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The Epidemiology of Asthma
Table I-Comparative Action ofAcetyl-p-methylcholine, HiatGmine, GndPollen Andgenl in Subjecta witla HtJfI Feoer; A8datrItJ GndNonatopic Subjecta* Mecholyl, 10 mglml Subjects Hay fever, 14 adults Average Range Asthma, 25 adults Average Range Nonatopic, 8 adults Average Range
Histamine Base,
Allergen, 10,000 PNU/ml
1 mg/ml
No. Inhalations
No. Post Responses
No. Inhalations
No. Post Responses
No. Inhalations
No. Pos Responses
77
8
81 30-150
6
40 3-75
11
2.8 1-12
25
24 .3-100
25
9.5 1-75
22
>150
0
>150
0
15-150
*Reprinted from reference 4 with permission of CV Mosby Co. tPositive response = 15 percent decrease in FEV•.
rhinitis could also develop bronchospasm when they inhaled solutions containing allergens. These early data, taken together with many subsequent studies" indicate that the common characteristic of all asthmatic patients is the "twitchy lung syndrome" or hyperreactive airways disease as measured by methacholine or histamine inhalation challenge." In fact, hyperreactive airways response to methacholine and/or histamine are so universal among asthmatic patients that a negative test strongly suggests another diagnosis such as vocal cord dysfunction7 as the source of intermittent airway obstruction. Because of these considerations, I believe that the only universal definition of asthma can be ccreversible obstructive airways disease of unknown etiology until proved otherwise." This is a very heterogeneous population of patients, wheezing on auscultation of the chest need not be present," and certainly known asthma need not be accompanied by any of the currently recognized allergic states. Persons with hyperreactive airways but without inflammation can also have a bronchospastic attacks from a variety of stimuli, ranging from exercise, exposure to a specific antigen to which they are sensitive, exposure to cold air or strong odors, and happy or sad emotional events. However, stripped to its essential, the common denominator among the patient population with asthma is hyperreactive airways. In summary, it is within the realms of this definition of asthma (ie, reversible obstructive airways disease of unknown etiology until proved otherwise) for patients who have emphysema, bronchitis and/or sinusitis, cystic fibrosis, or tuberculosis to be either asthmatic or nonasthmatic, depending upon whether they also have hyperreactive airways. Conversely, it is also possible for patients to be exquisitely sensitive to an allergen such as ragweed pollen and, in the absence of hyperreactive airways, not be asthmatic. Thus, in my view, asthma or hyperreactive airways disease mayor may not occur simultaneously with a variety of pulmonary illnesses or allergies. As a corollary to the previous statement, the asthmatic component should be considered and dealt with apart from the other underlying illnesses or stimuli. REFERENCES
1 Farr RS. Some comments regarding the allergic state. Arch Environ Health 1963; 6:92-98
2 Introduction. In: Middleton E, et al, eds. Clinical allergy: principles and practice, 2nd ed. S1. Louis: CV Mosby, 1983:xxi 3 Spector SL, Farr RS. Aspirin idiosyncrasy: a pseudo-allergy. In: Franklin E, ed. Clinical immunology update: review for physicians. New York: Elsevier North-Holland, 1981:197-225 4 Townley RG, Dennis M, Itkin IH. Comparative action of acetylbeta-methylcholine, histamine, and pollen antigens in subjects with hay fever and patients with bronchial asthma. J Allergy 1965; 36:121-37 5 Spector SL, ed. Provocative challenge procedures: bronchial, oral, nasal and exercise. Boca Raton, Fla: CRC Press, 1983 6 Farr RS. Asthma. National Institutes of Health. Bethesda, Md: DHEW publication no. (NIH) 73-462, 1971 7 Christopher KL, Wood RP n, Eckert RC, Blager FB, Raney RA, Souhrada JF: Vocal-cord dysfunction presenting as asthma. N Eng) J Med 1983; 308:1566 8 Farr RS, Spector SL. What is asthma? In: Petty TL, ed. The asthmatic patient in trouble. Greenwich: CPC Communications Inc, 1975:4-9 9 Farr RS, Kopetzky Ml: Spector SL, Hurewitz DS. Asthma without wheezing. Chest 1973; 63(suppl):64-68
The Epidemiology of Asthma* R. A Barbee, M.D., F.C.C.l; R. Dodge, M.D.; M. L. Lebowitz, Ph.D., F.C.C.l; and B. BufT0W8, M.D., F.C.C.l n contrast to the concerns for the individual patients which characterize clinical medicine, epidemiology deals with how disease processes occur in the community at large. The relationships of a variety of factors are considered in an attempt to determine the frequency and distribution of disease among the population and its natural history. Studies on the epidemiology of asthma are not new: In 1837, Armstrong' in his English treatise The Practice of Medicine, observed that asthma occurred more frequently in men than women, with attacks appearing more often during the heat of summer and in the winter, when fog and sharp cold winds prevailed in London. Despite its long epidemiologic history, considerable confusion exists in the literature concerning the prevalence of asthma, the incidence of new cases, factors relating to its
I
*From the Division ofResp~ry Sciences (Westend Laboratories), University of Arizona College of Medicine, Thcson. This work was supported by NIH SCOR IP'8Jlt HL-I4l36. Reprint f'8~: Dr. Barbee, Dioiaion Of Respiratory Sciences,
