American Journal of Respiratory and Critical Care Medicine

Rationale: Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections.

Methods: Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group.

Results: Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%).

Conclusions: Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases.


 Key Conclusions



Occupational Burden of Asthma Incidence

Occupational Burden of COPD and Chronic Bronchitis

Occupational Burden of IPF

Occupational Burden of PAP and Other Interstitial Lung Diseases

Occupational Burden of HP (Extrinsic Allergic Alveolitis) and Other Granulomatous Lung Diseases, Including Sarcoidosis

Occupational Burden of TB and CAP


Occupational exposures are important, frequently overlooked, and modifiable contributors to the burden of respiratory disease. Quantifying the occupational contribution to this disease burden is critical to preventing disease and improving lung health. To date, the question of the occupational burden in respiratory disease at the population level has been addressed primarily in relation to asthma and chronic obstructive pulmonary disease (COPD). This document reviews and synthesizes existing data to quantify the occupational contribution to the burden of nonmalignant respiratory diseases across a range of conditions frequently unrecognized as potentially work related.

Key Conclusions

A substantial evidence base indicates that the contribution of inhalational workplace hazards to the burden of nonmalignant lung diseases is substantial.

Conditions for which the estimated occupational burden is 10% or more include asthma, COPD, chronic bronchitis, idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), other noninfectious granulomatous lung diseases (including sarcoidosis), pulmonary alveolar proteinosis (PAP), and community-acquired pneumonia (CAP).

These findings highlight the need for greater awareness that work exposures contribute substantially across a range of respiratory diseases.

Strategies are needed to improve the recognition and prevention of the substantial occupational burden of nonmalignant respiratory diseases.

Inhalation of vapors, gas, dust, or fumes (VGDF) in the workplace is common worldwide, and occupation is an important global contributor to the burden of respiratory disease (1). For asthma and COPD, the contribution of workplace exposures has been a particular focus of attention in previous American Thoracic Society (ATS) policy statements (24). Occupational exposures also contribute to the disease burden in a number of other conditions, including interstitial disease diagnosed as IPF, HP, other noninfectious granulomatous lung diseases such as sarcoidosis, other interstitial lung diseases, and selected respiratory infections (59).

We synthesized data from multiple sources to quantify the occupational contribution to the burden of nonmalignant respiratory disease. The occupational burden in thoracic cancer (lung and pleura) has been well characterized elsewhere (1012). Of note, the classic pneumoconioses (including silicosis, coal workers’ pneumoconiosis, and asbestosis) remain an important, unabating global health problem that is not addressed in this document because the occupational contribution to these conditions is essentially 100%. That does not detract, however, from their public health importance.

In this statement, we assess the occupational burden in four categories of respiratory conditions: airway disease (asthma, COPD, and chronic bronchitis), interstitial lung disease (IPF as well as PAP and other uncommon interstitial diseases), granulomatous processes (HP and other noninfectious granulomatous diseases, including sarcoidosis), and selected respiratory infections (tuberculosis [TB] and CAP).

We searched the PubMed and Embase databases from their respective start dates through December 31, 2017, unless otherwise noted. A supplemental literature search was conducted covering January to September 2018. The search strategies, including start dates, rationale, and search terms, are shown in Table E1 in the online supplement. For asthma, COPD, and chronic bronchitis, searches took into account the previous ATS reports (24) and additional reviews (1320). We also reviewed reference citations in identified publications to identify relevant papers. Except when stated explicitly, all data were population based and were not limited to a specific industry or exposure. For asthma, COPD, chronic bronchitis, and IPF, we estimated the occupationally related population attributable fraction (PAF) reported by or derived from case–control and cohort studies. When needed, we calculated the PAF using the odds ratio (OR) and proportion of cases exposed [PAF = pc(OR − 1)/OR, where pc is the proportion of cases exposed] (3). We limited the analysis of asthma to incident data. For PAP, HP, and sarcoidosis, we extracted data from cases series in which the proportion of occupationally related cases was available. For TB, we used World Health Organization and World Bank databases (2123) for data on country-specific general population rates to estimate relative disease incidence by occupation. For CAP, we examined both PAF estimates and, within exposure cohorts, the attributable fraction (AF). We pooled published or derived PAF values (asthma, COPD, chronic bronchitis, and interstitial lung disease) and the occupationally attributable burden (PAP, HP, and sarcoidosis) to obtain weighted summary estimates using the metaproportion command in Stata 14.2 software (StataCorp). We used the exact method to compute the 95% confidence interval (CI) for each pooled estimate. Because we recognized that the heterogeneity among the studies was high, we calculated the pooled PAF or proportion using random effects modeling with case numbers informing the weights. We also estimated statistical heterogeneity using the I2 statistic, which in each case was consistent with high heterogeneity, as we expected (values not presented). We also calculated the pooled estimate excluding the highest and lowest values in the group, as well as calculating the median of the observed PAF or occupational burden values. For TB and CAP, we did not calculate weighted pooled values, limiting summary data to the median values among the estimates considered. For consistency, we use the term “occupational burden” across the various disease outcomes analyzed, even though in some cases the burden was derived from PAF estimates, whereas in others the burden was derived from attribution in case series, incidence rate ratios (IRRs), or AF within a group.

Work-related asthma is now the most commonly reported work-related respiratory disorder in many industrialized countries. Work-related asthma comprises occupational asthma, defined as asthma “caused” by the workplace, and work-exacerbated (or aggravated) asthma, meaning preexisting asthma with work-related worsening (24). Cross-sectional (prevalence) studies have dominated previous estimates of the occupational burden of disease. To build on earlier estimates, we limited our search to longitudinal, population-based studies that reported incident asthma and occupational risk factors.

We identified nine studies with longitudinal data relevant to occupation and incident asthma for inclusion (2533) (Table 1). Of these, six had been included in a previous review (20), including a study of Israeli military recruits (over 95% of the Jewish male population aged 18 yr) exposed across a range of vocations (30). Three newer studies have been published since the previous review (20). One study investigating asthma incidence among persons aged 13–44 years in Tasmania (Australia) reported a high cumulative incidence of asthma (37%) with a work-related job exposure matrix (JEM)-based PAF of 10% (26). A second study, using the RHINE (Respiratory Health in Northern Europe) adult study population aged 20–44 years, estimated a JEM-based PAF for occupation of 14% for males and 7% for females (28). A later reanalysis using a different JEM arrived at similar estimates (13% and 8% for males and females, respectively) (34). A third longitudinal study analyzed data from the United Kingdom. 1958 birth cohort limited to those without asthma by age 16 with later follow-up through age 42 (29). Using a JEM to assess exposure risk, the overall occupational PAF was 16%, with wide confidence intervals (95% CI, 3.8–27.1%).

