Inception Rates in United Kingdom, 1961
to 1962 Survey 53
23 Incapacity for Work Caused by Respiratory Disease in United
Kingdom, 1961 to 1962 Survey 54
24 Bronchitis Inception Rates in Men Aged 18 to 63 in United
Kingdom, 1961 to 1962 Survey 55
25 Bronchitis Inception Rates and Incapacity for Work Caused by
Bronchitis in Men Aged 1 8 to 63 in United Kingdom, 1961 to
1962 Survey 56
26 Population Surveys of Bronchitis and Ventilatory Capacity in
Men Working in High-Dust-Exposure Occupations 57
27 Respiratory Symptoms and Ventilatory Lung Function, by
Occupation, in Men Aged 25 to 74 in Staveley, England, 1966 .... 63
28 Extrinsic Allergic Alveolitis 66
29 Mortality Ratios for Bronchitis (502) and Emphysema (527.1),
by Smoking Habit, in Seven Prospective Studies 69
30 Mortality Ratios for Respiratory Diseases, by Smoking Habit,
in United States Veterans 70
31 Standardized Death Rates and Mortality Ratios, by Smoking
Habit, for Chronic Bronchitis in British Doctors 71
viii
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ABSTRACT
This review of published studies pertaining to the epidemiology of chronic respira-
tory disease focuses on three disorders — asthma, chronic bronchitis, and emphysema.
Particular emphasis is directed toward the latter two maladies. Chronic lung diseases
either cause or contribute to an increasing number of deaths throughout the world.
Practical measures for identifying persons who have chronic respiratory disease, par-
ticularly through the use of standardized questionnaires, are described. The review
cites studies from several countries that explore the distribution and etiology of chronic
respiratory disease, including the effect of air pollution. Most studies have confirmed
the initial observation that the most important factor in the natural history of chronic
respiratory disease is smoking, particularly cigarette smoking. Occupational exposure
is also important with workers in dusty occupations evidencing an excess of chronic
respiratory disease.
IX
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EPIDEMIOLOGY
OF
CHRONIC RESPIRATORY DISEASE:
A LITERATURE REVIEW
INTRODUCTION
HISTORICAL BACKGROUND
The chronic respiratory diseases include chronic bronchitis, emphysema,
asthma, bronchiectasis, pneumoconiosis, and chronic interstitial pneumonia. This
review/, however, will be chiefly concerned with the first three of these, and more
with the first and second than with the third.
The term chronic bronchitis was first used in 1808 by Badham, who recog-
nized acute and chronic varieties. In 1819, Laennec described chronic bronchitis
as "pulmonary catarrh," and classified it into chronic mucous, chronic pituitous,
suffocative, and dry varieties. Laennec is usually credited with the first descrip-
tion of emphysema, but he was actually preceded in this by Mathew Baillie, who
in 1793 observed the disease in the lungs of Dr. Samuel Johnson. In a recent re-
view of the early medical literature on emphysema, Rosenblatt attributes the earli-
est autopsy descriptions to Bonetus, Ruysch, and Floyer, " in the late 17th and
early 18th centuries; and notes that in 1764 Watson' described the clinical features
of emphysema, subsequently confirmed at autopsy, in a man -who died of respiratory
failure at the age of 28. The cardiac complications of chronic bronchitis -were de-
scribed in 1831 by Mackintosh, ° who noted that Morgagni and Valsalva were well
acquainted with the disease.
The clinical features of chronic bronchitis and emphysema were well known to
physicians in the nineteenth century. 9-14 Etiological factors such as climate,
weather, exposure to cold or damp, changes of temperature, and "long standing
local irritation from dust or overdried air"13 were believed to be important. Most
of these authors also considered family history to be significant and indicative of
hereditary influence. In addition, they speculated on the mechanism of production
of emphysema. 12
Interest in chronic respiratory disease, particularly in chronic bronchitis, de-
veloped in Britain after the Second World War, and was stimulated significantly by
the severe London fog of 1952. This interest has increased greatly and has been
accompanied by a growing interest in bronchitis in many European countries. More
recently, attention to the chronic respiratory diseases in the United States, Canada,
and Australia has also increased. A number of excellent reviews have recently
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been published, some general in scope " and others concentrating primarily on
one particular aspect of the subject. 2,5-34
DEFINITIONS
The terms chronic bronchitis, emphysema, and asthma have long been used diag-
nostically, but the criteria on which the respective diagnoses are based have only
lately been clearly stated. This is particularly true for certificates of mortality or
morbidity that form the basis for vital statistics. It has become apparent during the
past 20 years that chronic bronchitis and emphysema have often been used as if they
were synonymous. Furthermore, medical practice may result in the use of one
term in one country and another in a second. This clearly is the case in the United
States and the United Kingdom, where the diagnostic confusion was pointedly indica-
ted by Fletcher and his colleagues^? j_n a paper entitled "American Emphysema and
British Bronchitis. " An epidemiologist can do little to improve diagnoses already
certified, though combining the statistics on chronic respiratory diseases may re-
duce error. ^ Much can and has been done, however, to make the future diagnosis
of these diseases more precise, particularly in surveys designed to study them.
Ciba Conference Recommendations
The 1959 Ciba Conference on Terminology, Definitions, and Classification of
Chronic Pulmonary Emphysema and Related Conditions^? examined the general
principles of definition of emphysema, and recommended that definition and classi-
fication of emphysema be based on morbid anatomical terms. Clinical definitions
and classifications of the chronic respiratory diseases were also presented at the
Conference. The recommendations of the Conference follow..
Emphysema According to the Conference, "emphysema is a condition of the lung
characterized by increase beyond the normal in the size of the air spaces distal to
the terminal bronchiole either from dilatation or from destruction of their walls. "
Emphysema can be diagnosed and classified consistently only with preparations
from lungs distended and fixed before they are cut. The simplest technique is intra-
bronchial infusion of fixative. In some cases, identification of the anatomical origin
of enlarged spaces may require such methods as the study of serial sections or
stereoscopic microscopy of lung slices.
The Conference stressed the need to establish the normal range of air space
sizes according to age and sex by each technique of lung preparation in order to
establish the upper limits of normality. The two classifications suggested are out-
lined below.
A. First classification.
L Nonselective distribution beyond the terminal bronchiole
(panacinar emphysema).
a. Dilatation alone (for example, compensatory
emphysema and emphysema resulting from partial
obstruction of the main bronchus).
b. Destruction of the walls of the air spaces
(panacinar destructive emphysema).
2. Selective distribution beyond the terminal bronchiole.
a. Predominantly affects respiratory bronchioles.
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(1). Dilatation alone (for example, focal emphysema
resulting from dust).
(2). Destruction of -walls of air spaces (centri-
lobular emphysema).
b. Predominantly affects alveolar ducts and sacs.
(1). Dilatation alone.
(Z). Destruction.
3. Irregular distribution beyond the terminal bronchiole
(irregular emphysema).
B. Second classification.
1. Dilatation alone.
a. Nonselective distribution (compensatory emphysema
and emphysema resulting from partial obstruction
of the main bronchus).
b. Selective distribution predominantly affecting
respiratory bronchioles (for example, focal
emphysema resulting from dust).
2. Destruction of -walls of air spaces.
a. Nonselective distribution (panacinar destructive
emphysema).
b. Selective distribution that predominantly affects
respiratory bronchioles (centrilobular emphysema).
c. Irregular distribution (irregular emphysema).
Chronic nonspecific lung disease The term "chronic nonspecific lung disease"
was recommended by the Ciba Conference for the -whole group of diseases variously
referred to as "chronic bronchitis, " "asthma, " and "emphysema. " The group as a
whole was defined as comprising those diseases characterized by one or more of
the following: chronic cough with expectoration, and paroxysmal or persistent ex-
cessive breathles sness, neither of which is solely attributable to:
1. Localized lung disease of any kind (for example, tuber-
culosis, pneumonia, or bronchiectasis cystic disease).
2. Generalized specific infective lung diseases (for example,
miliary tuberculosis).
3. Pneumoconiosis.
4. Collagen diseases and the generalized pulmonary fibroses
and granulomata.
5. Primary cardiovascular renal diseases.
6. Diseases of the chest wall.
7. Psychoneurosis.
Chronic nonspecific lung disease may coexist with any of the diseases referred
to in 1 through 7 above. For instance, in a case of healed tuberculosis or of simple
pneumoconiosis, the symptoms may be the result of chronic nonspecific lung disease.
In such cases, two independent diagnoses should be made. Psychoneurosis is ex-
cluded only if there is no somatic effect; thus, psychogenic asthma is included if
there is narrowing of the airways.
In an attempt to clarify the present confusion in the clinical use of the terms
chronic bronchitis, asthma, and emphysema, the Ciba Conference proceeded to
-------
define these components as given below.
Chronic bronchitis Chronic bronchitis refers to the condition of subjects who have
chronic or recurrent excessive mucous secretion in the bronchial tree. The diag-
nostic criterion, which is clinical, is chronic or recurrent cough with expectoration
that is not attributable to conditions excluded from chronic nonspecific lung disease.
Infection of the bronchi is frequently but not necessarily present.
The Conference went on to point out that, not infrequently, subjects who produce
sputum deny cough. Such subjects are included as having bronchitis. Subjects who
habitually swallow sputum should also be included as having chronic bronchitis.
Opinion is divided concerning the significance of "dry" chronic bronchitis without
hypersecretion, which is excluded by this definition. In Britain, however, popula-
tion surveys suggest that persistent cough without expectoration is uncommon.
The words "chronic" or "recurrent" were defined as "occurring for most days
for at least 3 months in the year during at least 2 years. "
Generalized obstructive lung disease Generalized obstructive lung disease refers
to the condition of subjects who have widespread narrowing of the bronchial airways,
at least on expiration, that causes abnormal resistance to airflow.
There may be no clinical symptoms or signs in the presence of demonstrable
obstruction to bronchial airflow. Symptoms, when present, include paroxysmal or
persistent ureathlessness, tightness in the chest, and wheezing. The most charac-
teristic sign is sibilant rhonchi, but their presence is not closely related to the se-
verity of the obstruction.
1. Intermittent or reversible obstructive lung disease (asthma). Asthma refers
to the condition of subjects having widespread narrowing of the bronchial
airways that changes in severity over short periods of time, either spon-
taneously or as a result of treatment with bronchodilator drugs (including
corticosteroids).
2. Irreversible or persistent obstructive lung disease. Irreversible or per-
sistent obstructive lung disease refers to the condition of subjects having
widespread narrowing of the bronchial airways that has been present for
more than 1 year and that is unaffected by bronchodilator drugs (including
steroids).
These definitions were adopted in 1961 by the World Health Organization (WHO)
Committee on Cor Pulmonale. ^° With relatively minor alterations, they have been
accepted by the European Coal and Steel Community. 39
American Thoracic Society Recommendations
The Committee on Diagnostic Standards for Non-Tuberculosis Respiratory
Diseases of the American Thoracic Society suggested the definitions that follow.
40
Chronic bronchitis Chronic bronchitis is a clinical disorder characterized by ex-
cessive mucous secretion in the bronchial tree. It is manifested by chronic or re-
current productive cough, which, according to this definition, should be present on
most days for a minimum of 3 months in the year and for not less than 2 successive
-------
years. The diagnosis can be made only after excluding other bronchpulmonary or
cardiac disorders, which may cause identical symptoms, as the sole cause for the
symptoms.
Asthma Asthma is a disease characterized by increased responsiveness of the
trachea and bronchi to various stimuli and manifested by a widespread narrowing of
the airways that changes in severity spontaneously or as a result of therapy. The
term "asthma" is not appropriate for the bronchial narrowing that results solely
from widespread bronchial infection, such as acute or chronic bronchitis; from
destructive diseases of the lung, such as pulmonary emphysema; or from cardio-
vascular disorders.
Emphysema Pulmonary emphysema is an anatomic alteration of the lung character-
ized by an abnormal enlargement of the air spaces distal to the terminal, nonres-
piratory bronchiole, accompanied by destructive changes of the alveolar walls. The
Committee suggested the classification of emphysema given below.
1. Paracicatricial: Overdistension of air spaces and destruction
of alveolar walls anatomically adjacent to fibrotic lesions of
the lung.
2. Lobular: Overdistension of air spaces and destruction of
of alveoli within the secondary lobule. The lesions can be
subdivided on the basis of distribution and extent:
a. Centrilobular: Lesions are localized in relation to the
respiratory bronchioles and predominate in the central
part of the secondary lobule.
b. Panlobular: Lesions are distributed more or less
uniformly throughout the secondary lobule.
c. Unclassified: Overdistension of air spaces •with marked
destruction of most of the secondary lobule. Because
the intralobular changes are extensive, the original
localization of lesions within the lobule cannot be
defined.
To describe the extent of the lesions, a physician1 s report should indicate •whether
the disease is present in one or both lungs and should identify the specific segments
involved.
The Committee's report describes the clinical and radiological manifestations
of these diseases; indicates the main laboratory findings and physiological distur-
bances that may occur in each; and, finally, summarizes the pathological changes
that may be observed.
41,42
Reid ' points out that "dilatation" and "destruction" as used in this definition
imply a mechanism that is often not at work. She suggests, as a more suitable def-
inition, the more factual statement that emphysema is a condition of the lung char-
acterized by an increase beyond normal in the size of air spaces distal to the ter-
minal bronchiolus , that is , the acinus .
The Committee on the Etiology of Chronic Bronchitis of the British Medical Ke-
rch Council suggested the following simple classi
on the basis of the Ciba Conference recommendations:
search Council suggested the following simple classification of chronic bronchitis
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1. Simple chronic bronchitis. Chronic or recurrent increase
in the volume of mucoid bronchial secretion sufficient to
cause expectoration.
2. Mucopurulent chronic bronchitis. Chronic bronchitis in
-which the sputum is persistently or intermittently purulent
and the sputum purulence is not the result of localized
bronchopulmonary disease.
3. Chronic obstructive bronchitis. Chronic bronchitis with
persistent widespread narrowing of the bronchial airways,
at least on expiration, that causes increased resistance
to airflow. 44
SCOPE OF PROBLEM
Between 30, 000 and 40, 000 people die in the United States each year from chron-
ic respiratory diseases. An additional 50, 000 to 60, 000 deaths occur in which these
diseases are mentioned as contributory causes. The number of deaths from emphy-
sema and chronic bronchitis is doubling every 5 years: deaths from these causes
increased from 12, 426 in I960 to 23, 432 in 1965. About 15, 000 middle-aged Amer-
icans are disabled each year by these diseases. Social Security Administration re-
cords indicate that nearly 10 percent of all disability awards granted from 1959 to
1962 were for chronic respiratory diseases (Table 1). Emphysema (51, 508 awards
from 1959 to 1962) is now second to coronary heart disease (131, 160 awards in the
same period) as the leading cause of Social Security-compensated disability. The
Social Security Administration is paying out $90 million annually to support people
disabled by chronic respiratory diseases. Furthermore, it is estimated that in
addition to the toll taken by disablement 250 million man-hours are lost each year
because of these diseases.
Table 1. DISABLING RESPIRATORY CONDITIONS AMONG MEN UNDER 65 YEARS OF AGE GRANTED
45
DISABILITY AWARDS BY THE SOCIAL SECURITY ADMINISTRATION, 1959 to 1962
Condition
Chronic bronchitis
Pneumoconiosis of
occupational origin
Bronchiectasis
Emphysema
Total: Respiratory
Total: All causes
ISCa
502
523;524
526
527
Total j
2,846
9,538
906
51,508
64,798
691,028
Age 5 years
35
58
14
38
194
304
32,316
35-44
222
206
126
2,050
2,604
75,460
45-49
308
598
118
3,302
4,326
65,236
50-54
518
1,834
158
8,586
11,096
118,422
55-59
770
3,202
194
15,430
19,596
168,346
60-64
970
3,684
272
21,946
26,872
231,248
International Statistical Code.
In England and Wales, which have a total population one-fourth that of the Unit-
ed States, between 25, 000 and 30, 000 deaths have resulted from bronchitis each
year for many years, the number depending to some extent on the annual prevalence
-------
of influenza. Roughly 25 million working days are lost each year because of bron-
chitis " and about 10 percent of all contacts between patients and their general
practitioners is for treatment of bronchitis. The annual cost to the country has been
estimated at some 70 million pounds sterling ($175 million). ^7
In addition to the studies carried out in the United States and the United Kingdom,
studies on chronic respiratory diseases have been conducted in many other countries,
notably Belgium, The Netherlands, France, Germany, Czechoslovakia, Canada, and
Australia.24' 39-48-53
Deaths from chronic respiratory diseases in the United States comprise about
2 percent of all deaths (Table 2). This is slightly less than the proportion of deaths
attributed to cancer of the respiratory system, but about six times that now caused
by respiratory tuberculosis. Chronic respiratory diseases are responsible for 5. 8
percent of all deaths in England and Wales.
Table 2. DEATHS AND PERCENTAGE DISTRIBUTIONS OF RESPIRATORY DISEASE:
UNITED STATES AND UNITED KINGDOM, 1967
Cause of death
All causes
Chronic respiratory
disease
Asthma
Bronchitis
(chronic,
unqual if led)
Emphysema (no
mention of
bronchitis )
Pneumoconiosis
Other chronic
interstitial
pneumonia
Bronchiectasis
Other
Total
Cancer of trachea,
bronchus, and lung
Tuberculosis of
respiratory system
ISC
241
501;
502
527.1
523;
524
525
526
527.0;
527.2
162;
163
001-
008
United States
Number
of deaths
1,851,323
4,137
5,306
20,875
1,640
4,219
1,476
2,790
40,443
54,407
6,351
Respiratory disease,
% distribution
100.0
0.2
0.3
1.1
0.1
0.2
0.1
0.2
2.2
2.9
0.3
United Kingdom
Number
of deaths
542,516
1,757
25,887
1,225
566
467
1,177
279
31,358
28,252
1,798
Respiratory disease,
% distribution
100.0
0.3
4.7
0.2
0.1
0.1
0.2
0.1
5.8
5.2
0.3
Table 3 gives the number of deaths from chronic respiratory disease and the
death rates by sex and color for the United States and, for comparison, the
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Table 3. DEATHS AND DEATH RATES FOR DISEASES OF THE RESPIRATORY SYSTEM BY COLOR AND SEX:
UNITED STATES AND UNITED KINGDOM, 1967
Cause of death
Upper respiratory
infection
Infl uenza
Pneumonia
Bronchitis
Acute
Unqualified
Chronic
Other diseases of
respiratory system
Chronic inter-
stitial pneu-
monia
Bronchiectasis
Other diseases of
lung and pleura
Emphysema (no
mention of
bronchitis)
Cancer of trachea,
bronchi , or lung
Respiratory tuber-
culosis
Asthma
ISC
470 through 475
480 through 483
490 through 493
500 through 502
500
501
502
510 through 527
525
526
527
527.1
160 through 165
162; 163
001 through 008
241
United States
Number of deaths
White
Male
238
549
25,895
4,243
469
386
3,388
24,874
2,368
859
18,698
17,025
44,909
40,959
3,408
1,909
Female
194
695
20,620
1,497
337
279
881
6,279
1 ,201
496
3,520
2,808
9,408
8,217
1,188
1,490
Nonwhi te
Male
82
99
5,361
355
88
68
199
2,036
378
79
1,174
859
4,932
4,424
1,275
377
Female
78
132
3,541
169
64
56
49
788
272
42
273
147
953
807
480
361
Rate3
White
Male
0.3
0.6
30.4
5.0
0.6
0.5
4.0
29.2
2.8
1.0
22.0
20.0
52.8
48.2
4.0
2.2
Female
0.2
0.8
23.2
1 .7
0.4
0.3
1.0
7 1
1.4
0.6
4.0
3.2
10.6
9.3
1.3
1.7
Nonwhi te
Male
0.7
0.9
46.3
3.1
0.8
0.6
1.7
17.6
3.3
0.7
10.1
7.7
42.6
'38.2
11.0
3.3
Female
0.6
1 .1
28.6
1.4
0.5
0.5
0.4
6.4
2.2
0.3
2.2
1.2
7.7
6.5
3.9
2.9
England and Wales
Number of
deaths
Male
59
375
14,443
20,487
972
647
18,868
3,254
306
775
1 ,134
973
24,312
23,548
1,321
779
Female
62
501
17,683
7,324
952
624
5,748
1,641
161
402
370
252
4,977
4,704
477
978
Rate3
Ma 1 e
0.3
1.6
62.6
86.9
4.1
2.7
80.1
13.8
1.3
3.3
Female
0.2
2.0
72. 'J
29.5
3.8
2.5
23.2
6.6
0.6
1 .6
t
4.8 1.5
4.1
103.2
99.9
5.6
3.3
1.0
20.0
18.9
1.9
3.9
Deaths/100,000.
-------
corresponding figures for England and Wales. The higher rates for influenza, pneu-
monia, bronchitis, and respiratory cancer in England and Wales are striking, while
the higher rates for "other diseases of the respiratory system" in the United States,
particularly among the white population, are clear. The table also shows higher
rates for chronic bronchitis and "other diseases of the respiratory system' in men
than in women; higher rates for the white population than for the nonwhite; and
higher rates for pneumonia than for any other respiratory disease in the nonwhite
population.
These mortality statistics are based on the underlying cause of death, ft is now
generally recognized that chronic respiratory diseases may often be present at and
contribute to death but still not be reflected in the vital statistics. Moriyama54
concluded in 1963 that about 62 percent of all chronic respiratory disease present
at death was certified as the underlying cause of death; however, Table 4, from the
paper by Dorn and Moriyama, suggests that this was an overestimate. It indi-
cates that only about a third of all persons who die of chronic respiratory disease
are certified as dying of it. Furthermore, chronic obstructive lung disease is often
omitted as a contributory cause of death, with the result that the disease goes un -
r { c ~y ~
reported. -"-> > ^ <
Chronic respiratory disease is a common cause of morbidity and disability.
Data from the U.S. National Health Survey indicate that chronic respiratory disease'
comprises approximately 10 percent of all conditions that cause disability for 1
week or more. From July 1964 through June 1965, 1.9 percent of men and 2.0 per-
cent of women aged 17 years and over who were interviewed in the U.S. National
'Health Survey reported that they had chronic bronchitis and/or emphysema. 58
Epidemiological studies have indicated that the prevalence in the national population
of chronic respiratory disease of all degrees of severity varies from under 10 per-
cent to over 40 percent, depending on age, sex, and the definitions of chronic res-
piratory disease that are used.
Table 4. DEATHS FOR WHICH SELECTED DISEASES WERE CODED AS UNDERLYING AND AS
CONTRIBUTORY CAUSES OF DEATH: UNITED STATES, 1955a
Diagnosis
Asthma
Bronchitis, acute
Bronchitis, other
Other chronic inter-
stitial pneumonia
Bronchiectasis
Emphysema without
mention of bronchitis
Other lung diseases
ISC
241
500
501;
502
525
526
527.1
527.0;
527.2
Death
:ertificates
13,047
2,179
5,876
6,212
5,363
12,411
16,814
Deaths for which diagnosis
was selected as
Underlying
cause
5,904
1,067
2,025
2,289
2,197
3,902
2,129
Contributory
cause
7,143
1,112
3,851
3,923
3,166
8,509
14,685
Underlyi ng
cause,
% of total
45.3
49.0
34.5
36.8
41.0
31.4
12.7
aData from Dorn and Moriyama.
-------
DISTRIBUTION OF CHRONIC RESPIRATORY DISEASE
TEMPORAL EFFECTS
Secular Trends
In the United States, death rates from chronic bronchitis, emphysema, and
asthma declined steadily during the first half of the twentieth century. Since 1948,
however, rates have risen steadily for deaths resulting from, chronic respiratory
disease. "' ' ' The main rise has been in deaths from emphysema, but
there have been smaller rises in death rates for bronchitis (in men) and also for
"other chronic interstitial pneumonia" (Table 5). To what extent the trend in mor-
tality for emphysema is real, and to what extent it reflects changes in diagnostic
practice, is debatable. The rise is seen in men and women and in -white and non-
white persons. This might suggest that much of the rise is more apparent than real
inasmuch as the marked predilection of males for the disease might be expected to
result in a more rapid rise in them than in females. Supporting this interpretation
is the similarity in the trends in all states and several cities. °^ The increase is
not the result of a shift in reporting chronic respiratory diseases from contributory
to underlying cause of death, since the trend is seen for both categories. This
perhaps suggests that some of the trend in mortality reflects a real increase in in-
cidence.
Katz and Kunofsky"^ have attributed the rise in emphysema mortality to tuber-
culosis. They found an association between tuberculosis and emphysema in death
certificates in upstate New York in 1961, an association that was much less fre-
quent before the availability of antimicrobial drugs for the treatment of tuberculosis.
They also point out that a high frequency of emphysema was found by lung function
tests in patients with tuberculosis. They postulate that chemotherapy reduces
the number of deaths from tuberculosis and that as a result the patients live long
enough to develop emphysema secondary to the extensive destruction of lung tissue
caused by tuberculosis. The evidence for this hypothesis is unconvincing. The
high proportion of mortality from emphysema in tuberculous patients shown in their
paper is associated -with high proportional mortality from respiratory cancer. This
might suggest that respiratory causes of death tend to be better certified in tubercu-
lous patients than in-other people. The authors do not indicate whether the age dis-
tribution of those dying from tuberculosis is the same as that of the general popula-
tion. A difference in age could make a big difference in the proportional mortality
rates. A more likely explanation would seem to be that the rise is attributable to the
increase in cigarette consumption that occurred during the earlier decades of this
century. This explanation has been questioned, however, by Barach and Segal. °"
They note that the increase in reported deaths from chronic bronchitis and emphy-
sema have taken place during a period in -which there is evidence"' of a decline in
cigarette smoking. Damage to the lungs from smoking, however, may take place
many years before death. Consequently, one should not necessarily expect a close
association between incidence of smoking and mortality.