Arizona Health Sciences Cenfet; 7Uc8on 85724
CHEST / 87 /1 / JANUARY, 1985 / Supplement
218
development, and the fate of those who acquire the disease at any given age. At least part of this confusion derives from problems with the definition of the disease itself. As recently as the 19505,the de6nition frequently required the presence of allergy, the absence of which required an alternative diagnosis. More recently, the definition has focused on airway hyperreactivity with episodic airftow limitation in response to a variety of stimuli. While this broader de6nition is helpful clinically, especially in children and young adults, it is of considerably less value to the epidemiologist. In population studies, the diagnosis of asthma has been made in a variety of ways. Williams and McNicoll followed a sample of over 3,()()() school children in Australia. They reported that those with wheezy bronchitis and asthma had the same basic underlying disorder, In this population the point prevalence (current disease) of asthma in IO-year-olds was 3.7 percent, with a physician-confirmed cumulative prevalence of asthma or wheezy bronchitis of 11 percent. As reported in most other studies of childhood asthma, there was a preponderance of disease among boys, by a 6-t0-4 ratio. Other studies have utilized a variety of reporting methods to establish an asthma diagnosis, with differences in disease prevalence in part related to the diagnostic criteria. Frandsen," on the basis of questionnaires and interviews among Danish schoolchildren, reported a point prevalence of 0.8 percent. Among 5- to 9-year-old English schoolchildren, Smith" found a prevalence of current asthma of 2.3 percent and a cumulative prevalence of 4.2 percent. The prevalence of wheezing without an asthma diagnosis was slightly more than twice that of the speciflcally diagnosed disease. In the United States Broder et alareported the point prevalence of asthma in 5- to 9-year-olds in Tecumseh, Mich, to be 5.3 percent for boys and 3.0 percent for girls; the respective cumulative prevalences were 8.0 and 5.2 percent. A recent report by Speight et ale points out the problems inherent in the differing de6nitions and reporting methods employed in determining the epidemiology of asthma. In a survey of third-grade children in 'Iuneside, England, the authors found 297 (11 percent) with a history of wheezing episodes since beginning school. Two-thirds (197) of these 297 students were selected fur more intensive study. Among them were 150 who had had at least 1 wheezing episode within the previous yean Only 19 of these children had been given a diagnosis of asthma. Most (104) cases were called
No. of Subjects
Current Asthma Male,
Age
Male
Female
No. (%)
0-4. 5-9 10-14 15-19 20-29 30-39 40-49 50-59 60-69 70+
200 96 135 124 347 167 135 190 207 216 1,817
154 95 III 133 333 178 168 277 329 265 2,043
3 (1.5) 7 (7.3) 12 (8.9) 11 (8.9) 20 (5.8) 5 (3.0) 6 (4.0) 18 (9.5) 13 (6.3) 17 (7.9) 102 (5.6)
Total
228
allergic bronchitis, recurrent bronchitis, recurrent colds, or no speci8c diagnosis. An additional 16 were called wheezy bronchitis, and 11 had not been seen by a physician. While the authors did not imply that all of thse episodes were related to asthma, they believed that a significant underreporting of asthma in children occurs when the diagnosis is dependent on a physicians confirmation. Thiswas attributed at least in part to the reluctance of physicians to label children with the word asthma. Given these many problems in determining the prevalence of asthma, it is reasonable to assume that between 5 and 12 percent of children at some time will have a respiratory illness with wheezing which is comparable in many respects with asthma. Most studies report a greater prevalence in boys than girls, with the highest prevalence in children whose parents have evidence of allergic disease. Several years ago, in an attempt to overcome many of the difficulties in the epidemiologic study of asthma and other airway obstructive diseases (AOD), over 3,()()() subjects from the Tucson community were selected in a random, stratified manner to befollowed up in a longitudinal fashion. Details of this population and study methods have been reported previously," In an initial cross-sectional analysis, the prevalence of respiratory symptoms and physicians' diagnoses was determined by responses to standardized questionnaires. In addition to historical information, allergen skin test reactivity, total serum IgE levels, eosinophil counts, and pulmonary function measurements were obtained initially and repeated during the follow-up period. At the time of the initial survey, the prevalence of asthma was determined by a "yes" response to "Have you ever had asthma?" and "Have you seen a doctor about your asthma?" These data have been reported by Dodge and Burrows. 8 Table 1, taken from that report, details the asthma prevalence rate in the Tucson study by age and sex. Among 5- to 14-yearolds, point or current prevalence rates were virtually identicalfur boys and girls (8.23 vs 8.74). During the late teen-aged years, the rate for girls fell while male prevalence remained at the previously high level. In contrast, the female prevalence was almost twice the male rate from ages 30 to 49. Beyond age 50, the male rate was again generally higher, For all ages, the point prevalence of asthma was almost identical in males (5.6 percent) and females (5.9 percent). When a history of previous asthma is added to the percentage with