Table 1. Longitudinal Population-based Studies of Occupational Risk for Asthma

First Author, Year, Location (Reference)Study TypeIncident Cases (n [Total Population])Definition of ExposurePAF (%)
Katz, 1999, Israel (30)Population follow-up ages 18–21 yr at baseline588 (59,058)Military exposure combat or maintenance vs. clerical44
Karjalainen, 2001, Finland (31)Population follow-up ages 25–59 yr at baseline49,575 (1,852,848)Work-related compensation22
Eagan, 2002, Norway (25)Population follow-up ages 15–70 yr at baseline101 (2,723)Self-reported dust and fume exposure at baseline14
LeVan, 2006, Singapore (27)Population follow-up ages 13–44 yr at baseline1,426 (52,325)Occupations exposed to dust, smoke, or vapors8.6
Kogevinas, 2007, international (32)Population follow-up ages 20–44 yr at baseline133 (6,837)Exposure to high-risk substances by JEM11
Hedlund, 2006, Sweden (33)Population follow-up ages 36–37, 50–52, and 66–67 yr at baseline271 (5,933)Blue collar industrial workers vs. others9
Lillienberg, 2013, international (28)Population follow-up in RHINE population ages 20–44 yr at baseline129 males (5,933)Exposure to high-risk substances by JEM14
286 females (6,253)7
Hoy, 2013, Australia (Tasmania) (26)Population follow-up ages 13–44 yr at baseline290 (792*)Exposure to high-risk substances by JEM10
Ghosh, 2013, UK (29)Population follow-up of birth cohort up to age 42 yr611 (7,088)Any asthma JEM >016.3

Definition of abbreviations: JEM = job exposure matrix; PAF = population attributable fraction; RHINE = Respiratory Health in Northern Europe; UK = United Kingdom.

The pooled estimated PAF for the occupational contribution to incident asthma was 16% (95% confidence interval, 10–22%).

*Subjects with asthma at baseline excluded.

Total before subjects with childhood asthma were excluded.

Pooling data from all nine studies yielded an estimated PAF for the occupational contribution to incident asthma of 16% (95% CI, 10–22%) (Figure 1), which is comparable to prior estimates (2). Overall, longitudinal data from which inferences can be drawn on the occupational burden of incident asthma are limited. Of note, the studies considered were largely done in developed economic settings. Sex-stratified longitudinal data are even more limited; we identified only two such analyses, both with lower PAF estimates for women than for men.

Seven reviews published since the 2003 ATS statement (3, 1316, 18, 19) identified 33 papers relating to the occupational contribution to COPD or chronic bronchitis. Of note, two of these found a median PAF for the occupational contribution to COPD of 15% (13, 15); one meta-analysis estimated a pooled OR of 1.43 for COPD related to VGDF exposures (18), whereas another meta-analysis observed minimal excess risks (1.04–1.15) for separate JEM-defined exposures (16). The additional literature search for publications published between 2014 and 2017 identified a further 15 relevant citations not among the 33 included in the reviews noted above.

We retained population-based studies that included a range of potential occupations or case–control studies that clearly reflected the general population. Studies were excluded if they lacked a clear definition of the disease endpoint (e.g., either COPD or chronic bronchitis) or when key data were missing (e.g., studies not presenting the number of subjects exposed that would have allowed for a PAF calculation). When a study reported multiple endpoints or measures of exposure, we preferentially considered risk estimates for COPD defined by spirometry (using lower limit of normal, if reported) over self-reported COPD, and, similarly, we considered JEM-defined risk over self-reported exposure. In studies stratified by smoking status, the ever-smoking stratum was the one used in the pooled analysis of PAF. When data from a never-smoking stratum were available (in some cases the entire cohort analyzed), we used these in a separate pooled analysis of PAF among never-smokers. Results presented only in a stratified manner (e.g., by sex) were considered as separate estimates of risk.

We included 26 studies to estimate the contribution of occupational exposures to the burden of COPD (3560) and 7 for the contribution to chronic bronchitis (39, 40, 50, 51, 6163). Table 2 summarizes the 26 COPD studies considered, including 28 estimates of risk (taking into account sex-stratified data). The pooled PAF for the occupational contribution to the burden of COPD (including cohorts with mixed smoking status, adjusted for smoking) was 14% (95% CI, 10–18%) (Figure 2). The occupational PAF for COPD among never-smokers (not shown in table), estimated from six studies including stratified data (35, 47, 51, 6466), yielded a pooled PAF of 31% (95% CI, 18–43%).

Table 2. Population-based Studies of Occupational Risk for Chronic Obstructive Pulmonary Disease

First Author, Year, Location (Reference)Study Type and PopulationTotal (N)Number of CasesDefinition of COPDExposure InformationPAF (%)
Hnizdo, 2002, USA (35)Population based9,823693COPD = FEV1/FVC <0.7 and FEV1 <80% (pre-BD)Occupational groups19.6
Trupin, 2003, USA (36)Population based1,932377Self-reported doctor’s diagnosisSelf-reported20.0
de Marco, 2004, international (37)Population based14,3181,751COPD = FEV1/FVC <0.7 (pre-BD)Self-reported exposure to dust, gas, and fumes17.4
Lindberg, 2005 Sweden (38)Population based (longitudinal)1,10983COPD = FEV1/FVC <0.7 and FEV1 <80% (pre-BD)Socioeconomic classification (manual worker in industry)15.0
Sunyer, 2005, international (39)Population based (longitudinal), females3,27953COPD = FEV1/FVC <0.7 (pre-BD)VGDF by JEM (high exposure)1.0
Sunyer, 2005, international (39)Population based (longitudinal), males3,20261COPD = FEV1/FVC <0.7 (pre-BD)VGDF by JEM (high exposure)0
Jaén, 2006, Spain (40)Population based49773COPD = FEV1/FVC <0.7 (post-BD)Self-reported (any exposure to dust, gas, and fumes)9.0
Zhong, 2007, China (41)Population based20,2451,668COPD = FEV1/FVC <0.7 (post-BD)Self-reported (any exposure to dust, gas, and fumes)3.9
Weinmann, 2008, USA (42)Case–control744388COPD = FEV1/FVC below LLN or by algorithmJEM24
Blanc, 2009, USA (43)Case–control1,5041,202COPD = FEV1/FVC <0.7 (pre-BD)VGDF by JEM (high exposure)14.0
Blanc, 2009, USA (44)Case–control1,78879COPD = FEV1/FVC <0.7VGDF self-reported17.0
Melville, 2010, UK (45)Population based84184COPD = FEV1/FVC <70 and FEV1 <80% (post-BD)Self-reported occupational exposure at risk of COPD50.0
Idolor, 2011, Philippines (46)Population based722141COPD = FEV1/FVC <70 (post-BD)Self-reported exposure in a dusty job5.2
Mehta, 2012, Switzerland (47)Population based (longitudinal)1,958*43*COPD = FEV1/FVC below LLN stage II+ (pre-BD)VGDF by JEM (high exposure)23*
Lam, 2012, China (48)Population based8,216461COPD = FEV1/FVC below LLN (pre-BD)Self-reported (any exposure to dust, gas, and fumes)10.4
Darby, 2012, UK (49)Population based571197COPD = FEV1/FVC <70 (pre-BD)Self-reported VGDF exposure20
Hansell, 2014, New Zealand (50)Population based75083COPD = FEV1/FVC below LLN (pre-BD)VGDF by JEM (high exposure)2.7
Doney, 2014, USA (51)Population based3,508196COPD = FEV1/FVC below LLN and FEV1 below LLN (pre-BD)Self-reported (severe exposure)38.8
de Jong, 2014, Netherlands (52)Population based (LifeLine cohort),11,8511,754COPD = FEV1/FVC <0.7 (pre-BD)VGDF by JEM (high exposure)4.3
de Jong, 2014, Netherlands (52)Population based (Vlagtwedde-Vlaardingen cohort)2,364639COPD = FEV1/FVC <0.7 (pre-BD)VGDF by JEM (high exposure)9.7
Pallasaho, 2014, Finland (53)Population based (longitudinal)4,080140Self-reportedSelf-reported23.6
Scholes, 2014, UK (54)Population based7,6031,032COPD = FEV1/FVC below LLN (pre-BD)Job classification as routine occupation9.1
Paulin, 2015, USA (55)Population-based cohort of smokers1,075721COPD = FEV1/FVC <0.7 (post-BD)VGDF by JEM (intermediate/high risk)12.0
Würtz, 2015, Denmark (56)Population based4,132279COPD = FEV1/FVC below LLN (pre-BD)VGDF by JEM (high exposure)10.3
Obaseki, 2016, Nigeria (57)Population based87567COPD = FEV1/FVC below LLN (post-BD)Self-reported (dusty jobs)14.9
Tagiyeva, 2017, UK (58)Population based23763COPD = FEV1/FVC below LLN (post-BD)VGDF by JEM0
Sinha, 2017, India (59)Population based1,203122COPD = FEV1/FVC <0.7 (post-BD)Self-reported34.6
Torén, 2017, Sweden (60)Population based1,05250COPD = FEV1/FVC <0.7 + dyspnea, wheezing, or chronic bronchitisSelf-reported37