A trend of increasing mortality from chronic respiratory disease has been noted
in certain other countries. For example, in Canada, an increase in death rates for
emphysema and chronic bronchitis has occurred that is somewhat similar, though
less marked, to that seen in the United States.'*" Increases have also been noted in
11
-------
Table 5. TRENDS IN MORTALITY FROM MAJOR CHRONIC RESPIRATORY DISEASES IN THE UNITED STATES,
1940 THROUGH 196761
Year
1940
1941
1942
1943
1944
1945
1946
1947
1948
1949
1950
1951
1952
1953
1954
1955
1956
1957
1958
1959
1960
1961
Deaths/100, 000-yr
Cancer of lung
and bronchus
4.2
4.6
4.8
5.4
5.8
6.2
6.4
6.8
7.3
11.2
12.2
12.9
13.8
14.9
15.4
16.3
17.5
18.1
18.6
19.4
20.3
21.2
Tuberculosis
(respiratory system)
42.2
40.8
39.6
39.0
38.2
36.9
33.5
31 .0
27.7
24.2
20.6
18.5
14.4
11-. 3
9.3
8.3
7.8
7.3
6.6
6.0
5.6
5.0
Asthma
1.7
1.8
1.7
2.0
2.0
1.9
1.8
1.9
1.8
3.1
2.9
4.5
4.5
4.3
3.8
3.6
3.6
3.9
2.9
2.8
3.0
2.7
Chronic
bronchitis
2.1
1.9
1.9
2.0
1.9
1.8
1.7
1 .8
1.8
1.5
1.3
1.3
1.2
1.3
1.2
1.2 --
1.2
1 ,4
1.5
1.5
1.8
1.6
Bronchiectasis
__d
--
--
--
--
--
--
--
--
1.5
1.4
1.4
1.4
1.5
1.3
1.3
1.3
1.3
1.4
1.3
1.3
1.2
Other chronic inter-
stitial pneumonia
__d
--
--
--
--
--
--
--
--
0.6
0.7
0.8
1.0
1.2
1.2
1.4
1.6
1 .8
2.0
2.0
2.2
2.1
Emphysema
0.1
0.1
0.1
0.1
Subtotal13
c
--
--
--
0.2
0.2
0.2
0.2
0.3
0.6
0.8
1 .1
1 .2
1.6
1 .9
2.2
2.7
3.4
3.9
4.4
5.2
5.6
--
--
--
--
1.5
1.4
1.4
1.4
1 .5
9.4
9.7
10.4
11.8
11.7
12.0
13.5
13.2
Total b
c
--
__
--
--
--
--
--
--
42.7
39.9
40.5
37.5
36.1
34.1
34.3
35.7
37.2
36.9
37.4
39.4
39.4
-------
Table 5 (continued). TRENDS IN MORTALITY FROM MAJOR CHRONIC RESPIRATORY DISEASES IN THE UNITED STATES,
1940 THROUGH 196761
Year
1962
1963
1964
1965
1966
1967
Deaths/100, 000-yr
Cancer of lung
and bronchus
22.3
23.1
23.9
25.0
26.3
27.5
Tuberculosis
(respiratory system)
4.7
4.6
4.0
3.8
3.6
3.2
Asthma
2.6
2.7
2.3
2.3
2.2
2.1
Chronic
bronchitis
1.9
2.3
2.3
2.5
2.7
2.7
Bronchiectasis
1.1
1.1
1.0
0.9
0.8
0.7
Other chronic inter-
stitial pneumonia
2.2
2.3
2.2
2.2
2.2
2.1
Emphysema
6.7
8.0
8.3
9.6
10.3
10.6
Subtotal13
14.5
16.4
16.1
17.5
18.2
18.2
Total b
41.5
44.1
44.0
46.3
48.1
48.9
Includes unspecified chronic bronchitis.
"Asthma" through ''emphysema" columns.
cData not comparable.
Data not available.
-------
The Netherlands, in Israel,68 and in the United Arab Republic. o9
In England and Wales, mortality rates for bronchitis declined steeply from
about 1850 to 1940.~b The rates, which were always higher in men, declined some-
what less rapidly in men than in women. Since 1940, mortality rates in women
have shown a continuing decline, though the decline is slower than before 1940; b\.it
in men, a modest increase in mortality rates has occurred since 1940. There is
little indication that the mortality rates have been affected by the introduction of
antibiotic drugs. Chronic bronchitis is therefore in marked contrast to respiratory
tuberculosis in this respect. In Scotland, the death rates from bronchitis from
1940 to I960 were about 25 percent lower than in England and Wales. '0 During this
period, the rates declined in women, but showed an increase in men, especially
from the early 1950' s.
The major long-term trend in chronic respiratory disease mortality noted in
recent years in the United Kingdom is an increase in mortality rates for asthma.
72 The increase has affected mainly the 5 - to 34-year age group and is most pro-
nounced at ages 10 to 14 years. In this last age group, mortality rates increased
nearly eightfold in 7 years, and, in 1966, asthma accounted for 7 percent of all
deaths. Smaller increases have been noted in other countries; increases at ages 10
to 19 have been observed in Australia, Japan, Western Europe, and the United
7^75
States. In Britain, general practitioners' records provide no evidence for an
increase in prevalence; it therefore seems likely that there has also been an in-
crease in case fatality. No environmental hazards are known that could have in-
creased the severity of the disease. Thus, new methods of treatment, notably with
pressurized aerosols of sympathornimetic drugs, are believed to be responsible
for the observed increase in mortality rates. 7t>> 77
Seasonal Variations
Marked seasonal variations occur in mortality and morbidity from chronic
respiratory diseases through the year. Mortality for bronchitis in the United King-
dom is much higher in the winter than in the summer. Marked seasonal variations
in respiratory disease morbidity were also noted in the United States, according to
the U.S. National Health Survey.
SPATIAL EFFECTS
International Differences
Despite the obvious limitations of differences in diagnosis, certification, and
coding, mortality statistics have pointed to differences in chronic respiratory
disease frequency between countries; such differences have stimulated productive
research. ' • '"~°3 jn earlier years, comparative rates for .bronchitis were given
annually by the World Health Organization (Table 6).84 Statistics of this kind,
based on a single disease rubric, are particularly likely to exaggerate differences
between two countries when one of the countries classifies most of the respiratory
disease deaths under a different rubric. Comparisons are likely to be more valid
if all the chronic respiratory disease rubrics are considered, as is the present
practice of the World Health Organization. The forty-fold difference in bronchitis
mortality between the United Kingdom and the United States is reduced to a more
reasonable one of threefold to fourfold when all chronic respiratory diseases are
combined (Table 7). The World Health Organization now gives mortality rates for
bronchitis and other diseases of the respiratory system separately (excluding acute
infections and upper respiratory conditions) (Table 8).^5
14
-------
Table 6. BRONCHITIS MORTALITY RATES BY SEX FOR SELECTED COUNTRIES, 1962°
(deaths/100,000)
Country
England and Wales
Czechoslovakia
Italy
New Zealand
Australia
Belgium
Denmark
Japan
Sweden
United States
Israel
Male
103.1
54.4
38.7
35.9
28.6
25.0
22.4
3.5
5.1
3.6
3.4
Female
41.4
26.0
25.3
10.5
6.1
9.4
9.7
8.3
4.1
1.4
1.3
a 84
Data from WHO Annual Epidemiological and Vital Statistics.
Table 7. MORTALITY RATES FOR DISEASES OF THE RESPIRATORY SYSTEM IN THE
UNITED STATES, ENGLAND, AND WALES, 196285
(deaths/100,000)
Disease
All respiratory
Acute upper
Influenza
Pneumonia
Bronchitis
Other
ISC
470 through 475
480 through 483
490 through 493
500 through 502
510 through 527
Males
United
Kingdom
189.5
0.3
6.7
66.0
103.1
15.6
United
States
(white)
60.2
0.4
1.7
32.4
3.7
22.0
Females
United
Kingdom
124.4
0.2
7.5
69.7
41.4
6.8
United
States
(white)
' 34.0
0.3
1.8
24.6
1.4
5.9
IntranationaI Differences
Mortality rates for chronic respiratory diseases differ between parts of the
United States. Certain states have exceptionally high rates: -Arizona, Wyoming,
New Hampshire, Vermont, and Florida, among others. Differences in age dis-
tribution of the population of different states can explain some of the high rates.
Climate, air pollution, occupational exposures, and density of population may also
be contributing factors. In addition, immigration of persons with respiratory
disease into some of these states and climates also presumably plays a role in the
high rates.
15
-------
Table 8. MORTALITY RATES FOR BRONCHITIS AND OTHER CHRONIC
RESPIRATORY DISEASES BY SEX FOR SELECTED COUNTRIES, 1967a
(deaths/100,000)
Country
England and Wales
Italy
Australia
Belgium
Germany (Fed. Rep. )
Denmark
Netherlands
Canada
Norway
United States
Japan
Bronchitis ,
chronic and unqualified
Male
83.2
39.1
34.2
25.3
24.4
22.7
18.2
10.0
7.3
4.2
3.4
Female
25.7
20.3
6.2
7.2
8.5
8.9
5.7
2.1
3.0
1.3
2.7
Other chronic
respiratory diseases^1
Male
13.3
11.4
8.9
50.9
19.9
10.5
18.2
13.8
6.3
27.0
4.1
Female
6.2
4.8
4.1
17.4
5.9
4.1
6.1
4.3
2.6
6.7
2.1
-. o c
Data from WHO Annual Epidemiological and Vital Statistics.
Respiratory diseases other than bronchitis and acute infections
and upper respiratory conditions.
In Canada, Anderson has drawn attention to the large differences that exist
in the mortality rates for different chronic respiratory diseases in different pro-
vinces. Much of this variation is explained by diagnostic practice and the degree
to which lung function tests are used in different places. When diagnostic categor-
ies are combined, however, considerable variation still exists. ^6
In the United Kingdom, mortality-rates are high in the northeast, northwest,
and in South Wales; and low in East Anglia. Climate, weather, density of popula-
tion, industrial concentration, and pollution are some of the factors that are thought
to contribute to these differences.
Urban-Rural Differences
In England and Wales, a close association exists between bronchitis death rates
and density of population. For both men and women, regardless of age group, the
rates are approximately twice as high in cities with 100, 000 inhabitants and over
as in rural areas. One interesting change that has taken place during the past 10
years is that hardly any difference now exists between the bronchitis death rates
of conurbations and of other cities with 100,000 inhabitants or more. For men,
but not for women, differences between urban and rural mortality rates for chronic
respiratory disease are smaller in the United States than in the United Kingdom. 83'87
SOCIOECONOMIC EFFECTS
In England and Wales, mortality rates have for many years been roughly six
times greater in the lower socioeconomic strata than in the higher. 44> 8§> 90 ^
16
-------
the United States, also, a twofold difference exists in mortality rates for chronic
respiratory disease, among employed males, between the professional class and
those in unskilled jobs (Table 9). More recently, in Britain, a similar socioeconomic
gradient was shown to exist for morbidity. The possibility that differences in the
standards of medical care received by different segments of the population might
explain the observed mortality gradient is unlikely in view of the improvements that
followed the introduction of the National Health Service in Britain in 1948. Differen-
ces in the quality of care do not seem likely to account for the differences in mor-
bidity among social classes. Occupational factors, particularly differences in ex-
posure to respiratory irritants, will be discussed at length later. Other explana-
tions that have been offered are housing conditions, with domestic overcrowding
among the poor and, consequently, greater opportunity for cross-infection; the too
early return to work after a respiratory infection; the situation of the poor in the
more polluted areas of cities; and social drifts whereby those with chronic respira-
tory disease tend to decline in socioeconomic standing.
Table 9. MORTALITY RATIOS BY OCCUPATION FOR MEN AGED 20
THROUGH 64 IN THE UNITED STATES, 1950
Occupational level
All occupations
Professional workers
Technical, administrative, and
managerial workers'3
Clerical, sales, and skilled
workers
Semiskilled workers
Laborers^
Agricultural workers
Standardized mortality ratios
Diseases of
respiratory system9
100
72
52
87
149
157
75
Asthma
TOO
71
79
104
99
145
95
Influenza and pneumonia excluded.
''Farm workers excluded.
17
-------
METHODOLOGY FOR EPIDEMIOLOGICAL STUDIES
OF CHRONIC RESPIRATORY DISEASE
DIAGNOSIS AND INVESTIGATION
Standardized Questionnaires
It was noted early in epidemiological studies of chronic bronchitis that clinical
examination of the chest added little useful information. ^ Therefore this proce-
dure has been omitted in most surveys and reliance has been placed, instead, on
answers to questions about respiratory symptoms. In order to obviate the variation
that can occur when different observers question people about their respiratory
symptoms, "4 a great deal of effort has been devoted to the formulation of precise
questions, ' ~"° culminating in the publication by the British Medical Research
Council's Committee on Chronic Bronchitis of recommended questionnaires for re-
cording respiratory symptoms, together -with instructions for their use. ' ''
These questionnaires have been -widely distributed, translated into many languages,
and used for respiratory surveys in many different countries. uu-J-UJ Though there
are still problems with reproducibility, 104,105 ^g questionnaires have led to a con-
siderable degree of standardization of the results of different research workers and
to improved comparability of results.
Self-administered Questionnaires
Most questionnaires have been completed by physicians or health visitors in a
personal interview. Some attempts have been made to use information collected by
means of self-administered questionnaires. Fletcher and Tinker noted in a sur-
vey that answers on cough, phlegm, dyspnea, and smoking habits on a self-admin-
istered questionnaire disagreed somewhat from answers on an interviewer-admin-
istered questionnaire. The self-administered questionnaire was not returned, or
was incompletely filled in, however, by about Z5 percent of the men under study.
This error rate was only 7 percent in a. group of post office clerks and Fletcher and
Tinker concluded that the self-administered questionnaire might be especially use-
ful in persons accustomed to clerical work. Fletcher and his colleagues used a
self-administered questionnaire to detect men with persistent cough and sputum in
the first stage of their study of men engaged in clerical and light engineering work
in West London. McNab and his colleagues successfully surveyed men aged 55
to 64, living in several areas in East Anglia, by means of a self-administered ques-
tionnaire. Of the households selected, 86 percent responded; this response was in-
creased to 98 percent by home visitation. In the United States, Sharp and his col-
leaguesl"9 obtained good agreement between self-administered and interviewer-
administered questionnaires on respiratory symptom prevalence in an industrial
population of nearly 2000 men in Chicago. Interviewer- and self-administered
questionnaires have been used successfully by Higgins and his colleagues 110 in
Tecumseh, Michigan, but self-administered questionnaires were not satisfactory in
a survey carried out by Higgins and his colleagues in Marion County, West Vir-
ginia. Self-administered questionnaires were used successfully by Reid and his
colleagues-^ in their study of migrants and, more recently, by Lambert and Reid-"-"
in a large random sampling of the population of Britain. Self-administered question-
naires have also been used by Cederlof and his colleagues " to record res-
piratory symptoms in towns in Sweden.
19
-------
Cough and Sputum Tests
It is a well-known clinical observation that patients often say they have no cough
but at the same time present clear evidence to the contrary. A few research work-
ers, however, have made use of cough as an objective test. Thus, Greene and
Bercowitz118 used a preoperative test cough "of proved sensitivity and reliability"
to measure the prevalence of smokers' bronchitis in persons undergoing surgical
operations. More recently, Gandevia has also advocated the use of a test cough in
epidemiological studies of chronic respiratory disease. 119-121 The procedure is
as follows: the subject is asked to take a big breath, cover his mouth, and cough
hard. The sign is recorded as positive if he produces any sputum; the cough sounds
loose, or as if it could be productive on further effort; or the cough sounds as
though it was productive but the sputum is swallowed.
Collection and measurement of the sputum brought up during the first hour
after rising has been advocated by Elmes and his colleagues, who showed that
the volume of sputum correlated well with the FEV but that the degree of purulence
and presence of pathogenic organisms did not. These observations were subse-
quently confirmed by Fletcher and Tinker. 10° Simple methods for examining the
cellular content of sputum have been described by Miller, 124 who suggested a
scheme for the visual grading of purulence in relation to the cell count. He stressed
the importance of microscopic examination as an aid to differentiating purulent from
purulent-looking sputum that contains only epithelial debris. Subsequently, Ash-
croftl studied day-to-day variations in sputum volume in patients with chronic
bronchitis, and Miller and his colleagues 126 made similar studies of working men.
Variation from day to day was found to be considerable. Miller and his colleagues
suggested that it is better to collect sputum over several days. Collection of spu-
tum, measurement of its volume, and categorization of its nature have been includ-
ed in surveys by a number of workers. Sputum has seldom been studied micro-
scopically, however. The importance of detecting sputum eosinophilia in chronic
bronchitis has been stressed strongly by Mulder, 127 but the observation of eosino-
phils has been of rather questionable value in epidemiological surveys. Possibly
the greatest value of identifying sputum eosinophilia is in detecting cases of unsus-
pected asthma. It also provides some measure of allergy, which has often been
claimed to be a factor in chronic bronchitis. Chodoshl28 has recently emphasized
the importance of examining sputum to determine its detailed cytology. He has de-
scribed examination techniques, types of cell found and their distribution in com-
mon respiratory syndromes, and interpretation of the findings. Although epidemi-
ologists have certainly neglected this simple and useful procedure, it is clear that
in future surveys a greater effort should be made to include sputum cytology.
Bacteriological examination of the sputum has not proved of much value in epi-
demiological surveys, although it is, of course, essential in assessing the role of
infection and in controlling treatment. Bacteriological examination is considered
at greater length in a separate section.
Lung Function Tests
Simple lung function tests have been used in most surveys. Measurements of
the forced expiratory volume (FEV) and of the forced vital capacity (FVC) have
been most widely used. 129, 130 Currently, the 1-second volume is almost univer-
sally employed. In earlier surveys, however, the 0. 75-second volume was often
used. It has been generally agreed that the actual value measured, rather than
20
-------
some percentage of an expected normal value, should always be recorded and ana-
lyzed. (Formulae for prediction of normal values have been given by several
groups of workers. 1 31-1 33 ) Other indices of ventilatory lung function that have
been used in epidemiological studies include maximal expiratory flow rate (MEFR),
maximal mid-expiratory flow rate (MMEF), 134 an(j maximal voluntary ventilation
(MW). In general, these measures correlate highly with the FEV. They have not
been shown convincingly to be better than the FEV for field survey work.
Peak expiratory flow rates (PFR) have been measured in a considerable num-
ber of surveys. The popularity of this measure of ventilatory capacity resulted
from the production of the simple and portable Wright peak flow meter. ] 35
Certain epidemiological studies have included additional tests of lung function.
Nitrogen mixing has been used in a few studies. 81 Airways resistance, using a
Clements interrupter, was measured in an early survey in the Rhondda Fach (Med-
ical Research Council unpublished data). More recently, airways resistance has
been studied by means of the body plethysmograph, especially in relation to the ef-
fects of exposure to cotton dust and tobacco smoking. 136 ^ number of more sophis-
ticated tests of lung function have been used by Ferris and his colleagues in epi-
demiological surveys of respiratory disease. These include plots of volume versus
flow, measurement of carbon monoxide diffusing capacity or transfer factor, and
measurement of airways resistance by methods other than plethysmography.
Chest Radiographs
The radiographic signs of emphysema have been described by Kerley and his
colleagues; Parkinson and Hoyle; Lodge; and Simon and Galbraith.
The latter summarized the characteristic radiographic features as a low, flat dia-
phragm; narrow vertical heart; abnormal vascular pattern; and bullous changes.
These signs were essentially those used more recently by Simon (1964) (Table 10).
Table 10. RADIOGRAPHIC CRITERIA FOR DIAGNOSIS OF EMPHYSEMA3
Radiographic category
I. Excess air in the lungs
II. Cardiovascular changes
III. Bullae
Radiographic criteria
Low, flat diaphragm
Large retrosternal space
Poor diaphragmatic excursion
Narrow, vertical heart
Prominent pulmonary trunk, even
in the absence of right
ventricular hypertrophy
Large hilar-with small lung vessels
Avascular transradiant area
With or without definite demarcation
aAdopted from Simon.142
21
-------
Correlations between these abnormalities and diagnoses of emphysema based on
clinical and physiological criteria, attempted by W bitfield et al. , J were not good.
Knott and Chris tie 144 concluded that a single postero-anterior film was of doubtful
significance, and that even with a complete set of films 10 percent of emphysema
cases would be missed and a few normal individuals would be wrongly diagnosed as
having emphysema. The limitations of the chest radiograph in the diagnosis of
emphysema have also been noted by Reid and Millard145 ancj by Simon and Reid.
Better results have been obtained when radiographic changes have been correlated
with pathological changes found at autopsy. 147-149 Few surveys of respiratory
diseases have included lateral chest x-rays as well as a postero-anterior film. The
findings from these studies indicate that lateral films should in the future be includ-
ed in surveys of chronic obstructive lung disease. An additional advantage of using
lateral as well as postero-anterior films is that lung volumes can be obtained, in-
asmuch as lung volumes measured radiographically have been shown to correlate
highly with those measured by body plethysmography. 150
Morphological Changes
The morphological changes found in chronic bronchitis have been described by
Reid. ^ > 151, 152 The essential characteristic is an increase in the mucous -secret-
ing cells. Reid introduced simple measures for diagnosing and categorizing the
severity of the disease, the most useful and most -widely adopted of which has been
the determination of the ratio of the thickness of the mucous gland layer to the
thickness of the bronchial or bronchiolar wall- -the gland/wall ratio. 153 According
to Reid, the normal gland/wall ratio averages 0. 26, with a range of 0. 14 to 0. 36;
in patients -with chronic bronchitis, the average is 0. 59, with a range of 0. 41 to
0. 79. An increase in the number of goblet cells occurs pari passu with the increase
in glandular layer, and may be especially numerous in bronchioli where normally
they are sparse. The relationship of the gland/wall ratio to sputum production,
smoking, chronic bronchitis, and emphysema is the subiect of a number of stud-
ies. 153-158
The extent, severity, type, and distribution of emphysema have been studied
by many pathologists during the past 20 years!57, 159-164 an(j methods for assess-
ing the changes in the lungs have been developed within the past 15 years. 165-174
The diagnostic value of inflated lung sections, stressed by Gough et al. in 1952,
has been confirmed b,y subsequent studies. 1 ^3 , 176-1 79 Interpretations of the pres-
ence or absence of emphysema and its type, extent, and severity have been shown to
vary widely among different pathologists, 180 and measures for reducing these vari-
ations have been suggested. 181' AS an additional diagnostic aid, correlations be-
tween the morphological changes of emphysema and the preexisting clinical or
physiological state have been made by many investigators. 1°0> 179, 180, 182-184
Studies of the mechanisms of production of hypersecretion (such as by
and of emphysema (such as by Gross and his colleagues ) have been reviewed by
Reid 2 and by Wright and Kleinerman. 187
Measurement Reproducibi lity
The reproducibility of diagnostic measures of respiratory disease has been
studied by a number of workers. 95, 96, 98, 105, 106 The findings of Holland and his
colleagues 105 may be considered to be representative. These workers concluded
22
-------
that the answers to questions about respiratory symptoms in two standardized ques-
tionnaires were reasonably reproducible. The questionnaires also discriminated
fairly well among persons categorized on the basis of more objective measure-
ments such as the FEV or 1-hour sputum volume. The importance, however, of
the precise wording of individual questions and the careful design of the question-
naire was noted. The study also demonstrated fairly good reproducibility of mea-
surements of sputum volume and quality after an interval of 6 months.
STUDY POPULATIONS
The importance of the population used in studies of the epidemiology of respir-
atory disease has been discussed by Higgins. °" The problems of drawing conclu-
sions from hospital and clinic populations have been particularly stressed. Surveys
of occupational groups have many points in their favor, and have been recommended
by Reid. Such groups, which have been studied often, are usually readily ac-
cessible, relatively stable, and generally somewhat uniform in socioeconomic back-
ground. They are particularly useful for international comparisons when the occu-
pation is similar in different countries. 80, 189 Occupational groups do, however,
have the disadvantage that considerable selection, which may be impossible to eval-
uate, may occur. Representative samples of the whole community are clearly
preferable, although problems in defining and maintaining such groups may be
great. The liability of all study groups to selection either by death or by migration
has also been increasingly realized.
The vast majority of publications of surveys to date have been based on cross -
sectional studies. More longitudinal data are needed so that some of the potential
selection that has been suspected can be studied. A few longitudinal studies are
now being carried out, from which some publications have already resulted. HO, 190-194
The main population studies conducted in the United States °2> 1 09, 111, 1 95-21 2 ancj ^n
Britain and other European countries24-36,52,80,81,96,98,106,113, 189, 191, 210,
213-234 are summarized in Tables 11, 12, and 13. In addition to these, studies
have been carried out in South Africa,235'236 Australia, 237 India, 162' 238 and
Japan.
23
-------
Table 11. AMERICAN FIELD STUDIES OF THE PREVALENCE OF BRONCHITIS
Authors/yr
Pemberton, 1956
Bower, 1961
Schoettlin,
1962
Brinkman and
Coates, 1962
Ferris and
Anderson,
1962
Balchum et al . ,
1962
Goldsmith
et al . . 1962
Gocke and
Duffy, 1962
Prindle et al . ,
1963
Speizer and
Ferris, 1963
Hyatt et al . ,
1964
Refer-
ence
195
196
197
198
199
200
201
202
203 '
204
205
Area
Pennsylvania
Denver, Colorado
Los Angeles,
California
Detroit,
Michigan
Berlin,
New Hampshire
Vernon,
California
San Francisco,
California
Jersey City,
New Jersey
Seward and New
Florence,
Pennsylvania
Boston,
Massachusetts
Raleigh County,
West Virginia
Population
Mining, industrial ,
rural
Bank employees
(urban)
Veterans' Adminis-
tration domicili-
ary and chronic
disease hospital
Industrial and
other
Industrial
Urban employees
Longshoremen
(urban)
Housing units
(urban)
Rural
Road tunnel em-
ployees (urban)
Mining
Sample, type
and % of
population
Volunteers
Volunteers ,
77 to 80%
100%
Selected
Random,
95.9%
4505 chest
x-rays
Volunteers,
58%
90%
100%
97%
Union
members
Number
surveyed
611
95 men
77 women
2622
1317 men
(includes
men with
silicosis)
565 men
654 women
1456 men
3311 men
435 men
948 men
and women
60 men
267 men
Age range,
yr "
45 to 64
40 to 70
Elderly
males
40 to 65
25 to 74
10 to <60
20 to >80
40 to 59
<30
25 to 74
45 to 58
Methods
Questionnaire
Questionnaire,
MMEF
Questionnaire,
puff meter
Interview, VC,
FEVi.o, FEV3.0,
MMEF, chest
x-ray
Questionnaire
(MRCa), VC,
FEVT.o, PFR
Questionnaire,
VC, FEV] 0,
FEV3-0, Peak
flow
Interview, VC,
FEVi.o, puff-
meter, chest
x-ray
Questionnaire
(MRC), FEVT.o,
chest x-ray
Questionnaire,
luna function
tests
Questionnaire,
" VC, PFR, FEV1-C|
Questionnaire,
lunq function
tests
-------
Table 11 (continued). AMERICAN FIELD STUDIES OF THE PREVALENCE OF BRONCHITIS
Authors/yr
Refer-
ence
Area
Population
Sample, type
and % of
population
Number
surveyed
Age range,
yr
Methods
CO
Ul
Payne and Kjels^
berg, 1964
Coates et a!.,
1965
Deane et al.,
1965
Densen et al.,
1965
Wynder et al.,
1965
Holland and
Stone, 1965
Sharp et al.,
1965
Anderson et al.,
1965
Enter!ine and
Lainhart, 1967
Higgins et al.,
1968
206
207
208
62
209
210
109
211
212
in
Tecumseh,
Michigan
Detroit,
Michigan
San Francisco and
Los Angeles,
California
New York City
New York City, Los
Angeles and
Northern
Cal i form'a
Eastern U.S.
Chicago, Illinois
Chilliwack, Brit-
ish Columbia
Mull ins and Rich-
wood, West
Virginia
Marion County,
West Virginia
Urban
Postal workers
(urban)
Outside telephone
workers
Postal and transport
workers
Patients and
Seventh-Day
Adventists
Telephone workers
Industrial workers
(Western Electric)
Rural
Mining and other
Rural mining
Random,
87 to
79%.
