Type and Geographic Distribution of Studies
We ultimately identified 21 publications (based on data from 18 study populations) meeting inclusion criteria. Of these, six were longitudinal general population-based studies [
19‐
24], and four were case-control studies based on three populations [
26‐
29]. Eight other publications (based on data from seven data sets) were cross-sectional analyses of general population based samples [
30‐
37]. Finally, three other publications (based on two study populations) were based on analysis of incident cases from large insurance schemes characterized as closed-panel health maintenance organisations (HMOs) [
38‐
40]. There was a wide range of different countries represented in these studies, and altogether, 19 countries on six continents are represented in the studies analyzed.
Prospective Longitudinal General Population-based Studies
Table
2 summarizes data on PAR from the six longitudinal analyses included [
19‐
24]. A cohort of Israeli soldiers without asthma or asthma symptoms and with normal lung function were followed for 30 months [
19]. This study had been included in the data used for the ATS estimates, but not in our original review [
11]. Of 34,038 soldiers in the combat units, 405 soldiers developed asthma; of 16,054 soldiers in maintenance units, 131 developed asthma. This incidence compared to 52 new cases of asthma among 8,956 soldiers with clerical tasks. The relative risk estimates for new-onset asthma was 2.0 and 1.4 for the combat and maintenance units, respectively (p < 0.05). Based on these data, the derived PAR has been estimated to be 44% [
11].
Table 2
Description of longitudinal general population cohort studies of asthma published June 1999–2007 in which the population attributable risk (PAR) for occupational exposures and asthma was either published or can be derived.
19 | 59,058 588 | Israel | Physician-diagnosed | Military exposures: Combat or maintenance versus clerical | 44%* |
20 | 1,852,848 49,575 | Finland | Incident asthma symptoms and at least one criteria of airway reversibility | Occupations at baseline a priori classified as exposed | 29% men, 17% women, weighted 22% |
21 | 2,723†, 101 | Norway | Physician-diagnosed incident asthma | Self-reported exposure to much dust or fumes at baseline | 14% |
22 | 52,325 1,426 | Singapore | Adult-onset physician-diagnosed asthma | Occupations at baseline a priori classified as exposed to: I: dust, II:smoke, III: vapors | I – 2.7%*, II – 1.7%*, III – 4.2%*, cumulative 8.6% |
23 | 6,837 133 3,994 38 | International | A. Incident asthma symptoms or medication B. Incident asthma symptoms or medication and new hyperesponsiveness | I. Exposure to high-risk substances (at baseline and during follow-up) by job-exposure matrix II. Occupations a priori classified as exposed | AI – 11%, AII – 1.7%, BI – 23%, BII – 26%, mean 18.5%* |
24 | 5,933‡
271 | Sweden | Physician-diagnosed asthma | Manual workers in industry | 9% |
A study of three temporal cohorts of employed Finns (initiated 1985, 1990 and 1995; aged 25–59 years at each baseline) followed each group for five years each (thus without overlap) [
20]. This cohort overlaps, in part, with that in an earlier paper from Finland [
10,
17]. The onset of asthma during follow-up was determined through the Finnish National Register for Reimbursement of Asthma Medication. For the patient to qualify for reimbursement, a physician must certify a valid diagnosis of asthma, including objective documentation of variable airway obstruction. Those with asthma at baseline of each 5-year time cohort were excluded, allowing for identification of incident asthma cases. Exposure was defined
a priori on the basis of occupational titles dichotomized to administrative (referent) vs. non-administrative jobs. There were 20,777 and 28,798 incident cases of asthma among men and women, respectively. The exposure prevalence (occupations classified as exposed) among the cases was high, 94% (19,502/20,777) among the men and 82% (23,563/28,798) among the women. The incidence rate ratios of asthma were estimated comparing non-administrative work with administrative work resulting in relative risk of 1.45 in men and 1.27 in women. The incident asthma PAR associated with occupational exposure (non-administrative work) reported by the authors was 29% (95% Confidence Interval [CI] 25–33%) for men and 17% (95% CI 15–19%) for women, yielding a gender-weighted overall PAR value of 22%.
