Work related asthma. A causal analysis controlling the healthy worker effect

摘要

Objectives The healthy worker effect usually leads to underestimation of the association between occupational exposure and asthma. The role of irritants in workrelated asthma is disputed. We estimated the effect of occupational exposure on asthma expression in a longitudinal study, using marginal structural modelling to control for the healthy worker effect. Methods Analyses included 1284 participants (17-79 years, 48% men) from the follow-up (2003-2007) of the French Epidemiological study on the Genetics and Environment of Asthma (case-control study). Age at asthma onset, periods with/without attacks over lifetime and occupational history were recorded retrospectively. Exposures to known asthmagens, irritants or low level of chemicals/allergens were evaluated through a job-exposure matrix. The job history was reconstructed into 5-year intervals. Results Thirty-one per cent of subjects had ever been exposed to occupational asthmagens. Among the 38% of subjects who had asthma (ever), presence of attacks was reported in 52% of all time periods. Using standard analyses, no association was observed between exposure to known asthmagens (OR (95% CI): 0.99 (0.72 to 1.36)) or to irritants/low level of chemicals/allergens (0.82 (0.56 to 1.20)) and asthma attacks. Using a marginal structural model, all associations increased with suggestive evidence for known asthmagens (1.26 (0.90 to 1.76)), and reaching statistical significance for irritants/low level of chemicals/allergens (1.56 (1.02 to 2.40)). Conclusions The healthy worker effect has an important impact in risk assessment in work-related asthma studies. Marginal structural models are useful to eliminate imbalances in exposure due to disease-driven selection. Results support the role of irritants in workrelated asthma.