76 to 83%
Selected
96.9%
Random
Random,
95%
Matched
samples
miners and
nonminers
83%
2383 men
2607 women
1584 men
and women
508 men
5311 men
980 men
625 men
1887 men
711 men and
women
898
1106 men
16 to 79
>40
>40
35 to 60
<30 to >70
>40
43 to 58
25 to 74
21 to 64
20 to 69
Questionnaire,
FEVi.Q, VC
Questionnaire
(MRC), VC,
FEV],o> sputum
volume
Questionnaire
(MRC), VC,
FEV1-0, puff-
meter
Questionnaire
(MRC), FEV1<0,
absence records
Smoking and
symptomatic
inquiry
Questionnaire
(MRC), VC,
FEV-^Os sputum
volume
Questionnaire
(MRC), VC,
FEV1-Q, MEFR,
sputum volume
Harvard ques-
tionnaire, VC,
FEV1>0, PFR
Questionnaire,
FEV
Questionnaire,
FVC, FEVi.o
British Medical Research Council questionnaire.
-------
Table 12. BRITISH AND COMPARATIVE FIELD STUDIES OF THE PREVALENCE OF CHRONIC BRONCHITIS
Author
and year
Newell and Browne,
1955
Higgins et al . .
1956
Higgins, 1957
Clifton, 1957
Clifton, 1957
Higgins and
Cochrane, 1958
Higgins et al . . 1959
Fletcher et al.,1959
Fletcher and Tinker,
1961
College of General
Practitioners, 1961
Holland and Reid,
1965
Refer-
ence
213
214
215
216
216
217
98
96
106
218
219
Area
County Durham
Leigh (urban)
Vale of Glamorgan
(rural )
Sheffield (urban)
Wensleydale
(rural )
Annandale (rural)
Staveley (urban)
London
London
Rural and urban
London
Gloucester,
Norwi ch ,
Peterborough
Population
Miners
Miners and
nonminers
Men and women
Men and women
Men
Men and women
Miners, foundry
workers and
other men
Wives of men
aged 55 to 64
Post office men
and women
London transport
men
Men and women
Mail van drivers,
maintenance men
Mail van drivers,
engineering
workers
Sample,
type and %
of population
Al 1 men i n 4
collieries ,
89%
Random, 90%
Random, 91%
Volunteers,
91.7%
Volunteers ,
97%
Random, 91%
Random, 95%
Random
Random, 91%
Random, 94%
London, 93.7%
Country towns ,
94.6%
Number
surveyed
5,723
245
631
2,519
570
206
776
334
384
513
1,630
477
293
Age
range,
years
15 to 65
55 to 64
25 to 74
15 to >60
>30
55 to 64
25 to 34
55 to 64
40 to 59
30 to 59
40 to 64
40 to 59
Methodsa
Questionnaire, chest
x-ray
Questionnaire, FEVQ.75,
chest x-ray
Questionnaire, FEVo.75,
peak flow rate, chest
x-ray
Questionnaire, MBC,
chest x-ray
Questionnaire
Questionnaire, FEVo.75,
chest x-ray
Questionnaire, FEVo.75,
chest x-ray
Interview
Questionnaire, FEV].Q.
sputum volume
Questionnaire, peak flow
rate, sputum volume
Questionnaire, peak flow
rate
MRC short questionnaire,
McKessen vitalor, FEVi.Q:
peak flow rates
ro
-------
Table 12 (continued). BRITISH AND COMPARATIVE FIELD STUDIES OF THE PREVALENCE OF CHRONIC BRONCHITIS
Author
and year
Meadows et al . , 1 965
Higgins et al . . 1968
Holland et al . . 1969
Ashford et al . , 1970
Colley and Reid,
1970
Lambert and Reid,
1970
01 sen and Gil son,
1960
Mork, 1962
Reid et al . . 1964
Refer-
ence
220
191
221
222
223
113
81
80
36
Area
London
Stave! ey (urban)
4 areas of Kent
United Kingdom
England and
Wales
England, Wales
and Scotland
Bornholm, Denmark
Bergen , Norway
London
England and
Wales
Population
Senior industrial
staff (men)
Miners, foundry
and other men
School children
Miners
Primary school
children in con-
trasting urban
and rural areas
Representative
sample of men
and women
Comparative
Small town
(R0nne)
Transport workers
Post office
transport
workers
Random samples
Sample,
type and %
of population
Random, 97%
Random, 90%
94% of those
residing and
attending
school in
the area
Men in 25 col-
lieries, 100%
97.8%
74% of those
approached
and able to
respond in
age group
35 to 69
Studies
Random,
91.5%
98.4%
96.8%
Selected from
original
samples
Number
surveyed
224
1,400
10,971
29,984
11,135
9,975
183
189
150
1,258
Age
range,
years
30 to 69
25 to 74
5 to 16
15 to 65
6 to 10
35 to 69
55 to 64
40 to 59
45 to 64
Method3
Questionnaire
Questionnaire, sputum
volume, FEV-].o> FEVg.75
Questionnaire completed
by parents: PFR
NCB questionnaire, FEV,
FVC
Questionnaire to parents,
examination by school
medical officers
Mailed self-administered
questionnaire
Questionnaire, FEVg.ys,
PFR, chest x-ray
Questionnaire, PFR,
sputum volume
Questionnaire, PFR
CO
-J
-------
Table 12 (continued). BRITISH AND COMPARATIVE FIELD STUDIES OF THE PREVALENCE OF CHRONIC BRONCHITIS
Author
and year
Reid et al . . 1964
(continued)
Holland et al . ,
1965
Refer-
ence
189
210
Area
Berlin, New
Hampshire
London and small
towns
U.S. East Coast;
Washington;
Baltimore;
Westchester, N.Y.
Population
Post office van
drivers
Outside telephone
workers
Sample
type and %
of population
96.8 to 98% of
available men
Number
surveyed
546
736
708
Age
range,
years
45 to 64
40 to 59
40 to 59
Method3
Questionnaire (MRC),
FEV]_o> sputum volume
Questionnaires used in these surveys were either the original Medical Research Council (MRC) form or were modeled on it.
tv
00
-------
Table 13. EUROPEAN STUDIES OF THE PREVALENCE OF CHRONIC OBSTRUCTIVE LUNG DISEASES
Author
and year
Finland
Huhti, 1965
Poppius et al .,
1965
France
Kourilsky
et al., 1966
Freour et al . ,
1966
Sweden
Tibblin et al .,
1965
Julin and
Wilhelmsen,
1964-1965
Czechoslovakia
Stanek et al . ,
1966
Jancik, 1968
Boudik et al . ,
1970
The Netherlands
Van der Lende,
1968
Refer-
ence
224
225
52
226
227
228
229
230
231
24
Area
Harjavalta
47 sites, E.
Finland;
controls,
adjacent
area
Paris
Bordeaux
Goteborg
Goteborg
Prague
Brno
Prague
Meppel
Vlagtwedde
Vlaardingen
Population
Rural
Rural
Industrial
Urban
Urban
Urban
Urban
Urban
72.8%
Rural
Urban
Sample,
type and %
of population
Total
Random sample
Sample
Representative
sample
Random sample
Stratified
Random sample,
92.2%
Random sample;
1 : 6 men ,
(93.7%)
92% of one
town district
All men in
area of
Prague 2
Random samples
Number surveyed
761 men, 925 women
975 forest workers
329 controls
4992 men
484 women
Men
339 men
1054 men
1113 women
473 men
2736 men
8292
3798 men
1604 women
Age
range,
years
40 to 64
20 to 59
30 to 60
30 to 70
50
16 to 64
60 to 64
40 to 64
50 to 65
40 to 64
Methods
Questionnaire, FEV, FVC
MRC questionnaire, peak
expiratory flow
Questionnaire, FEV, FVC
Symptoms, lung function
MRC questionnaire
MRC questionnaire,
physical exam, Wright
peak flow rate
Questionnaires (MRC, WHO),
spirometry, chest x-ray,
physical examination
Mailed and MRC question-
naires, FEV, FVC, PFR,
chest x-ray (inspiratory/
expiratory PA, inspira-
tory/lateral )
MRC questionnaire, FEV] Q,
FVC, PEFR
MRC questionnaire, FEVi.Q,
bronchial reactivity, etc.
ro
-------
Table 13 (continued). EUROPEAN STUDIES OF THE PREVALENCE OF CHRONIC OBSTRUCTIVE LUNG DISEASES
Author
and year
The Netherlands
(continued)
Biers teker,
1969
Italy
Petrilli
et_a_L, 1966
Paccagnella
et al., 1969
Refer-
ence
232
233
234
Area
Rotterdam
Genoa:
Industrial
residential ,
and suburban
areas
Ferrara
Population
Urban
Urban
All children
in three
schools in
appropriate
age
Sample,
type and %
of population
Male municipal
employees
Women non-
smokers who
had never
worked in
industry
Elementary
school
children
Number surveyed
1000
313
335
Age
range,
years
30 to 64
>65
7 to 12
Methods
NCB questionnaire, PFR
MRC questionnaire,
morbidity
Daily examination to
detect onset of acute
respiratory disease
00
o
-------
FACTORS IN THE ETIOLOGY OF CHRONIC RESPIRATORY DISEASE
AGE, SEX, AND RACE
Mortality and Morbidity Rates
In nearly all countries, the age-adjusted and age-specific mortality rates for
chronic respiratory diseases are higher in men than in women. In adult life, the
mortality rates increase with age in both sexes. In many countries, however, the
rate of increase is greater in men than in women. 15,16,82 jn Engian<3 arKi Wales,
for example, the sex ratio of mortality from chronic bronchitis at all ages for men
and women is 3 to 1 at ages 35 to 44, 9 to 1 at ages 65 to 74, and about 5 to 1 for
all age groups (Table 14).
Table 14. MORTALITY RATES BY SEX FOR CHRONIC BRONCHITIS AND
OTHER CHRONIC RESPIRATORY DISEASES IN MALES AND FEMALES IN THE
UNITED STATES, 1967a
Age group, yr
0
1-4
5-14
15-24
25-34
35-44
45-54
55-64
65-74
> 75
All ages
Chronic bronchitis (A 93)b
Males
4.9
0.6
0.1
0.1
0.1
0.5
2.5
9.9
26.3
45.7
4.2
Females
2.9
0.4
0.1
0.1
0.2
0.3
1.0
2.5
4.7
10.7
1.3
Ratio
1.7
1.5
1.0
1.0
0.5
1.7
2.5
4.0
5.6
4.3
3.2
All other respiratory
diseases (A 97)
Males
42.0
1.5
0.3
0.5
1.0
3.4
15.2
67.6
182.6
269.1
27.0
Females
35.1
1.0
0.3
0.3
0.7
1.9
5.4
12.6
23.8
55.1
6.7
Ratio
1.2
1.5
1.0
1.7
1.4
1.8
2.8
5.4
7.7
4.9
4.0
aDeaths/100,000 population.
Number in parentheses is the International Statistical Code.
Crofton and Crofton studied changes in the sex ratio in respiratory disease
mortality in England, Wales, and Scotland by studying mortality rates from those
diseases that are possibly connected with smoking in cohorts born between 1846 and
1855 and between 1896 and 1905. The results suggest that smoking has been ex-
erting an effect on mortality longer in England and Wales than in Scotland. The
31
-------
vn
recent rise in mortality from bronchitis that has been noted in Scotland could be
the result of smoking, which is now beginning to exert an influence there on the
death rates of middle-aged men.
Most morbidity surveys have shown a clearly excessive prevalence of cough
and sputum in men compared -with women. ^4,b2,96, 199, 206, 215, 224 Much of the
sex difference for these symptoms is probably the result, however, of differences
in smoking habits. 24,241 wheezing in the chest follows a somewhat similar pat-
tern, ^ but chest illness during the past 3 years has usually been found to be equal-
ly prevalent in men and women. 24, 206 , 21 5 , 224 Breathlessness has been either
equally prevalent in the two sexes or more frequent in women. ' '
Findings on the relationship between age and respiratory morbidity have been
less consistent. Some surveys have shown the persistent cough and sputum in-
crease with age, 80,96, HI, 215, 242, 243 but others have found little increase with
age in the prevalence of these symptoms, 199,206,224 except tna(; most studies have
shown a consistent increase in the prevalence of breathlessness. 24, 80, 96, 211, 215, 244
The trend is often less consistent in women than in men. The prevalence of the
other symptoms, namely, chest illness in the past 3 years and wheezing in the
chest, are somewhat inconsistently related to age. Whether an increase in the pre-
valence of chronic respiratory disease with increase in age is noted or not clearly
depends to some extent, therefore, on the diagnostic criteria used. When breath-
lessness is included, an age-related trend is likely to be noted; when only cough
and sputum are used, there may or may not be an age-related trend. Cough and
phlegm and, to a lesser degree, wheezing in the chest, are determined mainly by
smoking habits; the other symptoms, though apparently influenced to a slight extent
by cigarette smoking, are determined mainly by other factors. Cough and phlegm,
however, may also be a manifestation of air pollution when the pollution is severe
enough. For example, Holland and his colleagues ' noted a clear relationship be-
tween age and the prevalence of cough and sputum in London, but a relationship was
much less apparent in persons living in country towns in England or in cities in the
United States.
Attention has already been drawn to the differences in overall mortality rates
for respiratory diseases between -whites and nonwhites in the United States. Metro-
politan Life Insurance records show that the death rates from chronic bronchitis
and emphysema for 1958 through 1961 were lower in black male than in white male
industrial policy holders.,245 A racial difference in incidence of chronic bronchitis
has been suggested by Massaro and his colleagues on the basis of findings in United
States' veterans admitted to hospitals. 246, 247 Thus, in a review of 964 patients
admitted to the Veterans' Administration Hospital, Washington, D. C. , Massaro and
his colleagues ° showed that the prevalence of bronchitic symptoms was lower in
black than in white persons. The difference was due in part to the lower proportion
of smokers among the blacks. Among nonsmokers, however, the prevalence of
bronchitis among the blacks was still half that of the white nonsmokers. In the
largest study in which race has been considered, Densen and his colleagues 244
studied 12, 604 male New York transport and postal workers. The study revealed
a lower prevalence of respiratory symptoms and bronchitis among the black workers
than among the white. Among nonsmokers, however, there was little difference be-
tween the two races in the prevalence of symptoms. This would suggest the possi-
bility that most of the racial differences in symptom prevalence can be explained by
differences in smoking habits.
32
-------
Lung Function Levels
The influence of age and sex on the forced expiratory volume test is fairly
clear. Many studies have shown that from about the age of 25 there is a fairly uni-
form decline in FEV with increasing age. Although some studies have suggested
that the decline is not linear, most observations have indicated that any deviation
from such a trend with age is not marked and that for practical purposes a linear
decline can be accepted as occurring. A number of studies in which the forced ex-
piratory volume was used have been reviewed by Cotes and his colleagues. 131 The
similarity in the age trends in more or less comparable groups studied in the United
Kingdom, United States, and Europe is striking. Cotes and his colleagues combined
a number of surveys and presented an overall regression for use in predicting nor-
mal values, taking age and height into consideration. The regression is:
FEV1 - (3.62 x height)
(0. 031 x age) 1 . 41 (SD +_ 0. 5 ) (1 BTPS)
where height is in meters, age is in years, and the final factors are corrections for
standard deviation and body temperature and pressure saturated with water vapor.
A summary of the regression relationships between FEV and age and height that
•were found in different surveys and used to derive this equation is given in Table 15.
Table 15. REGRESSION RELATIONSHIPS OF FEV-]_0 ON AGE AND HEIGHT
131
Survey sample
Veteran's Administration
United States
Berlin, New Hampshire
United States
Goteborg, Sweden
Pneumoconiosis Research Unit
United Kingdom
Height,
m
3.70
3.60
3.75
3.46
Age,
yr
-0.028
-0.027
-0.036
-0.033
Constant
-1.59
-1.65
-1.09
-1.12
The FEV in women is approximately 75 percent of that found in men of the
same age. 24, 206 Most of the difference is attributable to the shorter height of
women. Some of the residual difference in the overall regression of FEV on age
between men and women when height is held constant is attributable to cigarette
smoking. Occupational exposures also^ appear to influence the level and slope of
the regression in men in some areas.
248'
A lower vital capacity in black children compared with children of other races
was observed early in this century. Thus, in 1922, Wilson and Edwards ° found
that in children aged 8 to 14 years the vital capacity was strikingly lower in blacks
than in other groups. In 1950, Roberts and Crabtree^O aiso found that the vital
capacity was lower in black than in white children of the same age and that the dif-
ference was greater for boys than for girls. In adults, a low vital capacity in blacks
was noted more recently by Nahmias and his colleagues. 251
o c o
Gilson and his colleagues, in a survey of cotton ginneries in Africa, noted
that the average forced expiratory volume was at least 0. 5 liter lower in Africans
than would have been expected for Europeans of the same age. About half the
33
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difference was attributable to shorter sitting height, but the remaining difference
was unexplained.
Abramowitz and his colleagues "3 examined normal hospital employees and
resident and full-time physicians of the Veterans' Administration Hospital, East
Orange, New Jersey. In males, both the FEVj g and the FVC were lower in blacks.
In females, though the differences were in the same direction, they were not statis-
tically significant; however, the white women were 4 years older than the black wo-
men and the differences observed are therefore smaller than the true differences
between the two groups.
In a comparison of 392 white and 61 black soldiers aged 18 to 29 years, Damon
noted that the black soldiers had a 13 percent smaller 1-second and total vital ca-
pacity and a 10 percent slower midexpiratory flow rate, even though the white sol-
diers smoked more. The differences could not be explained by shorter trunk and
smaller chest expansion of the blacks. Damon observed that differences of this
magnitude had been reported for almost 100 years and that they were not attributa-
ble to prior pulmonary disease.
In Densen's study in New York City, ^55 (fog forced expiratory volume was lower
in black than in white persons and the difference persisted after adjustment for sit-
ting height. The rate of decline also appeared to be different in white and black men.
Thus, in men under 35 years of age, the average FEV was 0. 30 liter greater in
whites than in blacks; but in men aged 60 and over, the difference was only 0. 05
liter.
GENETICS AND PHYSIOLOGY
Heredity
In the early study carried out by Oswald and his colleagues, ^56 a higher pro-
portion (about threefold more) of first-degree relatives of bronchitis patients than
of controls were reported as having bronchitis. Similarly, Ogilvie and Newell, '
who studied bronchitis in Newcastle, England, found that twice as many parents and
sibs of bronchitics were reported to have bronchitis compared with the relatives of
controls. The importance of a family history of bronchitis was also noted by Clifton
in Sheffield. *" Since the diagnosis of bronchitis in the relatives was based on his-
tory taking, the possibility that bronchitis patients remember and recall relatives
who have bronchitis better than those who do not cannot be excluded.
257
Layland made an attempt to assess the importance of heredity by comparing
the experience of wives and sisters of men with and without bronchitis. Patients
admitted to hospitals or attending hospital clinics were used. Among the relatives
of men without bronchitis and with a normal FEV, 4. 5 percent of the wives and 2. 25
percent of the sisters were found to have bronchitis. Among the relatives of men
with bronchitis, the corresponding frequencies were 6. 0 and 21. 5 percent, respec-
tively. Since men probably know the symptoms of their wives better than those of
their sisters, the findings were considered to indicate a familial tendency. The
possibility that a similar environment in childhood could explain the findings pre-
vented the author from concluding that this familial tendency was genetic.
34
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Familial Aggregation
Familial aggregation of chronic obstructive lung disease has been noted by
Larson and Barman,258 who showed that the relatives of a small number of bron-
chitis patients had a history of a higher prevalence of cough and dyspnea and had a
lower ventilatory capacity than the relatives of patients with miscellaneous nonob-
structive pulmonary disease.
Disease among Twins
Studies of twins based on the Swedish twin registry and, more recently, on the
United States veterans' registry were carried out by Cederlof and his colleagues,
'»"' who collected the information by mailed questionnaires. The validity
of the questionnaire method with regard to the determination of zygosity, smoking
habits, and medical information had been tested on subgroups and was considered
adequate by the authors. Cough was used as an index of respiratory disease. Peo-
ple were classified into those with "cough" and those without, according to their
answer to the question: "Do you regularly have a cough, or do you at least have a
cough for long periods at a time? " Those who also said that this "cough" lasted for
3 months or more in succession were classified as having "bronchitis. " "Bronchi-
tis" was apparently only one-fourth as prevalent as "cough, " namely, 2 percent com-
pared with 8 percent. The concordance rates for cough among nonsmokers were
higher in the monozygotic than in the dyzygotic pairs. The rates were higher in
women than in men and in younger persons than in older. The authors concluded
that this indicates a genetic influence on the development of the symptom. Further-
more, through comparison of the prevalence of cough or "bronchitis" found in mono-
zygous twin pairs--who differed with respect to such factors as smoking or urban
or rural residence--with the appropriate values for the general population, an esti-
mate was obtained of the relative importance of heredity and environment in the
production of such symptoms. Such analyses indicate that smoking is more likely
than genetic predisposition to cause cough.
Familial Emphysema
In 1959, Hurst studied two families in which emphysema was a major dis-
abling problem. He reviewed the earlier literature on the subject and stressed the
difficulty of differentiating genetic factors from those resulting from cross-infection.
He concluded, however, that a familial tendency was likely.
Hole and Wasserman described a case of familial emphysema with a
pedigree dating back approximately 150 years. The disease appeared to follow the
familial distribution of an autosomal dominant trait having variable phenotypic ex-
pression. Neither cystic fibrosis nor an autoimmune mechanism were though to be
likely explanations for the aggregation.
Mu covi scidosis
The possible role of mucoviscidosis in chronic respiratory disease has been
investigated. Karlisch and Tarnoky ^"2 examined the electrolyte content of sweat
and found it to be abnormally high in a large proportion of patients with chronic res-
piratory disease. The possibility that heterozygosity for the mucoviscidosis trait
might play a role was suggested; however, further studies have failed to support
the original observation. 263-268 Furthermore, Hallett and his colleagues269 have
35
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shown that persons who are heterozygous for the mucoviscidosis trait are no more
liable than others to respiratory disease; nor does their perspiration contain higher
concentrations of chloride.
A I phai -a nt it ry ps i n Deficiency
Deficiency of a serum protein, alphaj -antitrypsin, may lead to the development
of chronic obstructive lung disease at a relatively early age. ' ' ~ The
characteristic features of the disease are an early onset, a family history of pul-
monary disease, often involving women, and, frequently, an absence of a history of
of chronic bronchitis. Abnormal lung function has been shown to occur in persons
who have the deficiency but who have no symptoms.
Alpha i -antitrypsin deficiency is found in less than 2 percent of all cases of
severe emphysema. It seems unlikely, therefore, that it is a very important factor
in the development of most cases of chronic obstructive lung disease. It has been
suggested, however, that up to 7. 5 percent of the American population may be het-
erozygous carriers of the deficiency gene. Some studies suggest that the inci-
dence of chronic obstructive lung disease may be increased in such carriers.
At least one study has failed to support this suggestion. 2 it seems clear that
further observations are needed on samples more representative of the population
than those that have been studied to date.
Blood Groups and Secretory Function
Blood-group frequency in patients with six respiratory disorders were studied
by Lewis and Woods at the Brompton Hospital in London. They found no evi-
dence of any association between blood group and cases diagnosed, as bronchitis and
emphysema. Higgins and his colleagues 2°-L investigated A, B, O, and Rhesus blood
groups and secretor status in an age-stratified sample of miners and ex-miners
living in a Welsh mining valley. They found no evidence that these factors were re-
lated to chronic respiratory disease.
AIR POLLUTION
The main types of epidemiological studies conducted to assess the effects of
air pollution are summarized in Table 16.
Acute Episodes
Acute episodes of high pollution, such as those that have occurred in the
Meuse Valley, Belgium;282 Donora, Pennsylvania;2831 London;284 New York City;285'
28° Osaka, Japan; 177 and elsewhere provide the most convincing and dramatic
evidence for an effect of air pollution on health.
From December 5 to 8, 1952, dense fog covered the Greater London area.
During the following week, death rates reached a level that had been exceeded only
rarely during the preceding 100 years, in the cholera epidemic of 1854 and the in-
fluenza epidemic of 1918-1919, for example. It was subsequently estimated that
approximately 4000 deaths were attributable to the fog. Persons of all ages were
affected but particularly those aged 45 years and over. There was an eightfold in-
crease in deaths attributed to bronchitis, a threefold increase in deaths from pneu-
monia, and a considerable increase in deaths caused by other respiratory and
36
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Table 16. MAIN TYPES OF EPIDEMIOLOGICAL INVESTIGATIONS
OF EFFECTS OF AIR POLLUTION ON HEALTH
Specific studies
Follow-up of Donora, Pennsylvania, episode
Study of Yokohama and New Orleans asthma
General types of studies
Variation in-mortality, morbidity, and lung function
over time
Day-to-day variation in residents of large cities
Day-to-day variation in patients with respiratory disease
Long-term changes in lung function
Geographical comparisons
International
Regional
Urban-rural
Uniform occupational groups
Comparisons between cities
Comparisons within cities
Studies of children
Miscellaneous studies
Migrants
Twins
Athletes
cardiac diseases. Morbidity also increased, as shown by claims for sickness bene-
fit received by the Ministry of Pensions and National Insurance, applications for
admission to hospitals through the Emergency Bed Service Bureau, notification of
pneumonia, and the observations of interested general practitioners on the number
of new cases, seen during the episode compared with those occurring at other
7 oy 288
times. ' Lethal fogs in London were documented for the years 1873, 1880,
1882, 1891, 1892, and 1948, 289' and several similar fogs have occurred in London
and in other British cities since 1952. 290-295 A(. fche heigllt of t^e ponution in
London in 1952, the concentration of smoke was 4. 46 milligrams per cubic meter
and that of sulfur dioxide (802) was 1. 34 parts per million (2. 86 milligrams per
cubic meter). The maximum smoke concentrations at individual sites were 3 to 12
times the normal values, while the maximum concentrations of SC>2 at individual
sites were between 3 and 10 times normal. ' Burgess and Shaddick^^l reviewed
some of the difficulties encountered in relating mortality to levels of air pollution
and suggested that in London a smog episode was likely to occur -when smoke con-
centrations rose above 2000 micrograms per cubic meter and SC>2 concentrations
rose above 0.4 part per million (1144 micrograms per cubic meter).
Episodes of pollution have also been responsible for increased mortality and
morbidity in New York City,285' 28^> 297-300 but these appear to have been consid-
erably less lethal there than in London. Thus in the episode in New York in 1953,
37
-------
it was estimated that there were about 200 excess deaths; in 1963, between 200 and
400; and, in 1966, 163 excess deaths. In New York City, episode-related deaths
have been attributed to influenza, pneumonia, vascular lesions of the nervous sys-
tem, cardiac diseases, and "all other diseases. " Those aged 45 years and over
have been predominantly affected. Increased morbidity, particularly for upper
respiratory and cardiac disorders, and sometimes for asthma, was noted as a re-
sult of studying emergency visits to a number of hospitals. In a study carried out
at the time of the Thanksgiving holiday fog in 1966, Becker and his colleagues30
showed that as pollution levels rose, complaints of cough, sputum, wheezing,
breathlessness, and eye irritation increased.
The increased mortality and morbidity that have occurred in these acute epi-
sodes of pollution probably affected predominantly those who already were suffering
from some chronic illness, particularly of the heart or lungs. Evidence, however,
that fog may initiate illness as well as exacerbate it is provided by the descriptions
of effects on animals during several episodes of fogs. In both the Meuse Valley
episode and the London fog of 1952, cattle sickened and some died, while in Donora,
ten dogs, three cats, and two canaries -were reported to have died.
