Inhalational exposures associated with risk of interstitial lung disease: a systematic review and meta-analysis
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Rationale: Inhalational exposures are associated with risk of developing interstitial lung disease (ILD), yet the relationship between specific exposures and ILD is poorly characterized.
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 until 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 multi-level meta-analysis was specified using a random effects model. Sources of heterogeneity and risk of bias were assessed.
Main Results: Ninety-six studies were included in the systematic review, representing 40,819,116 subjects (295,167 had ILD, 40,523,949 controls). For the meta-analysis, fifty-four 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 1.47-1.94), organic exposures (OR 1.56, 95% CI 1.12-2.16), metals (OR 1.52, 95% CI 1.07-2.16), dust (OR 1.45, 95% CI 1.20-1.76), and asbestos (OR 1.53, 95% CI 1.08-2.15). Silica and fumes had positive associations with ILD that trended toward 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, characterize the gene-environment interaction, and develop preventative strategies.
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 until 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 multi-level meta-analysis was specified using a random effects model. Sources of heterogeneity and risk of bias were assessed.
Main Results: Ninety-six studies were included in the systematic review, representing 40,819,116 subjects (295,167 had ILD, 40,523,949 controls). For the meta-analysis, fifty-four 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 1.47-1.94), organic exposures (OR 1.56, 95% CI 1.12-2.16), metals (OR 1.52, 95% CI 1.07-2.16), dust (OR 1.45, 95% CI 1.20-1.76), and asbestos (OR 1.53, 95% CI 1.08-2.15). Silica and fumes had positive associations with ILD that trended toward 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, characterize the gene-environment interaction, and develop preventative strategies.
Date Issued
2025-12-01
Date Acceptance
2025-05-09
Citation
Thorax, 2025, 80 (12), pp.918-926
ISSN
0040-6376
Publisher
BMJ Publishing Group
Start Page
918
End Page
926
Journal / Book Title
Thorax
Volume
80
Issue
12
Copyright Statement
© Author(s) (or their employer(s)) 2025. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Publication Status
Published
Date Publish Online
2025-06-15