Female,
Male,
No. (%)
No. (%)
3 (2.0) 9 (9.5) 9 (8.1) 9 (6.8) 15 (4.5) 14 (7.9) 12 (7.1) 11 (4.0) 21 (6.4) 17 (6.4) 120 (5.9)
1 1 10 3 26 7 2 4 10 8 72
(0.5) (1.0) (7.4) (2.4) (7.5) (4.2) (1.5) (2.1) (4.8) (3.7) (4.0)
Female,
Cumulative Prevalence, 'I>
No. (%)
Male
Female
1 (0.6) 4 (4.2) 3 (2.7) 5 (3.8) 16 (4.8) 13 (7.3) 7 (4.2) 17 (6.1) 9 (2.7) 5 (1.9) 80 (3.9)
2.0 8.3 16.3 11.3 13.3 7.2 5.9 11.6 11.1 11.6 9.6
2.6 13.7 10.8 10.5 9.3 15.2 11.3 10.1 9.1 8.3 9.6
AdwIncea i'I DiIlgnoIIa& 1hMIIrnent ~ Asthma
active disease, the cumulative prevalence rate for both sexes is also identical, at 9.6 percent. An age dependence in the cumulative prevalence of disease is also apparent. The somewhat higher asthma rate in the Thcson population compared to other communities is probably accounted for, at least in part, by the prior immigration of families with respiratory disease. If one accepts a current history of episodic shortness of breath with wheezing as an asthma equivalent, the prevalence for all age groups over age 4 exceeds 10 percent, with a peak of 15 percent between ages 45 and 64. In addition to prevalence data, it is of considerable epidemiologic interest to study the incidence of asthma, that is, the number of new cases which develop in a population per person-yean In their 1980 report, Dodge and Burrows" reported 49 new cases of asthma during a mean follow-up period of 3.5 years among 3,432 Tucson study subjects who denied having asthma on their initial questionnaire. The incidence of new asthma in this population was 1.6 percent, with a peak in young children and the lowest percentage in late adolescence. Young boys developed asthma 1.5 times as often as young girls, while over age 40, a new diagnosis of asthma was made almost exclusively in women. Also, new disease which developed before age 40 was associated with prior allergen skin test reactivity. This was not the case over age 40, where a history of previous respiratory symptoms in the absence of an overt pulmonary diagnosis was common, but not in association with demonstrated allergy. Thus, it appears that a different set of circumstances surrounds the appearance of "new" asthma, depending on one's age and to a certain extent ones sex. Recent analysis of the longitudinal data in the Tucson population has allowed the authors to determine the incidence of not only new asthma, but also of emphysema and chronic bronchitis. Among the 3,239 subjects who were eligible, 351 new diagnoses of asthma, emphysema, or chronic bronchitis were made. The basis of such diagnoses was a denial on the initial evaluation and subsequent positive response to either of the follow-up questions: 1. During the past year have you seen a doctor for: Asthma? Emphysema? Chronic Bronchitis? 2. Did a doctor ever tell you that you had: Asthma? Emphysema? Chronic Bronchitis?
Categories of disease were mutually exclusive in the calculation of incidence. For example, one who had asthma and a second airway diagnosis as well is included only under asthma. Similarly, a new diagnosis ofemphysema was categorized emphysema, even if chronic bronchitis was also diagnosed. In each diagnostic group the mean follow-up period was 8.1 years. The incidence of new diagnoses of these three airway diseases is shown in Figure 1. New asthma incidence was highest in those under age 5 at the beginning of the study, and fell rapidly by the second decade. Although not shown separately, the lowest incidence was among 15- to 19year-olds (.09). From age 20 on, the rate remained constant. Not surprisingly, the age relationship for new emphysema was in the opposite direction. Only two cases occurred before age 30. A progressive increase was evident through the seventh decade. The incidence of new chronic bronchitis was constant throughout all age groups, with a slight peak between ages 30 and 39. Of perhaps greater interest than the overall incidence data are questions related to characteristics ofthe individuals who received these new AOD diagnoses. 1. What is the extent to which new AOD diagnoses are pure vs superimposed on prior AOD, or accompanied by second new diagnosis? 2. What are the clinical and laboratory features of those who are given new AOD diagnoses? Among the 351 new AOD diagnoses made during the follow-up period, 95 were asthmatic. Twelve of these had a previous diagnosis of emphysema, and 16 had chronic bronchitis at the time of the initial survey. Thus, 29 percent of new asthma patients were superimposed on prior AOD. For the 67 cases in which no previous diagnosis had been made, 38 were pure in the sense that they were diagnosed without another AOD, and 29 were given a diagnosis of emphysema, chronic bronchitis, or both in addition to asthma. Only 38 (40 percent) of the 95 new asthma cases occurred in the absence of either a previous or accompanying diagnosis of chronic bronchitis, which occurred in 33 subjects. In 16, asthma had been diagnosed prior to a new emphysema label. Lack of a clear separation between the several AODs makes epidemiologic data concerning the prevalence of specific obstructive diseases difficult to interpret. This is
2.0
Asthma
1.5 1.0
C.B.