Definition of abbreviations: BD = bronchodilator; COPD = chronic obstructive pulmonary disease; JEM = job exposure matrix; LLN = lower limit of normal; PAF = population attributable fraction; UK = United Kingdom; USA = United States; VGDF = vapors, gas, dust, or fumes.

The pooled PAF for the occupational contribution to COPD was 14% (95% confidence interval, 10–18%). The pooled PAF for the occupational contribution to COPD in nonsmokers (references not in table [35, 47, 51, 6466]) was 31% (95% confidence interval, 10–18%).


Table 3 summarizes the seven chronic bronchitis studies used (eight estimates of risk). The pooled PAF for chronic bronchitis was 13% (95% CI, 6–21%) (Figure 3). Only two studies allowed estimation of the occupational PAF for chronic bronchitis among never-smokers, yielding values of 8.3% (51) and 12% (67). Several publications excluded from the tables nonetheless warrant mention. Accelerated annual decline in FEV1 in males with early COPD was observed in association with occupational exposures (68). An ecological analysis of three large international studies estimated a 0.8% increase in COPD prevalence per 10% increase in occupational exposures, taking into account the concomitant prevalence of smoking (43). Several large population-based studies have addressed the association between various occupations and COPD (11, 69, 70). Also of note, other researchers have investigated large occupational cohorts, including construction workers exposed to dust (71, 72).

Table 3. Population-based Studies of Occupational Risk for Chronic Bronchitis

First Author, Year, Location (Reference)Study Type and PopulationTotal (N)Cases (n)ExposurePAF (%)
Montnémery, 2001, Sweden (61)Population based8,469390Self-reported11.0
Lange, 2003, Denmark (62)Population based3,736602Self-reported16.0
Sunyer, 2005, international (39)Population based (longitudinal), males3,951273VGDF by JEM15.0
Sunyer, 2005, international (39)Population based (longitudinal), females4,312250VGDF by JEM0.0
Jaén, 2006, Spain (40)Population based57669Self-reported29.4
Doney, 2014, USA (51)Population based3,508280Self-reported (severe exposure)23.1
Hansell, 2014, New Zealand (50)Population based1,01786JEM (high exposure)13.1
Axelsson, 2016, Sweden (63)Population based1,17284Self-reported8.6

Definition of abbreviations: JEM = job exposure matrix; PAF = population attributable fraction; USA = United States; VGDF = vapors, gas, dust, or fumes.

The pooled PAF for the occupational contribution to chronic bronchitis was 13% (95% confidence interval, 6–21%).

In summary, an impressive body of new data on the occupational burden of COPD, and to a lesser degree chronic bronchitis, has been published since the original 2003 ATS statement. In aggregate, participant numbers are large and international in scope. The pooled estimates of the occupational PAF of 14% for COPD and 13% for chronic bronchitis are in line with those of the previous ATS statement and interval reviews. Moreover, the higher occupational PAF for COPD among never-smokers (31%) suggests that occupational exposures contribute more substantially to the burden of COPD in nonsmokers.

IPF is a diagnosis of exclusion made in the presence of a usual interstitial pneumonia pattern on biopsy or with a consistent appearance on a high-resolution computed tomographic scan. The IPF diagnosis presumes that known causes of interstitial lung disease have been excluded (e.g., drug toxicity; connective tissue disease; and domestic, occupational, or environmental exposures) (73). Therefore, studies of cohorts with a diagnosis of IPF presumably already exclude persons with a recognized occupational cause of fibrosis, such as asbestosis.

We identified four reviews of occupational exposures in IPF (5, 7476) that collectively included 10 relevant case–control studies. One of these, a meta-analysis of six studies, reported a PAF for several exposure categories ranging from 3.5% (silica) to 20% (agriculture) (5). Adding more recent citations (n = 5), we identified a total of 15 relevant case–control studies addressing the question of occupational exposures associated with IPF (7791). Four of the 15 publications were not included in our PAF estimates: one because data were not available on the proportion of cases with specific occupational exposures (78), two because of methodological issues in exposure assignment (85, 86), and one because of overlap with an included study (90). We initially included one publication that appeared in abstract form only (92), because we were aware that the full paper was forthcoming (89). The remaining 11 case–control studies provided data permitting analysis of occupational exposures in five exposure categories: VGDF, metal dust, wood dust, silica dust, and agricultural dust. For the IPF analysis, VGDF represents an inclusive category combining any of multiple exposures, defined variously by each study.

Thirty-nine risk estimates from 11 studies (1,229 IPF cases in total) contributed to these pooled PAF estimates (Table 4) (77, 7984, 87, 88, 91, 92). The burden of each pooled exposure type was based on 5–11 individual risk estimates (Table 5). The pooled OR for agricultural work (five studies) was elevated but not statistically significant (OR, 1.6; 95% CI, 0.8–3.0), with a PAF of 4%. The pooled ORs for each of the remaining exposure categories were elevated and statistically significant. These pooled PAFs were as follows: silica (3%), wood dusts (4%), metal dusts or fumes (8%), and VGDF (26%). A forest plot for the estimates for VGDF, the broadest exposure category, is presented in Figure 4.

