Occupational Contribution to Idiopathic Pulmonary Fibrosis

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic diffuse parenchymal lung disease that by definition is of unknown etiology. Multiple studies have identified occupational exposures associated with IPF. We sought to estimate the occupational contributions to IPF using a meta-analytic approach. Methods: We identified relevant publications through September 2016 by searching PubMed and EMBASE, manually reviewing their references, and consulting additional sources. Included studies had a case-control design; provided a clear case definition (using clinical criteria, histological diagnosis, autopsy records, or death certificate notation of IPF); and assessed occupational exposure (through questionnaire or supporting records). Two investigators independently reviewed and abstracted data for four exposure categories common to multiple studies: “any dust,” “metal dust,” “wood dust,” and “agricultural dust.” One study did not provide a risk estimate for an exposure (wood dust) that was not reported by any controls; we estimated an odds ratio (OR) by substituting 0.5 for 0. One study reported population attributable fraction (PAF); for all others, we calculated PAF as follows: PAF=pc(RR – 1)/RR, where pc is the proportion of cases exposed and RR is the risk estimate. We calculated pooled OR and pooled PAF for occupational exposures using fixed effects models and random effects models in Stata. When the results of the models differed substantively, we used the results of the fixed effects model, which were more conservative. The pooled PAF relied on the ratio of attributable cases to all cases underlying each risk estimate. Results: We included 32 risk estimates from 12 publications (one in abstract form only), totaling 1949 IPF cases. Each exposure category was assessed with 6-10 risk estimates. Pooled ORs were significantly elevated for each category; the pooled PAF estimates by category ranged from 4-13% (Table). Conclusions: IPF is associated with occupational exposure to dust generally and specifically, wood, metal, and agricultural dusts. Some of the observed excess risk could represent disease misclassification of pneumoconiosis or hypersensitivity pneumonitis, but this phenomenon is unlikely to fully explain the observed effects. Our analysis supports an etiologic role of some occupational exposures in IPF, potentially explaining up to 13% of the burden of disease and highlighting a possible role of workplace exposure reduction in disease prevention.