There is little doubt that these exceptional episodes of high pollution may cause
mortality and morbidity, but much more uncertainty exists about the effects of low-
er, more sustained levels of pollution and their long-term effects.
In 1948, immediately after the disaster in Donora, Pennsylvania, a probability
sample of the inhabitants of the town was studied by the United States Public Health
78^ • ^ n ?
Service. Ten years later, Ciocco and Thompson followed up this sample and
found that the group who had reported being affected by the fog had higher mortality
and morbidity during the next 10 years than those who had not been affected. Most
of the excess, however, was in persons who had reported having chronic illness be-
fore the fog. This suggests that the fog mainly exacerbated existing disease rather
than initiated illness. Even among those with no prior chronic illness in 1948,
however, mortality rates were slightly but consistently higher in persons who had
been affected by the fog. The authors of the study also compared the prevalence of
heart disease, asthma, and arthritis and rheumatism in survivors of the 1948
Donora episode with that found in residents of two neighboring Pennsylvania com-
munities. They found little difference between the groups. They concluded, there-
fore, that the fog appeared to have had little effect on the prevalence of these dis-
eases. In view of the excess mortality over the 10 years in those who had reported
being affected by the fog, a lower prevalence among the Donora survivors might
perhaps have been expected. The equal rate of prevalence found might therefore
reflect some increase in disease frequency.
Variation in Mortality, Morbidity, and Lung Function with Time
Daily measurements of smoke and sulfur dioxide have been related to daily
deaths and illnesses in London since 1958. The aim has been to establish a dose/
response curve, and, particularly, to determine the maximum acceptable levels
of these pollutants. The deviation in the number of deaths or illnesses from a 7-
or 14-day moving average is used. Mortality and morbidity for all causes and for
certain respiratory diseases were rather highly correlated with both smoke and
SO2 levels until 1962; but since 1962-1963 there has been little evidence of any ef-
fect of pollution on mortality or morbidity. It seems reasonable to attribute
this change to the great reduction in pollution that has been achieved in London
38
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during the past 10 years. During this period the annual smoke concentrations have
fallen from about 300 micrograms per cubic meter (pg/m ) to aboiat 60 Jjg/m , and
from about 250 yg/m3 to 175 jjg/m3. 303
Fletcher and his colleagues 1 07 > 190 made regular observations on 1000 men
aged 30 to 59 living in North London from 1961 to 1966. The incidence of respira-
tory illnesses (coryza, chest colds, mucopurulent bronchitis , wheezy attacks ,
"flu, " or acute respiratory disease) were found to be related to both smoke and
sulfur dioxide levels. During the period of observation the volume of morning spu-
tum produced by the men under observation declined. This could have resulted
from the concurrent reduction in air pollution, but it might also have resulted from
a reduction in the tar content of cigarettes, which occurred at the same time. It is
interesting to note in this connection that Waller and his colleagues 3^3 observed a
progressive improvement in peak expiratory flow rates in four trained subjects be-
tween I960 and 1965. >i
In New York City, day-to-day studies of mortality have indicated that periodi-
cally there are days when high pollution levels occur in association with unexpect-
edly high mortality rates. 300 , 304 The increase in deaths occurs immediately after
the pollution levels rise. It is usually followed by a drop below the expected num-
ber of deaths the following day, but the decrease is never sufficiently large to com-
pensate for the excess deaths. Consequently, these deaths are not thought to occur
only among those with terminal illnesses,
McCarroll and his colleagues -*™-1 followed a segment of the population of Man-
hattan Island for a 2 -year period, during which information on 25 symptoms -was
reported daily by I860 people. Even more information -was collected by weekly in-
terviews. The findings in 1090 persons indicated that complaints of cough and eye
irritation were correlated with increases in levels of SO2 and particulates.
In an attempt to study a more susceptible group of people, Lawther and his
colleagues303 , 306-31 0 made observations on bronchitis patients. Each patient kept
a daily record in a pocket diary of changes in his health by recording whether his
chest was better, worse, or the same as usual. A close correlation between the
concentrations of smoke and SC>2 and the clinical condition of the patients -was first
noted during the winter months. In the earlier years of the study (1959-1960), the
correlations were higher than 5 years later (1964-1965), when the concentration of
smoke in London had been considerably reduced. The patients appeared to be most
sensitive to changes in pollution early in the winter. The minimum pollution level
leading to a significant response was about 500 ug/m3 SC>2 and about 250 ug/m3
smoke.
In studies of bronchitic patients carried out in Chicago by Burrows and his col-
leagues, 311 the severity of symptoms in bronchitic patients appeared to vary -with
temperature and SO2 level. If season and daily temperature were held constant,
however, only hydrocarbon levels showed an independent correlation with symptoms.
The authors concluded that air contaminants did not appear to play a major role in
the daily variation in the patients' symptoms; however, Carnow and his colleagues,
who also studied patients in Chicago, showed that in certain groups of bronchitic
patients there was an increase in illness with increase in SC>2 concentrations.
Physiological measurements of lung function have been included in some stud-
ies of the effects of air pollution on respiratory disease. For example, Bates and
39
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his colleagues J' carried out repeated tests of lung functions in Canadian vet-
erans with chronic bronchitis (in Winnipeg, Montreal, Halifax, and Toronto). They
observed that the veterans in Winnipeg were less severely affected and had better
lung function--which declined less during the period of observation — than veterans
in the other cities. Winnipeg is the least polluted of the four cities. Whether
the differences observed were caused by the differences in pollution or by other
factors, such as selection of patients, is, however, uncertain.
Changes in lung function in relation to pollution were studied in small groups
of patients with respiratory disease by Spicer and his colleagues. 315 Results of
the lung function tests indicated that the patients tended to vary as a group, which
suggested the influence of some common environmental factor. In a later paper,
temperature, wind speed, barometric pressure, and SC>2 levels appeared to be the
most important factors influencing lung function in these patients. Certain changes
in lung function in cardiorespiratory cripples were attributed to concentrations of
^ 1 Y "3 1 R
suspended particulates in reports by Shephard and his colleagues. ->1'>->* °
Insurance records and absence from work as a result of illness have often proved
to be useful indices in studies of the effects of air pollution. 319-323 'por example,
industrial absenteeism caused by upper respiratory tract infections was related to
air pollution in Philadelphia by Ipsen and his colleagues. ^21 Workers in the Cam-
den plant of the Radio Corporation of America and in the Curtis Publishing Company
were studied from I960 to 1963. High respiratory morbidity was found to be pre-
ceded by a week in which air pollutants exceeded their normal seasonal level. It
•was also found to be associated -with seasonably low temperature, high humidity,
and higher than normal -wind velocity.
o o O "2 "J 'i
Sterling and his colleagues-5^ ' studied hospitalization in relation to air
pollution using records from Blue Cross and Blue Shield of Southern California.
They found that admission to the hospital and duration of stay for diseases and other
conditions that they categorized as relevant to air pollution were significantly cor-
related with pollutant levels, including levels of sulfur dioxide. These findings are
surprising in that the average level of SC>2 in the air during the period of study was
around 13 parts per billion (37 ,ug/m3). It is difficult to believe that concentrations
in this range can exert much effect on health.
Geographical Differences
Because air pollution gradients exist within and between cities, rural areas,
and even countries, comparative studies constitute one means of studying the effects
of air pollution on health.
International differences The large differences in bronchitis mortality between
different countries have sometimes been attributed to differences in pollution be-
tween them, but it has become increasingly clear that diagnostic practices differ in
different countries and that variations in death certification account for much of the
variation. When these are allowed for, however, differences in mortality and mor-
bidity still exist between different countries. "78, 80 , 81 , 324', 325 Some of these
differences could be the result of differences in air pollution levels.
Some of the difficulties inherent in carrying out international comparisons are
indicated by the studies conducted by Ferris and Anderson. ^ These authors
40
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compared respiratory disease and lung function in representative samples of the
inhabitants of two towns that differed in their degree of air pollution. In 1961 they
studied one of each 10 adults living in Berlin, New Hampshire. Two years later,
in 1963, they carried out a comparable study of one in each seven inhabitants aged
25 to 74 of Chilliwack, British Columbia. In each survey, methods were compar-
able and the observers the same, thereby largely eliminating one major cause of
differences between surveys. Information about respiratory symptoms and smoking
habits was obtained using a prototype of the British Medical Research Council's
respiratory symptoms questionnaire. Forced expiratory volume (FEV) and peak
expiratory flow rate (PFR) measurements were used to assess ventilatory lung
function. On the basis of the age-specific prevalence of symptoms in both surveys,
expected rates for nonsmokers were claculated, while from the multiple regression
equations on age and height for FEV and PFR for Berlin, expected lung function
values were calculated for Chilliwack. Respiratory disease prevalence for male
nonsmokers differed little from that expected, but in women the prevalence was
slightly below expectation. Lung function values were also consistently slightly
higher than expected in both men and women in Chilliwack for all smoking categor-
ies. These differences are in the direction one would expect if pollution -were ex-
erting an effect. As the authors point out, however, differences could be the result
of ethnic differences between the two populations.
The possibility that international differences in chronic respiratory disease
mortality might be attributable to different opportunities for contracting respiratory
infections -was the basis of a study carried out by the MRC on the respiratory ex-
perience of students from abroad -who -were attending British universities. 326 jt
•was thought that students from other countries might experience a higher incidence
of respiratory infections from British macrobiological flora than students -who were
accustomed to such infectious agents. No evidence -was obtained to support this
hypothesis. The findings were, in fact, just the opposite; namely, that the British
students under 25 years had a higher frequency of colds, especially of more severe
colds, than the overseas students of the same age had.
Urban-rural Differences A striking feature of the mortality statistics of certain
countries is a pronounced gradient in death rates for chronic respiratory disease
between urban and rural areas. This trend is pronounced in the United Kingdom
for both men and women. In the United States, a similar though much less im-
XV
pressive trend has been observed for men but not for women.0' These observa-
tions have stimulated a great deal of research. In the earliest of such studies,
mortality rates in different areas -were related to levels of air pollution where
327333
pollution data were available. '•'-->->J Mortality from bronchitis was found to be
correlated with indices of pollution, social circumstances, and density of popula-
tion. More recently, urban-rural differences in bronchitis mortality have been
demonstrated in male and female nonsmokers .332, 333 ^ pronounced urban-
rural gradient of bronchitis symptoms, comparable to the gradient that exists
for bronchitis mortality, was shown in a survey of a random sample of men and
women who were patients of 92 general practitioners in Britain. 218
In 1961 and 1962, a nationwide study, "Enquiry into the Incidence of Incapacity, "
was carried out in the United Kingdom. 91 The incidence of incapacity for work in
different areas and among different occupations in random samples of all employed
men and women was studied. Incapacity because of bronchitis was found to be sig-
nificantly correlated with ambient concentrations of smoke and sulfur dioxide in
each of four 10-year age groups. 334 The interpretation of the findings is, however,
41
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somewhat uncertain because similar correlations were also observed between the
levels of these pollutants and arthritis and rheumatism. This suggests that differ-
ences in factors other than pollution levels may also have been present, one of the
more likely of which is social class.
Intercity Differences Comparisons have sometimes been made among towns hav-
ing different levels of air pollution. Dohan and Taylor335, 336 related claims for in-
surance benefits for female employees of Radio Corporation of America to levels
of pollution in five cities. They found a high correlation between respiratory ill-
nesses of 7 days' duration or more and average levels of suspended particulate sul-
fates for the years 1955, 1956, and 1957. Age distribution, conditions of work, and
social and climatic factors did not appear to account for the observed fivefold
variation in the incidence of these illnesses in the cities..
A comparison of respiratory disease and lung function in two towns in Pennsyl-
vania that had contrasting levels of air pollution -was carried out by the United
States Public Health Service. ^"3 Average dustfall in Seward, the more polluted
town, was 3. 2 times and SC>2 was 6. 2 times that of New Florence. Age- and height-
adjusted mean values of most of the lung function tests were considered by the in-
vestigators to be remarkably similar in the two towns. Values for air-way resist-
ance times volume were the only statistically different results; each was higher in
Seward than in New Florence. Nevertheless, there were also small but consistent
differences in maximum breathing capacity, 1-second forced expiratory volume,
and maximum mid-expiratory flow, each value being lower in Seward. It is diffi-
cult to attribute these physiological differences solely to the greater air pollution
in Seward because there were other differences between the two towns (for example,
Seward's population included a higher proportion of coal miners. )
Intracity Differences - Differences in mortality and morbidity often occur in differ-
ent areas of a single large city. It is sometimes possible to correlate these with
differences in air pollution. In London, Reid"?, 338 showed that the mortality and
morbidity of postmen were related to an index of pollution based on fog frequency.
The study subsequently carried out by the Ministry of Health, along with other stud-
ies, supported and extended these findings. "•*• > **• '< 3<^0
Burn and Pemberton -^ ' studied morbidity and mortality in relation to pollution
in Salford, England, for the years 1958 and 1959. They noted a twofold or greater
increase in new attacks of bronchitis during four out of five smog episodes. They
also noted that mortality and morbidity rates from bronchitis were higher in more
polluted areas of the city than in less polluted areas. They 'were not, however,
able to exclude the possibility that overcrowding or other social factors could have
been responsible. Nor were they able to exclude a relationship between smoking
and bronchitis because their study included no data on smoking habits.
In the United States, studies correlating mortality rates with levels of pollution
in different parts of the city were carried out in Buffalo, New York.339, 340
Pollution in Buffalo was monitored from 1961 to 1963 and particulate levels and
sulfation rates were related to mortality for 1959 to 1961. Total mortality rates
for men and -women aged 50 years and over and respiratory disease mortality for
men 50 to 69 were both significantly correlated with suspended particulate concen-
trations (Table 17). ' There was also a correlation between sulfation and mor-
tality rates for chronic respiratory disease for men aged 50 and over.
42
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One of the most detailed studies of air pollution was conducted by the United
States Public Health Service in Nashville, Tennessee, ^1 -343 where pollution was
monitored by a network of 123 stations. Mortality rates from 1949 to I960 -were
correlated \vith pollution levels. Age-specific death rates for respiratory disease
for ages 25 to 74 -were directly related to sulfation levels and cardiovascular mor-
tality was related to soiling by particulate pollution. Various indices of morbidity,
such as the frequency of asthma attacks, have also been related to pollutant levels
in Nashville.
Unfortunately, in neither Buffalo nor in Nashville -was attention directed to
o A A
smoking habits or to occupation. More recently, however, Winkelstein and KantorJ^'i
have studied the relationship of respiratory symptoms to air pollution in a random
sample of white women in Buffalo. They found that among nonsmokers aged 45 and
over there was a positive association bet-ween cough and phlegm and suspended par-
ticulate levels. There also appeared to be a relationship between residential mo-
bility and respiratory symptoms among smokers. Among smokers who did not
change residences, cough and sputum were positively correlated -with air pollution
at the place of current residence; but among those who had moved -within the past
5 years there -was a negative association. The associations found -were not attribut-
able to social class. No association was found bet-ween sulfur oxide levels and res-
piratory symptom prevalence.
Table 17. MEAN ANNUAL MORTALITY RATES FROM ASTHMA, BRONCHITIS, OR EMPHYSEMA3
BY ECONOMIC STATUS AND POLLUTION LEVEL FOR WHITE MALES AGED 50 to 69
YEARS IN BUFFALO, NEW YORK, 1959 to 1961b
(deaths/100,000)
Median family
income, $
3005 to 5007
5175 to 6004
6013 to 6614
6618 to 7347
7431 to 11,792
Mean annual particulate concentration,
j=80
--
136
--
70
79
Z80
126
154
74
80
109
>100
271
172
110
177
0C
Z135
392
199
128
--
aBased on appearance anywhere on death certificate of asthma, bronchitis,
or emphysema.
bAdapted from Uinkelstein.339
°Rate based on fewer than 5 deaths.
One of the most interesting studies of the effects of pollution in different parts
of a town was conducted in Genoa, Italy, by Petrilli and his colleagues. 233 Genoa
is a rapidly growing industrial city situated between the Appennines and the Medi-
terranean. As a result of Genoa's topography, the local climate may differ strik-
ingly in different parts of the city. From 1954 to 1964, pollution was assessed at
19 sites. Sulfation rates, SO£, carbon monoxide, lead, dustfall, and suspended
particulates (estimated gravimetrically and by particle size), and 3, 4-benzpyrene
were monitored. Mean values for available data from 1962 to 1964 showed an in-
crease of about 20 percent over 1954 to 1961. Respiratory symptoms were studied
43
-------
in nonsmoking -women aged 65 years and over who had not -worked in industry but
who had resided for a long period in the same area. The results were also analyzed
by floor level (height above ground level) of residence. Strong associations -were
shown between the frequency of respiratory disease and the concentration of SC>2.
Annual morbidity rates for bronchitis and other respiratory diseases (1961 and
1962) in seven districts -where air pollution -was measured continuously also showed
that these varied -with the average annual SO£ concentrations. Unfortunately, anal-
ysis of the data -was inadequate to permit a firm judgment about the effectiveness
•with which the authors standardized for socioeconomic factors.
Disease among Homogeneous Occupational Groups
To obviate the confounding of differences in exposure to air pollution -with dif-
ferences in social class, Fairbairn and Reid 345 studied British postmen, a homo-
geneous occupational group -who receive the same pay wherever they -work and -who,
once established, tend to remain in the same area. They found that premature
retirement and death from bronchitis and pneumonia were related to thick and pre-
sumably polluted fog and were independent of domestic overcrowding or population
density. Somewhat similar observations have been made of British transport
workers. °
In this country, special surveys of Bell Telephone employees have been carried
out by Holland and his colleagues and by Deane and her colleagues. The re-
sults have been compared with studies carried out in a comparable manner in
London and smaller towns in England. ' Differences in symptom prevalence,
morning sputum volume, and lung function -were observed that -were in the direction
to be expected if pollution -were playing a role.
Disease among Children
325 3 47
Studies by Reid ' have shown the value of studying children to elucidate
the effects of pollution on health; children are particularly suitable because they are
usually nonsmokers and for the most part are not occupationally exposed to high
dust levels. They may also be exceptionally sensitive to the effects of pollution.
Wahdan34^ compared children in Sheffield, England, a polluted city, with children
living in the Vale of Glamorgan, an area of unpolluted countryside. He found that
the frequency of sinus opacity and otitis media was higher in Sheffield.
In Japan, Toyama3/*9 an(j Watanabe '' "9 found that school children living in
Kawasaki and Osaka, two polluted cities, had lower peak expiratory flow rates than
children living in less polluted areas. One of the more interesting studies of chil-
dren was carried out in Britain by Douglas and Waller, who initiated a study of
child health and development in 1946. A longitudinal study of all children born
in a 1-week period in March 1946 was conducted until the children left school at age
15. Subsequently, the illness experience of the children was related to the areas
in which they had lived and thus to the probable levels of pollution experienced
through life. The results showed that lower respiratory tract infections were con-
sistently related to pollution (Table 18) but that upper respiratory tract infections
were not. Both the frequency and severity of such infections increased with the
amount of pollution. The lowest levels of smoke and SO£ observed were 67 ug/m^
and 90 jag/m , respectively. In all cases, higher illness rates -were noted for the
higher pollution levels.
44
-------
Table 18. FREQUENCY BY POLLUTION LEVELS OF LOWER RESPIRATORY TRACT
INFECTIONS IN BRITISH CHILDREN3
(percent)
Lower respiratory
tract infections
First attack within first 9 months
At least one attack within first
2 years
More than one attack within first
2 years
Boys
Girls
Middle class
Manual working class
Cause of admission to hospital
within first 5 years
Lower respiratory infection
Bronchitis
Pneumonia
Mean annual pollutant concentration,
pg/m3
Part. = 67
S02 = 90
7.2
19.4
4.3
5.7
2.9
3.0
5.1
1.1
0.0
1.1
Part. = 132
S02 = 133
11.4
24.2
7.9
8.1
7.7
4.0
10.8
2.3
0.9
1.4
Part. = 205
S02 = 190
16.5
30.0
11.2
10.9
12.1
7.7
13.9
2.6
1.0
1.6
Part. = 190
S02 = 251
17.1
34.1
12.9
16.2
9.7
9.3
15.4
3.1
1.4
1.8
aAdopted from Douglas and Waller.350
An interesting piece of evidence supporting the importance of home residence
in early life to susceptibility to respiratory disease was found by Rosenbaum, "1
who correlated respiratory disease incidence in national servicemen with their
home localities. Prior residence in industrial areas seemed to enhance suscepti-
bility to and/or severity of illness during national service.
L/unn and his colleagues-^-3'* studied the pattern of respiratory illness in young
children in Sheffield. They found that both upper and lower respiratory infections
were related to the area in which the child lived, which in turn reflected pollution
levels. FEV and FVC were also low in the most polluted areas.
More recently, Holland and his colleagues 221 studied some 10,000 school chil-
dren in four areas in Kent. Peak expiratory flow rates were found to be related to
residence, social class, family size, and past history of pneumonia, bronchitis, or
asthma. These four factors appeared to act independently, but the effects were ad-
ditive. The findings suggested that early environment can produce adverse changes
that may persist and contribute to the subsequent development of chronic respira-
tory disease.
Colley and Holland ^ attempted to assess the varying influences of smoking,
area of residence, place of work, overcrowding, family size, social class, and
genetic factors in the etiology of chronic respiratory symptoms and lung function in
all members of families. A preliminary study of cough in 2342 families living in a
45
-------
London suburb showed that in fathers exposed to both home and occupational hazards
smoking and social class influenced the prevalence of cough but area of residence
did not. In mothers, on the other hand, smoking and area of residence were im-
portant but social class was not. In the children, an effect of area of residence was
also shown.
Colley and Reid^^ have studied respiratory disease in over 10, 000 children
aged 6 to 10 years living in contrasting urban and rural areas of England and Wales.
The,re was a pronounced social-class gradient in the frequency of chronic cough and
history of bronchitis, and in the occurrence of diseases of the ears and nose as
well. A consistent rise in the frequency of chest illnesses with increasing local
levels of air pollution -was seen only in children of semiskilled and unskilled work-
ers. These trends paralleled similar trends in the frequency of killing and disabling
bronchitis among adults in the same area. They were not explained by difference
in domestic circumstances such as average number of persons per room, persons
per dwelling, or rooms per dwelling.
Recently, Shy and his colleagues studied the effects of community ex-
posures to nitrogen dioxide. Elementary school children living in four areas of
Chattanooga, Tennessee, -were selected. One area, in close proximity to a TNT
plant, had high ambient levels of NC>2. The second area had relatively high levels
of particulates. The third and fourth areas served as controls. Respiratory ill-
ness rates were consistently higher among all family segments in the high-NO2-
pollution area. The relative excess of respiratory illness among families exposed
to high NC>2 compared with controls was 18. 8 percent. The corresponding excess
among families exposed to high particulates was 10. 4 percent. Ventilatory lung
function as measured by the 0. 75 -second forced expiratory volume (FEVg yg) was
also significantly lower in the high-NC>2 area compared -with the controls. The dif-
ferences in FEV, however, -were neither as large nor as consistent as those be-
tween the high-NC>2 and the two control areas when these were considered sepa-
rately. The biological implications of the statistically significant differences found
when results from the control areas were pooled seem uncertain.
Yokohama and New Orleans Asthma Studies
In 1948, a respiratory condition was observed in American servicemen serving
in the Yokohama- Tokyo area. Subsequently known as Yokohama asthma, the
condition was characterized by a persistent, irritating cough and asthmatic attacks
with coughing and wheezing. It was found to be more prevalent in cigarette smokers
than in uonsmokers. Although it was first believed to be confined to American ser-
vicemen, it was subsequently found to occur in the Japanese. At autopsy, changes
that resembled chronic bronchitis rather than asthma were noted. The condition is
believed to result in part from industrial pollution in the Kanto Plain. The precise
pollutants have not, however, been clearly identified. 349,358-362
Since 1958, epidemics of asthma have occurred in New Orleans that are recog-
nized as such by sudden increases in the number of people seeking treatment at the
emergency room of Charity Hospital. Characteristically, the epidemics occur in
the first and third weeks of October, following the calendar rather than the weather.
There is no day-of-the-week pattern; Saturdays and Sundays are as frequently in-
volved as other days. Pollution described as "poor-combustion particles with as-
sociated silica" from burning dumps and dust from the New Orleans grain elevator
have been suggested as possible causes, but neither suggestion is tenable. Increases
46
-------
in asthma attacks may also be occurring concomitantly in other cities in Louisiana.
The occurrence of a rather specific allergen in the city at certain times of the year
has been postulated. 3°3
Dose-response Relationships
Although some idea has been obtained of the levels of smoke and sulfur dioxide
that may cause acute health effects (Table 19), 91 , 11 3 , 1 90,291-294,300,303,312,340,
350,364 it is important to realize that these two pollutants may not be the most
important pollutants, but may only be indices of others that are more important.
In London, excess mortality clearly resulted when 24-hour concentrations of smoke
rose to 1000 'to 2000 ug/m3 and concentrations of SO2 rose to 750 ug/m3. Levels
of this magnitude may occur with average annual concentrations of 300 to 400 yg/m3
smoke and 250 to 300 jig/m3 SC>2. No one can doubt that these concentrations are
far too high and should not be allowed.
In London, 24-hour values of about 500 ;ug/m3 smoke and 400 ug/m3 SC>2 have
led to exacerbations among bronchitis patients. Now that the average concentration
of smoke in London is about 60 .ug/m3 and that of SC>2 is about 170 ,ug/m3, it will be
interesting to see if there is still some response among these susceptible patients
to the highest levels that occur in the winter.
In the whole of Britain, correlations that appear to be linear can be shown for
absenteeism'resulting from bronchitis when winter smoke and SC>2 are 100 ug/m
and over. Furthermore, lower respiratory illnesses in children appear to be as-
sociated -with average annual levels of smoke and SC>2 of 80 ;ag/m3 and over.
In New York City, 24-hour averages of 5 coh (soiling index of particulates) and
2000 ug/m SO2 have resulted in mortality and 3 coh and 700 _ug/m3 SC>2 in morbid-
ity. In Chicago, exacerbations of bronchitis have been associated with levels of
SC>2 of about 750 jag/m3. The particulate levels associated with the SC>2 pollution
were not stated; however, the average annual value for Chicago for the appropriate
years of the study, as reported by the National Air Surveillance Network, was 148
Oig/m3. In Buffalo, New York, there was a steady gradient in respiratory mortal-
ity corresponding to a pollutant gradient. The lowest levels were under 80 ug/m
particulates and sulfation of less than 0.45 mg/cm -30 days.
Although these are rather inadequate data, it -would perhaps be reasonable to
conclude that average annual levels of particulates and of sulfur dioxide should
both be under 100 .ug/m3.