Table 4. Case-Referent Studies of Occupational Risk Factors for Idiopathic Pulmonary Fibrosis

First Author, Year, Location (Reference)Cases (N)IPF Case Definition CriteriaOR (95% CI)PAF (%)
Scott, 1990, UK (77)40Clinical, CXR, PFT1.3 (0.8–2.0)11.0 (2.3–52.4)2.9 (0.9–9.9)10.9 (1.2–96)1.6 (0.5–4.8)171210125
Hubbard, 1996, UK (79)218Clinical, CXR, CT, PFTNA1.7 (1.1–2.7)1.7 (1.0–2.9)NANANA106NANA
Mullen, 1998, USA (80)15Clinical, lung biopsy, CT2.4 (0.7–8.4)NA3.3 (0.4–25.8)NA11.0 (1.1–115)20NA7NA20
Baumgartner, 2000, USA (81)248Clinical, biopsy, CTNA2.0 (1.0–4.0)1.6 (0.8–3.3)1.6 (1.0–2.5)3.9 (1.2–12.7)NA5372
Hubbard, 2000, UK (82)22Death certificateNA1.1 (0.4–2.7)NANANANA5NANANA
Miyake, 2005, Japan (83)102Lung biopsy, BAL, CT5.6 (2.1–17.9)9.6 (1.7–181.1)6 (0.3–112.4)NA1.8 (0.5–7.0)26114NA5
Gustafson, 2007, Sweden (84)140Pulmonary fibrosis requiring tissue1.1 (0.7–1.7)0.9 (0.5–1.6)1.2 (0.7–2.2)NA1.4 (0.7–2.7)6NA3NA3
García-Sancho, 2011, Mexico (87)100Clinical, CT, lung biopsy2.8 (1.5–5.5)NANANANA50NANANANA
Awadalla, 2012, Egypt (Men) (88)95Clinical, CT, PFTNA1.6 (0.7–3.6)2.7 (1.1–6.8)1.0 (0.4–2.3)1.1 (0.5–2.7)NA69NA1
Awadalla, 2012, Egypt (Women) (88)106Clinical, CT, PFTNANA4.3 (0.8–22.1)3.3 (1.2–10.1)NANANA614NA
Paolocci, 2013, Italy (92)65Clinical, CTNA2.8 (1.1–7.2)1.1 (0.4–3.3) (soft wood)NA2.0 (0.9–4.4)NA90NA11
0.9 (0.3–2.8) (hard wood)0
Koo, 2017, Korea (91)78Clinical, CT2.7 (0.7–10.9)5.0 (1.4–18.2)2.5 (0.5–12.4)NA1.2 (0.4–3.8)35225NA5

Definition of abbreviations: Ag = agricultural dusts; CI = confidence interval; CT = computed tomography; CXR = chest radiograph; IPF = idiopathic pulmonary fibrosis; NA = not applicable; OR = odds ratio; PAF = population attributable fraction; PFT = pulmonary function test; UK = United Kingdom; USA = United States; VGDF = vapors, gas, dust, or fumes, which represent all the exposure categories shown combined and, in selected studies, additional exposures as well.

All studies had case–control designs, with most by interview-based self-reported exposure assessment (Hubbard exposure by job category). Awadalla and colleagues stratified their study sample by male (n = 95) and female (n =  106). The study by Paolocci and colleagues, which estimated risk with two separate wood variables, later appeared as a full publication (89).

Table 5. Pooled Population Attributable Fraction Estimates for Occupation and Idiopathic Pulmonary Fibrosis

ExposureRisk Estimates (N)Pooled OR (95% CI)Pooled PAF (%) (95% CI)
VGDF62.0 (1.2–3.2)26 (10–41)
Metal dusts92.0 (1.3–3.0)8 (4–13)
Wood dusts111.7 (1.3–2.2)4 (2–6)
Agricultural dusts51.6 (0.8–3.0)4 (0–12)
Silica81.7 (1.2–2.4)3 (2–5)

Definition of abbreviations: CI = confidence interval; OR = odds ratio; PAF = population attributable fraction; VGDF = vapors, gas, dust, or fumes, which represent all the other exposure categories shown combined and, in selected studies, additional exposures as well.

In summary, our findings suggest that occupational exposures contribute substantially to the burden of disease otherwise considered idiopathic and labeled “IPF.” It is also interesting to note that in one Korean study, patients with IPF who had been occupationally exposed to dust had earlier onset of disease and worse prognosis (93). A major challenge in assessing the occupational burden of IPF disease is differentiating between disease misclassification (e.g., chronic HP or one of the classic pneumoconioses [e.g., asbestosis, silicosis] misdiagnosed as IPF) and a causative role of work exposures in usual interstitial pneumonia–like processes. Another important challenge is exposure misclassification, especially when estimating chronic inhalational work exposures over many years. For example, asbestos exposure was common in metal and wood industries and could have contributed to these exposure-associated PAFs for IPF.

PAP has been categorized as primary (idiopathic), secondary, or congenital (94, 95). Primary PAP involves autoantibodies to granulocyte–macrophage colony–stimulating factor (94); secondary PAP is attributed to a variety of occupational exposures, most notably silica (96108). Cases of autoimmune PAP have been reported in occupationally exposed persons (98, 99, 109111).

We included 29 relevant publications since 1958 subsuming 1,539 PAP cases (with a range of 10–241 cases per series) (112140), excluding overlapping reports (141144). The reported occupational exposure prevalence ranged from 0% to 67%, with a pooled prevalence of 29% (95% CI, 21–37%) (Table 6). A range of exposures was reported, including vapors or gases (cleaning fluids, gasoline, hairspray, paint, and pesticides), inorganic dusts (asbestos, cement, chalk, coal, glass fiber, and silica), organic dusts (cotton, flour, wood, and wool), and metal dusts or fumes (aluminum, copper, indium, iron, and zirconium). Among 19 publications that specifically reported on silica (786 PAP cases), the exposure prevalence ranged from 0% to 22%, with pooled prevalence of 5% (95% CI, 2–8%) (112, 114120, 124127, 129, 133, 135137, 139, 140). Among the five publications describing 345 autoimmune PAP cases, occupational exposure prevalence ranged from 26% to 55% (121, 132, 133, 139, 141).

Table 6. Occupational Exposures in Pulmonary Alveolar Proteinosis

First Author, Year, Location (Reference)Exposure MeasureCases (N)Occupational Burden (%)
Davidson,1969, international (112)Reported history13950
McEuen, 1978, USA (113)Lung tissue particles3735
Rubin, 1980, Canada (114)Reported history1315
Kariman, 1984, USA (115)Reported history230
Prakash, 1987, USA (116)Reported history349
Asamoto, 1995, Japan (117)Reported history6815
Goldstein, 1998, USA (118)Reported history2450
Kim, 1999, Korea (119)Reported history1040
Briens, 2002, France, Belgium (120)Questionnaire4139
Inoue, 2008, Japan (121)Questionnaire19926
Fang, 2009, China (122)Reported history1118
Xu, 2009, China (123)Reported history2418
Byun, 2010, Korea (124)Reported history380
Bonella, 2011, Germany (125)Questionnaire7051
Fang, 2012, China (126)Reported history2536
Campo, 2013, Italy (127)Reported history7336
Zhao, 2013, China (128)Reported history3067
Fijołek, 2014, Poland (129)Reported history1724
Ilkovich, 2014, Russia (130)Reported history6859
Yang, 2014, China (131)Reported history1020
Akasaka, 2015, Japan (132)Reported history3126
Xiao, 2015, China (133)Questionnaire4538
Bai, 2016, China (134)Questionnaire10150
Deleanu, 2016, Romania (135)Reported history2020
Hadda, 2016, India (136)Reported history3514
Huang, 2016, China (137)Reported history1729
Mo, 2016, China (138)Reported history1118
Guo, 2017, China (139)Reported history3749
Hwang, 2017, Korea (140)Reported history7148

Definition of abbreviation: USA = United States.

All studies are case series except four case–control studies (113, 126, 133, 158) and one national registry (121). “Reported history” refers to occupational or exposure history from the clinical record. Occupational burden is based on the prevalence among cases of occupations likely to involve inhalational exposures or inhalational exposures likely to be occupational. The pooled occupational burden was 29% (95% confidence interval, 21–37%).

