title: Work related asthma. A causal analysis controlling the healthy worker effect.
abstract: OBJECTIVE
  The healthy worker effect usually leads to underestimation of the association between occupational exposure and asthma. The role of irritants in work-related 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 work-related asthma.
authors.affiliation: Inserm, Center for research in Epidemiology and Population Heatlh (CESP), U1018, Respiratory and Environmental Epidemiology team, F-94807, Villejuif, France. orianne.dumas@inserm.fr
authors.forename: Orianne
authors.initials: O
authors.lastname: Dumas
authors.forename: Nicole
authors.initials: N
authors.lastname: Le Moual
authors.forename: Valérie
authors.initials: V
authors.lastname: Siroux
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.forename: Judith
authors.initials: J
authors.lastname: Garcia-Aymerich
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Varraso
authors.forename: Francine
authors.initials: F
authors.lastname: Kauffmann
authors.forename: Xavier
authors.initials: X
authors.lastname: Basagaña
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D059366:Asthma, Occupational / Q000453:epidemiology* / Q000209:etiology* / Q000503:physiopathology; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005602:France / Q000453:epidemiology; D015989:Healthy Worker Effect; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D009790:Occupations; D016017:Odds Ratio; D012016:Reference Values; D012720:Severity of Illness Index; D017678:Sex Distribution; D055815:Young Adult