Lambert and Reid-'--'-3 have recently published the findings from a study that
supports these conclusions. They carried out a survey by mail of respiratory
symptoms in a representative sample of men and women living in England, Wales,
and Scotland. Of the men and women believed to be aged 35 or over in the house-
holds sampled, 9975, thought to represent 74 percent of those aged 35 to 69 and
able to respond, were analyzed. An increasing prevalence of persistent cough and
phlegm and of chronic bronchitis with increasing age and with increasing cigarette
consumption was confirmed. Chronic bronchitis was defined in this case as per-
sistent cough and phlegm, breathlessness on walking, and a period of increased
cough and phlegm lasting 3 weeks or more in the past 3 years. There was an ex-
cess in male nonsmokers as well as in smokers. Urban-rural gradients in this
-------
Table 19. PARTICULATE AND SULFUR DIOXIDE LEVELS AND EFFECTS ON HEALTH
Averaging time
for pollution
measurements
24 hours
Winter
Annual
Place
London
New York
Chicago
Britain
Britain
Britain
Buffalo
Parti culates
jug/m
2000
1000
250
200
Not
spec-
ified
200
70
100
100
cohs
6
S02
jug/m
1000
500
500
250
1500
700
200
90
100
mg/100 cm -30 days
0.30
Effect
Mortal ity
Mortal ity
Exacerbations of
bronchitis
Increased absence from
work
Mortal ity
Exacerbations of
bronchitis
Correlation of
pollutants with
bronchitis incidence
Lower respiratory in-
fections in children
Bronchitis prevalence
Respiratory mortality
Author and year
Scott, 1959
Gore and Shaddick,
1958
Burgess and Shaddick,
1959
Martin, 1964
Waller et al . , 1969
Angel et al . , 1965
McCarrol and Bradley,
1966
Carnow et al . , 1968
Ministry of Pensions
and National Insur-
ance, 1965
Douglas and Waller,
1966
Lambert and Reid,
1970
Winkel stein et al . ,
1967 and 1968
Reference
293
292
291
364
303
190
300
312
91
350
113
294,
340
-------
increased with increasing air pollution independently of cigarette consumption.
Local pollution appeared to have little effect in nonsmokers, but in smokers high
levels of pollution were associated with more frequent respiratory symptoms. Pre-
valence of symptoms increased progressively from the lowest (<100 pig/m3 smoke
and SC>2 per year, on the average) to the highest (2200 ^g/m^) pollutant levels.
This study indicates, then, that pollution had a clear effect on respiratory symp-
toms, after age and cigarette smoking were taken into consideration. There was
also an interaction between smoking and pollution.
Miscellaneous Studies
Various other epiclemiological studies relative to air pollution have been car-
ried out. Observations have, for example, been made on the mortality and morbid-
ity of migrants in their country of adoption and have been compared with mortality
and morbidity of the population, of their country of origin and of the indigenous pop-
ulation in their country of adoption. The results suggest that a specific urban fac-
tor, possibly pollution, is playing a role. The importance of constitutional and en-
vironmental factors in the pathogenesis of chronic respiratory disease has been
studied in Sweden using twin registry data. The authors found little evidence for
a specific urban effect in Sweden, but concluded, rather, that air pollution there is
of secondary importance to smoking in causing respiratory symptoms. Similar
twin studies are being carried out in this country. Such studies would also be val-
uable in Britain, where the pollution levels are higher than in Sweden.
The effects of oxidant pollution on athletic performance -were studied in Los
Angeles and Seattle. In Los Angeles, the levels of oxidant and suspended particu-
lates appeared to affect the times recorded; in Seattle they did not, possibly be-
cause the levels of the pollutants were lower.
Instead of relying on the somewhat unpredictable vagaries of nature to vary
pollution levels, some investigators have carried out studies on patients by exposing
them to polluted or filtered air in a specially designed room. In this -way, Motley
and Phelps^oS showed subjective and objective improvement in patients with chron-
ic obstructive lung disease -who were supplied -with pollutant-free air.
OCCUPATION
General Industrial Studies
Many irritants of the respiratory tract are encountered in industry. They
range from relatively inert, insoluble dusts to fumes from the salts of rare metals,
such as platinum, which can provoke dramatic sensitization manifested by asthma. °6
They include substances such as cadmium and toluene di-isocyanate, which appear
to have rather specific effects on the respiratory system. Gilson^Q' has classified
the industrial pulmonary diseases as (1) mineral dust pneumoconioses, (2) vegetable
dust pneumoconioses, and (3) pulmonary diseases caused by soluble gases and aer-
osols. This review is concerned less with these fairly specific occupational di-
seases than with the role of occupational exposures in the pathogenesis of chronic
obstructive lung disease. Pneumoconiosis will be considered mainly in the light of
its relationship to nonspecific chronic respiratory disease.
Dust exposure has been considered to be an important determinant of chronic
respiratory disease at least since the time of Ramazzini (circa 1700). Nineteenth-
49
-------
century clinicians stressed its importance, as the following rather characteristic
passage indicates:
The diseases of the respiratory organs, so frequently caused by
various arts and employments, especially. . . dry grinders and
needle pointers; flax dressers and pearl and bone button makers;
iron, brass, and metal filers; stone cutters, millstone makers,
miners, and quarriers, particularly sandstone; wool carders and
feather dressers, sawyers, turners, weavers, bakers, and starch
makers. All these suffer more or less. . . from chronic bronchitis. . .
persons thus occupied should be induced to preserve the beard on
the upper lip, or the moustache, in order to intercept during res-
piration the mineral, vegetable or animal molecules diffused in
the air surrounding them.
368
Greenhow, who probably knew more about industrial pulmonary diseases than
any of his contemporaries (I860), never doubted the etiological importance of dust
exposure. In this century, Collis, ^69 £n j-^g ]ymrc,y lecture of 1931, maintained
that bronchitis -was the first of the dust diseases, and Haldane believed that the dis-
ability from which British coal miners suffered in the first quarter of the 20th cen-
tury was caused by bronchitis rather than by pneumoconiosis.
Mortality statistics support the view that occupation is a factor in chronic res-
piratory disease. Table 20 shows standardized mortality rates (SMRs) for pneu-
monia and bronchitis for certain occupational groups in the United Kingdom from
1949 through 1953.3'" The table includes the socioeconomic class allocated to the
various occupational groups. The low mortality ratios of men -who -worked in agri-
culture, forestry, and gardening were noted in both the 1931 and 1951 censuses.
Table 20. STANDARDIZED MORTALITY RATIOS
FOR BRONCHITIS IN MEN AGED 20 TO 64
AND THEIR WIVES IN ENGLAND AND WALES
370
Occupation of men
Miners
Hewers and getters
Others underground
Surface
Foundry workers
Moulders and core makers
Furnacemen
Laborers
Furnacemen
Openers, sorters,
blenders, and carders
Mortality ratios
Men
135
200
93
131
174
194
135
159
177
156
Wives
175
190
177
139
-
217
-
-
160
(500)
50
-------
On the other hand, high ratios were observed on both occasions in hewers and get-
ters of coal, furnacemen, moulders, masons, dock laborers, and general laborers.
British coal miners have had consistently high death rates from bronchitis since
1900; however, their rates vary widely in different areas.
98,369
Information on occupational mortality in the United States is limited, but
Guralnick and Enterline have published analyses of data from the 1950 U.S.
census. Table 21, adapted from Guralnick and from U.S. Public Health Service
data, presents standardized mortality ratios for diseases of the respiratory sys-
tem for different occupations. The exceptionally high ratios for miners are strik-
ing. The magnitude of the difference between their ratios and those of other work-
ers is quite different from that found in the United Kingdom, which to a large ex-
tent reflects the inclusion of pneumoconiosis in the American statistics. 372 When
such deaths are excluded, the ratios in the two countries become much more
comparable.
Table 21. STANDARDIZED MORTALITY RATIOS GREATER THAN 150, BY OCCUPATION,
FOR DISEASES OF THE RESPIRATORY SYSTEM EXCLUSIVE OF INFLUENZA
AND PNEUMONIA IN UNITED STATES, 1950a
Occupation
Standardized
mortality ratio
Mine operatives and laborers (n.e.c.)
Holders, metal
Laborers (n.e.c.), transportation equipment
Operatives and kindred workers, stone, clay, and glass products
Laborers (n.e.c.), primary metal industries
Taxicab drivers and chauffeurs
Laborers (n.e.c.), wholesale and retail trade
Operatives and kindred workers (n.e.c.), primary metal industries
Cooks, except private household
Laborers (n.e.c.), wholesale and retail trade
Laborers (n.e.c.), furniture; saw and planing mills;
miscellaneous wood products
Lumbermen, raftsmen, and wood choppers
Operatives and kindred workers (n.e.c.), transportation,
communication, and other public utilities
933
500
433
250
258
225
215
195
195
170
154
154
153
aAdopted from Guralnick.
Not elsewhere classified.
The interpretation of mortality statistics is difficult. Apart from diagnostic
errors, it has been increasingly recognized that there may be serious biases be-
tween the occupational groups designated at the time of the census and those applic-
able at the time of death. 373 There is also a tendency for a man's widow, when
registering his death, to promote him. Thus, a coal miner will often be recorded
by his next of kin as having been a collier, whereas he would be correctly classified
51
-------
(and usually he will have reported himself as such at the census) as a worker under-
ground but not on the coal face. The problems of differentiating between the effects
of occupational exposures and those of socioeconomic circumstances associated
with the occupation--for example, family income, education, housing, childhood
infections, and quality of medical care—are great. Attempts have been made to
separate these factors by studying the mortality ratios of the wives of men in dif-
ferent occupations. The findings of such studies indicate that the wives of men who
work in occupations with high SMRs for bronchitis also tend to have high ratios.
This has been interpreted as indicating social rather than occupational factors in
the genesis of bronchitis. Recently, Lowe 374 questioned the validity of this inter-
pretation on the grounds that the mortality rates of women are only a fraction of
those of their husbands. It is not clear, however, why a lower absolute mortality
rate among women should make the interpretation invalid. The relative trends in
mortality with social class are roughly the same in men and women and this trend
would appear to be more significant than the absolute levels of mortality.
A higher prevalence of respiratory symptoms in the wives of workers exposed
to dust has been reported in several surveys. 98, 212, 243 in Wales, the higher pre-
valence of symptoms was associated with a lower average FEV, but in Mullens,
West Virginia, there was no difference in lung function between the wives of miners
and the wives of nonminers. The full implications of the correlation in the preval-
ence of symptoms between husbands and wives is not clear at the moment. The
finding is an interesting one, however, and deserves further study.
Morbidity by Occupation Information on morbidity for the working population of
Britain has been available since 1948 through the Ministry of Pensions and National
Insurance. Periods of absenteeism resulting from bronchitis are high in miners
and foundry -workers but low in persons engaged in agriculture or forestry. Ab-
sence rates are likely to be influenced by the heaviness of the job and also by wheth-
er or not any payment is made to a workman when he is sick. The heaviness of the
job seems to play a role in the high respiratory disease rates among coal miners. 375
From June 5, 1961, to June 2, 1962, a survey of sickness rates in a 5 percent
sample of men and a 2. 5 percent sample of women in the United Kingdom was car-
ried out by the Ministry of Pensions and National Insurance. 91 Certificates of in-
capacity for all illnesses that caused absence from work of 3 days or more were
analyzed. The results for 620, 000 men and 90, 000 women were analyzed by occu-
pation for 220 occupations and for 210 areas of residence. Table 22 shows the in-
cidence (inception rates) and Table 23 shows days of incapacity for men aged 18 to
63 and for married and other women aged 18 to 58. 91 The increasing inception
rates for bronchitis with age in both men and women is clear; a smaller trend to-
ward increase in inception with age is noted for pneumonia. The inception rates
for bronchitis were, however, higher in women, particularly the married women,
than in men. Days of incapacity follow the trends of the inception rates; they in-
drease with age in men and women and are higher in women than in men. In view
of the almost universal finding of a higher prevalence of chronic respiratory dis-
ease in men than in women, the higher frequency of attacks of bronchitis in women
suggests that respiratory disease is more likely to be acute than chronic in women.
This may be the result of a lesser exposure to respiratory irritants in women, or
it could reflect more adequate management of an attack of bronchitis in them. One
might recall the suggestion by Goodman and his colleagues88 that one possible eti-
ological factor in male chronic bronchitis is a too early return to work, particularly
heavy and dusty work, after an attack of bronchitis.
52
-------
Table 22. RESPIRATORY DISEASE INCEPTION RATES IN UNITED KINGDOM, 1961-1962 SURVEY
(inception/100 sample population)
91
Disease
All causes
Asthma
Diseases of
respiratory
system
Acute upper
respiratory
infection
Influenza
Pneumonia
Bronchitis and
emphysema (no
mention of
bronchitis)
Chronic
sinusitis
ISCa
241
470-527
470-475
480-483
490-493
500-502
527.1
513
.
Sex
M
Flb
F2
M
Fl
F2
M
Fl
F2
M
Fl
F2
M
Fl
F2
M
Fl
F2
M
FT
1
F2
M
Fl
F2
Age, yr
All
28
38
34
0.2
0.2
0.2
14
17
19
5
7
9
6
7
7
0.2
0.1
0.1
4
4
3
0.4
0.6
0.7
<24
30
42
38
0.2
0.2
0.2
16
19
22
8
9
12
7
7
8
0.1
0.04
0.1
2
3
2
0.5
0.6
0.9
25-34
26
38
30
0.2
0.2
0.2
14
18
16
6
8
7
6
7
6
0.1
0.1
0.1
2
3
2
0.5
0.7
0.6
35-44
25
35
27
0.1
0.4
0.2
13
17
13
4
6
5
6
6
5
0.1
0.1
0.1
3
5
3
0.5
0.8
0.5
45-54
27
37
29
0.2
0.2
0.2
13
17
13
3
5
4
5
6
5
0.2
0.2
0.2
5
5
4
0.3
0.4
0.4
55-59
33
36C
29
0.2
0.1
0.2
16
17
13
3
5
4
5
6
5
0.3
0.2
0.3
8
7
4
0.2
0.4
0.3
60-63
37
0.2
19
3
6
0.4
10
0.2
International Statistical Code.
kp, = married women; F£ ~ other women.
cAges 55-58.
Table 24 shows the age-standardized inception rates for bronchitis among vari-
ous occupational groups. 91 The high rates, approximately twice the average, for
miners and quarrymen are well known, as are the low rates for workers in farming
and forestry. Some of the differences between the occupational groups can be attrib
uted to social class (Table 25), though within the social classes there appeared to
be differences in incidence related to the heaviness of the job. 91 Differences were
also shown in this study among different geographic areas. Bronchitis rates were
particularly high in South Wales and northwest and northeast England; but, though
evidence for it is not given, the comment is made that a quarter to a third of the
high inception rates among the miners could be attributed to the geographic
53
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Table 23.
INCAPACITY FOR WORK CAUSED BY RESPIRATORY DISEASE
IN UNITED KINGDOM, 1961-1962 SURVEY91
(days/100 sample population)
Disease
All causes
Asthma
Respiratory
diseases
Acute upper
respiratory
infection
Influenza
Pneumonia
Bronchitis
Sinusitis
ISCa
,
241
470-527
470-475
480-483
490-493
500-502
1
Sex
M
FT
F2
M
F]
F2
M
FT
F2
M
Fl
F2
M
Fl
F2
M
FT
F2
M
F2
M
Fl
F2
All
885
1393
863
7
11
7
285
340
271
52
90
101
72
95
81
7
5
4
124
117
55
6
10
9
<24
552
1253
757
4
4
4
183
286
288
70
108
128
68
93
86
3
1
3
24
51
38
5
9
11
25-34
584
1197
743
4
10
5
187
281
229
59
96
81
69
91
80
3
3
2
36
62
41
7
12
8
Age, yr
^35-44
711
1347
933
5
16
10
209
365
238
48
85
62
70
88
68
6
6
2
63
151
85
7
13
9
45-54
984
1522
1188
8
13
11
307
386
260
40
78
55
73
101
72
9
11
9
150
167
101
5
8
6
55-59
1524
1906C
1369
12
18
14
513
453
286
41
67
51
80
102
80
16
6
18
320
235
112
4
7
8
60-63
2163
15
756
43
90
20
531
4
International Statistical Code.
FT = Married women; F2 = other women.
CAges 55-58.
distribution of the coal-mining regions. One fact that makes the interpretation of
these high bronchitis rates among miners difficult is the observation made in this
survey that the incidence of arthritis and rheumatism and, to a lesser extent, the
incidence of psychosis and psychoneurosis also show rather similar gradations.
Field studies comparing different occupations - An early study of the prevalence of
54
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Table 24. BRONCHITIS INCEPTION RATES IN MEN AGED 18-63
IN UNITED KINGDOM, 1961-1962 SURVEY91
Occupation
All
Miners and quarrymen
Laborers (n.e.c.)
Operators of stationary engines, cranes, etc.
Furnace, forge, foundry, and rolling mill workers
Gas, coke, and chemicals makers
Warehousemen, storekeepers, packers, bottlers
Glass and ceramics makers
Transport and communications workers
Construction workers
Engineering and allied trades workers (n.e.c.)
Service, sport, and recreation workers
Painters and decorators
Makers of other products
Textile workers
Food, drink, and tobacco workers
Electrical and electronic workers
Woodworkers
Leather workers
Paper and printing workers
Clerical workers
Clothing workers
Farmers, foresters, and fishermen
Sales workers
Professional, technical workers, artists
Administrators and managers
Bronchitis inception
(standardized for age)
Rate,
inception/100
men
3.69
7.24
5.59
4.96
4.71
4.48
4.17
4.13
4.11
4.10
3.80
3.79
3.78
3.56
3.53
3.46
3.43
3.27
3.17
2.87
2.67
2.42
2.25
2.11
1.89
1.08
Ratio,
RSO/RAOa
100
196
151
134
128
121
113
112
in
111
103
103
102
96
96
94
93
89
86
78
72
66
61
57
51
29
aRatio of rate for specific occupation (RSO) to rate for all occupations
(RAO); for example, rate for miners and quarrymen, 7.24, divided by rate
for all occupations, 3.69, is 196.
symptoms of chronic bronchitis was carried out by Clifton in an industrial firm in
Sheffield in 1951. She found that heavy cigarette smoking, past work in dusty
jobs, and a. family history of bronchitis were important factors. Since then many
studies have been conducted that compare different occupational groups. Table 26
shows a number of population surveys of bronchitis and ventilatory capacity in men
55
-------
Table 25. BRONCHITIS INCEPTION RATES AND INCAPACITY FOR WORK
CAUSED BY BRONCHITIS IN MEN AGED 18-63 IN UNITED KINGDOM,
1961-1962 SURVEY91
Occupational category
Rates,
inception/1000 men
(standardized for age)
Incapacity,
days/1000 men
All categories
Professional and Intermediate
(I and II)
Skilled (nonagricultural) (III)
Heavy
Medium
Light
Partly skilled (IV)
Agricultural
Nonagricultural
Heavy
Medium
Light
Unskilled (nonagricultural) (V)
Heavy
Medium
36.9
15.4
35.1
50.0
35.9
25.8
47.7
19.3
60.1
47.1
38.9
57.1
50.1
1235
354
1040
1442
1106
679
1573
506
2196
1540
1429
2306
2364
1732
•who •work in dusty occupations that have been carried out in a manner comparable
to the study by Clifton. 98, 111,214,235,243, 376-378 T^e ratio of the percentage
of bronchitis among the dust-exposed compared to that among the unexposed varies
from about 1 to 1 to 3 to 1, with an exceptionally high ratio of 5 to 1 among fluor-
spar -workers in Canada. At the same time, the average ventilatory capacity
(FEVj Q) -was consistently lower among the dust-exposed groups.
Specific Occupational Studies
Coal Miners
Miners versus nonminers - As early as 1924, Shurman^?? found that the
prevalence of bronchitis in underground workers was double that of mine office
workers who had never been exposed to dust. Later, Bohme and Lent compared
the frequency of bronchitis in hospital patients and found that the prevalence was
29. 1 percent in miners compared with 15.5 percent in nonminers. More recent
surveys have almost invariably indicated a higher prevalence of symptoms and of
bronchitis in miners and ex-miners than in nonminers. 98, 1 95, 21 2, 214, 243, 381 -386
212
Enterline and Lainhart reported on surveys carried out in two coal mining
areas, Mullens and Richwood, in West Virginia. Each community has a population
of about 5000 inhabitants. Mullens, where mining began in 1912, is situated in
east-central West Virginia, 100 miles east of Charleston. Mining has been carried
56
-------
Table 26. POPULATION SURVEYS OF BRONCHITIS AND VENTILATORY CAPACITY IN MEN WORKING IN
HIGH-DUST-EXPOSURE OCCUPATIONS
Country
England
Leigh
Staveley
Wales
Rhondda
USA (West
Virginia)
Marion County
Mullens
Richwood
Canada
South Africa
Northern Ireland
Author and year
Higgins et al . ,
1956
Higqins et al . ,
1959
Higqins et al . ,
1961
Hiqqins et al . ,
1968
Enter line,
1967
Enterline,
1967
Parsons et al . ,
1964
Sluis-Cremer
et al..
1967
Pemberton et
al_. , 1968
Refer-
ence
214
98
243
111
376
376
377
235
378
Industry
Coal mining
Coal mining
Foundry work
Coal mining
Coal mining
Coal mining
Coal mining
Fluorspar
Gold mining
Flax
Age
55-64
55-64
55-64
35-64b
20-79b
21-64b
21-64b
20-70b
^35b
^35
Sample
population
HDEa
132
149
64
275
425
225
175
301
546
262
Control
84
81
81
262
399
224
153
56
263
594
Incidence of
bronchitis, %
HDE
23.5
20.8
7.8
28.5
4.8
nac
13. Od
8.9
21.3
10.6
12.6
Control
10.7
14.8
14.8
9.2
4.0
na .
6.5d
9.1
4.0
3.8
5.6
Ratio,
HDE/C
2.2
1.4
0.5
3.1
1.2
na
2.0
1.0
5.3
2.8
2.3
Ventilatory capacity
HDE
2.17
2.44
2.36
2.53
3.41
3.01
3.29
2.86
3.12
na
Control
2.39
2.52
2.52
2.87
3.53
3.18
3.28
3.09
3.27
na
Difference,
HDE-C
-0.22
-0.12
-0.16
-0.34
-0.12
-0.17
+0.01
-0.23
-0.15
na
HDE = high dust exposure; C = control.
Age-adjusted to the total population in the study.
°Not available.
Cough and sputum for - 3 months.
-------
on in that community since 1940. Representative samples of miners and other
workers aged 21 to 64, arid their wives, were studied using standardized methods
that included questionnaires and simple ventilatory lung function tests. In Mullens,
miners had a higher prevalence than nonminers of respiratory symptoms, particu-
larly cough, wheezing, and breathlessness; previous history of pneumonia and
pleurisy; and lower mean ventilatory lung function. In Richwood, no difference was
found between miners and nonminers in either symptoms or lung function. In
Mullens, miners' wives also had a higher prevalence of symptoms and past chest
illnesses, but in Richwood there were no differences between the wives of miners
and the wives of other men.
Higgins and his colleagues *• '-^ studied mining communities in Marion County in
northern West Virginia, where they found a slightly higher prevalence of respiratory
symptoms and lower ventilatory lung function only in miners aged 50 years and
over. The findings in these two surveys suggest that any differences in respiratory
symptom prevalence and lung function between miners and nonminers in these areas
are small. The areas studied may not, however, be representative of all mining
areas in the United States. For example, Hyatt and his colleagues reported a
much higher prevalence of respiratory symptoms in a sample of miners selected
from labor union records. This was associated with a high prevalence of pneumo-
coniosis. It is possible, therefore, that differences in dust dosage might have ac-
counted for the differences in respiratory disease found. The FEV appeared, how-
O O *•?
ever, to be rather similar in this study to that found by Higgins and his colleagues,
so that observer variation cannot be excluded as a contributing factor in the differ-
ences found in symptom prevalence.
That there may be regional differences in the amount of respiratory disease
found in different areas is well recognized. Regional differences in Britain have
been discussed by Cochrane and his colleagues. Differences in the prevalence
of pneumoconiosis among different areas have been noted by Lieben and McBride, "'
Lainhart, 39°' 391 and by O'Shea and his colleagues. 15°
Beckenkamp3 ' has stressed the fact that choice of occupation may play an im-
portant role in determining the prevalance of disease in particular occupational
groups. Mine entrants in Germany during the 1950's and 1960's, for example,
tended to be shorter, lighter, and less physically fit and mentally able than men
entering other occupations. In a study conducted in the Rhondda Fach (Wales), how-
ever, Higgins and his colleagues found no evidence to support the hypothesis that
mine entrants at that time were physically less able than men taking up other jobs.
They pointed out that such selection could have occurred in the past but that there
was no -way now of establishing that fact.
Miners with pneumoconiosis versus miners without Conflicting results have
been obtained for the prevalence of bronchitis in miners with and without pneumo-
coniosis. In the United Kingdom, Hart and Aslett393 found that among Welsh coal
miners aged 40 to 64 years, the prevalence of chronic bronchitis increased with
radiological category. Newell and Brown concluded from a study of 5117 working
coal miners in four collieries in County Durham that symptoms and disability, as
measured by withdrawal from coal-face work to less strenuous employment, were
not related to the radiographic category of pneumoconiosis. In Germany, Traut-
man ' found that in "silicosis" Stages I and II the prevalence of bronchitis was not
especially high, but that in Stage III it might reach 60 percent. Beckman395 found
a higher prevalence of bronchitis in those with "silicosis" than in those without,
58
-------
while Zorn, ^°6 and Worth and Dickmans " ' noted an increase in prevalence of
bronchitis with increase in grade of "silicosis. " On the other hand, Bohme and
Lent, ^ studying a group of miners -who -were no longer capable of -work, found a
higher prevalence of bronchitis in those -without "silicosis" than in those -with Stages
I and II. Reichel and his colleagues ^9° reviewed the German literature on obstruc-
tive bronchitis in miners and reported findings for 674 miners \vithout pneumoconi-
osis, 645 miners with various categories of pneumoconiosis, and a comparative
group of 946 workers in the steel industry. They found a higher prevalence of
cough and sputum among the miners than among the steel workers. There was no
consistent relationship between the prevalence of cough and sputum and the x-ray
category of pneumoconiosis. A lower prevalence of cough and sputum was noted,
for example, among those having pneumoconiosis of radiographic categories B and
C than among those with pneumoconiosis of categories O to A. Persons exposed to
mine dust had slightly increased lung volumes and slightly reduced arterial oxygen
tensions regardless of x-ray category. Increased airflow resistance -was found on-
ly in those with advanced pneumoconiosis. The authors concluded that the chronic
obstructive bronchitis observed was not caused mainly by exposure to mine dust.
It is clear that the findings may be influenced greatly by the choice of population.
In a series of studies of representative samples of mining communities, for in-
stance, Higgins and his colleagues^" > 2 14, 243founcj little difference in the prevalence
of bronchitis or in the mean FEVg 75 between those -with and those -without simple
pneumoconiosis.
A slightly higher prevalence of respiratory symptoms and lower ventilatory
lung function in those -with simple pneumoconiosis was noted by Ashford and his col-
leagues '" in their studies of 30, 000 coal miners in Britain, and by Hyatt™-> and
Higgins-'-1 1 in the United States.