Although PAP has a more robust literature relevant to the occupational burden of disease, there are a number of other respiratory syndromes in which occupational associations have been observed in disease outbreaks, in certain work settings, or after suspect exposures (142, 145161). Table E2 provides selected examples of these reported associations, which include bronchiolitis and the flavoring chemical diacetyl; cryptogenic organizing pneumonia and textile dye (“Ardystil syndrome”); and diffuse pulmonary hemorrhage and trimellitic anhydride (142, 145161).

We synthesized data from 15 relevant publications for HP, the earliest paper dating from 1983 (see Table 7). We excluded case series limited to a single avocation or occupation (e.g., bird fanciers or machinists) (162, 163), if there were insufficient data to determine the proportion due to an occupational exposure (164), or if there were overlapping cases (165) that were included in another publication (166). The studies included (166180) were all case series (or registries), except for one case–control design (167), but used variable criteria for diagnosing HP and assessing causation. For the case series, we considered the work-related cases within a larger series to represent the occupational burden of disease. The estimated occupational burden of disease (Figure 5) ranged from 0% to 81.3%, with a weighted metaproportion of 19% (95% CI, 12–28%).

Table 7. Occupational Associations with Hypersensitivity Pneumonitis

First Author, Year, Location (Reference)Study TypeCases (N)Disease DefinitionExposure/Job InformationCommentsOccupational Burden (%)
Kawanami, 1983, USA (168)Case series18Clinical, radiographic, physiologic, and laboratory dataHistory, clinical data, and serologic testing in 13 patients72.2% environmental; 27.7% unknown cause0
Yoshida, 1995, Japan (169)Case series835Criteria of the Japan Research Committee on Diffuse Pulmonary Disease for Hypersensitivity PneumonitisHistory, clinical data, and serologic testing79.4% environmental; 6.8% unknown cause13.8
Yoshizawa, 1999, Japan (170)Case series36Clinical and imaging criteriaHistory, clinical data, and serologic testing61.4% environmental; 13.9% unknown cause, series limited to chronic HP25.3
Thomeer, 2001, Belgium (171)Multicenter disease registry47A set of clinical and imaging criteria; data from the nationwide electronic registerNot clearly stated76.6% environmental; 23.4% unknown cause0
Bang, 2006, USA (172)Death certificate date814Death certificate codingOccupationally related ICD codes for causes>100% due to multiple coded causes of HP38.4% occupational; 55.6% unknown cause40.5
Hanak, 2007, USA (173)Case series from a single center85Clinical and imaging criteria from the Mayo Clinic databaseHistory, clinical data, and serologic testing64.7% environmental; 24.7% unknown cause10.6
Olson, 2008, USA (174)Case series from a single center4Retrospective case review; only cases with acute exacerbation of fibrotic HPHistory, clinical data, and serologic testing; biopsy confirmation50% environmental; 50% unknown cause0
Selman, 2010, multicountry (166)Prospective multicenter cohort study199Clinical and imaging data, supported by the experts’ opinionHistory, clinical data, and serologic testing76.9% environmental; 1.5% unknown cause21.6
Cımrın, 2010, Turkey (175)Review of published cases22Based on cases as defined in publications reviewedHeterogeneous66.6% environmental; none of unknown cause33.3
Caillaud, 2012, France (176)Case series, multicenter139Clinical and imaging criteriaHistory, clinical data, and serologic testing18.7% environmental; none of unknown cause81.3
Alhamad, 2013, Saudi Arabia (177)Case series21A set of clinical and imaging criteria followed by expert reviewQuestionnaire42.9% environmental; 33.3% unknown cause23.8
Castonguay, 2015, USA (178)Case series40Clinical and imaging criteriaHistory, clinical data, and serologic testing; case overlap with Hanak et al., 2007 (173)55% environmental; 37.5% unknown cause7.5
Millerick-May, 2016, USA (179)Case series19ATS guidelines for the diagnosis of ILDHistory, clinical data, and serologic testing51.9% environmental; none of unknown cause42.1
Singh, 2017, India (180)Prospective registry513Diagnostic criteria, expert reviewQuestionnaire69.4% environmental; 24.8% unknown cause5.8
Cramer, 2016 Denmark (167)Retrospective cohort study6,920Cases identified from records in Danish National Patient RegisterData on occupation were provided by Statistics DenmarkOR, 1.55 (95% CI, 1.40–1.72); cases exposed = 46%20.2

Definition of abbreviations: ATS = American Thoracic Society; CI = confidence interval; HP = hypersensitivity pneumonitis; ICD = International Classification of Diseases; ILD = interstitial lung disease; OR = odds ratio; USA = United States.

Occupational burden is derived from the proportion of occupationally attributed cases in the series or, in the case of Cramer and colleagues (167), derived from the OR and proportion of exposed cases. The overall burden of occupationally attributed HP is 19% (95% CI, 12–28%).

In addition to HP, we also considered the occupational burden of other noninfectious granulomatous lung diseases. Inhalation of beryllium can cause granulomatous lung disease that mimics sarcoidosis; other metals have also been associated with granulomatous responses; and sarcoidosis prevalence has been reported to be elevated among various occupational groups, including firefighters, navy recruits, workers in the lumber industry, rock or glass wool workers, salespeople, and World Trade Center disaster emergency responders (181, 182). Several large case-referent studies of patients with sarcoidosis who were not beryllium sensitized have found that occupational exposures to organic dusts, bioaerosols, and metals increased risk of sarcoidosis (183185). A study of sarcoidosis prevalence in Switzerland found higher frequencies in regions with metal industry and intense agriculture (186). In a large U.S. study using national death certificate data, sarcoidosis mortality risk was significantly elevated in association with metalworking, health care, teaching, sales, banking, and administration (181). Mortality data also suggest that occupational exposures may increase risk for a more severe sarcoidosis phenotype (187).

Epidemiological evidence on the proportion of chronic beryllium disease misdiagnosed as sarcoidosis is limited to a few case series (188192) and one case-referent study (193). Combining beryllium-focused studies of sarcoidosis with other studies that estimated occupational risk, we identified seven studies to use to estimate the occupational burden of sarcoidosis (Table 8) (181, 183, 184, 188190, 193). The pooled estimated occupational proportion of sarcoidosis ranged from 0% to 54%, with a weighted metaproportion of 30% (95% CI, 17–45%).

Table 8. Occupational Proportion of Granulomatous Disease Diagnosed as Sarcoidosis

First Author, Year, Location (Reference)Study TypeCases (N)Disease DefinitionExposure/Job InformationCommentsOccupational Burden (%)
Fireman, 2003, Israel (190)Case series47Tissue diagnosis with positive beryllium lymphocyte transformation testPossible occupational exposure to berylliumCase series from one outpatient clinic6.4
Kucera, 2003, USA (185)Sibling case–control303Clinicoradiographic presentation consistent with sarcoidosisStructured occupational history questionnaireACCESS questionnaire for occupational history37
Barnard, 2005, USA (183)Case–control706Tissue diagnosis with negative beryllium lymphocyte proliferation testStructured occupational history questionnaireMulticenter study, ACCESS questionnaire for occupational history51.6
Müller-Quernheim, 2006, Germany (189)Case series84Clinicoradiographic presentation consistent with sarcoidosis and positive beryllium lymphocyte proliferation testPossible occupational exposure to beryllium, determined by questionnaireProspective study over 7 yr40.4
Ribeiro, 2011, Canada (188)Case series121Clinicoradiographic presentation consistent with sarcoidosis and positive beryllium lymphocyte proliferation testPossible occupational exposure to beryllium, determined by questionnaireNo positive beryllium lymphocyte proliferation test results0
Cherry, 2015, Canada (193)Case-referent63Medical record review, cases with diagnosis of sarcoidosis, referents with other chronic lung diseasePatient interview, employment in an industry with possible exposure to berylliumChronic beryllium disease diagnosis based on Glu69 status46
Liu, 2016, USA (181)Population-based mortality3,393Sarcoidosis death based on cause of death listed on death certificateUsual occupation on death certificateLarge national dataset53.8

Definition of abbreviations: ACCESS = A Case-Control Etiologic Study of Sarcoidosis; USA = United States.

