Effects of Air Pollution Exposure and the MUC5B rs35705950 Variant on Interstitial Lung Disease Risk in Patients With Rheumatoid Arthritis

ABSTRACT Background and Objective Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) and idiopathic pulmonary fibrosis share common risk factors, including the MUC5B promoter variant (rs35705950). We examined the contribution of air pollutants to ILD risk in an RA population and assessed the modifying effect of genetic susceptibility. Methods This study included patients with RA who had undergone chest HRCT. MUC5B status was collected when available. Exposure levels to NO 2 , PM 10 , and PM 2.5 were estimated based on residential postal code using a dispersion model. Logistic regression analysed the influence of air pollution on ILD occurrence, and the interaction between air pollution and MUC5B status was evaluated. Results We included 594 patients with RA (mean age: 58 ± 12 years, 71% women, 44% current or ex‐smokers), of whom 227 (38%) had ILD and 292 patients were genotyped for MUC5B rs35705950. Increased long‐term exposure to NO 2 (OR: 1.04 [1.01–1.06]), PM 2.5 (OR: 1.11 [1.10–1.24]), and PM 10 (OR: 1.15 [1.05–1.26]) was associated with ILD, after adjusting for age, sex, smoking status and HRCT year. A negative interaction between PM 10 /PM 2.5 exposure and the T allele suggested pollution's effect on ILD risk was attenuated in the presence of the minor T allele. Conclusion Long‐term exposure to air pollution is an independent risk factor for RA‐ILD and its effect may be modified according to MUC5B rs35705950 genotype.