Exposome-wide associations and polyexposure risks of workplace chemical exposures on adult asthma: The Personalized Environment and Genes Study (PEGS).

Many potential occupational asthmagens remain unrecognized, and their co-exposure risks are underestimated. We conducted an exposome-wide association study (ExWAS) to systematically explore occupational chemical exposures and estimate their joint association with asthma outcomes using polyexposure risk scores (PXS). This North Carolina-based cross-sectional study included 3148 adults. Standardized questionnaires assessed occupational exposure to 93 chemical agents across 18 classes (>15 min/week, ever or never) and personal protective equipment (PPE) use. Current adult asthma was defined as self-reported doctor-diagnosed asthma with recent attacks. Respiratory multimorbidity was ascertained if asthma coexists with allergic rhinitis or chronic obstructive pulmonary disease. Logistic regression-based ExWAS analyzed associations for individual chemicals. Weighted standardized PXS were developed for predefined known asthmagens (PXS known) and suspected or novel risk agents (PXS suspected or novel) selected from ExWAS through LASSO regularization. Ever exposure to classes of cleaning liquids, heavy metals, dust, and combustion emissions was positively associated with asthma [adjusted odds ratio (aOR): 1.50-2.10; false discovery rate<0.05], with findings on mineral dust replicated using an independent NHANES dataset. The top individual risk agents were talc, ammonia, bleach, silica, and carbon monoxide. PXS known (four agents) and PXS suspected or novel (six agents) showed positive associations with asthma and multimorbidity (aOR: 1.22-1.94 per 0.1 increments). Participants using PPE had reduced asthma odds in relation to PXS suspected or novel (Pinteraction< 0.05). This study identified six suspected and novel chemical risk agents not yet recognized as occupational asthmagens by major classification systems. The findings enhance understanding of chemical-induced asthma risks and highlight the potential impact of combined exposures in occupational settings.