0.5 Emphysema
AGE
0-4
5·9
-- -10-19 20·29
_._30·39
-40·49
50·59
60-69
70 +
1. The incidence (number of cases/lOO subject-years) of new physician-diagnosed asthma, emphysema, and chronic bronchitis in the Thcson epidemiologic study population is plotted against age. The population at risk for asthma was 1,899, and the follow-up period was slightly in excess of 8 yean. FIGURE
CHEST I 87 I 1 I JANUARY, 1885 I Supplement
238
Table !-CluJracterUtica ofNew Physician-confirmed AinDtJfl DitJgnoBea Under Age 40 Diagnosis
No. % Male % Ever smokers % Current wheeze % Current dyspnea % Current cough % Current attacks of shortness of breath with wheeze % Atopic Mean eosinophil count Geometric mean IgE Mean % predicted FEV 1
None
Asthma
(Only Asthma)
Chronic Bronchitis
894 50.0 46.3 19.7 2.0 28.5
43 46.5 52.2 79.1 28.6 69.8
(47.8) (53.8) (73.9) (8.7) (60.9)
(23)
61 45.9 62.3 45.9 14.8 47.5
8.1 59.0 90.0 34.5 103.6
52.2 92.6 163.3 132.6 100.5
(60.5) (93.8) (158.3) (224.6) (104.7)
16.4 45.9 75.5 18.7 98.1
especially true among older subjects in whom chronic bronchitis, emphysema, and asthma are often linked diagnostically or included in some combination with the more general term chronic obstructive pulmonary disease (COPD or COLD). An analogy may be drawn between the confusion that exist in adults and the problem alluded to by Speight et ale in children, when "wheezy bronchitis" and "asthma" are used both exclusively and synonymously. Perhaps a more effective way of separating the obstructive pulmonary diseases epidemiologically is to examine the clinical characteristics and laboratory findings of those subjects who are given new diagnoses and compare them with non diagnosed control subjects. This has recently been done by Dodge et aleamong subjects in the Tucson study. The data for subjects under age 40 at the time of the first survey are shown in Table 2. Because only five emphysema diagnoses were made in this age group, they have been excluded. Also excluded are those subjects who had combined asthma and emphysema diagnoses and those with chronic bronchitis superimposed on prior asthma or emphysema. The asthma categories are divided into those with chronic bronchitis in addition (43) and those with only an asthma diagnosis (23). A rather remarkable similarity among the disease groups exists for most characteristics. There were slightly more females than males, and over 50 percent had been smokers at some time. Not surprisingly, wheeze was significantly more frequent in the "disease" than in the "none" groups. Only
attacks of shortness of breath with wheeze separated the asthmatic from chronic bronchitic patients (52.2 and 60.5 percent vs 16.4 percent).
A greater degree of separation occurred among laboratory values. Percent of atopy, mean eosinophil count, and geometric mean 19E values all were significantly greater in the asthmatic than in any other group. These data suggest that among younger individuals, episodic wheezing attacks and markers of clinical allergy are utilized in separating asthma from chronic bronchitis. A similar comparison for subjects over 40 years old is included in Table 3. Because only 7 "asthma-only" diagnoses were made in this age group, thiscategory was excluded from statistical comparison. While the disease groups differ from those with no disease in most respects, interesting differences (and similarities) are evident from one disease category to another, Specifically, despite a similar smoking history, asthma and chronic bronchitis are diagnoses made primarily in females, while emphysema is male oriented. Not shown is the fact that 9 of the 11 new asthma diagnoses in subjects over age 60 were in women. Given the same complex of new symptoms, males were Significantly more likely to be labeled emphysema. As was true in younger subjects, attacks of shortness of breath with wheeze were most frequent among asthmatic patients, but only signmcantly when compared to chronic bronchitis patients.
Table 3-ChartJCfe1Vtica ofPhrlsician-confirmed N6tD AinDtJrI DiNGae Over Age 40 Diagnosis None No. Male Ever smokers Current wheeze Current cough Current dyspnea Current attacks of shortness of breath with wheeze % Atopic Mean eosinophil count Geometric mean IgE Mean % predicted FEV.
% % % % % %
248
Asthma
(Only Asthma)
732 39.6 51.4 15.3 29.6 13.3
17 17.6 64.7 64.7 64.7 41.2
(7) 0 (71.4) (42.9) (28.6) (42.9)
13.8 41.3 81.3 19.4 101.5
70.6 50.0 135.6 17.7 85.4
(71.4) (22.2) (138.3) 34.2
(99.1)
Emphysema
Chronic Bronchitis
40 57.5 82.5 52.5 72.5 43.2
53
47.5 28.6 121.7 38.1
BO.5
24.5 58.5 45.3 62.3 32.0 32.1 33.3 128.6 20.1 90.5
Advance8 In DIegnosIs & 1hNdment~ AsIhma
In older subjects, clinical markers of allergy did not separate asthmatic patients from the other disease categories. As one would expect, diagnoses had lower pulmonary function than the "none" group. Only for emphysema and asthma was this difference signi6cant.
a!l
SUMMARY
Signi6cant strides have been made in recent years in the epidemiologic study of obstructive lung diseases including asthma. Community population samples are being evaluated prospectively and followed up longitudinally to document the appearance of morbidity and clinical diagnoses. Also, a variety of environmental, physiologic, and immunologic variables are being collected on a serial basis to correlate changes with the appearance (or disappearance) of recognizable disease. Unfortunately, until the semantics and diagnostic labeling of airway abnormalities becomes more precise, especially in the older population, the incidence and prevalence of disease will lack the precision it should have.
REFERENCES 1 Armstrong XX. Practice of medicine. London: 1837 2 Williams H, McNicol K. Prevalence, natural history, and relationship of wheezy bronchitis and asthma in children. Br Med J 1969; 4:321-5 3 Frandsen S. Bronchial asthma among school children in Copenhagen. Acta Allergy (KBH) 1958; 12:341 4 Smith JM. A five-year prospective survey of rural children with asthma and hay fever. J Allergy 1971; 47:23 5 Broder I, Higgins MW, Matthews K~ Keller JB. Epidemiology of asthma and allergic rhinitis in a total community, Tecumseh, Michigan: ~ Natural history. J Allergy Clin Immunol 1974; 54:100-10 6 Speight AN~ Lee DA, Hey EN. Underdiagnosis and undertreatment of asthma in childhood. Br Med J 1983; 286:1253-6 7 Lebowitz MD, Knudson RJ, Burrows B. Thcson epidemiologic study of obstructive lung disease: I. Methodology and prevalence of disease. Am J Epidemiol1975; 102:137-52 8 Dodge RR, Burrows B. The prevalence and incidence of asthma and asthma-like symptoms in a general population sample. Am Rev Respir Dis 1980; 122:567-75 9 Dodge R, Cline MG, Burrows B. The development of asthma, emphysema, and chronic bronchitis in a community population sample. (Am Rev Respir Dis, submitted).