In a. survey of some 3700 -working and non-working Appalachian coal miners,
Lainhart and his colleagues found that the prevalence of breathlessness and per-
sistent cough and sputum -was higher in those with pneumoconiosis than in those
without. The difference in cough -was confined to -working miners and the difference
in breathlessness was small — about twofold--but there -was no standardization for
age. The prevalence of these symptoms also increased with the duration of under-
ground -work. Ventilatory lung function, especially the FEV, appeared to be lower
than expected in miners irrespective of their category of pneumoconiosis. The
discrepancy between observed and predicted FEV values was slightly greater for
those with x-ray changes in pneumoconiosis than for those without. There appeared
to be a progressive decrease in lung function with increasing duration of under-
ground work. This partly reflected age differences, but some decline persisted
after these were allowed for. Brasseur^OO concluded in a study that micronodular
or nodular categories of simple pneumoconiosis are associated with a decrease in
ventilatory function and that, from category 1 to category 3 pneumoconiosis, a rise
in pulmonary arterial pressure is seen, but that these changes are insufficient to
affect a man's working capacity.
It seems reasonable to conclude that any effect simple pneumoconiosis may
have on either symptom or bronchitis prevalence or ventilatory lung function is
small. This conclusion is supported to some extent by^ the study by Caplan and his
colleagues, who examined 100 chest radiographs of miners with no pneumoconi-
osis and of those with categories 1, 2, and 3 simple pneumoconiosis for radiological
evidence of emphysema. There was no evidence .that radiologically detectable em-
physema was related to dust deposition in the lungs. Certain observations on miner
59
-------
mortality also support these findings. Cochrane and his colleagues °2 studied the
mortality of miners and ex-miners living in the Rhondda Fach during the 6-year
period, 1950 to 1956. Miners there had a higher mortality from all causes, partic-
ularly from respiratory diseases, than nonminers. The highest mortality rates
were found among miners with progressive massive fibrosis. The radiographic
category of simple pneumoconiosis was not, however, related to mortality.
Relation of respiratory symptoms and lung function to duration of underground
and coal-face work A number of attempts have been made to relate the prevalence
of respiratory symptoms, bronchitis, and ventilatory lung function to long-term
dust exposure by comparing miners who spent different periods in either under-
ground or coal-face work. The results have been conflicting, some having shown
a reduction in lung function and an increase in symptoms with increasing duration
of exposure, 205, 243, 381, 386, 391,403,404 but others having shown little or no such
effect. 2^8 It seems safe to conclude that the dose/response relationships bet-ween
dust exposure, when this is assessed by lifetime exposure, and the prevalence of
-symptoms or level of lung function are inconsistent. There are many reasons -why
this could be true: (1) the numbers studied have usually been small and thus liable
to random fluctuation; (2) the small numbers have precluded adequate standardiza-
tion for smoking; (3) selection into and out of each exposure category may be occur-
ring for respiratory reasons; and, above all, (4) those capable of working in dust
for 20 years or more must be the healthier survivors of those -who originally started
to -work in mining. Possibly more important than any of the findings, however, is
the concept that respiratory symptoms should be determined by a lifelong duration.
of dust exposure rather than by present concentration. In analyses based on this
principle, concentration differences in exposure are ignored; therefore this factor
may not be appropriate. Although a relationship has been demonstrated between
prevalence of cough and sputum and current number of cigarettes smoked, no cor-
relation was attempted between these symptoms and duration of smoking.
235
Gold Miners - Sluis-Cremer and his colleagues studied gold miners living in a
community in the Transvaal, Republic of South Africa. Miners were compared
with nonminers in a study of 827 men aged 35 years and over who lived in Carlton-
ville on the Witwatersrand. Chronic bronchitis was more prevalent in smoking
miners than in smoking nonminers for every age category, but this difference was
not found in nonsmokers. Chronic bronchitis was slightly more prevalent in those
with silicosis than in those without, but the difference was small and statistically
insignificant. The prevalence of bronchitis -was related to duration of occupational
exposure to dust. The greatest difference in prevalence appeared to be between
those with less than 1 year of service, in whom bronchitis was less prevalent, and
those with 1 year or more. This observation .is similar to those made by Higgins
and Cochrane in studies of coal miners in the Rhondda Fach in South Wales, and
by Hyatt and his colleagues in West Virginia, United States. Together these
observations might suggest that the influence of dust exposure is relatively acute,
which would corroborate the observation by Newell and Browne213 in 1955 that
there might be a sudden increase in symptoms in coal miners within about 5 years
of starting coal-face work.
In a further paper on ventilatory lung function in the same group of men, Sluis-
Cremer and Sichel405 showed that there was no difference in FEVj 0 between
those exposed and those not exposed to dust, though somewhat lower values
were found in those with bronchitis compared with the others. In this respect,
60
-------
their study would seem to differ from other studies in -which the ventilatory capaci-
ty in British coal miners has been found to be lower than that in nonminers.
An important study designed to correlate clinical, radiological, and physiolog-
ical findings in life with post-mortem findings in the lungs was recently reported
by Ryder and his colleagues. 406 Observations were made on 247 coal miners who
died between July 1965 and May 1967 and who, at the time of death, lived in an area
of East Glamorgan, South Wales, A control group matched for age and sex was
drawn from 1000 necropsies performed from 1964 through 1966 at the Cardiff Royal
Infirmary. All the miners had been examined by the pneumoconiosis panel and
most of them -were receiving compensation for disability from pneumoconiosis.
Emphysema -was found approximately three times as frequently among the miners
as among the nonminers. It -was slightly more severe in those men whose chest x--
rays had been categorized B or C than in those with categories O through A, but
there were inconsistencies within the individual age groups, particularly among
men aged 60 to 69 (the largest group), in -whom the mean emphysema count was
slightly less in those of categories- B and C than in the rest. Extensive emphysema
was found somewhat more often in men whose x-rays showed simple punctiform
pneumoconiosis than in those with micronodular or nodular opacities. The extent
of the emphysema was closely related to ventilatory impairment as indicated by the
1-second FEV test. Ryder's survey indicates that in this group of men emphysema
was more frequent in miners than in other men but that it was poorly related to the
radiological category of pneumoconiosis. The study has been criticized on the
grounds that the sample of miners studied -was unlikely to be representative of all
miners. Fletcher^O? noted the lack in Ryder's study of any appreciable age gradi-
ent in emphysema and FEV levels. Gilson and Oldham pointed out that the re-
lationship bet-ween age and radiological category of pneumoconiosis that Cochrane
found in the Rhondda Fach -was not seen in Ryder's study. These commentators
also noted that in comparing emphysema counts from x-rays that showed puncti-
form pneumoconiosis -with those that showed microno'dular and nodular types insuf-
ficient attention had been paid to age.
Uranium Miners - Archer and his colleagues '' studied the prevalence of
respiratory symptoms and lung function in relation to ionizing radiation in uranium
miners. They found an increase in the prevalence of persistent cough, shortness
of breath, emphysema, and penumoconiosis with increasing duration of underground
work. Their lung function results are difficult to interpret. After age and ciga-
rette smoking were taken into consideration, ventilatory lung function was found
to be lower than normal in those who had received a higher dose of radiation during
their working lives; however, the FEV values were higher in those currently ex-
posed to high radiation levels. The authors suggest that either selection of men
with lower ventilatory lung function for jobs involving high radiation exposure or a
possible beneficial effect of such exposures on bronchiospasm could explain the
findings. They conclude, however, that long-term exposure to radiation adds to
the loss in ventilatory function produced by aging and smoking.
Other Metal Miners - In 14, 076 currently employed metal miners in the United
States, Flinn and his colleagues** studied ventilatory function and prevalence of
respiratory symptoms and chest illnesses in relation to age; duration of occupation;
x-ray changes attributable to silicosis; and smoking habits. They found that breath-
lessness increased with age from below 5 percent in men under 35 years to 18. 4
percent in those 55 years and over. Breathlessness was twice as prevalent in those
with simple silicosis as in those without. It also tended to increase with
61
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increasing duration of employment in the industry. The prevalence of bronchitis
increased slightly with age and was somewhat greater in those with silicosis. The
relationship to ventilatory lung function of age, smoking, and duration of employ-
ment at underground mining was studied. Aging was found to have the largest effect;
thus, between the ages of 35 and 55 years there was a reduction of 23 percent in
FEV, Q. This compared with a reduction of 10 percent attributable to heavy smok-
ing and 2 percent attributable to 20 years of underground mining. The authors con-
cluded that complicated pneumoconiosis probably had almost as much effect on pul-
monary function as 20 years of aging and that cigarette smoking was of considerable
importance compared with silicosis, although the tables presented by the authors
do not indicate how this conclusion was reached. Simple silicosis was shown to be
associated with a reduction of 4 percent and complicated silicosis with a reduction
of 10 percent of observed as opposed to predicted FEV. This reduction appears to
be the same as that attributed to heavy smoking but only about half that attributed
to aging.
41 2
Pyrites Miners In 1969, Sartorelli and his colleagues compared respiratory
symptoms and ventilatory lung function in 984 miners working in a pyrites mine in
Tuscany, Italy, with symptoms and function in 345 control •workers who lived in
the same area but who were not exposed to dusts or irritant gases. Chronic bron-
chitis \vas defined as presence of persistent cough and sputum for 3 months in the
year for 2 or more successive years; physical signs of bronchitis on chest exam-
inations; or a reduction in FEVj Q of more than 15 percent in comparison with ex-
pected, predicted normal values. Clear effects from both smoking and occupation
were shown. Among nonsmoking miners, the prevalence of bronchitis was 6.8,
17.8, and 23.2 percent at 18 to 35, 36 to 50, and 51 to 68 years, respectively, com-
pared with 0.0, 3.3, and 5.5 percent for these age groups in nonsmoking controls.
Among smokers of 1 to 15 cigarettes per day, the findings in miners were 13.0,
32.7, and 39.8 percent compared with 3.8, 11.7, and 25 percent in controls. Among
the heavier smokers (15 cigarettes per day and over), the corresponding figures
were 31.8, 38.6, and 57.5 percent for miners and 4.0, 20.5, and 44. 4 percent for
controls. There was no significant difference in this study between miners with
simple pneumoconiosis and those without. The higher prevalence of bronchitis and
lower lung function in the pyrites miners was attributed to dust, sulfur dioxide, and
thermal gradients, especially before ventilation was improved and dustiness re-
duced in 1963 and 1964.
Foundry Workers The situation is perhaps even less clear in foundry workers
than in miners. Keatinge and his colleagues compared foundry workers with
wagon builders. They found a higher prevalence of bronchitis in the foundry work-
ers (20.6 percent) than in the wagon builders (14.9 percent). The foundrymen,
however, lort less time from work for this cause than the wagon builders. Some
of the difference was probably attributable to smoking since a higher proportion
of the foundrymen were smokers. These workers suggested that the excess bron-
chitis mortality observed in foundry workers and their wives was the result of the
geographical distribution of foundries rather than of the work carried out in them.
Higgins and his colleagues^" studied foundry workers, as well as coal miners and
other workers not exposed to dust or fumes, from a representative sample of the
population of Staveley, Derbyshire, England. Men who had been employed in foun-
dry work only did not differ in prevalence of respiratory symptoms or in FEVg. 75
from men who had never been exposed to dust, but foundry workers who had also
worked in mining and other dusty jobs had more prevalent symptoms and a lower
FEVQ.75 than the corresponding nonexposed workers. Insofar as mining is
62
-------
associated with respiratory symptoms and reduced lung function, this might have
been expected. Alternatively, those who move from job to job may be more liable
to respiratory disease than those who are more stable, or those who move may do
so because of their ill health.
In a further study of the same town, the original sample was followed up after
9 years. At the same time, a new sample similar to that originally seen, but strat-
ified by age and occupation, was also studied. ° A higher mortality in foundry
workers was noted over the 9 years, particularly in the foundry workers who had
simple pneumoconiosis. The mean FEV of those followed up was slightly lower in
the foundry workers than in the group not exposed to dust, but the decline in FEV
over the years appeared to be no different in the two groups. Among the foundry
workers, however, those with simple pneumoconiosis had a lower average FEV and
a somewhat greater average annual decline than those without. In the new cross-
sectional study, the foundry workers recorded a slightly higher prevalence of
breathlessness, chest illness, and chronic bronchitis--defined as persistent spu-
tum and at least one chest illness in the past 3 years--than non-dust-exposed work-
ers, but a similar prevalence of persistent cough and sputum (Table 27). They
also recorded slightly lower average lung function values.
The findings in these surveys may be compared with a study carried out by
Lloyd-Davies. In a sample of 1 to 40 foundries in Great Britain, he surveyed
1911 men aged 35 to 64 and succeeded in examining 93.0 percent of them. After
differences in smoking habits were taken into account, the prevalence of bronchitis
was shown to be slightly but significantly higher in foundrymen than in men of sim-
TABLE 27. RESPIRATORY SYMPTOMS AND VENTILATORY LUNG FUNCTION
BY OCCUPATION, IN MEN AGED 25-74 IN STAVELEY. ENGLAND, 1966a'191
Sympton
Cough
Sputum
Cough and sputum
Wheezing (most of time)
Breathlessness
Grade 2 and over
Grade 3 and over
Chest illness within
past 3 years
(Duration of > 1 week)
Chronic bronchitis
Mean FEV, liters
Mean FVC, liters
Mean FEV, percent
Occupations with no
dust exposure
n=159
32.8
31.1
27.0
5.9
12.9
1.5
5.8
2.7
2.84
4.15
67.9
Miners and
ex-miners
n=179
45.2
51.8
38.1
18.1
30.9
13.9
23.6
17.4
2.56
4.01
62.4
Foundry and
ex-foundry workers
n=97
32.7
40.9
27.3
5.9
16.9
5.7
15.4
14.1
2. -69
. 4.13
64.6
Other
n=443
42.9
47.7
35.4
12.3
18.1
7.4
20.3
14.3
2.67
4.11
64.2
Age-adjusted to the total population.
-------
ilar age employed in factories. The regression of FEV on age showed a steeper
decline in foundrymen than in other workers.
Steel Workers - In a survey of a group of 20,000 South Wales steel workers, Lowe
and his colleagues415 used standard survey procedures and carried out a compre
hensive environmental study. Both dust and sulfur dioxide (SO2> were present in
the steel mills and the men were categorized into four groups according to whether
they were exposed to: (1) high dust and high SOg; (2) high dust and low SC>2; (3) low
dust and high SC>2; or (4) low dust and low SO2- No relationship was found between
ventilatory capacity or respiratory symptoms and exposure to either dust or SC>2
in this study.
Other Furnace and Chemical Workers Higgins and his colleagues^" found a high
prevalence of respiratory symptoms and low lung function in a number of other
groups in their study in Staveley, England. Furnace workers and chemical work-
ers have a high prevalence of symptoms and a low average FEV. Coke-oven work-
ers did not appear to differ greatly from non-dust-exposed workers in their expe-
rience of respiratory symptoms, but they had a lower FEV. More detailed analyses
of these groups suggested that, apart from the particular occupations mentioned,
these men had also been exposed to dust in other jobs. To some extent, their
respiratory condition may therefore be attributed to mixed exposures. In addition,
the chemical workers tended to be heavy smokers and this must have contributed
to their disease.
Doll and his colleagues, in a study of all employees and pensioners of four
London area gas boards, showed that degree of exposures in coke-carbonizing and
other gas-producing plants is related to mortality from lung cancer and bronchitis.
Death rates from bronchitis were 126 percent higher in the most highly exposed
groups than in those not exposed.
Textile, Grain, and Vegetable-product Workers Textile workers have long been
known to suffer from a high prevalence of respiratory disease. * '<4^ ° While
byssinosis, the specific occupational disease, is responsible for some of the
symptoms in workers exposed to cotton, flax, and hemp, 19-422 ^ seems ciear
that exposure to such dusts may also result in the production or exacerbation of
respiratory symptoms characteristic of bronchitis. '' Exposure to
cotton, flax, and hemp dust may result in a reduction in ventilatory function during
the working day. 424, 427-430 Apparantly this reduction does not occur in persons
exposed to man-made fiber s. 43*> 432 The decline is greatest on Mondays, which
is the first day of return to work after absence from the mill, and becomes pro-
gressively smaller during the week. While the decline is usually greater in those
subjects who are diagnosed as having byssinosis, it may also occur in persons
without symptoms. The daily changes in ventilatory function may eventually lead
to permanent disability and low ventilatory lung function.
Some studies have been conducted of workers who were exposed to mixtures of
vegetable dusts. For example, Smith and his colleagues433 observed that in both
men and women the prevalence of persistent cough and phlegm was higher and ven-
tilatory lung function was lower in those who worked amid higher concentrations of
flax and hemp dust than in those exposed to lower concentrations.
64
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Cough, dyspnea, wheezing, and "grain fever, " which is characterized by mal-
aise, chills, and fever that usually occur several hours after the employee leaves
work, has been noted by Kleinfeld and his colleagues^4 in grain handlers. A pre-
vious history of pneumonia, dermatitis, or peptic ulcer was commoner in these
workers than in the general population. Age, duration of dust exposure, allergy,
and smoking were predisposing factors. In a similar study of grain handlers,
Skoulas and his colleagues435 aiso observed that these symptoms increased with
age, duration of service, and increased smoking. They noted that barley dust ap-
peared to be the most pathogenic grain handled and that pathogenicity of grain dusts
decreased in the order oats > rye > wheat. A previous history of allergy -was found
in a. high proportion of cases. A reduction in ventilatory capacity within half an
hour of starting work was observed by Gandevia and Ritchie^o in men exposed to
•wheat dust; these researchers also demonstrated a similar though smaller decline
in men exposed to phosphate dust. The decreases were greater, or more consist-
ent, in men who had persistent cough and sputum or who had a "productive cough
on request" than in other -workers.
Allergic sensitivity to various dusts is well recognized. Asthma and dermati-
tis or rhinitis, for example, have been shown to result from exposure to various
wood dusts. ' 44J-The allergic reactions that may occur as a result of inhalation
of organic dusts have been summarized by Pepys. 442 Such reactions are charac-
teristic of those seen in farmer's lung, baggassosis, and pituitary snuff taker's
lung; and of those that occur among mushroom-compost and other -workers, and
among bird fanciers. Precipitating antibodies to the appropriate antigens are usu-
ally present in these cases. The main features of this group of respiratory dis-
eases are summarized in Table 28. 276,443-465
Workers Exposed to Toluene Di-isocyanate - Exposure to toluene di-isocyanate (TDI)
results in changes in ventilatory lung function during the course of a working day
and over longer periods of time. ' ' In studying 34 workers exposed to TDI,
Peters and his colleagues °° noted a decline of 0. 16 liter in FEVj Q during the day
that did not return to the base line by the following day. Follow-up after 6 months
showed that there was a high correlation between the total decline in FEV over this
period, and the daily decline. The rate of decline over 6 months -was much greater
than would have been expected on the basis of other studies of samples of the gen-
eral population. Subsequently, Peters and his colleagues^' 0 reviewed this same
group of workers after 18 months. They noted an increasing decline in FEV that
•was greater in workers -with respiratory symptoms than in those without. The
similarity of the changes' occurring during the day upon exposure to TDI to those
resulting from exposure to certain vegetable dusts suggests that elucidation of the
mechanism of reduction of lung function in TDI exposure might shed light on the
mechanism of decline in other conditions as well. It is also possible that there
may be other substances that could affect the lungs in a way similar to TDI.
ALLERGIES
Reactivity to Common Allergens
Turner -Warwick has recently (1969) reviewed hyper sensitivity mechanisms
and discussed the characteristics of each type. 4'1 Reaginic hypersensitivity,
which is more often important in asthma caused by external allergens than in other
conditions, is described as having the following characteristics: (1) the reagin binds
strongly and lastingly to cell surfaces; (2) the reagin is not precipitating, agglutin-
ating, or complement-fixing; (3) the Prausnitz-Kustner reaction gives an immedi-
ate flare and wheal; and (4) IgE immunoglobulins are increased in about 60 percent
65
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Table 28. EXTRINSIC ALLERGIC ALVEOLITIS
Alveolitisa
Farmer's lung
Bagassosis
Mushroom worker's
lung
Foa-fever in
cattle
Suberosis
New Guinea
lung
Maple-bark
pneumonitis
Malt worker's
lung
Bird fancier's
lung
Pituitary snuff
taker's lung
Wheat weevil
disease
Sequoiosis
Source
of antigen
Moldy hay
Moldy bagasse
Mushroom
compost
Moldy hay
Moldy oak bark
cork dust
Moldy thatch
dust
Moldy maple
bark
Moldy barley;
malt dust
Pigeon; bud-
gerigar; par-
rot; hen
droppings
Heterologous
pituitary
powder
Infested wheat
flour
Moldy redwood
sawdust
Antigen of
precipitins present
Micropolyspora
faeni
Thermoactinomyces
vulgaris
T. vulqaris
M. faeni and T.
vulgaris
M- faeni
Moldy cork dust
Thatch of huts
Cryptostroma
(Coniosporium)
cortical e
Aspergil lus
clavatus
Aspergillus
fumiqatus
Serum protein and
droppings antigens
Serum protein and
pituitary antigens
Si tophi lus
granarius
Graphium, Aureoba-
sidium pul lulans
(Pullularia)
Author and year
Pepys and Jenkins,
1965
Kobayashi et al . ,
1963
Emanuel et al , 1964
Salvaqgio et al . ,
1967
Hearn and Holford-
Strevens, 1968
Hargreave, Pepys, and
Holford-Strevens,
1968
Sakula, 1967
Jenkins and Pepys,
1965
Avila and Villar,
1968
Blackburn and Green,
1966
Emanuel et al . , 1966
Riddle and Grant, 1967
Vallery-Radot and
Giroud, 1928
Filip and Barborik,
1966
Reed et al . , 1965
Hargreave et al . ,
1966
Fink et al., 1967
Stiehm et al . , 1967
Pepys et al . , 1966
Mahon et al , 1967
Lunn, 1966;
Lunn and Hughes, 1967
Cohen et al.. 1967
Refer-
ence
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
276
465
Probable similar diseases include
Foreman, 1963;466 and (2) paprika
(1) smallpox handler's lung, Morris-Evans and
splitter's lung, Hunter, 1959.467
of the cases to a mean level about six times greater than normal. The measurement
of IgE immunoglobulins is valuable in differentiating between allergic and nonaller-
gic asthma in which skin tests are negative, since in the latter condition normal or
low IgE values have been found. Nonreaginic hyper sensitivity may cause asthma
66
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that comes on 4 to 5 hours after exposure to antigen. Precipitating, heat-stable
antibody, characteristic of Type III arthus reactions, can usually be demonstrated.
A delayed response to skin testing or inhalation challenge usually takes place.
Sometimes both immediate and delayed responses occur; this dual asthma response
is usually associated with dual responses to skin or inhalation challenge.
Eosin op hi li a
Blood and tissue eosinophilia is found in both intrinsic and extrinisic types of
asthma. Recent experimental work suggests that the marrow stimulus for the pro-
duction of eosinophils is mediated by lymphocytes, but their role in the asthmatic
reaction is as yet unknown.
The tendency to allergy may be indicated by positive skin tests to common al-
lergens or by blood or tissue eosinophilia. In addition to these two manifestations,
hyperreactivity of the bronchial tree is often considered to be further evidence of
an allergic tendency. Van der Lende24 studied the relation of respiratory symp-
toms to each of these indices of allergy in three communities in The Netherlands.
The skin test was considered in his study to be positive if a positive reaction was
obtained to at least one of four allergens. An allergy score based on both the num-
ber of positive skin tests and the degree of reaction was also used. Neither of
these indices appeared to be related to age, sex, or the presence of respiratory
symptoms. In the most polluted community, however, a considerably higher pro-
portion of positive skin reactions was observed than in the other two communities.
In women studied, the mean number of eosinophils in the blood was higher in
those with respiratory symptoms than in those without. In men, however, a simi-
lar difference "was suggested in only one of the three communities, and even here
the difference between those with symptoms and those without was small and statis-
tically insignificant. When the population was classified according to the presence
or absence of blood eosinophilia (defined as >_ 276 eosinophils/mm^), respiratory
symptoms -were more prevalent in those with eosinophilia than in those -without.
The differences were larger for those -who had wheezing and asthmatic attacks than
for those with persistent cough, sputum, or breathlessness.
Bronchial Hyperreactivity
Van der Lende used histamine inhalation studies to assess hyperreactivity of
the bronchial tree. A positive test was defined as a decrease of 10 percent or more
in the FEVi Q or FVC upon inhalation of a concentration of histamine solution of 32
pg/ml or less. Hyperreactivity was found to be more frequent in those with respir-
atory symptoms than in those without. The proportion of positive reactors increased
•with age both for those without as well as for those with symptoms, although the
trend with age was less consistent for the former group.
These observations seem to indicate that allergy as indicated by standard skin
tests plays a rather small role in most cases of chronic obstructive, respiratory
disease, a conclusion that has been reached by other worker s. 472, 473 On the other
hand, both iosinophilia and bronchial hyperreactivity appear to be associated with
symptomatology. The time relations of the associations are as yet inadequately
defined, although there are some indications that the symptoms follow the consti-
tutional predisposition of the individual. ' Some researchers, however, have
noted that the tendency to hyperreactivity is not highT correlated with the occurrence
67
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of allergy. ~ It seems clear, therefore, that more attention should be paid in
future epidemiological studies to these aspects of respiratory disease.
SMOKING
The role of smoking in the pathogenesis of chronic respiratory disease has been
reviewed so thoroughly in reports issued by the Surgeon General, U.S. Public Health
Service, 27,28,479,480 that any attempt at comprehensive coverage here is clearly
unnecessary. Instead, a number of aspects of smoking and respiratory disease will
be surveyed with a view to reaching some conclusions on what further research is
needed.
Mortality Rates
The higher mortality rates for bronchitis and "other diseases of the respiratory
system" in men compared with women have long been apparent in the vital statistics
of the United States and of other countries. Occupational exposures and smoking,
especially cigarette smoking, seem to be the two most likely explanations for these
sex differences. Evidence accumulated in recent years indicates that smoking is
the more important of the two factors. It should be noted, however, that male chil-
dren in Britain have a higher mortality from bronchitis than female children. To
the extent that this occurs before any significant smoking is indulged in, it indicates
that other factors, possibly constitutional in character, must be involved. Rela-
tively little attention has been paid to trends in the sex ratio of mortality during the
past few decades. The studies of Crofton and Crofton240 have already been men-
tioned. Fletcher4"^ has pointed out that the trends in the male/female mortality
ratios for bronchitis since 1916 in England and Wales have been similar to the male/
female mortality ratios for lung cancer. It is likely that both trends are the result
of the same cause or similar causes. Arguing by analogy, the most likely cause is
cigarette smoking. Similar studies would be useful in countries where there are
adequate vital statistics, notably the United States.
Prospective studies of mortality in relation to smoking habits have indicated
that smoking is an important factor in death from chronic respiratory disease.
Seven prospective studies were combined in the Surgeon General's Report34 to ob-
tain mortality ratios for bronchitis and emphysema for smokers and nonsmokers.
Cigarette smokers had a mortality ratio for these diseases that was 6. 1 times that
of nonsmokers. Within different studies, the ratios varied from 2. 3 in men in nine
states to 12. 5 in British doctors (Table 29).27
Subsequently, Kahn published the results of an 8-1/2-year follow-up of mor-
tality in United States veterans. The age-adjusted mortality ratios found in this
study for various categories of respiratory disease according to smoking habits are
shown in Table 30. The ratios increased most markedly for deaths certified as re-
sulting from emphysema (527. 1), but only a slight increase occurred in ratios for
deaths attributed to bronchitis with or without emphysema (500 to 502). It is inter-
esting that the converse situation was found in Canadian veterans;4**3 this finding
suggests again that diagnostic practices in the United States and Canada differ.