A Norwegian study consisted of follow-up of a general population sample of 3,886 subjects [
21]. The baseline cross-sectional analysis of this cohort was included in the previous reviews of PAR [
10,
16]. The age range at baseline was 15 to 70 years. At ten year follow-up (1996), approximately 2,819 subjects, asthma-free at baseline, were successfully re-examined. Incident asthma was defined as an affirmative answer to "having been hospitalized or treated by a physician for asthma." The occupational exposure was defined by self-report to dust or fumes. The exposure prevalence was 28%, with a considerable difference between men (44%) and women (13%). Based on the data presented, the exposure prevalence among the subjects with asthma was 39%. The relative odds (OR) estimate for incident asthma in relation to being ever-exposed to dust or fumes was 1.6 (95% CI 1.01–2.5) using adjusted logistic regression models. The dust and fume-associated PAR for incident asthma reported by the authors was 14% (95% CI -1.2 – 27.6). Of note, although the OR was statistically significant, the CI for the PAR estimate did not exclude the zero value.
In a study of the ethnic Chinese population in Singapore 63,257 randomly selected subjects completed a questionnaire about comprising 45 items about occupation and a medical history [
22]. Their age at baseline was 45 – 75 years. After about 6 years, 52,325 subjects (83%) answered a follow-up questionnaire including items about physician-diagnosed asthma with onset of symptoms after 18 years of age. Subjects with childhood asthma were excluded, but other subjects with asthma at baseline were not. Thus, this study design can be best described as a longitudinal study with prevalent cases of adult asthma. The ORs for adult-onset asthma in relation to baseline occupational exposures based on job categories were: 1.14 (95% CI 1.90–1.30) for dust, 1.34 (95% CI 1.15–1.56) for vapors, and 1.13 (95% CI 0.97–1.33) for smoke. Based on occupations, dust exposure assigned to 22% of the cases, vapour to 17% and smoke to 14%. The derived PAR estimates are shown in Table
2. Although data on overlapping exposures were not provided, the method of job-based assignment appeared to generate mutually exclusive categorizations, although this was not explicit in the methods as described. Moreover, the ORs were calculated such than anyone with concomitant exposure would have been included in the referent (non-exposed group), biasing the estimated risks toward the null. Thus, it is reasonably conservative to add together these PAR estimates, yielding an overall value of 8.6%.
The European Respiratory Health Survey (ECRHS) began as an international cross-sectional study from 28 centers in 13 countries. An analysis of cross-sectional data from the ECRHS I yielded a PAR estimate of 9% for occupation and prevalent asthma [
10,
18]. Approximately ten years after baseline, an international follow-up was carried out (ECRHS II). Subjects with asthma, wheezing and dyspnoea at baseline were excluded. Incident asthma was defined in two principal ways: first, based on a reported asthma attack or use of asthma medication in the 12 months preceding the interview, and second, a more restrictive case definition also requiring a positive methacholine challenge test [
23]. Exposure in ECRHS II was also assessed by two methods, one using a broad at-risk occupational classification and the second linking the occupations to an asthma-specific JEM comprising 18 substances
a priori classified as carrying high risk for asthma. The OR for asthma defined by symptoms or medication was 1.6 (95% CI 1–1 – 2.3) and for the latter in combination with a positive metacholine challenge test, based on a smaller sample size with available test data, 2.4 (95% CI 1.3–4.6). The associated PAR estimates are shown in Table
2. The average PAR derived from these estimates is 18.5%.
A study on a random general population sample from northern Sweden comprised 6,837 subjects aged 35 to 75 yrs at baseline which were followed-up after 10 years with a respiratory questionnaire [
24]. Subjects with physician-diagnosed asthma at baseline were excluded. The risk for incident asthma in among manual workers in industry was increased (OR = 1.7, 95% CI 1.0–2.7); the reported PAR was 9% (95% CI 0–14%).