CHEST / 87 /1 / JANUARY, 1985 / Supplement
25S
Histamine Base,
Allergen, 10,000 PNU/ml
1 mg/ml
No. Inhalations
No. Post Responses
No. Inhalations
No. Post Responses
No. Inhalations
No. Pos Responses
77
8
81 30-150
6
40 3-75
11
2.8 1-12
25
24 .3-100
25
9.5 1-75
22
>150
0
>150
0
15-150
*Reprinted from reference 4 with permission of CV Mosby Co. tPositive response = 15 percent decrease in FEV•.
rhinitis could also develop bronchospasm when they inhaled solutions containing allergens. These early data, taken together with many subsequent studies" indicate that the common characteristic of all asthmatic patients is the "twitchy lung syndrome" or hyperreactive airways disease as measured by methacholine or histamine inhalation challenge." In fact, hyperreactive airways response to methacholine and/or histamine are so universal among asthmatic patients that a negative test strongly suggests another diagnosis such as vocal cord dysfunction7 as the source of intermittent airway obstruction. Because of these considerations, I believe that the only universal definition of asthma can be ccreversible obstructive airways disease of unknown etiology until proved otherwise." This is a very heterogeneous population of patients, wheezing on auscultation of the chest need not be present," and certainly known asthma need not be accompanied by any of the currently recognized allergic states. Persons with hyperreactive airways but without inflammation can also have a bronchospastic attacks from a variety of stimuli, ranging from exercise, exposure to a specific antigen to which they are sensitive, exposure to cold air or strong odors, and happy or sad emotional events. However, stripped to its essential, the common denominator among the patient population with asthma is hyperreactive airways. In summary, it is within the realms of this definition of asthma (ie, reversible obstructive airways disease of unknown etiology until proved otherwise) for patients who have emphysema, bronchitis and/or sinusitis, cystic fibrosis, or tuberculosis to be either asthmatic or nonasthmatic, depending upon whether they also have hyperreactive airways. Conversely, it is also possible for patients to be exquisitely sensitive to an allergen such as ragweed pollen and, in the absence of hyperreactive airways, not be asthmatic. Thus, in my view, asthma or hyperreactive airways disease mayor may not occur simultaneously with a variety of pulmonary illnesses or allergies. As a corollary to the previous statement, the asthmatic component should be considered and dealt with apart from the other underlying illnesses or stimuli. REFERENCES
1 Farr RS. Some comments regarding the allergic state. Arch Environ Health 1963; 6:92-98
2 Introduction. In: Middleton E, et al, eds. Clinical allergy: principles and practice, 2nd ed. S1. Louis: CV Mosby, 1983:xxi 3 Spector SL, Farr RS. Aspirin idiosyncrasy: a pseudo-allergy. In: Franklin E, ed. Clinical immunology update: review for physicians. New York: Elsevier North-Holland, 1981:197-225 4 Townley RG, Dennis M, Itkin IH. Comparative action of acetylbeta-methylcholine, histamine, and pollen antigens in subjects with hay fever and patients with bronchial asthma. J Allergy 1965; 36:121-37 5 Spector SL, ed. Provocative challenge procedures: bronchial, oral, nasal and exercise. Boca Raton, Fla: CRC Press, 1983 6 Farr RS. Asthma. National Institutes of Health. Bethesda, Md: DHEW publication no. (NIH) 73-462, 1971 7 Christopher KL, Wood RP n, Eckert RC, Blager FB, Raney RA, Souhrada JF: Vocal-cord dysfunction presenting as asthma. N Eng) J Med 1983; 308:1566 8 Farr RS, Spector SL. What is asthma? In: Petty TL, ed. The asthmatic patient in trouble. Greenwich: CPC Communications Inc, 1975:4-9 9 Farr RS, Kopetzky Ml: Spector SL, Hurewitz DS. Asthma without wheezing. Chest 1973; 63(suppl):64-68
The Epidemiology of Asthma* R. A Barbee, M.D., F.C.C.l; R. Dodge, M.D.; M. L. Lebowitz, Ph.D., F.C.C.l; and B. BufT0W8, M.D., F.C.C.l n contrast to the concerns for the individual patients which characterize clinical medicine, epidemiology deals with how disease processes occur in the community at large. The relationships of a variety of factors are considered in an attempt to determine the frequency and distribution of disease among the population and its natural history. Studies on the epidemiology of asthma are not new: In 1837, Armstrong' in his English treatise The Practice of Medicine, observed that asthma occurred more frequently in men than women, with attacks appearing more often during the heat of summer and in the winter, when fog and sharp cold winds prevailed in London. Despite its long epidemiologic history, considerable confusion exists in the literature concerning the prevalence of asthma, the incidence of new cases, factors relating to its
I
*From the Division ofResp~ry Sciences (Westend Laboratories), University of Arizona College of Medicine, Thcson. This work was supported by NIH SCOR IP'8Jlt HL-I4l36. Reprint f'8~: Dr. Barbee, Dioiaion Of Respiratory Sciences,
Arizona Health Sciences Cenfet; 7Uc8on 85724
CHEST / 87 /1 / JANUARY, 1985 / Supplement
218
development, and the fate of those who acquire the disease at any given age. At least part of this confusion derives from problems with the definition of the disease itself. As recently as the 19505,the de6nition frequently required the presence of allergy, the absence of which required an alternative diagnosis. More recently, the definition has focused on airway hyperreactivity with episodic airftow limitation in response to a variety of stimuli. While this broader de6nition is helpful clinically, especially in children and young adults, it is of considerably less value to the epidemiologist. In population studies, the diagnosis of asthma has been made in a variety of ways. Williams and McNicoll followed a sample of over 3,()()() school children in Australia. They reported that those with wheezy bronchitis and asthma had the same basic underlying disorder, In this population the point prevalence (current disease) of asthma in IO-year-olds was 3.7 percent, with a physician-confirmed cumulative