The Occupational Exposome and New-Onset COPD: Longitudinal Analyses of Two European Cohorts.

OBJECTIVES:Occupational exposures may contribute to the development of COPD, a leading cause of morbidity and mortality globally. Using an exposome approach in a follow-up design, we aimed to examine the association between the occupational exposome and new-onset COPD in 2 population-based cohorts: the European Community Respiratory Health Survey (ECRHS) with 2 follow-ups (n = 4,087; observations = 6,224) and the CONSTANCES cohort with 1 follow-up (n = 8,255). METHODS:COPD was defined by respiratory symptom(s) and forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) below the lower limit of normal. Occupational exposures were assessed through long-term job histories linked to 6 job exposure matrices representing 49 different chemical, ergonomic, and physical exposures. Cumulative occupational exposures until baseline were assigned to each participant. Three analytical approaches were used: Exposome-Wide Association Study (ExWAS), Least Absolute Shrinkage and Selection Operator (LASSO), and Boruta Random Forest. RESULTS:In ECRHS, across the 3 analytical approaches, the most important exposures associated with increased COPD were heavy lifting, forward-bent posture, gases and fumes, mineral dust, house dust mites, and kneeling/squatting. In CONSTANCES, the most important exposures were diesel exhaust fumes, respirable crystalline silica, other solvents, organic solvents, indoor cleaning, and mineral dust. Differences in follow-up time and cohort characteristics may explain cohort discrepancies. CONCLUSION:We confirmed the importance of several chemical occupational exposures for COPD and observed new associations between ergonomic and physical occupational exposures and COPD. These associations more likely reflect broader occupational exposure patterns than independent effects and should be interpreted in that context. Despite complexities in interpretation, the results underline the importance of implementing new analytical approaches, as it provide opportunities to identify the interplay of occupational exposures in an occupational exposome context.