Case-Control Studies
As shown in Table
3, four papers reporting data from three case-control studies of asthma and occupation met inclusion criteria [
26‐
29]. In a Swedish study, prevalent cases of asthma among persons 20–65 years of age within a defined geographic area were identified as all subjects seeking medical care for asthma during a period of 18 months, using computerized data from multiple regional sources [
26] The diagnosis was based on a combination of symptoms and objective signs of reversible airway obstruction. There were 120 cases of adult-onset asthma included in the analysis, along with 446 referents randomly selected from the general population. Occupational exposures (based on a JEM and by self-report) before the onset of asthma (and a corresponding anchor year for the controls) were considered. Among the asthma cases, occupational exposure (dust, fume or vapors) prevalence was 52% as assessed by job-exposure matrix and 43% based on self-report. Exposure was associated with asthma by both measures: by JEM, OR = 1.5 (95% CI 1.0–3.3); by self-report, OR = 2.5 (95% CI 1.5–3.9). The estimated PAR values that can be derived from these data are 17.2% and 25.5%, respectively, with an average value of 21.4%.
Table 3
Description of case-control studies published June 1999–2007 where population attributable risk (PAR) for occupational exposures and asthma was either published or could be derived.
26 | 120 | 446 | Sweden | Adult onset asthma based on diagnosis in medical records | I. Occupations classified as exposed. | I. 25.5%* |
| | | | | II. Self-reported exposure | II. 17.2%* |
| | | | | | Mean 21.4%* |
27 | I. 172 | I. 285 | France | I. Asthma, any age onset | Occupations at risk, defined a priori by a job-exposure matrix | I. 10.0%* |
28 | II. 48 | II. 228 | | II. Adult-onset, severe | | II. 29.7%* |
| III. 43 | | | III. Adult-onset, mild | | III. 2.7%*†
|
| | | | II.+III. All adult onset asthma | | II+III. 16.9%* |
| | | | | | Mean 13.5%* |
29 | 373 | 4,329 | Australia | Adult-onset physician-diagnosed asthma | Occupations or exposures a priori classified as having an increased risk | 9.5%‡ |
A second case-control investigation, a French asthma genetics study, used a job-exposure matrix to classify exposure in two separate analyses of the data set [
27,
28]. In the first, 172 ever-employed asthma cases (adults with asthma since childhood and adult-onset, combined) and 285 controls were analyzed [
27]. For cases, exposure by the JEM was based on the job held at the time of asthma, while for childhood-onset asthma the assignment was based on current job. Exposure based on the JEM classification was associated with risk of asthma (OR 1.7; 95% CI 1.1–2.7); the associated PAR (derived from these data) is 10%. A further analysis of this case-control data set re-applied the same job-exposure matrix (based on current job), but analyzed severe and mild adult-onset asthma separately [
27]. In this analysis, 19 (40%) of 48 severe cases were exposed compared to 34 (15%) of 228 controls (OR 4.0; 95% CI 2.0–8.1). The associated PAR (derived from these data) is 29.7%. The OR for mild adult-onset asthma was minimally elevated (OR 1.2; 95% CI 0.5–3.0) and dilutes the overall PAR% of mild and sever asthma combined to 16.9%. The overall average of the two reports is 13.5%.
In a third case-control study, from Australia, a random population sample of 5,331 subjects aged 18–49 yrs completed a questionnaire comprising items about physician-diagnosed asthma and occupational exposures, with a somewhat restricted study n = 4,366 used in the key analysis [
29]. For the analysis of occupational risk, cases were defined as persons reporting adult-onset asthma; referent subjects never reported asthma, asthma medications, or asthma symptoms. Only occupational exposures (34% among cases) before the onset of asthma (and a corresponding anchor year for the controls) were considered. Exposure to any high risk exposure was associated with adult-onset asthma (OR = 1.51, 95% CI 1.19–1.92). The reported PAR for
a priori high-risk jobs or reported high risk exposures was 9.5%.
Cross-sectional Studies
Eight reports of cross-sectional analyses met study inclusion criteria (Table
4) [
30‐
37]. A random population survey was carried out in six Canadian communities following the ECHRS baseline protocol [
30]. These data, however, were not included in the baseline ECHRS cross-sectional analysis [
18] and no follow-up has taken place. Exposure was defined as work in a high risk occupation-industry (
a priori) or report of a specific occupation before or at the time of adult onset asthma. Among 2,974 subjects analyzed, 166 had adult-onset asthma. Preceding exposure was associated with asthma (OR 1.48; 95% CI 1.05–2.09). The estimated PAR, as reported, was 18.2%.