Occupational burden is derived from the proportion of occupationally attributed cases in series or derived from a reported odds ratio and proportion of exposed cases. The overall burden of occupationally attributed sarcoidosis is 30% (95% confidence interval, 17–45%).

Certain occupational groups are at increased risk for TB infection or bacterial CAP. The occupational burden of these infectious diseases, however, has been infrequently quantified (194197). Searching back to 1990, we identified 9 silica-related and 17 healthcare worker (HCW)-related relevant studies for inclusion in this analysis (198222) (Tables 9 and 10). We excluded studies that dealt exclusively with latent TB, did not use diagnostic criteria for TB, or were reviewed in previous analyses (and thus were not included in our estimates) (195, 223).

Table 9. Tuberculosis among Silica-exposed Workers

First Author, Year, Location (Reference)Study TypeTB Definition/DiagnosisExposure/Job InformationPopulation Cases (n)/Control or Total Population (N)Risk Estimates (95% CI when available)Occupational Burden (%)
Rosenman, 1996, USA (209)Case–controlBacteriological or reporting of treatmentSIC and SOC codes used as proxy for exposuresHIV-positive and foreign-born individuals excluded; 149 cases from New Jersey TB Register, 209 control subjects from previous cancer studiesAdjusted OR for silica industries: 1.6 (0.7–3.8)4.9
Chen, 1997, USA (210)Case–controlDeath certificate data from NOMS databaseSilica-exposed workers8,740 cases: 2% intermediate, 14% high; 83,338 control subjectsORintermed: 1.1 (0.8–1.5)Intermediate: 0.2
ORhigh: 1.3 (1.1–1.5)High: 3.2
Calvert, 2003, USA (211)Case–controlDeath certificate data from NOMS databaseSubjects assigned to a qualitative silica exposure category6,570 cases: medium (11.7%), high (9.5%), super high (0.6%), 32,843 TB control subjectsORmed: 1.3 (1.2–1.5)Medium: 3.04
ORhigh: 1.6 (1.5–1.8)High: 3.4
ORsuper high: 2.5 (1.7–3.7)Super high: 3.6
Kleinschmidt, 1997, South Africa (212)CohortBacteriological and clinical diagnosisGold miners from a single mine, followed from 1975 to 1996449 cases (total cohort = 4,976 gold miners)IRR, 2.52.3
Murray, 1999, South Africa (213)CohortCulture-positive sputumGold miners from four mines376 cases (total cohort = 28,522 gold miners)IRR, 4.24.8
Churchyard, 2000, South Africa (214)CohortBacteriological and clinical diagnosisGold miners at a single mine followed from 1993 to 19972,893 casesIRR, 7.57.9
Sonnenberg, 2005, South Africa (215)CohortCulture-positive “probable TB” = score of radiography, sputum, tuberculin, histology, and trialGold miners from four mines followed from 1991 to 1997747 cases (total cohort = 23,874)IRR, 3.93.8
Glynn, 2008, South Africa (216)CohortCulture and clinical findingsGold miners from four mines followed from 1991 to 2004620 new cases among 7,583 participantsIRR, 4.32.0
van Halsema, 2012, South Africa (217)CohortCultureGold miners from two mines followed from 2002 to 20084,268 TB/19,476 (mine A)IRR, 3.1 (mine A)Mine A: 1.1
1,472 TB/8,414 (mine B)IRR, 2.5 (mine B)Mine B: 0.8

Definition of abbreviations: CI = confidence interval; IRR = incidence rate ratio; NOMS = National Occupational Mortality Surveillance; OR = odds ratio; SIC = Standard Industrial Classification; SOC = Standard Occupational Classification; TB = tuberculosis; USA = United States.

Except for publications providing an OR, the occupational burden is estimated from an IRR derived from World Bank and World Health Organization data for the silica-exposed labor force and national TB rates. The median silica-associated burden of TB was 2.3% (range, 0.8–7.9%).

Table 10. Tuberculosis among Healthcare Workers

First Author, Year, Location (Reference)Study TypeTB Definition/DiagnosisExposure/Job InformationCases (n)/Control or Total Population (N)Risk EstimateOccupational Burden (%)
Rosenman, 1996, USA (209)Case–controlBacteriological or treatment reportingSIC and SOC codes used as proxy for exposuresHIV-positive, foreign-born cases excluded; 149 cases from TB registry; 290 cancer referentsOR, 2.8 (95% CI, 1.4–5.7)8.2
Raitio, 2000, Finland (203)National register reviewBacteriologically, histologically, and/or clinicallyAll HCWs assessed for occupational TB, extracted from national register658 cases between 1966 and 1995IRR, 0.670
Laraqui, 2001, Morocco (218)Cross-sectionalCase notificationAll HCWs notified by health services between 1994 and 1997130 cases among 152,447 HCWsIRR, 0.720
Eyob, 2002, Ethiopia (204)CohortSputum culture or clinical or radiological findingsHCWs at a specialist TB center24 cases among 175 HCWsIRR, 7.2*0.4
Jiamjarasrangsi, 2005, Thailand (198)CohortTB diagnoses in medical records databaseThai HCWs observed at a single hospital78 cases among 3,894 HCWsIRR, 3.50.1
Tam, 2006, Hong Kong (219)National registry records reviewNot statedSurveillance data of occupational TB reported to the Labor Department141 cases among 57,869 HCWs over 5 yrIRR, 0.50
de Vries, 2006, Netherlands (200)Records reviewRestriction fragment length polymorphism typing (DNA fingerprinting)Cases ‘‘working in the healthcare/social-welfare sector’’ from a national TB registry94 cases among 126,500 HCWsIRR, 0.80
Ong, 2006, USA (201)Cohort studyTB reported to San Francisco Department of Public HealthAll cases of TB reported over multiple years33 cases among HCWs among 2,510 cases reportedIRR, 1.21.0
Pazin-Filho, 2008, Brazil (205)Database reviewClinical, sputumHCWs at a university hospital21 cases among HCWsIRR, 2.6* nurse technicians1.4
Roche, 2008, Australia (199)Database reviewLaboratory, clinical diagnosis of TBHCWs recorded in National Notifiable Diseases Surveillance System65 cases among HCWs reported in 2006IRR, 2.14.0
Costa, 2011, Portugal (206)CohortClinical, bacteriological, radiologicalHCWs at the São João Hospital followed from 2005 to 201062 cases among 6,112 HCWsIRR, 3.24.4
Lambert, 2012, USA (202)Database reviewReview of National TB Surveillance System recordsTB cases reported to the CDC6,049 cases among HCWs among the 200,774 casesIRR, 0.80
Tudor, 2014, South Africa (207)Retrospective cohortBased on records capturedHCWs in three hospitals with specialist MDR-TB wards112 cases among 1,313 HCW records reviewedIRR, 2.0*1.3
Toms, 2015, Australia (220)National database reviewNational Notifiable Diseases Surveillance SystemWorking in a healthcare setting in the past 12 mo24 cases among HCWs in 2013IRR, 1.10.1
Klimuk, 2014, Belarus (208)Retrospective record reviewSputum smear, culture, drug susceptibility testingReview of records from TB healthcare facilities116 cases among 5,441 HCWsIRR, 5.48.9
O’Hara, 2017, South Africa (222)National database reviewLaboratory-confirmed diagnosisAll HCWs in a particular province in South Africa2,677 cases of TB among 32,039 HCWs over 11-yr periodIRR, 1.14*1.2
Davidson, 2017, UK (221)National TB surveillanceNotified TB cases from surveillance databaseHCW work information extracted from database2,320 cases of HCW TB between 2009 and 2013IRR, 1.5*2.8