prevalence of asthma or wheezy bronchitis of 11 percent. As reported in most other studies of childhood asthma, there was a preponderance of disease among boys, by a 6-t0-4 ratio. Other studies have utilized a variety of reporting methods to establish an asthma diagnosis, with differences in disease prevalence in part related to the diagnostic criteria. Frandsen," on the basis of questionnaires and interviews among Danish schoolchildren, reported a point prevalence of 0.8 percent. Among 5- to 9-year-old English schoolchildren, Smith" found a prevalence of current asthma of 2.3 percent and a cumulative prevalence of 4.2 percent. The prevalence of wheezing without an asthma diagnosis was slightly more than twice that of the speciflcally diagnosed disease. In the United States Broder et alareported the point prevalence of asthma in 5- to 9-year-olds in Tecumseh, Mich, to be 5.3 percent for boys and 3.0 percent for girls; the respective cumulative prevalences were 8.0 and 5.2 percent. A recent report by Speight et ale points out the problems inherent in the differing de6nitions and reporting methods employed in determining the epidemiology of asthma. In a survey of third-grade children in 'Iuneside, England, the authors found 297 (11 percent) with a history of wheezing episodes since beginning school. Two-thirds (197) of these 297 students were selected fur more intensive study. Among them were 150 who had had at least 1 wheezing episode within the previous yean Only 19 of these children had been given a diagnosis of asthma. Most (104) cases were called
No. of Subjects
Current Asthma Male,
Age
Male
Female
No. (%)
0-4. 5-9 10-14 15-19 20-29 30-39 40-49 50-59 60-69 70+
200 96 135 124 347 167 135 190 207 216 1,817
154 95 III 133 333 178 168 277 329 265 2,043
3 (1.5) 7 (7.3) 12 (8.9) 11 (8.9) 20 (5.8) 5 (3.0) 6 (4.0) 18 (9.5) 13 (6.3) 17 (7.9) 102 (5.6)
Total
228
allergic bronchitis, recurrent bronchitis, recurrent colds, or no speci8c diagnosis. An additional 16 were called wheezy bronchitis, and 11 had not been seen by a physician. While the authors did not imply that all of thse episodes were related to asthma, they believed that a significant underreporting of asthma in children occurs when the diagnosis is dependent on a physicians confirmation. Thiswas attributed at least in part to the reluctance of physicians to label children with the word asthma. Given these many problems in determining the prevalence of asthma, it is reasonable to assume that between 5 and 12 percent of children at some time will have a respiratory illness with wheezing which is comparable in many respects with asthma. Most studies report a greater prevalence in boys than girls, with the highest prevalence in children whose parents have evidence of allergic disease. Several years ago, in an attempt to overcome many of the difficulties in the epidemiologic study of asthma and other airway obstructive diseases (AOD), over 3,()()() subjects from the Tucson community were selected in a random, stratified manner to befollowed up in a longitudinal fashion. Details of this population and study methods have been reported previously," In an initial cross-sectional analysis, the prevalence of respiratory symptoms and physicians' diagnoses was determined by responses to standardized questionnaires. In addition to historical information, allergen skin test reactivity, total serum IgE levels, eosinophil counts, and pulmonary function measurements were obtained initially and repeated during the follow-up period. At the time of the initial survey, the prevalence of asthma was determined by a "yes" response to "Have you ever had asthma?" and "Have you seen a doctor about your asthma?" These data have been reported by Dodge and Burrows. 8 Table 1, taken from that report, details the asthma prevalence rate in the Tucson study by age and sex. Among 5- to 14-yearolds, point or current prevalence rates were virtually identicalfur boys and girls (8.23 vs 8.74). During the late teen-aged years, the rate for girls fell while male prevalence remained at the previously high level. In contrast, the female prevalence was almost twice the male rate from ages 30 to 49. Beyond age 50, the male rate was again generally higher, For all ages, the point prevalence of asthma was almost identical in males (5.6 percent) and females (5.9 percent). When a history of previous asthma is added to the percentage with
Female,
Male,
No. (%)
No. (%)
3 (2.0) 9 (9.5) 9 (8.1) 9 (6.8) 15 (4.5) 14 (7.9) 12 (7.1) 11 (4.0) 21 (6.4) 17 (6.4) 120 (5.9)
1 1 10 3 26 7 2 4 10 8 72
(0.5) (1.0) (7.4) (2.4) (7.5) (4.2) (1.5) (2.1) (4.8) (3.7) (4.0)
Female,
Cumulative Prevalence, 'I>
No. (%)
Male
Female
1 (0.6) 4 (4.2) 3 (2.7) 5 (3.8) 16 (4.8) 13 (7.3) 7 (4.2) 17 (6.1) 9 (2.7) 5 (1.9) 80 (3.9)
2.0 8.3 16.3 11.3 13.3 7.2 5.9 11.6 11.1 11.6 9.6
2.6 13.7 10.8 10.5 9.3 15.2 11.3 10.1 9.1 8.3 9.6
AdwIncea i'I DiIlgnoIIa& 1hMIIrnent ~ Asthma
active disease, the cumulative prevalence rate for both sexes is also identical, at 9.6 percent. An age dependence in the cumulative prevalence of disease is also apparent. The somewhat higher asthma rate in the Thcson population compared to other communities is probably accounted for, at least in part, by the prior immigration of families with respiratory disease. If one accepts a current history of episodic shortness of breath with wheezing as an asthma equivalent, the prevalence for all age groups over age 4 exceeds 10 percent, with a peak of 15 percent between ages 45 and 64. In addition to prevalence data, it is of considerable epidemiologic interest to study the incidence of asthma, that is, the number of new cases which develop in a population per person-yean In their 1980 report, Dodge and Burrows" reported 49 new cases of asthma during a mean follow-up period of 3.5 years among 3,432 Tucson study subjects who denied having asthma on their initial questionnaire. The incidence of new asthma in this population was 1.6 percent, with a peak in young children and the lowest percentage in late adolescence. Young boys developed asthma 1.5 times as often as young girls, while over age 40, a