Table 4
Cross-sectional general population studies published June 1999–2007 where the population attributable risk (PAR) for occupational exposures and asthma was either published or derived.
30 | 2,974 166 | Canada | Adult-onset physician-diagnosed |
A priori high risk occupations or a report of exposure before onset of asthma | 18.2% |
31 | 14,151 976 (ever asthma) 13,445 270 (asthma, current job) | France | A. Ever asthma attack or dyspnea with wheezing; B. Adult-onset during or after current job | I. Self-reported exposure to gases, dusts and fumes II. Job-exposure matrix (excluding jobs with imprecise estimates, n = 10,560) | A., I. 9% A., II 1%* B., I. 14% B., II. 7% Mean 7.8%†
|
32, 33 | 5,022 185 | US | Physician-diagnosed, ever | I. Occupations a priori classified at-risk II. Industries a priori classified at-risk | I. 26.0% II. 36.5% Mean 31.3%†
|
34 | 1,482 77 | U.S. | Physician diagnosed, adult-onset | I. Self-reported exposure, vapors, gas, dust or fume II. Job-exposure matrix III. Both I and II | I. 17% II. 5%‡
III. 14%‡
Mean 12%†
|
35 | I.16,646 1,471 II. 11,337 641 | U.S. (three states) U.S. (two states) | Both use self-reported, health professional- diagnosed adult-onset asthma | Told by a health care provider that asthma was work-related | I.6.0%† II.8.1%†
Mean 7.0%†
|
36 | 1,922 227 | Brazil | Bronchial hyperresponsiveness and adult-onset asthma symptoms | Self-reported exposure, vapors, gas, fumes or humidity | 22.9%†
|
37 | 13,826 523 | South Africa | Physician diagnosed asthma, ever | Ever regularly exposed to smoke, dust, fumes or strong smells or worked underground in a mine | 13.6% |
In a French study, 14,151 subjects were investigated in 1975 with a questionnaire regarding self-reported asthma, occupations and self-reported exposure to dusts, gases and fumes [
31]. The exposure in the current or most recent job was assessed either by self-report or by a job-exposure matrix. For the latter, a number of subjects with imprecise job-exposure estimates were excluded form a final analysis. It is also noteworthy that households headed by manual workers were excluded from the cohort at inception. This suggests that PAR estimates from this cohort are likely to be conservative given that those most likely to be exposed were not studied. The different reported PAR values are presented in Table
4. This average value we calculated based on these was 7.8%.
Arif and co-workers have published two cross-sectional analyses of the NHANES III data drawn from a national U.S. weighted randomized sample [
32,
33]. In the first publication, they analysed the risk for work-related asthma based on industry of employment considered
a priori to carry increased risk [
32]. The exposure prevalence among the 185 cases of asthma was high (89%), with an associated PAR estimate reported to be 36.5%. In a second analysis, the risk for work-related asthma was based on occupation (also categorized for risk on an
a priori basis). The exposure prevalence among the same 185 cases of asthma was also high (68%), with an estimated PAR reported to be 26%. The averaged value of the two estimates we derived is 31.3%.
A U.S. random-digit-dial survey used data from 1484 older adults (aged 55–75 years, of whom 77 reported a physician's diagnosis of adult-onset asthma) to estimate the PAR for asthma comparing a JEM to self-report of vapors, gas dust and fume [
34]. The analysis used the longest held job without regard to age during adulthood in regard to employment; subjects with chronic obstructive pulmonary disease or childhood onset asthma were excluded. Asthma was associated with occupation based on self-reported exposure (OR 1.7; 95% CI 1.03–2.8), but only weakly by JEM (OR 1.2; 95% CI 0.7–21). The PAR was 17% (95% CI 0–32%) and 5% (95% CI -11–19%), respectively. The average of these two reported values is 11%.
In another cross-sectional study from the U.S., adults who were identified by a random-digit-dial in three states completed a telephone survey [
35]. The prevalence of work-related asthma was defined by one measure asking if the subjects with physician-diagnosed asthma were ever told by a health care provider that their asthma was work-related or whether they had ever told a provider this was the case. Although California was also surveyed, only for Massachusetts (approximately n = 449) and Michigan (approximately n = 193) were data specific for adult-onset asthma available. For these two samples, 8.1% and 6.0% had work-related asthma by this definition, respectively. This yields a sample size-weighted average value of 7.0%.
