Inhalational exposures associated with risk of interstitial lung disease: a systematic review and meta-analysis.

RATIONALE Inhalational exposures are associated with risk of developing interstitial lung disease (ILD), yet the relationship between specific exposures and ILD is poorly characterised. OBJECTIVE Identify inhalational exposures associated with ILD and estimate the effects of exposures on ILD risk. METHODS MEDLINE and EMBASE databases were searched from 1990 to 2022 to identify inhalational exposures associated with ILD diagnosis. ILDs where causality is well-established (hypersensitivity pneumonitis, pneumoconiosis) and sarcoidosis were excluded. Two independent reviewers screened abstracts with full-text review and data extraction of eligible studies. Where possible, data were pooled and multilevel meta-analysis was specified using a random effects model. Sources of heterogeneity and risk of bias were assessed. MAIN RESULTS 96 studies were included in the systematic review, representing 40 819 116 subjects (295 167 had ILD, 40 523 949 controls). For the meta-analysis, 54 studies were included (40 490 793 subjects: 273 899 ILD, 40 216 894 controls). Exposures associated with significantly increased ILD risk included smoking (OR 1.69, 95% CI 1.47 to 1.94), organic exposures (OR 1.56, 95% CI 1.12 to 2.16), metals (OR 1.52, 95% CI 1.07 to 2.16), dust (OR 1.45, 95% CI 1.20 to 1.76) and asbestos (OR 1.53, 95% CI 1.08 to 2.15). Silica and fumes had positive associations with ILD that trended towards significance. CONCLUSIONS This systematic review and multilevel meta-analysis is the first to comprehensively assess the effect of inhalational exposures on overall risk of ILD, with multiple putative exposures identified. Future work should investigate novel occupational exposures associated with ILD, characterise the gene-environment interaction and develop preventative strategies. PROSPERO REGISTRATION NUMBER CRD42022292908.