In the 10-year follow-up of mortality in British doctors, a pattern of chronic
bronchitis mortality similar to that of lung cancer was found. 4&4 The gradient in-
creased with increased smoking, was higher in cigarette smokers (particularly in
inhalers), and declined in those who gave up smoking. The standardized death rates
68
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Table 29. MORTALITY RATIOS FOR BRONCHITIS (502)
AND EMPHYSEMA (527.1), BY SMOKING HABIT,
IN SEVEN PROSPECTIVE STUDIES9
Study-
British doctors
Men in 9 states (U.S.)
United States Veterans
California occupational
California Legion
Canadian veterans
Men in 25 states (U.S.)
Total
Mortality ratios
for ciaarette smokers'3
12.5
2.3
9.8
4.3
8,4
4.6
7.5
6.1
aDerived from Reference 27.
Ratio for nonsmokers = 1.0.
for bronchitis, including emphysema (502, 527. 1), and mortality ratios at the end
of 10 years of observation in the study of British physicians are shown in Table 31
for comparison. The ratios are remarkably similar to those for United States vet-
erans.
67
Hammond determined the mortality rates for bronchitis and emphysema in
women according to their smoking habits on the basis of a. sample of 1 million men
and women in the United States. The ratios for cigarette smokers are somewhat
lower in -women than in men in this study.
Morbidity Rates
Many studies of Jaoapital and clinic patients, 118,241,256,485-490 of working
groups, 86, 90,106, 201,^10, 219, 244,491,492 representative samples of the commun.
ityf 24, 98, 199, 205, 214, 215, 243, 493 total communities, 206, 224, 494-496 andmis-
cellaneous groups'*' ' have shown that smoking is an important factor in the preval-
ence of respiratory disease. In many of these studies, standardized methods have
been used and the relationship of smoking to various symptoms, as well as the re-
lationship of certain clearly defined indices of bronchitis, have been presented.
These studies, many of which are admirably reviewed in the Surgeon General's
Report, should perhaps be summarized briefly. In both men and women the pre-
valence of cough and sputum is higher in smokers than in nonsmokers and increases
with the amount smoked. The findings are much less consistent for other respira-
tory symptoms. Wheezing in the chest often shows a trend which is similar, though
much less marked, to that seen for cough and sputum. The similarity may exist
in part because some of the wheezing reported is caused by sputum in the respira-
tory tract. Chest illnesses during the past 3 years, breathlessness, bouts of
coughing lasting 2 weeks or more--standard symptoms questioned in surveys--
though usually more prevalent in smokers than in nonsmokers, have often been
69
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Table 30. MORTALITY RATIOS FOR RESPIRATORY DISEASES, BY SMOKING HABITS,
IN UNITED STATES VETERANS3
Disease
Bronchitis
Emphysema
Other respiratory
diseases
ISCb
(500-502)
(527.1)
(470-475,
510-526,
527.1)
Nonsmokers
1.0
1.0
1.0
Current cigarette consumption,
cigarettes/day
1-9
2.13
5.58
1.36
10-20
4.34
11.94
1.25
21-39
4.01
16.27
1.57
>40
6.91
20.86
2.50
Total
2.86
9.09
1.22
Ex-smokers
2.48
9.15
1.26
Pipe and/or cigar
only
0.48
1.34
0.69
aAdopted from Kahn.482
International Statistical Code.
-------
Table 31. STANDARDIZED DEATH RATES AND MORTALITY RATIOS,
BY SMOKING HABITS, FOR CHRONIC BRONCHITIS IN BRITISH DOCTORS
Smoking habits
All men
Nonsmokers
Cigarette smokers
1-14/day
15-24/day
25 and over
All amounts
Ex-cigarette smokers
Mixed smokers
Pipe and cigar smokers
Chronic bronchitis
(n HI)
Rate,
deaths/1000
0.34
0.05
0.34
0.64
1.06
0.58
0.38
0.33
0.15
Ratio
6.8
1 .0
6.8
12.8
21.2
11 .6
7.6
6.6
3.0
Chronic bronchitis
in association with
cardiovascular disease
(n = 55)
Rate,
deaths/1000
0.17
0.03
0.15
0.20
0.30
0.21
0.16
0.21
0.12
Ratio
5.7
1 .0
5.0
6.7
10.0
7.0
5.3
7.0
4.0
Adapted from Doll and Hill.
484
found to be inconsistently related to the quantity of tobacco smoked. An explanation
that has been offered and that seems plausible is that smokers are likely to reduce
their smoking when they develop breathlessness or chest illnesses that are more
disabling than a mere "smoker's cough. " This selection out of the category of less
fit heavy smokers into the lighter smoking group could account for the inconsistent
findings. Such an explanation needs to be tested, however, and to date there have
been few attempts to measure this and various other forms of selection that are
believed to occur.
Lung Function Tests
The vast majority of epidemiological results refer to some measurement of the
ventilatory capacity, the most widely used of which has been the measurement of
forced expiratory volume. 81,98,109,199,200,202,206,207,224,255,262,367,498-501
A considerable number of surveys, however, have-used the peak expira-
tory flow, usually measured with the Wright peak flow meter. 81, 137,Z15,218,224,
228,235,236,502 Other measurements of ventilatory capacity, such as the mid-
maximal expiratory flow, 503 flow rates at certain specified lung volumes, 496,499
and airways resistance1 3^ have sometimes been used in epidemiological studies.
Other tests of lung function--nitrogen mixing, 81 lung volumes, °4 and diffusing
capacity1"1--have been used only rarely.
The findings could be summarized by saying that lung function is consistently
worse in smokers than in nonsmokers. Forced expiratory volume has almost in-
variably been found to be lower in smokers than in'nonsmokers, and also usually
lower than in ex-smokers; so, too, have peak expiratory flow rates, midmaximal
expiratory flow rates, and flow rates at certain specified lung volumes. Vital
71
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capacity is usually lower in smokers than in nonsmokers but the difference in vital
capacity between the two groups is often less than the difference in FEV. Conse-
quently, the ratio, FEV/FVC, may be the most discriminating simple index of lung
function. Residual volume and residual volume as a percentage of total lung volume
is higher in smokers than in nonsmokers. Mean lung function values within cate-
gories of smokers classified by number of cigarettes smoked are sometimes incon-
sistent. Thus, as in the case of the prevalence of symptoms, there is often little
difference in lung function between light and heavy smokers. This is an unexpected
finding, for which selection is the explanation most often advanced. The expected
findings are those reported from studies of college students, in which differences
in morbidity and lung function between smokers and nonsmokers were demonstrated
after relatively short periods of exposure to cigarette smoke. 7,77
Epidemiological studies^°>206 have shown that the FEV is lower in persons
with respiratory symptoms than in those -without. Lower values have been found
in those with persistent cough and sputum or sputum alone. In view of the marked
association of smoking 'with cough and sputum, the lower lung function values in
smokers might be the result of cough and sputum, but some studies have shown
that cigarette smoking, even in the absence of symptoms, is associated with a dim-
inution of approximately 5 percent in such functions as the FEV or peak flow
rate. 201,358,500
A few researchers have examined the trends over time in ventilatory lung func-
tion by conducting follow-up studies of groups after varying time periods. 10f.lyl,
192,505,506 These studies have shown that decline in FEV is related to smoking
habits. In the follow-up after 9 years of a sample of the population of an industrial
town, '•*• Higgins and his colleagues showed that the rate of decline in FEVg -j^ was
higher in cigarette smokers than in nonsmokers or ex-smokers. The rate of de-
cline -was also higher in heavier than in lighter smokers.
Decline in ventilatory function with smoking has also been shown to be partly
dependent on hyper secretion. lUr^D05 Gregg, for example, found that in asympto-
matic smokers there was no correlation between consumption and duration of
smoking and impairment of peak expiratory flow (PEF). 505 jn smokers with hyper-
secretion, however, impairment of PEF was found increasingly in heavy smokers
and in older smokers. It appears, therefore, that the impairment of PEF produced
by smoking is caused at least partly by mucous hypersecretion. Fletcher and his
colleagues10' pointed out the difficulty of separating the effects of sputum volume
and of smoking on decline in FEV; since, to a great extent, sputum production is
dependent on smoking. In their study, they were unable to detect any additional
effect of sputum volume over and above the effect of smoking on the decline in FEV.
It is not clear, however, whether the effect they attributed to smoking was mediated
through sputum production in the way Gregg suggests. Carey and his colleagues
studied daily changes in ventilatory capacity and related these to smoking habits.
In a group of public health inspectors in Belfast, Ireland, they found that the aver-
age morning and afternoon FEVj_ Q was lower in smokers than in nonsmokers. The
diurnal decline in FEV also tended to be greater in smokers than in nonsmokers.
Effects of Cessation of Smoking
The benefit of giving up smoking has long been noted by physicians. 486,508
The effect of stopping smoking on subsequent mortality from bronchitis and
emphysema has been shown in several prospective studies. 482, 484, 509 Kahn, for
72
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example, has noted that the age-specific probabilities of death for ex-smokers are
lower than those for smokers when standardized for number of cigarettes smoked.
Doll and Hill found that the mortality ratios for those who gave up smoking first
rose and then fell below the level for all smokers. In the 9-year follow-up of an
English industrial population, the mortality of ex-smokers aged 55 to 64 was simi-
lar to that found in nonsmokers and was approximately half that of smokers. *°*
Clinicians have long advocated giving up smoking in cases of chronic respiratory
disease. Systematic observations of the changes that occur after people quit smok-
ing have, however, been relatively infrequent.
In an experimental clinic designed to help patients who have early symptoms of
chronic bronchitis give up smoking, Wood and Meadows51 ° noted that cough and
sputum production were reduced in those who gave up smoking.
Campbell and Elder51 ^compared chronic bronchitics who continued to smoke
with chronic bronchitics who no longer smoked. Apart from the smoking habit,
the two groups were similar. Smokers had more exacerbations, lost more time
from work, and were bedridden more than ex-smokers. They also had more vis-
its to their medical practitioners and reported less favorably on the progress of
their general condition, the nature of their cough, and the amount of sputum pro-
duced. In another group of 18 patients with chronic productive cough who had not
smoked for several years, 10 reported that sputum production had ceased and 3
more reported that it had been considerably reduced.
Mitchell and his colleagues '^advised their patients to give up smoking and
42 percent did. Two-thirds of those who stopped experienced a striking relief from
coughing. Mortality rates in these patients during the 20 years after the onset of
their dyspnea was lower than that of the patients who continued to smoke. On the
other hand, Burrows and Earle were unable to show a reduction in mortality
rate among patients who stopped smoking even when differences in FEV were al-
lowed for.
Wynder and his colleagues-'15 folio-wed up a group of 224 ex-cigarette smokers.
They noted that more than three-fourths of the group experienced one or more
withdrawal symptoms, particularly an urge to have something in the mouth, irrita-
bility, inability to concentrate, and disorientation. Persistent cough was the symp-
tom that showed the greatest improvement, ceasing in 77 percent of the subjects
and improving in 17 percent. Throat-clearing ceased in about half the subjects.
Weight gain occurred in 68 percent. These authors urged that further epidemiolog-
ical studies of changes long believed to occur in ex-smokers be carried out.
1 Q 1
In the 9-year follow-up study conducted by Higgins and his colleagues, a
lower incidence of symptoms in those who originally had no symptoms and a higher
remission of symptoms in those who originally had symptoms was noted in ex-smok-
ers in comparison with current cigarette smokers.
INFECTIONS AND THERAPY
Bacterial (Bronchial)
The bronchi are sterile, 51 6-520 ^j. Sputum may often be contaminated by orga-
nisms from the pharynx. In chronic bronchitis, a variety of organisms can be iso-
lated from the sputum and also from the bronchi at bronchoscopy, the two most
73
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important of which are Haemophilus influenzae and Diplocococcus pneumoniae.
534 The proportions in which they are found depend upon the group of patients being
studied; the degree of purulence of the sputum, though this has been found in one
study to be less important than is often thought;525 and the methods used to identify
them, in particular, whether sputum examinations are performed once or repeated-
ly. The results in single sputum samples are affected by the inhomogeneity of the
sputum. 522 During exacerbations of the disease, the flora, of the bronchial tree
appears to undergo a quantitative rather than a qualitative change. For example,
Cooper and his colleagues noted a high or increased count of Haemophilus influ-
enzae either alone or in conjunction with pneumococci in 40 out of 48 sputum speci-
mens collected during acute exacerbations. Of 48 exacerbations, 21 were associ-
ated with high or increased counts of pneumococci either alone or in conjunction
with H. influenzae. The importance of H. influenzae in chronic bronchitis was
first suggested by Wilder in 1938. Additional support for the association is pro-
vided by serological demonstration of antibodies using tanned-red-cell antigens,
complement fixation, and agglutinin and precipitin techniques. ->^V-Dol While
high antibody titres may be demonstrated in cases of chronic bronchitis, these ap-
pear to have little relation to the duration or severity of the disease or to the pres-
ence of an exacerbation. ->^' The results therefore support the view that H. influ-
enzae colonizes the lower respiratory tract in chronic bronchitis but not that it
causes the exacerbations.
Laurenzi e_t aL and Green and Kass have shown that in experimental an-
imals inhaled bacteria are rapidly removed from the lungs. Hypoxia, alcohol,
cold, and tobacco smoke interfere with this mechanism. Kass and his colleagues5 33
have also shown that, in mice, influenza virus interferes -with the clearance of in-
haled staphylococci. It is possible, therefore, that in chronic bronchitis the pres-
ence of bacteria in the lower respiratory tract indicates a failure to clear organ-
isms that normally are inhaled but cleared by the lungs.
Viral and Mycopiasmal
The importance of viral infection in the pathogenesis of chronic bronchitis has
been considered by a number of workers. Stuart-Harris e_t al_. noted that fatal
illnesses in patients -with bronchitis increased during influenza epidemics. They
also showed that influenza virus could be recovered from bronchitis patients during
exacerbations. Subsequently, many other viruses have been associated with exac-
erbations; for example, respiratory syncytial virus; ' parainfluenza and in-
fluenza viruses, 3o-5 38 ancj rhinoviruses. 539, 540 Nonetheless, the role of viruses
in chronic bronchitis is still uncertain. Fisher and colleagues studied exacer-
bations of bronchitis in male bronchitics in Edinburgh, Scotland. They •were able
to show a significant increase in bacterial (pneumococci and H. influenzae), viral,
and mycoplasmal pathogens during exacerbations compared with quiescent periods.
Infective agents, though, -were isolated in less than half the exacerbations and
these workers concluded that viral and mycoplasmal infections did not appear to
play a large part in exacerbations of chronic bronchitis. They did suggest, how-
ever, that this observation might reflect the limitations of methods currently avail-
able and that closer associations between viruses and chronic bronchitis might be
found if newer techniques such as tissue culture 2 •were used.
Attempts to assess the importance of various infections in the pathogenesis of
respiratory disease have sometimes been made retrospectively. Thus Oswald
et al. 25° compared the frequency of colds in bronchitis patients and controls. They
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found that the mean annual number of colds reported by the bronchitis patients -was
higher than that reported by the controls. Furthermore, whereas 27 percent of the
colds in the controls "-went down on the chest, " 90 percent of the colds of the bron-
chitis patients did so.
In a study of a rural population, Higgins^lS observed that the average annual
number of colds reported in the whole sample was two for both men and women and
that 32 percent of these "went down on the chest" in men compared -with 35 percent
in women. Those with "chronic bronchitis," however, reported more colds--3 per
annum in the men and 2. 7 per annum in the women; 62 percent "•went down on the
cnest" in the men and 88 percent in the women. In the same study, a higher fre-
quency of previous pneumonia or bronchitis was reported by persons -with persistent
cough and sputum or "chronic bronchitis. "
Because respiratory infections early in life are a possible cause of chronic
disabling respiratory disease later, Reid325 has stressed that infections in child-
hood are an important aspect of the natural history of this disease. Reid and his
colleagues have also shown that many of the international differences in mortality
are apparent in the young. 83 it is likely that the increasing interest in conducting
studies in young people^21 , 543 wjji lead to advances in our understanding of the
pathogenesis of respiratory disease.
Observations on the influence of exacerbations on the course of chronic respir-
atory disease during its early stages have been few. Angel's study showed that
•when exacerbations occurred any concomitant fall in ventilatory function was tran-
sitory. " Thus it appears that if bronchial infection causes chronic obstructive
bronchitis it must do so gradually and not by any sudden, dramatic decline. No
relationship was detected in this study between the degree of purulence of the spu-
tum and the level or rate of decline in lung function. This suggests that infection
cannot have played a major role in the course of the disease. In an attempt to iden-
tify causes of sputum production other than smoking, Fletcher**" 1 compared smok-
ers and nonsmokers of similar age -who produced similar amounts of sputum. Child-
hood bronchitis was significantly more common and asthma and discharging ears
were somewhat more frequent among the nonsmokers. Fletcher concluded that
childhood respiratory tract infections might initiate persistent hyper secretion in
some subjects, who may in turn be less likely to take up cigarette smoking than
their more fortunate fellows.
Chemotherapy
Many controlled trials of antibiotic drugs in chronic bronchitis have been car-
99?^
ried out during the past 18 years. ^^'L:> They have usually shown that penicillin
or tetracycline given daily will reduce the duration of exacerbations of bronchitis
and the number of days lost from work, but that they have no striking effect on the
number of attacks of bronchitis or on the rate of decline in ventilatory lung function.
The rate of decline of ventilatory lung function as measured by the FEV is greater
in those with advanced disease. Most trials have been concerned with advanced
cases of bronchitis, although the trial organized by the Medical Research Council's
Working Party on Chemoprophylaxis and Chemotherapy in Early Chronic Bronchi-
tis and those carried out by the British Tuberculosis Association544'545 are ex-
ceptions. The Medical Research Council trial, furthermore, lasted for 5 years.
Four hundred ninety-seven men aged 40 to 59, with recurrent chest illness and
with an FEV of 1. 4 liters or over, were treated with oxytetracycline or placebos
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continually from September to April. They initially -were treated with 0. 5 gram
daily, but the dose was increased in the last 2 years of the trial to 1 gram and fin-
ally to 2 grams daily. Chloramphenicol (2 grams daily) or sulphamethoxypyridaz-
ine (0. 5 gram daily) -was given as treatment of exacerbations. Combinations of
prophylactic and therapeutic regimes -were allocated at random. Despite careful
diagnostic standardization and selection, there -was a wide variation in type of pa-
tients treated at the different clinics. Both the number and duration of exacerba-
tions of bronchitis showed a large variation bet-ween clinics and a highly skewed
distribution. This made it difficult to derive any simple index of the effect of either
prophylaxis or treatment, and adjustment had to be made for interclinic variation.
Oxytetracycline alone appeared to have no effect on the number of illnesses. In
those patients who also received chloramphenicol, there was a significant reduction
in the number -who had many illnesses. Oxytetracycline appeared to reduce by one-
third the total amount of time lost from work, but this estimate is uncertain be-
cause of a large range in the estimated values. Ventilatory capacity declined more
rapidly in the patients than -would have been expected for men of their age and
smoking habits. Neither prophylaxis nor therapy had any effect on the rate of de-
cline of FEV or on the volume or purulence of sputum. A similar conclusion has
since been reached by other workers. 5"*6, 547 This depressing and, at first sight,
surprising finding might perhaps have been anticipated from the observation of
Elmes and his colleagues548 that any improvement produced by Ampicillin therapy
during exacerbations of bronchitis is only temporary; Cherniak and his colleagues, "*9
however, noted in 1967 that repeated and protracted acute lower respiratory tract
infections in patients -with bronchiectasis leads to a greater decline in vital capaci-
ty and maximum breathing capacity than shorter and less frequent infections.
A number of studies have been reported on the effect of prednisolone therapy
on chronic obstructive lung disease. Clifton and Stuart-Harris observed clini-
cal improvement and increase in the FEV in about half of their patients, but the FEV
returned to its previous level or below despite maintenance of steroid therapy.
Long-term benefits from steroid therapy have been claimed by Ulmer and Nicolas.
In general, however, improvement from steroid therapy in patients with severe
emphysema or obstructive air-way disease has been slight or absent. 552,553
The effect of bronchodilators, either alone or in combination with wetting
agents, was assessed by Wilson and Wilson, mainly in patients with advanced di-
sease. 554-557 jt woui,j appear unlikely that therapy would improve the course of
the disease at that stage. It seems desirable, however, for these measures to be
instituted at an earlier stage of the disease to see if they are effectived Controlled
trials have been advocated by Jones and Fletcher. 558 Various authors have em-
phasized the greater improvement produced by aerosols in asthmatic compared
with bronchitic patients. 559,560
SOCIOECONOMIC STATUS
An inverse relationship between family income and mortality rates for pneu-
monia in white children under 1 year of age was shown in the U. S. National Health
Survey in 1935 and 1936. 5°1 In the national growth and development study already
described in the section on air pollution, Douglas562 foun(j that lower respiratory
tract infections, as measured by episodes of bronchitis or pneumonia sufficiently
severe to require treatment from a general practitioner or admission to hospital,
were about four times as high in the first 6 months of life for infants of manual
workers as for infants of other salaried or professional -workers. Douglas
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believed that this probably reflected the home conditions and pattern of living of
the manual -workers. He pointed out that from an early age the infants were taken
°n buses and trains and had contact with neighbors, friends, and relations, with a
resultant increased frequency of early infections. The incidence of colds was
found to be higher in the infants of the poor and more of their colds occurred at
earlier ages.
Goodman and his colleagues^ suggested that the fivefold social class mortal-
ity gradient might be caused by overcrowding, infection, malnutrition, and the in-
ability to treat respiratory infections with enough care. Meadows'^ also indicated
that a downward drift in social class may occur in those who have chronic bronchi-
tis.
All children born (1142) in May and June 1947 to women residents in New-
castle, England, were enrolled in a prospective study known as the 1000 Families
Study. 3,3o4 Bronchitis and pneumonia in the first year were significantly re-
lated to social class, overcrowding, and standards of maternal care. A tenfold
increase was found in the mean number of attacks of severe respiratory disease a-
mong unskilled as opposed to professional families. Subsequently, in a survey in
Newcastle of chronic bronchitis morbidity in persons over 30 years of age, Ogilvie
and Newell found a significant association between morbidity and social class
and morbidity and unemployment. This association was considered to be economic
rather than occupational.
The California Health Survey ' also showed an increased prevalence of chron-
ic bronchitis in those with a family income of less than $2000 per annum, but a high
proportion of those with incomes in this range were aged 65 years and over. Much
of the apparent effect of low income on bronchitis prevalence in this survey ap-
peared really to be a reflection of age.
An association between educational level and prevalence of respiratory symp-
toms and level of ventilatory lung function -was noted by Enterline and Lainhart^lZ
in their studies of mining communities in southern West Virginia. The association
387
was subsequently supported by studies carried out in the northern part of the state.
Some, but not all, of the association could be explained by differences in height or
smoking habits, which also differed among the respective educational categories of
the study population.
WEATHER AND CLIMATE
Weather and climate have long been believed to play a role in the pathogenesis
of chronic respiratory disease. Most of the observations seem to have been made
in the United Kingdom, presumably because of the important role the weather plays
in daily life there. Farr^°4 observed in 1885 that the commonest causes of death
during the cold months were pulmonary diseases and the cerebral diseases of the
aged. Young later found that deaths from bronchitis and pneumonia in children were
correlated with ambient temperature during the preceding week. 5^6 In 1927, Woods
noted that low temperature was correlated with pneumonia deaths in persons aged
5 to 40 but not in children under 5 years. ^° ' The Payling-Wrights, however, ob-
served similar correlations in young children. ->68 More recently, Boyd found that
mortality from chronic respiratory disease in England and Wales was correlated
with temperature and absolute humidity. ° Holland and his colleagues, using as
their index the requests made for admission to hospitals through the Emergency
77
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Bed Service in London from 1955 through 1958, showed that, allowing for seasonal
effects, morbidity from respiratory diseases was related to temperature for per-
sons aged 15 years and over. 570
Cough prescriptions have been used by Loudon as a measure of cough fre-
quency. He correlated prescription frequency in two Dallas hospitals with nine
meteorological measurements. By means of factor analysis he was able to show
correlations between prescription frequency and temperature, hours of sunshine
and humidity, and both relative and total precipitation.
McKerrow and Rossiter3"7 have drawn attention to cyclical changes in ventil-
atory capacity that take place during the year. In repeated measurements of the
FEV in retired coal miners with pneumoconiosis -who -worked at a light engineering
factory, they found that the FEV -was lowest in the winter and highest in the sum-
mer months. The reason for this cyclical fluctuation in FEV is not known. Neither
change in clothing nor environmental changes appeared responsible. The winter
decline was not clearly related to respiratory infection inasmuch as it occurred
in normal subjects who had no respiratory infections. These authors suggested
that the cyclical changes were caused by a biological rhythm linked to environmen-
tal temperature. In this study, a greater deterioration in FEV with age was noted
in subjects -who had attacks of purulent sputum. Cyclical variation in airways re-
sistance comparable to the variation in FEV has been reported by several
authors.316-572'573
Cassell and his colleagues57^ pointed out the difficulties of assessing the in-
fluence on health of a number of related environmental factors, particularly when
these are interrelated. These -workers followed a panel of New York families,
comprising 1747 persons, for 45 -weeks. Weekly interviews -were conducted and the
information that -was obtained was related to indices of air pollution and various
meteorological measurements. They -were able to show relations between weather,
particularly cold weather and humidity, and frequency of cough, sore throat, and
the common cold.
MISCELLANEOUS FACTORS
Poisonous Gas Exposure in World War I
There have been a few studies of the effects of gassing, in World War I, on
respiratory diseases. Among residents of Staveley, Derbyshire, England, Higgins
and his colleagues'^ noted an exceptionally high prevalence of chronic bronchitis in
men aged 55 to 64 who said they had been gassed in the war. More recently, Wada
and his colleagues575 studied the clinical and pathological manifestations of respir-
atory damage in retired -workers who were exposed to poisonous gases while -work-
ing in a poison gas factory. A high incidence of malignancy was noted and most
diseases were superimposed on chronic bronchitis. Exposure to mustard gas ap-
peared to be especially significant. Case and Lea57& in 1955, found a very high
prevalence of chronic bronchitis in British World War I veterans -who had been pen-
sioned because of mustard gas poisoning. This, of course, could be explained by
postulating that men who had been gassed and who also developed chronic bronchitis
-would be those most likely to apply for a pension. In a comparable investigation
conducted by Beebe, however, this postulation does not seem to be a valid expla-
nation for the high incidence of bronchitis found in American veterans who had been
gassed. 577 Reduced expiratory flow rates and a high rate of incidence of chronic
78
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bronchitis have recently been demonstrated in former employees of a poison gas
factory in Japan. 5?8
Infection of Teeth and Sinuses
Joules included infection of the teeth and sinuses in his list of factors involved
in chronic bronchitis. °° Corroborating Joules' premise, Summers and Oberman,
in a study of oral disease in relation to 12 selected variables in Tecumseh, Mich-
igan, found that periodontal disease was inversely related to FEV in both men and
women. In men, an association between smoking and periodontal disease ex-
plained most of the relationship, but in women, after allowing for smoking, the
FEV was still significantly related to periodontal disease. A few observations have
been made on sinus infection, though perhaps fewer than might have been expected
from the widespread use of such clinical terms as "sino-bronchitis. " A major dif-
ficulty lies in the wide variability in interpretations of the kind of sinus x-rays that
can be obtained in epidemiological surveys. In a study of men aged 55 to 64, there
appeared to be little relationship between the condition of the sinuses and either
chronic respiratory symptoms or lung function (Pneumoconiosis Research Unit,
Medical Research Council, U.K. ; unpublished observation). It is possible that a
closer relationship between sinus infection contracted at an earlier age and subse-
quent chronic lung disease might be observed. Further work in this area might be
profitable.