Definition of abbreviations: CI = confidence interval; HCW = healthcare worker; IRR = incidence rate ratio; MDR-TB = multidrug-resistant tuberculosis; OR = odds ratio; SIC = Standard Industrial Classification; SOC = Standard Occupational Classification; TB = tuberculosis; UK = United Kingdom; USA = United States.

Except for one publication providing an OR, the occupational burden is estimated from an IRR either reported or derived from World Bank and World Health Organization data for the HCW labor force and national TB rates. The median HCW-associated burden of TB was 1.0% (range, 0.8–9%).

*Author-reported IRR.

We considered TB in two distinct occupational risk groups: those exposed occupationally to silica and those exposed as HCWs. For TB among the silica exposed, three U.S. studies and six South African studies allowed estimation of an occupation-associated burden of disease (209217). For the U.S. studies, the estimated burden ranged from 3.2% to 4.9%. For the South African studies using gold miner cohorts, the occupational burden was estimated by deriving an IRR for miners relative to national rates of disease; the median silica-associated burden was 2.3% (range, 0.8–7.9%) (Table 9). One other estimate of the occupational burden from an Iranian study, strikingly higher than all other studies (36%), was omitted because selection bias may have been present (224).

As shown in Table 10, we found little consistency in estimates of the occupational burden of TB in HCWs. In five studies, the incidence rate among HCWs was lower than that of the general population (200, 202, 203, 218, 219), yielding an estimated burden of zero. Among those with an appreciable burden (IRR ≥ 1), the occupational burden ranged from 0.1% (198) to 8.9% (198). In one of these studies (221), even though there was an increased TB IRR overall, this was accounted for by foreign-born HCWs, and work-acquired infection was confirmed in only a handful of cases. Based on all 17 HCW studies, the overall median estimate was 1.0% (range, 0–8.9%) (Table 10). A previous review of TB among HCWs (195) reported similar occupational burdens of disease among low– and high–TB incidence countries.

We identified 15 publications relevant to the occupational burden of CAP. Six were population-based case–control studies estimating CAP risk (225230). Of these, the earlier of two overlapping publications from the same Spanish research group was excluded (225), as well as the earlier of two related publications from Canada (226). The four remaining case-referent studies (Table 11) yielded a median PAF of 10% (range, 3–45%) for the occupational burden of pneumonia.

Table 11. Studies Used to Calculate the Occupational Population Attributable Fraction and Attributable Fraction in Community-acquired Pneumonia

First Author, Year, Location (Reference)Type of StudyPopulation/Cases/Control SubjectsPneumonia Type/DefinitionExposure InformationPAF or AF (%)*
Occupational PAF of pneumonia     
 Farr, 2000, UK (227)Case–control175 cases from British Thoracic Society study of patients with community-acquired pneumonia; 385 control subjectsAcute respiratory infiltrate; Mycoplasma excluded; 70% with streptococcal pneumonia confirmationSelf-reported dusty occupation (OR, 1.71)16
 Palmer, 2003, UK (228)Case–control525 cases, 1,222 referents aged 20–64 yr; 158 lobar; 142 segmental; 225 bronchopneumoniaNew/worse respiratory infection, new chest radiograph opacity, hospital admissionSelf-reported metal fumes in prior year; OR, 1.6, all; OR, 1.8, lobar pneumonia3, 4
 Neupane, 2010, Canada (230)Case–control365 cases of pneumonia; 494 control subjectsAdmission to hospital for pneumonia, temperature >38°C, new opacitySelf-reported exposure to VGDF (OR, 5.78)45
 Almirall, 2015, Spain (229)Case–control1,336 cases of pneumonia; 1,326 control subjectsAcute respiratory illness, new radiographic findings, antibioticsSelf-reported exposure to dust (OR, 1.7)3
Occupational AF of pneumonia in specific cohorts     
 Beaumont, 1980, USA (235)Cohort mortality8,679 metal trades union; 3,247 weldersAll pneumoniaJob classification based on union records41
 Newhouse, 1985, UK (236)Cohort mortality1,027 welders at a shipyardAll pneumoniaPersonnel records from shipyard: job title, tasks; SMR for pneumonia, 26946
 Coggon, 1994, UK (237)Cohort mortalityMale welders England and Wales, 1979–1980 and 1982–1999; 55 pneumonia deathsLobar pneumoniaOPCS; welders PMR, 25562
 Graham, 2004, USA (233)Cohort mortality5,408 Vermont granite workers; 2,539 deceased, determined by death certificatesAll pneumonia, ICD codesEmployment records SMR, <1000
 Veiga, 2006, Brazil (234)Cohort mortality2,856 coal minersAll pneumoniaEmployment records SMR for pneumonia in miners, 26362
 Palmer, 2009, UK (238)Population mortalityOccupations with exposure to metal fumes, aged 18–64 yrLobar pneumonia, ICD-9 codesOPCS; welders PMR, 242 (166–342)59
 Wong, 2010 Canada (239)Retrospective chart review1,768 cases of pneumococcal disease; 863 cases aged 18–65 yr; 18 cases in weldersInvasive pneumococcal disease, positive culture results (blood, CSF, other)Self-reported current occupation OR for welders, 2.763
 Koh, 2011, Korea (231)Retrospective cohortMineral dust– and metal fume–exposed workers: 365 cases (59 in foundry workers); control group (noise-only exposure), 927 casesAll pneumonia (viral, bacterial, fungal), >1-d hospitalization; SAR for pneumoniaNational Health Insurance claims, employer, SIC codes; foundry workers SAR, 1.64 (men)38
 Torén, 2011, Sweden (232)Prospective cohort of construction workers183,194 construction workers aged 20–64 yr; followed for 32 yr; 145 deaths resulting from pneumonia, 62 deaths resulting from lobar pneumoniaMortality of all infectious pneumonia, lobar pneumonia, pneumococcal pneumonia; viral and fungal pneumonia excluded; Swedish Cause of Death RegisterSelf-reported job title, JEM 
Relative risk for all and lobar pneumonias 
 Inorganic dusts 
  All pneumonia, 1.8747
  Lobar pneumonia, 3.3770
 Metal fumes 
  All pneumonia, 2.3157
  Lobar pneumonia, 3.6773

Definition of abbreviations: AF = attributable fraction; CSF = cerebrospinal fluid; ICD = International Classification of Diseases; JEM = job exposure matrix; OPCS = Office of Population Censuses and Surveys; OR = odds ratio; PAF = population attributable fraction; PMR = proportionate mortality ratio; SAR = standardized admission ratio; SIC = Standard Industrial Classification; SMR = standardized mortality ratio; UK = United Kingdom; USA = United States; VGDF = vapors, gas, dust, or fumes.