new diagnosis of asthma was made almost exclusively in women. Also, new disease which developed before age 40 was associated with prior allergen skin test reactivity. This was not the case over age 40, where a history of previous respiratory symptoms in the absence of an overt pulmonary diagnosis was common, but not in association with demonstrated allergy. Thus, it appears that a different set of circumstances surrounds the appearance of "new" asthma, depending on one's age and to a certain extent ones sex. Recent analysis of the longitudinal data in the Tucson population has allowed the authors to determine the incidence of not only new asthma, but also of emphysema and chronic bronchitis. Among the 3,239 subjects who were eligible, 351 new diagnoses of asthma, emphysema, or chronic bronchitis were made. The basis of such diagnoses was a denial on the initial evaluation and subsequent positive response to either of the follow-up questions: 1. During the past year have you seen a doctor for: Asthma? Emphysema? Chronic Bronchitis? 2. Did a doctor ever tell you that you had: Asthma? Emphysema? Chronic Bronchitis?
Categories of disease were mutually exclusive in the calculation of incidence. For example, one who had asthma and a second airway diagnosis as well is included only under asthma. Similarly, a new diagnosis ofemphysema was categorized emphysema, even if chronic bronchitis was also diagnosed. In each diagnostic group the mean follow-up period was 8.1 years. The incidence of new diagnoses of these three airway diseases is shown in Figure 1. New asthma incidence was highest in those under age 5 at the beginning of the study, and fell rapidly by the second decade. Although not shown separately, the lowest incidence was among 15- to 19year-olds (.09). From age 20 on, the rate remained constant. Not surprisingly, the age relationship for new emphysema was in the opposite direction. Only two cases occurred before age 30. A progressive increase was evident through the seventh decade. The incidence of new chronic bronchitis was constant throughout all age groups, with a slight peak between ages 30 and 39. Of perhaps greater interest than the overall incidence data are questions related to characteristics ofthe individuals who received these new AOD diagnoses. 1. What is the extent to which new AOD diagnoses are pure vs superimposed on prior AOD, or accompanied by second new diagnosis? 2. What are the clinical and laboratory features of those who are given new AOD diagnoses? Among the 351 new AOD diagnoses made during the follow-up period, 95 were asthmatic. Twelve of these had a previous diagnosis of emphysema, and 16 had chronic bronchitis at the time of the initial survey. Thus, 29 percent of new asthma patients were superimposed on prior AOD. For the 67 cases in which no previous diagnosis had been made, 38 were pure in the sense that they were diagnosed without another AOD, and 29 were given a diagnosis of emphysema, chronic bronchitis, or both in addition to asthma. Only 38 (40 percent) of the 95 new asthma cases occurred in the absence of either a previous or accompanying diagnosis of chronic bronchitis, which occurred in 33 subjects. In 16, asthma had been diagnosed prior to a new emphysema label. Lack of a clear separation between the several AODs makes epidemiologic data concerning the prevalence of specific obstructive diseases difficult to interpret. This is
2.0
Asthma
1.5 1.0
C.B.
0.5 Emphysema
AGE
0-4
5·9
-- -10-19 20·29
_._30·39
-40·49
50·59
60-69
70 +
1. The incidence (number of cases/lOO subject-years) of new physician-diagnosed asthma, emphysema, and chronic bronchitis in the Thcson epidemiologic study population is plotted against age. The population at risk for asthma was 1,899, and the follow-up period was slightly in excess of 8 yean. FIGURE
CHEST I 87 I 1 I JANUARY, 1885 I Supplement
238
Table !-CluJracterUtica ofNew Physician-confirmed AinDtJfl DitJgnoBea Under Age 40 Diagnosis
No. % Male % Ever smokers % Current wheeze % Current dyspnea % Current cough % Current attacks of shortness of breath with wheeze % Atopic Mean eosinophil count Geometric mean IgE Mean % predicted FEV 1
None
Asthma
(Only Asthma)
Chronic Bronchitis
894 50.0 46.3 19.7 2.0 28.5
43 46.5 52.2 79.1 28.6 69.8
(47.8) (53.8) (73.9) (8.7) (60.9)
(23)
61 45.9 62.3 45.9 14.8 47.5
8.1 59.0 90.0 34.5 103.6
52.2 92.6 163.3 132.6 100.5
(60.5) (93.8) (158.3) (224.6) (104.7)
16.4 45.9 75.5 18.7 98.1
especially true among older subjects in whom chronic bronchitis, emphysema, and asthma are often linked diagnostically or included in some combination with the more general term chronic obstructive pulmonary disease (COPD or COLD). An analogy may be drawn between the confusion that exist in adults and the problem alluded to by Speight et ale in children, when "wheezy bronchitis" and "asthma" are used both exclusively and synonymously. Perhaps a more effective way of separating the obstructive pulmonary diseases epidemiologically is to examine the clinical characteristics and laboratory findings of those subjects who are given new diagnoses and compare them with non diagnosed control subjects. This has recently been done by Dodge et aleamong subjects in the Tucson study. The data for subjects under age 40 at the time of the first survey are shown in Table 2. Because only five emphysema diagnoses were made in this age group, they have been excluded. Also excluded are those subjects who had combined asthma and emphysema diagnoses and those with chronic bronchitis superimposed on prior asthma or emphysema. The asthma categories are divided into those with chronic bronchitis in addition (43) and those with only an asthma diagnosis (23). A rather remarkable similarity among the disease groups exists for most characteristics. There were slightly more females than males, and over 50 percent had been smokers at some time. Not surprisingly, wheeze was significantly more frequent in the "disease" than in the "none" groups. Only
attacks of shortness of breath with wheeze separated the asthmatic from chronic bronchitic patients (52.2 and 60.5 percent vs 16.4 percent).