Postoperative Pulmonary Complications
Albert and his colleagues^"'-' have drawn attention to the high frequency of pul-
monary complications that have followed high laparotomy, especially when the op-
eration was performed in an emergency. During I960 and 1961, among 4784 oper-
ations performed in a department of general surgery, 60 patients (1. 3 percent) de-
veloped postoperative pulmonary complications. In patients undergoing high lapa-
rotomy, pulmonary complications occurred in 5 percent, and when it was an emer-
gency operation, the incidence was 12 percent. The long-term implications of this
phenomenon for chronic respiratory disease are not known. It is an area that
might repay further study.
FOLLOW-UP STUDIES OF CHRONIC RESPIRATORY DISEASE
A number of valuable clinical investigations have been made in which carefully
studied groups of bronchitis patients have been observed over a number of years in
order to determine the course and outcome of the disease. Platts and her colleagues
found that ventilatory capacity, MBC, and residual air as percentage of total lung
volume were of little prognostic value in patients with chronic bronchitis in Shef-
field, England. Mitchell and his colleagues followed 150 patients with chronic
obstructive bronchopulmonary disease. They noted the risk of cardiac complica-
tions and the serious prognostic implications of alterations in the arterial blood
gases. The use of lung function tests to assess prognosis •was first used by Bates
and his colleagues^"^ in 59 patients with emphysema and bronchitis. Ventilatory
capacity, functional residual capacity, and mixing efficiency of the lungs were
found to be of little value in prognosis; however, DL^O underwent a progressive
fall? especially before the onset of right ventricular failure. Boushy and Coates583
followed 83 patients with diffuse obstructive emphysema for 2 to 6 years, during
which time 48 of them died. The degree of impairment of forced vital capacity
(VC), the maximum voluntary ventilation (MVV),' the height of PaCO2, and the level
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of SaC>2 all correlated with the poorness of the prognosis. In a major study carried
out by the Veterans' Administration in the U.S. , a total of 487 patients, selected on
the basis of a high residual lung capacity/total lung capacity ratio, were admitted
into the study between 1958 and I960. 584 In the 4-1/2-year period of follow-up,
48 percent of the patients died, which was five and one-half times the mortality ex-
pected. Impairment of ventilatory function and gas exchange -were significant prog-
nostic indicators.
Oswald and his colleagues and Medvei and Oswald1"1 carried out a study
of 312 civil servants attending the Brompton Hospital in London. They presented
their findings after 5 and 10 years. Mortality in excess of normal was approxi-
mately fourfold, largely from respiratory or cardiac causes. The serious prog-
nostic implication of generalized emphysema detected by the chest x-ray was noted.
Earle and Burrows586, an(} Burrows and Earle514 published their findings
in 200 patients who were enrolled in a special follow-up clinic at the University of
Chicago Hospitals between I960 and 1964. The mean age of these patients was 59
years and their mean FEVj Q was 1. 02 liters, indicating a moderately severe level
of impairment. Prognosis was related to the degree of airways obstruction as in-
dicated by such ventilatory function tests as the FEV^ 0> VC> and MVV; to cor pul-
monale and a group of factors such as resting heart rate, presence of peripheral
edema, and EGG changes considered to be related to cor pulmonale; to bronchopul-
monary infections indicated by recurrent winter illnesses, chronic or continuous
sputum production, and ability to •work; and to miscellaneous factors including
physician assessment of dyspnea during a standard exercise test. Of these, the
most valuable pulmonary function tests for assessing prognosis were those indicat-
ing airways obstruction.
Davies and McClement carried out a 10- to 13-1/2-year follow-up of 95 patients
who were admitted to the Emphysema Clinic at Bellevue Hospital, New York, be-
tween April 1955 and July 1957. 587 At 5 years, 58 percent of the patients had died,
which was some four times the expected rate for men of similar age and the same
race in the general community. The patients who survived the 5-year period had
death rates that approximated those of the United States general population. The
authors concluded that patients with less severe types of disease might have a nor-
mal life expectancy. The study confirmed the serious prognostic implications of
chronic arterial oxygen unsaturation, chronic CO2 retention, a persistently low
MBC, or corpulmonale.
Howard followed a group of 125 patients (112 male and 13 female) at 1- or 2-
month intervals for a number of years. 5°6. The FEV was measured each time the
patient was seen. The regression of the change of FEV with time was calculated
for the whole period of observation and the slope or regression coefficient was ex-
pressed in liters per year. The mean age of the patients was 60. 7 years and the
mean period of follow-up was 7. 1 years. The mean initial FEV was 1. 2 liters.
Wide swings in the FEV were found in asthmatic patients. The rate of decline
tended to remain constant for long periods, though temporary seasonal and spon-
taneous fluctuations were also noted. In 21 cases in which a decline in FEV occur-
red within 6 months that was greater than two standard deviations of the regression,
an acute exacerbation could be implicated in 10. The patients in whom these sharp
falls in FEV occurred were much heavier smokers than the other patients. Howar
concluded that although clinically recognizable bacterial infection and frequent ex
acerbations might contribute to the decline in ventilatory function, they were not
essential to it.
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These clinical observations have been based on patients with advanced chronic
respiratory disease. Few observations have been made on more representative
groups of people.
Higgins and Oldham folio-wed up, after 5 years, a random sample of miners and
nonminers living in the Rhondda Fach in South Wales. 190 They found that the aver-
age rate of decline in FEVQ 75 was 0. 046 liter each year. Subsequently, in a 9-
year follow-up of an industrial town population, Higgins and his colleagues found a
decline of 0. 03 liter per year in men aged 25 to 34 and 0. 04 liter per year in men
aged 55 to 64. The decline -was inconsistently related to occupational exposure but
was higher in smokers than in nonsmokers or ex-smokers. 1 91 in these surveys,
mortality was higher in those with many symptoms than in those without symptoms.
The degree of breathlessness that was recorded on the first survey appeared to be
the most useful symptomatic indication of prognosis. Mortality in men aged 55 to
69 was related particularly to FEV. 34
Wilhelmsen and his colleagues measured the ventilatory capacity in a group of
313 men (aged 50 years) in 1963 and again in 1967. They found that vital capacity,
forced expiratory volume, and maximum expiratory flow all fell more in smokers
than in nonsmokers or ex-smokers. Lesser declines were also observed in those
who gave up smoking during the 5 years. ^88
Comstock and his colleagues followed up 670 male telephone company workers
aged 40 to 59 years after 6 years. There was a greater decline in FEVj Q and a
greater increase in sputum volume among those who continued to smoke cigarettes,
especially in the heavy smokers and those who used nonfilter cigarettes. The
smallest decline in FEV occurred among those who gave up smoking cigarettes.
Fletcher and his colleagues studied approximately 1250 working men aged 30 to
59 who were seen at 6-month intervals from 1961 to 1966. 107,407 Standardized
questions, FEV|_ Q, and measurements of sputum volume and cytology were made.
A mean decline in FEV of 0. 026 liter per year was noted. The decline in FEV was
related to level of FEV, a greater decline being observed for those with an initially
low FEV. This decline was shown to be particularly related to the ratio between
FEV and FVC. The decline in FEV was greater in cigarette smokers than in non-
smokers and was greater in heavier than in lighter smokers. Chest illnesses did
not appear to influence the rate of decline of FEV, although chest illnesses were
more frequent in those with a low FEV and, especially, in those with a low FEV to
FVC ratio. Sputum volume, apart from cigarette smoking, did not appear to in-
fluence the rate of decline in FEV. Chest infections were much more frequent in
those with sputum than in those without and tended to increase with increasing spu-
tum volume. Mucous hypersecretion and low FEV/FVC appeared to increase the
liability to chest illnesses independently.
In 1959 and I960, in Tecumseh, Michigan, 5140 adults were classified on the
basis of respiratory symptoms, respiratory disease, and ventilatory capacity.
Mortality during the next 4 years was related to the initial observations. Chronic
respiratory disease was an underlying or contributory cause in 4 percent of all
deaths. Subjects with respiratory disease, or with decreased ventilatory lung func-
tion or respiratory symptoms had higher mortality rates than those without these
conditions. Mortality among men and women with cough and sputum, shortness of
breath, or low levels of FEVj Q exceeded the number of deaths from coronary
heart disease. Shortness of breath was the best single predictor of death, especially.
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of death from coronary heart disease. Cough and phlegm were not associated with
increased mortality in the absence of shortness of breath. Among men, cigarette
smokers suffered more deaths than nonsmokers of the same age, but the rates in
smoking and nonsmoking women were similar.
The average annual decline in FEV in patients with respiratory disease is high
er than the decline found in these population surveys. Thus, in the trial of chemo-
therapy in early bronchitis carried out by the British Medical Research Council,
an average decline of 0. 08 liter per year was found. Howard observed a similar
average decline in hospital patients -with bronchitis.
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RECOMMENDATIONS FOR FURTHER RESEARCH
ETIOLOGY OF RESPIRATORY DISEASE
Cigarette smoking is generally agreed to be the most important factor in the
development and progression of respiratory disease, but why some people are af-
fected by smoking and develop hypersecretion -with cough and sputum while others
are apparently more resistant or even remain unaffected is much less certain.
Clearly, attempts to identify those individuals who are susceptible and to identify
factors, such as infections, that could interact with tobacco smoke to initiate res-
piratory disease are urgently needed. The role of other suspected etiological fac-
tors either as initiators of disease or as aggravating influences on it once it has
started is much less certain. These comments apply (1) to air pollution, in gener-
al, and, in particular, to air pollution in the United States, since so much of the
research that has led to its indictment as a factor in respiratory disease has been
conducted in other countries; (2) to exposure to occupational irritants, particularly
to dusts, fumes, and gases; and (3) to infections, both bacterial and viral.
Longitudinal studies are needed of people who are exposed to varying degrees
and types of pollution and to various occupational irritants --and -who have suffered
from various respiratory and other infections --to determine the role of these fac-
tors as initiators of chronic respiratory disease and, wherever possible, to estab-
lish dose/response relationships. Such studies would also shed light on the poten-
tial of these factors to exacerbate disease and influence its course. The study
would have to be conducted on large groups of adults so that any findings can be
standardized for different smoking habits. Recent studies indicate, however, that
the seeds of chronic respiratory disease may be sown in childhood. Children are
therefore particularly useful for evaluating the role of certain pollutants and irri-
tants, as well as of other factors. Since smoking is rare until at least the age of
15 years, it is possible that deleterious effects can be demonstrated in smaller
numbers of children than of adults. It is important that, whenever possible, obser-
vations be made before any potentially harmful exposures occur. In industry, pre-
employment examinations should include at least the questions recommended in the
short Medical Research Council Questionnaire and should include a competently
performed test of FEV and FVC. If there is likelihood of pneumoconiosis, a base
line chest radiograph should also be included.
Constitutional predisposition to respiratory disease has been studied, primar-
ily by workers in The Netherlands and in Sweden. Increasingly, evidence points to
consititutional differences that may influence susceptibility to respiratory disease.
It is essential that this be studied adequately in representative samples of the com-
munity and not merely in hospital and clinic patients or in otherwise highly selected
groups. Not only should population surveys for respiratory disease include tests
for such conditions as alpha^-antitrypsin deficiency and cystic disease, but they
should also include measurements of (1) skin sensitivity to common allergens, (2)
bronchial reactivity to histamine inhalation, and (3) sputum and blood eosinophilia.
At present, it is difficult to ascertain whether these so-called indices of allergic
tendency precede or follow the development of bronchial hypersecretion.
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DIFFERENTIATION OF CHRONIC RESPIRATORY DISEASE
One cannot help being impressed by the crudity of the present classifications
of respiratory conditions used in most surveys. Studies are needed, therefore, to
develop indices by which to differentiate asthma and emphysema from chronic
bronchitis. Recent evidence suggests that radiological differentiation of emphysema
from chronic obstructive bronchial disease may be more feasible than has been
thought. Further work is needed also to determine which tests are most suitable
5 QO
for field surveys. '
The differentiation of asthma will probably be accomplished best on the basis
of tests of bronchial reactivity and evidence of skin sensitivity. Few surveys to
date have included such tests. Inclusion of observations on immunoglobulins should
also be considered.
FACTORS INVOLVED IN EXACERBATIONS OF DISEASE
The recurrent exacerbations of acute illness to which patients with chronic
bronchitis are liable are a source of much disability. It is essential that every-
thing be done to identify the factors responsible for these attacks, so that appropri-
ate measures for prevention and control may be adopted. The surprising finding
that antibacterial chemotherapy, while it reduces the duration of illness and thus
shortens sickness absence, apparently does not affect the incidence of exacerba-
tions or the natural history of chronic respiratory disease in'sofar as this is indica-
ted by decline in the FEV should not lead to the conclusion that infection is of no
importance. Viral or mycoplasmal agents could still play a significant role. Much
more must be known about their occurrence, particularly in the early stages of
respiratory disease, inasmuch as there is increasing evidence that these agents
are involved in a considerable proportion of exacerbations. Limitations in field
techniques for identification of viral and mycoplasmal agents almost certainly lead
to a current underestimation of their presence and role. It is difficult, however,
to escape the conclusion reached by Fletcher that infection cannot be a major factor
in the natural history of chronic bronchitis, since acute attacks of bronchitis do not
necessarily influence the course of the disease. This important conclusion certain-
ly needs confirmation through additional surveillance of stable groups of people.
FACTORS INVOLVED IN DECLINE IN VENTILATORY LUNG FUNCTION
In the few longitudinal studies in which this question has been examined, ciga-
rette smoking, next to aging, has been found to be the most important determinant
of the rate of FEV decline. Neither occupational exposures to dusts nor respira-
tory infections appear to influence the rate of decline, but the volume of sputum
produced during the first hour after rising from sleep, which again is mostly de-
termined by cigarette smoking, has been shown to be related to the rate of decline.
Longitudinal studies of hospital or clinic patients have usually shown that the
rate of decline in FEV of these patients is approximately double that which would
be expected in the general community of persons of the .same sex, age, and smoking
habits. Furthermore, exacerbations of disease in patients, as in more represent-
ative samples of the community, apparently play little part in the rate of decline.
The FEV may decline suddenly for no apparent reason. Having dropped, it may
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remain at the lower level. It is clearly important to discover the reasons for these
mystifying changes.
INTERVENTION TO ALTER THE NATURAL DISEASE COURSE
The use of antibiotics to alter the course of chronic bronchitis in patients ear-
ly in its development has not been effective. It is possible that even in the Medical
Research Council trial of chemotherapy the disease was too firmly established in
the patients for antibiotic drugs to produce any real impact on its course. The use
of antibiotic drugs earlier in the course of the disease might be more successful.
On the whole, however, this seems unlikely. Furthermore, any suggestion of
giving such drugs to persons with such minor symptoms as persistent cough and
sputum would raise serious ethical objections. While the MRC findings certainly
need to be confirmed in this country, there is little reason for much optimism.
A more promising form of intervention now being carried out by Reid in Britain
consists of a controlled trial of antismoking propaganda in a group of highly moti-
vated and intelligent civil servants who have certain respiratory symptoms and
electrocardiographic abnormalities but who are other-wise -well and -working. Per-
suasion has been effective in changing the habits of half of those with the specified
abnormalities. Some 60 percent have remained ex-smokers for 1 year or more.
While the results of this trial will be awaited with interest, a similar attempt at
intervention is clearly needed in the United States.
Legislation to reduce air pollution has already resulted in a remarkable re-
duction in pollution in Britain and a considerable reduction may be expected from
measures being taken in the United States. The opportunity to measure what effects
such legislation has on health in general and on the occurrence, progression, and
outcome of respiratory disease in particular should not be missed. Similarly, im-
provements in industrial hygiene that have resulted in reduction of dust or fume de-
mand that well-designed studies be conducted to assess the effects of these changes
on human health.
CORRELATION OF CLINICAL AND PHYSIOLOGICAL CHANGES
Correlations of clinical findings with pathology in persons studied in epidemi-
ological surveys are sparse. This is not surprising, since the problems of obtain-
ing permission for autopsies in the general community are great; however, because
the vast majority of persons in the United States die in hospitals, the problems
should not be insuperable. A greater effort should be made by all who conduct sur-
veys to ensure that competently performed examinations of the lungs are carried
out at death on those who were part of a study population.
It is clear that we are far from understanding the complex interactions of fac-
tors that lead to disability and death from chronic respiratory disease, although
clinical, epidemiological, and statistical studies have enabled us to form some idea
of the complexity of such interactions. Although it has emerged as a very impor-
tant and probably the most important factor, cigarette smoking is certainly not the
only factor, and the way in which it interacts with other factors (infection, respir-
atory irritants, heredity, and constitution) requires much more study. Such stud-
ies should be coordinated with investigations into the mechanisms underlying the
development and progression of chronic respiratory disease. The need for an
85
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integrated attack on the problem through clinical, physiological, morphological,
biochemical, immunological, and other means has been recognized in the current
funding of Specialized Centers of Research by the National Heart and Lung Institute.
Such an integrated attack should result in increased knowledge and understanding of
chronic respiratory disease during the next decade and should enable us to reverse
the present trends in mortality and disability through more effective prevention and
control.
86
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SUMMARY
During the past 20 years, much progress has been made in defining and classi-
fying the components of chronic obstructive respiratory disease. The Ciba Confer-
ence on Terminology, Definitions, and Classification of Chronic Pulmonary Emphy-
sema and Related Conditions;37 the Committee on Diagnostic Standards for Nontu-
berculous Respiratory Diseases of the Amercian Thoracic Society;104 and the Com-
mittee on Cor Pulmonale of the World Health Organization38 have established
sound bases for the diagnosis of asthma, chronic bronchitis, and emphysema.
The practical measures for identifying persons in the community who have
these chronic respiratory diseases have been developed by many groups of workers.
They have been succinctly described by the British Medical Research Council's
Committee on the Etiology of Chronic Bronchitis, 43 and, more recently, by the
Committee on Standards for Epidemiologic Surveys in Chronic Respiratory Disease
of the American Thoracic Society104 in their respective publications on standard-
ized methods for respiratory disease surveys. Standardized questions about res-
piratory symptoms, smoking habits, occupational and residential exposures, col-
lection of sputum during the first half hour or hour after rising, and simple tests
of ventilatory lung function (FEV and FVC) form the basis for any adequately con-
ducted study. Additional tests may be added but should not be substituted.
Examination of the reproducibility and discrimination of these tests has led
most wokers to conclude that they are sufficiently good for epidemiological work.
More recently, studies have shown that, as assessed by subsequent mortality rates,
answers to questions about respiratory symptoms and measures of ventilatory lung
function have considerable validity as epidemiological study indicators.
These methods have been applied to different types of populations. More sur-
veys have been made of occupational groups than of the general population, though
the number of these has been increasing during the past decade. In earlier epide-
miological studies, adults alone were considered. More recently, in light of the
realization that the genesis of chronic respiratory disease may occur early in life,
children have received increasing attention. To date, the published work on chil-
dren has been largely British and Japanese, but studies are in progress in the
United States and other countries. Studies of children are of particular value
for the light they shed on factors other than smoking that are involved in the
etiology of respiratory disease.
Most studies have confirmed the initial observations that the most important
factor in the natural history of chronic respiratory disease is smoking, particular-
ly cigarette smoking. Prevalence, incidence, and remission of symptoms; level
and decline over the years of ventilatory lung function; mortality from all causes
and from respiratory diseases specifically--all of these suggest that there is a
consistency in the findings about smoking that holds for no other factor.
In contrast, the relationships of general air pollution and of occupational ex-
posures to chronic respiratory disease have been observed to be less consistent.
87
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In the case of air pollution, it has been known for many years that episodes of ex-
ceptional pollution can cause appreciable mortality and morbidity. Much of this
mortality and morbidity has no doubt occurred in persons already disabled with
heart or lung diseases. The initiating effect of air pollution has been harder to
establish. It now seems clear, particularly from the studies conducted in Britain
on young people, that residence in polluted areas plays a significant part in the
early development of chronic respiratory disease.
Assessment of the importance of occupational exposures has been plagued by
the difficulty of allowing adequately for socioeconomic circumstances and for smok-
ing. There is, however, a great deal of evidence pointing to the conclusion that
coal miners and other workers in dusty occupations have an excess of chronic res-
piratory disease. Not only do the vital statistics and morbidity data indicate this,
but surveys that have compared dust-exposed workers with other workers have
nearly always shown consistently higher respiratory disease rates and lower lung
function values in the dust-exposed groups. Two considerations have indicated that
the role of dust exposure in the development- of chronic respiratory disease is not
as simple as it might appear at first sight. First, in some areas the differences
between dust-exposed and nondust-exposed -workers are small--indeed, in at least
one area in this country there appeared to be no difference. Second, dust dosage,
whether this is equated with the development of simple pneumoconiosis or with the
number of years of underground or coal-face work, has not shown any very consis-
tent relationship with either respiratory symptoms or level of lung function. This
could reflect inadequate indices of dosage; it could result from an inability to allow
adequately for differences in smoking habits between different exposure groups; or
it could reflect selective factors, that is, those who have worked for long periods
represent the healthier survivors of all the workers who originally started. It is
difficult to avoid the conclusion that occupational dust exposures can contribute to
chronic respiratory disease, sometimes substantially. Whether this contribution
is by interaction with other factors or whether it is best described as initiation or
aggravation can only be answered by -well-designed experiments. It seems prob-
able, too, that concentrations, and perhaps the composition, of dust in the working
environment influence its effects on the respiratory tract.
Earlier studies established the relationship of Haemophilus influenzas and
Diplococcus pneumoniae to chronic bronchitis, but there is still uncertainty as to
the action of these organisms. During exacerbations the bacterial flora in the logw-
er respiratory tract undergoes a quantitative rather than a qualitative change. This
implies a change in the resistance of the host rather than a new infection or an al-
teration in bacterial virulence. Possibly such changes can be brought about by
inhalation of irritants on the job or by general atmospheric pollution. It seems
likely that they may often be precipitated by virus infections inasmuch as an in-
creasing number of viruses have been shown to be associated with exacerbations of
chronic respiratory disease. At present, however, a virus can be incriminated in
only about half of all exacerbations. The reasons for the other exacerbations are
as yet undetermined. The frequency of exacerbations is not reduced by antibacter-
ial chemotherapy, though their duration may be reduced by up to one half with ap-
propriate antibiotics. This is probably what would be expected if most exacerba-
tions were precipitated by virus infections and subsequently underwent bacterial
complication. A surprising finding has been that exacerbations of acute illness do
not appear to influence the natural history of chronic respiratory disease, at least
insofar as this is measured by the decline in FEV over the years. Perhaps this is
-------
not a good index of the course of the disease. It is certainly desirable that the ef-
fect of exacerbations on the deterioration of other aspects of lung function should
be assessed in addition to confirming this unexpected finding. It is difficult to be-
lieve that infection does not contribute to the development and course of chronic
respiratory disease. Possibly the type of infection and perhaps its site of
localization in the respiratory tract, particularly, are important factors that have
not as yet been adequately studied. Possibly it is the treatment (or lack of it) that
infections receive that is important. It may be that a "cold on the chest" that is
ignored can lead to a greater decline in lung function than an attack of pneumonia
that requires admission to hospital. All of these factors, plus the interaction of
infection with other etiological factors, require further study.
The influence of hereditary and constitutional factors has received rather little
study in epidemiological surveys to date, though the studies of twins have been an
exception. The obvious importance of the discovery of alpha}-antitrypsin and its
relationship to emphysema clearly indicates that more attention should be paid to
these factors in the future. Allergy, at least insofar as this has been defined clin-
ically, does not appear to be a very important factor in chronic respiratory disease;
but bronchial reactivity, -which may occur both in asthma and in chronic bronchitis,
might provide a better measure of intermittent respiratory obstruction than the
clinical indices that have been used to date. Measurement of immunoglobulins,
•which is becoming a praticable procedure, may also add precision to the diagnosis
of the condition being investigated.
A number of miscellaneous factors have been linked with chronic respiratory
disease in addition to the major ones mentioned above. Among these factors are
infection of the gums and paranasal sinuses; exposure to poison gas; abdominal
operations and the postoperative effects of anaesthesia; the influence of weather and
climate; and a number of socioeconomic variables. Although relationships have
been observed between these factors and chronic respiratory disease, the precise
nature of those relationships remains undetermined and constitutes an area that
demands--and deserves --further scrutiny.
89
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TECHNICAL REPORT DATA
(Please read instructions on the reverse before completing)
1. REPORT NO.
EPA-650/1-74-007
3. RECIPIENT'S ACCESSION-NO.
4. TITLE AND SUBTITLE
EPIDEMIOLOGY OF CHRONIC RESPIRATORY DISEASE:
A LITERATURE REVIEW
5. REPORT DATE
August 1974
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
8. PERFORMING ORGANIZATION REPORT NO.
Dr. I.T.T. Higgins
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Department of Epidemiology
School of Public Health
University of Michigan
Ann Arbor, Michigan 48104
10. PROGRAM ELEMENT NO.
1AA005
11. CONTRACT/GRANT NO.
PH-86-68-142
12. SPONSORING AGENCY NAME AND ADDRESS
Human Studies Laboratory
National Environmental Research Center
Research Triangle Park, N.C. 27711
13. TYPE OF REPORT AND PERIOD COVERED
Final
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This review of published studies pertaining to the epidemiology of chronic respiratory
disease focuses on three disorders -- asthma, chronic bronchitis, and emphysema. Par-
ticular emphasis is directed toward the latter two maladies. Chronic lung diseases
either cause or contribute to' an increasing number of deaths throughout the world.
Practical measures for identifying persons who have chronic respiratory disease, par-
ticularly through the use of standardized questionnaires, are described. The review
cites studies from several countries that explore the distribution and the etiology of
chronic respiratory .disease, including the effects of air pollution. Most studies have
confirmed the initial observation that the most important factor in the natural his-
tory of chronic respiratory disease is smoking, particularly cigarette smoking. Occu-
pational exposure is also important, with workers in dusty occupations evidencing an
excess of chronic respiratory disease.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.IDENTIFIERS/OPEN ENDED TERMS
c. COSATI Field/Group
Air pollution
Chronic bronchitis
Emphysema
Asthma
Epidemiological studies
13. DISTRIBUTION STATEMENT
Release unlimited
19. SECURITY CLASS (This Report)
Unclassified
21. NO. OF PAGES
138
20. SECURITY CLASS (This page)
Unclassified
22. PRICE
EPA Form 2220-1 (9-73)
129
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