The median PAF among four population-based studies (top rows) is 10% (range, 3–45%); the median AF within cohorts is 52.5% (range, 38–73%).

*PAF for “Occupational PAF of pneumonia” and AF for “Occupational AF of pneumonia in specific cohorts”.

We identified nine cohort studies focusing on specific exposures or a single industry (231239). Seven estimated risk of pneumonia in welders or in individuals with metal fume exposure (231, 232, 235239); two also estimated risk for inorganic dusts (231, 232). For metal fume/welding exposures, the median AF was 52.5% (range, 38–73%). Four studies considered risk associated with inorganic dust (231234). The AF estimates from these studies varied widely (Table 11).

This comprehensive literature review and analysis of nonmalignant respiratory disease demonstrates a substantial occupational burden for multiple respiratory conditions not typically considered potentially work related (Figure 6). The findings for asthma, COPD, and chronic bronchitis build on prior estimates and reinforce the validity of an occupational PAF in the 15–20% range. The occupational contribution to the burden of cases diagnosed as IPF, other interstitial lung diseases, HP and other noninfectious granulomatous diseases (including sarcoidosis), and selected respiratory infections has not been estimated previously using an in-depth literature review and data synthesis approach.

One limitation of this review is that we censored study eligibility for the purposes of data synthesis after December 2017. To address this potential shortcoming, after completing the main analyses, we performed a supplemental literature review covering January through September 2018, identifying three additional publications that would have met criteria for inclusion to estimate occupational burden, one each relevant to COPD, chronic bronchitis, and HP (240242). All three studies’ results were consistent with our original findings. A 20-year longitudinal follow-up study of 3,343 participants of the population-based European Community Respiratory Survey found that work exposures, assessed by JEM, increased the risk of developing COPD (240). The PAF for VGDF yielded by the data from this study was 14.1%, consistent with our estimate. A cross-sectional study of 5,539 Colombians reported increased risk of chronic bronchitis associated with self-reported VGDF exposure, yielding a PAF of 16.1% (242), also consistent with our findings. The final recent publication, a U.S. retrospective health claim–based study that estimated the incidence and prevalence of HP, found that 17.0% of HP cases had occupational exposure–associated International Classification of Diseases codes, also consistent with our findings (241).

Several other limitations of this in-depth literature review and data synthesis should be noted. The literature we identified was extremely heterogeneous and not amenable to a formal systematic review that could apply all of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. Thus, we have avoided applying the label “systematic review” to this analysis. In particular, we made no attempt to formally grade publication quality, to apply methodologic restrictions on acceptability (beyond limiting the asthma analysis to prospective studies), or to weight results (beyond taking into account study size in pooled estimates). Study heterogeneity necessitated using differing approaches (e.g., PAF and prevalence) to estimate the occupational contribution to the burden of the various respiratory conditions.

Study heterogeneity also likely contributed to the wide range in the observed values for the estimated occupational burdens within the conditions we studied. To better assess this potential limitation, we also estimated all of the pooled burdens, excluding the highest and lowest values, as well as calculating the median rather than the pooled value. Reanalyses after excluding outlying values yielded point estimates that were similar to the original pooled estimates, as were the median values, neither of which were consistently lower or higher than the initial estimates (data not shown).

Across conditions, a differential in burden estimates is biologically plausible, consistent with differing potencies of risk depending on the nature of the exposure and the pathogenesis of the disease in question. It would be speculative, however, to make causal inferences from these findings, precisely because of the within- and across-condition variability that characterizes this literature.

Yet another limitation of this analysis is that it lacks data that might serve to estimate disability-adjusted life-years lost, a metric that could provide more quantitative assessment of the health impact of different work exposures and comparison across populations. Also of note, this analysis does not include classic pneumoconioses such as silicosis and asbestosis. These are conditions for which the occupational contribution is essentially 100%, obviating the need for an analysis of the estimated burden of those diseases. The pneumoconioses remain important, underrecognized global health problems associated with considerable morbidity and mortality (243247).

This assessment of the occupational burden of nonmalignant respiratory disease has clinical, research, and ultimately policy implications. There is a pressing need to improve clinical recognition and widen public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases. Greater attention should be given to reducing this occupational disease burden by identifying and implementing effective preventive interventions. In that light, the importance of preventing these diseases needs to be recognized. Policy makers, especially those who set regulatory standards and oversee their enforcement, should reassess current protections for workers around the world who are exposed to recognized hazardous inhalational exposures.

This official statement was prepared by an ad hoc task force representing the American Thoracic Society and the European Respiratory Society.

Members of the task force are as follows:

  • Paul D. Blanc, M.D., M.S.P.H. (Co-Chair)1

  • Carrie A. Redlich, M.D., M.P.H. (Co-Chair)2

  • Isabella Annesi-Maesano, M.D., Ph.D.3

  • John R. Balmes, M.D.1

  • Kristin J. Cummings, M.D., M.P.H.4

  • David Fishwick, M.D.5

  • David Miedinger, M.D., Ph.D.6

  • Nicola Murgia, M.D., Ph.D.7

  • Rajen N. Naidoo, M.D., Ph.D.8

  • Carl J. Reynolds, M.D.9

  • Torben Sigsgaard, M.D., Ph.D.10

  • Kjell Torén, M.D., Ph.D.11

  • Denis Vinnikov, M.D., Ph.D.12,13

1University of California San Francisco, San Francisco, California; 2Yale University, New Haven, Connecticut; 3Paris, France; 4National Institute for Occupational Safety and Health, Morgantown, West Virginia; 5Centre for Workplace Health, Health and Safety Laboratory, Buxton, United Kingdom; 6University of Basel, Basel, Switzerland; 7University of Perugia, Perugia, Italy; 8University of KwaZulu-Natal, Durban, South Africa; 9Imperial College School of Medicine, London, United Kingdom; 10Aarhus University, Aarhus, Denmark; 11University of Gothenburg, Gothenburg, Sweden; 12Al-Farabi Kazakh National University, Almaty, Kazakhstan; and 13National Research Tomsk State University, Tomsk, Russian Federation

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Correspondence and requests for reprints should be addressed to Paul D. Blanc, M.D., M.S.P.H., University of California, 350 Parnassus Avenue, Suite 609, San Francisco, CA 94143. E-mail: .

This Official Statement was approved by the American Thoracic Society May 2019 and the European Respiratory Society March 2019

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institute for Occupational Safety and Health.

This article has an online supplement, which is accessible from this issue’s table of contents at

Author Disclosures: J.R.B. was a physician member of the California Air Resources Board. D.M. serves as Chief Occupational Health Officer and owns shares and stock options for F. Hoffmann-La Roche Ltd. N.M. received nonfinancial support from AlkAbello, GlaxoSmithKline, and Teva. P.D.B., C.A.R., I.A.-M., K.J.C., D.F., R.N.N., C.J.R., T.S., K.T., and D.V. reported no relationships with relevant commercial interests.


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