Late Breaking Abstract - Interaction of High Air Pollution Exposure and MUC5B rs35705950 on Interstitial Lung Disease Risk in Rheumatoid Arthritis Patients

<bold>Background:</bold> Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis share common risk factors, including the gain-of-function MUC5B promoter variant (rs35705950). We investigated the contribution of air pollutants to the ILD risk in a RA population, and assessed the modifying effect of genetic susceptibility. <bold>Methods:</bold> This multicenter French retrospective study involved RA patients who had undergone thoracic CT. We estimated exposure levels to NO2, PM10, and PM2.5 related to the patients' area zip code addresses using a dispersion model. Logistic regression was used to analyze the influence of air pollution on ILD occurrence. Then, the interaction between air pollution and MUC5B rs35705950 was estimated by the RERI. <bold>Results:</bold> We included 594 RA patients with thoracic CT (mean age: 58±12 years, 419 (71%) women, 261 (44%) current or ex-smokers). ILD was identified in 227 (38%) cases. The presence of ILD was associated with long-term exposure to PM2.5 [OR: 1.04,(1.02-1.07), p=0.007], PM10 [OR: 1.11, (1.06-1.69), p<0.001], and NO2 [OR: 1.07, (1.03-1.12), p=0.001] after adjusting for sex, age, and smoking. MUC5B rs35705950 genotypes were available for 292 patients. In this subgroup, the contribution of PM2.5, PM10, and NO2 remains statistically significant after adjusting for the above-cited covariates and the MUC5B rs35705950 status. A positive interaction (RERI > 0) was observed between high exposure (above the median level) to each air pollutant (PM2.5, PM10, and NO2) and the presence of MUC5B T risk allele. <bold>Conclusion:</bold> Air pollution and MUC5B interact to increase risk of ILD in patients with RA