A greater degree of separation occurred among laboratory values. Percent of atopy, mean eosinophil count, and geometric mean 19E values all were significantly greater in the asthmatic than in any other group. These data suggest that among younger individuals, episodic wheezing attacks and markers of clinical allergy are utilized in separating asthma from chronic bronchitis. A similar comparison for subjects over 40 years old is included in Table 3. Because only 7 "asthma-only" diagnoses were made in this age group, thiscategory was excluded from statistical comparison. While the disease groups differ from those with no disease in most respects, interesting differences (and similarities) are evident from one disease category to another, Specifically, despite a similar smoking history, asthma and chronic bronchitis are diagnoses made primarily in females, while emphysema is male oriented. Not shown is the fact that 9 of the 11 new asthma diagnoses in subjects over age 60 were in women. Given the same complex of new symptoms, males were Significantly more likely to be labeled emphysema. As was true in younger subjects, attacks of shortness of breath with wheeze were most frequent among asthmatic patients, but only signmcantly when compared to chronic bronchitis patients.
Table 3-ChartJCfe1Vtica ofPhrlsician-confirmed N6tD AinDtJrI DiNGae Over Age 40 Diagnosis None No. Male Ever smokers Current wheeze Current cough Current dyspnea Current attacks of shortness of breath with wheeze % Atopic Mean eosinophil count Geometric mean IgE Mean % predicted FEV.
% % % % % %
248
Asthma
(Only Asthma)
732 39.6 51.4 15.3 29.6 13.3
17 17.6 64.7 64.7 64.7 41.2
(7) 0 (71.4) (42.9) (28.6) (42.9)
13.8 41.3 81.3 19.4 101.5
70.6 50.0 135.6 17.7 85.4
(71.4) (22.2) (138.3) 34.2
(99.1)
Emphysema
Chronic Bronchitis
40 57.5 82.5 52.5 72.5 43.2
53
47.5 28.6 121.7 38.1
BO.5
24.5 58.5 45.3 62.3 32.0 32.1 33.3 128.6 20.1 90.5
Advance8 In DIegnosIs & 1hNdment~ AsIhma
In older subjects, clinical markers of allergy did not separate asthmatic patients from the other disease categories. As one would expect, diagnoses had lower pulmonary function than the "none" group. Only for emphysema and asthma was this difference signi6cant.
a!l
SUMMARY
Signi6cant strides have been made in recent years in the epidemiologic study of obstructive lung diseases including asthma. Community population samples are being evaluated prospectively and followed up longitudinally to document the appearance of morbidity and clinical diagnoses. Also, a variety of environmental, physiologic, and immunologic variables are being collected on a serial basis to correlate changes with the appearance (or disappearance) of recognizable disease. Unfortunately, until the semantics and diagnostic labeling of airway abnormalities becomes more precise, especially in the older population, the incidence and prevalence of disease will lack the precision it should have.
REFERENCES 1 Armstrong XX. Practice of medicine. London: 1837 2 Williams H, McNicol K. Prevalence, natural history, and relationship of wheezy bronchitis and asthma in children. Br Med J 1969; 4:321-5 3 Frandsen S. Bronchial asthma among school children in Copenhagen. Acta Allergy (KBH) 1958; 12:341 4 Smith JM. A five-year prospective survey of rural children with asthma and hay fever. J Allergy 1971; 47:23 5 Broder I, Higgins MW, Matthews K~ Keller JB. Epidemiology of asthma and allergic rhinitis in a total community, Tecumseh, Michigan: ~ Natural history. J Allergy Clin Immunol 1974; 54:100-10 6 Speight AN~ Lee DA, Hey EN. Underdiagnosis and undertreatment of asthma in childhood. Br Med J 1983; 286:1253-6 7 Lebowitz MD, Knudson RJ, Burrows B. Thcson epidemiologic study of obstructive lung disease: I. Methodology and prevalence of disease. Am J Epidemiol1975; 102:137-52 8 Dodge RR, Burrows B. The prevalence and incidence of asthma and asthma-like symptoms in a general population sample. Am Rev Respir Dis 1980; 122:567-75 9 Dodge R, Cline MG, Burrows B. The development of asthma, emphysema, and chronic bronchitis in a community population sample. (Am Rev Respir Dis, submitted).
CHEST / 87 /1 / JANUARY, 1985 / Supplement
25S