To investigate passive smoking throughout the life course and the risk of rheumatoid arthritis (RA), while accounting for personal smoking.
We analyzed the Nurses’ Health Study II prospective cohort, using information collected via biennial questionnaires. We assessed the influence of (1) maternal smoking during pregnancy (in utero exposure), (2) childhood parental smoking, and (3) years lived with smokers since age 18. Incident RA and serostatus was determined by medical record review. Using the marginal structural model framework, we estimated the controlled direct effect of each passive smoking exposure on adult incident RA risk by serologic phenotype, controlling for early-life and time-updated adult factors including personal smoking.
Among 90,923 women, we identified 532 incident RA cases (66% seropositive) during 27.7 years (median) of follow-up. Maternal smoking during pregnancy was associated with RA after confounding adjustment (HR 1.25 [95% CI 1.03, 1.52]), but not after accounting for subsequent smoking exposures. Childhood parental smoking was associated with seropositive RA after adjusting for confounders (HR 1.41 [95% CI 1.08, 1.83]). In the controlled direct effect analyses, childhood parental smoking was associated with seropositive RA (HR 1.75 [95% CI 1.03, 2.98]) after controlling for adult personal smoking, which was accentuated among ever smokers (HR 2.18 [95% CI 1.23, 3.88]). There was no significant association of adult passive smoking with RA (20+ years lived smoker: HR 1.30 [95% CI 0.97, 1.74] vs. none).
We found a potential direct influence of childhood parental smoking on adult-onset incident seropositive RA even after controlling for adult personal smoking.

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