Rheumatoid arthritis and risk of chronic obstructive pulmonary disease or asthma among women: A marginal structural model analysis in the Nurses' Health Study

Abstract

Objective: We investigated whether RA increases risk for chronic obstructive pulmonary disease (COPD) or asthma independent of factors occurring before RA onset or mediating these respiratory morbidities after diagnosis, such as cigarette smoking.

Methods: Within the prospective Nurses' Health Study (n = 121,701 women; 1976-2014), we identified an incident RA cohort and matched each woman with RA to 10 comparators without RA by age and year at index date of RA diagnosis, excluding women with COPD or asthma at baseline. Data were obtained through biennial questionnaires and medical records. We used marginal structural models to determine the independent effect of RA on incident COPD or asthma adjusting for confounders and time-varying mediators through inverse probability weighting.

Results: We identified 843 women with RA, matched to 8,399 comparators without RA. Mean age was 59.8 years and mean follow-up after index date was 18.6 years (SD = 9.0) for women with RA, and 18.8 years (SD = 9.5) for comparators. We identified 68 (8.1%) incident COPD and 40 (4.7%) asthma cases among women with RA, and 459 (5.5%) COPD and 268 (3.2%) asthma cases among comparators. RA was associated with increased risk of COPD (HR = 1.52, 95% CI: 1.17-1.97) and asthma (HR = 1.55, 95% CI: 1.11-2.16) compared to comparators adjusted for the matching factors of age and calendar year at index date. After further adjustment for confounders and time-varying mediators occurring after index date, including smoking, RA was significantly associated with COPD (HR = 1.68, 95% CI: 1.36-2.07), but not asthma (HR = 1.11, 95% CI: 0.59-2.09) compared to non-RA comparators. Women with seropositive RA (HR = 1.60, 95% CI: 1.17-2.19) and seronegative RA (HR = 1.62, 95% CI: 1.09-2.40) had similar increased risk for COPD compared to non-RA comparators.

Conclusion: In this prospective cohort study, RA was associated with increased risk for incident COPD, independent of lifestyle confounders and mediators after diagnosis, including smoking.

Keywords: Asthma; COPD; Causal inference; Epidemiology; Respiratory; Rheumatoid arthritis.