Impact of sex, serostatus, and smoking on risk for rheumatoid arthritis‐associated interstitial lung disease subtypes

ObjectivesRA‐associated interstitial lung disease (RA‐ILD) includes multiple subtypes with varying histopathology, prognosis, and potential treatments. Limited research has investigated risk factors for different RA‐ILD subtypes. Therefore, we examined demographic, serologic, and lifestyle associations with RA‐ILD subtypes.MethodsWe systematically identified RA‐ILD cases and RA‐noILD controls in the Brigham RA Sequential Study and Mass General Brigham Biobank RA cohort. We determined RA‐ILD subtype (usual interstitial pneumonia [UIP], nonspecific interstitial pneumonia [NSIP], and other/indeterminate) through chest high‐resolution computed tomography imaging pattern. We investigated associations between demographic, lifestyle, and serologic factors and major RA‐ILD subtypes using multivariable logistic regression.ResultsAmong 3328 RA patients, we identified 208 RA‐ILD cases and 547 RA‐noILD controls. RA‐UIP was associated with older age (OR 1.03 per year, 95%CI 1.01 to 1.05), male sex (OR 2.15, 95%CI 1.33 to 3.48), and seropositivity (OR 2.08 95%CI 1.24 to 3.48) while RA‐NSIP was significantly associated only with seropositive status (OR 3.21, 95%CI 1.36 to 7.56). Non‐fibrotic ILDs were significantly associated with smoking (OR 2.81, 95%CI 1.52 to 5.21). Having three RA‐ILD risk factors (male, seropositive, smoking) had an OR of 6.89 (96%CI 2.41 to 19.7) for RA‐UIP compared to having no RA‐ILD risk factors.ConclusionsOlder age, seropositivity, and male sex were strongly associated with RA‐UIP while RA‐related autoantibodies were associated with RA‐NSIP. These findings suggest RA‐ILD sex differences may be driven by RA‐UIP and emphasizes the importance of further studies to clarify RA‐ILD heterogeneity and optimize screening and treatment approaches.