In a cross-sectional analysis of a general population-based sample from Brazil, subjects with a positive bronchial methacholine challenge test who also reported a temporal association between asthmatic symptoms and work were compared with referents with a negative bronchial methacholine challenge test [
36]. The PAR of asthma related to self-reported exposure to dusts, gases, fumes, vapors, chemical products, paints and humidity is 23%, based on this raw incidence value. Based on the design of this study, there was likely to be inclusion of subjects with work-aggravated asthma, even though the authors did classify pre-existing childhood-onset asthma separately. Hence the PAR may overestimate asthma attributable to work etiologically. Nonetheless, the study is important because the paucity of such data from countries with emerging economies.
Data from a South-African national health survey were used to estimate the risk for ever physician-reported asthma in relation to "ever worked in a job regularly exposed to smoke, dust, fumes or strong smells or ever worked underground in a mine" [
37]. The PAR reported from that study was 13.6%.
Asthma Incidence in Health Maintenance Organization (HMO) Populations
In addition to the data in Table
4, two relevant analyses have been published based on incident cases of asthma identified through prospective study of HMO cohorts. In the baseline populations, asthmatic subjects (based on diagnosis and medication use) were excluded. Each new case of asthma was classified based on asthmagenic workplace exposures and whether symptoms were work-related. In one of these studies, 1747 potential incident asthma cases were identified, of which 352 were interviewed and confirmed [
38]. Ultimately, 33% of these were classified as work-related. In another study based in an entirely different U.S. HMO but employing comparable methods, 24% of all 405 incident or "reactivated" cases of asthma were attributed to occupational exposures [
39]. Interim data from the same group found that only 5% of incident cases were diagnosed by a treating clinician as occupational in aetiology, but since only 7% were documented to have been asked about work, the 5% value is likely to be an overly conservative underestimation of the PAR [
40].
Data Synthesis
Table
5 presents a synthesis of available studies from the current analysis and from our previous review. As shown in Table
5, there were six longitudinal studies included, and, based on these studies, 16.3% (median) of all asthma, adult-onset by the nature of these studies, is attributable to occupational exposures. Table
5 also includes six PAR estimates derived from case-control studies; three of these estimates (two based on means of more than one estimate) were also included in Table
3 and three others were included in both our previous review and in the ATS statement [
41‐
43]. Three case-control studies from our previous review have not been included, as they were either published only as abstracts or only use a case definition comprising wheeze only. Taken together, the six studies yield a median PAR estimate of 12.2%. A PAR estimate (median) 17.6% is obtained from the 14 cross-sectional studies included in Table
5[
31‐
37,
44‐
51]. Few studies have separated the analysis with regard to gender. We identified five papers with separate estimates for males [
17‐
20,
43] and females [
17,
18,
20,
43,
45]. The resulting median estimates are 9.1% for males and 11.5% for females.
Table 5
Synthesis of previously and currently reviewed studies regarding population attributable fraction (PAR) for occupational exposures and asthma.
Current review | | | | | |
Longitudinal | 6 | 19–24 | 8.6%–44% | 19.3% | 16.3% |
Case-control | 3 | 26–29 | 9.5%–21.4% | 14.8% | 13.5% |
Cross-sectional | 7 | 31–37 | 7.0%–31.3% | 16.1% | 13.6% |
Current and earlier review | | | | | |
Longitudinal | 6 | 19–24 | 8.6%–44.0% | 19.3% | 16.3% |
Case-control | 6 | 26–29, 41–43 | 9.5%–36.0% | 20.7% | 12.2% |
Cross-sectional | 14 | 31–37, 44–51 | 7%–51% | 21.2% | 17.6% |
All | 26 | See above | 7%–51% | 20.7% | 17.6% |
All, adult-onset asthma only | 17 | 19–24, 26, 28–31, 34–36, 42, 43, 45 | 8.6%–44.0% | 18.8.5% | 16.9% |
Altogether, the median PAR value among all 26 studies included in Table
5 is 17.6%. We also made a separate estimation limited to analyses based on 17 values for adult-onset asthma only; this yielded a median PAR estimate of 16.9%.