Abstract

Background:Interstitial lung disease (ILD) is characterized by progressive inflammation and fibrosis, and accumulating evidence have shown that exposure to air pollutants was associated with the development of ILD. Autoimmune diseases are highly correlated with ILD, including connective tissue disease-associated ILD (CTD-ILD) as well as interstitial pneumonia with autoimmune features (IPAF), and the development of ILD is a crucial cause of morbidity and mortality in patients with autoimmune diseases. One recent Taiwanese study reported that exposure to air pollutants was associated with incident systemic lupus erythematosus (SLE). However, the impact of air pollutants on the development of ILD among patients with autoimmune diseases remains unknown.Objectives:The study aimed to address the impact of accumulating exposure to air pollutant above moderate level, defined by Air Quality Index (AQI) value higher than 50, on the development of ILD in patients with autoimmune diseases including SLE, rheumatoid arthritis (RA) and primary Sjögren’s syndrome (SS).Methods:We used a National Health Insurance Research Database in Taiwan to enroll patients with SLE (International Classification of Diseases (ICD)-9 code 710.0, n=13,211), RA (ICD-9 code 714.0 and 714.30–714.33, n=32,373), and primary SS (ICD-9 code, 710.0, n=15,246) between 2001 and 2013. We identified newly diagnosed ILD cases (ICD-code 515) between 2012 and 2013 and selected age, sex, disease duration and index-year matched (1:4) patients as non-ILD controls. The hourly levels of air pollutants one year prior to the index-date were obtained from 60 air quality monitoring stations across Taiwan, and the air pollutants in the present study consisted of particulate matter <2.5 μm in size (PM2.5), particulate matter <10 μm in size (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2) and ozone (O3). We used a spatio-temporal model built by a deep-learning mechanism to estimate levels of air pollutants at 374 residential locations based on data of 3 air quality monitoring stations near the location (8). Notably, we used cumulative exposed hours to air pollutants higher than modest level, defined by AQI criteria, given that daily mean level of air pollutants might possibly underestimate the triggered inflammatory effect by a temporary exposure of high-level air pollutant. A conditional logistic regression was used to determine the association between exposure to air pollutant and the development of ILD, adjusting age, gender, Charlson Comorbidity Index (CCI), urbanization, family income, and medications for autoimmune diseases.Results:A total of 272 patients with newly diagnosed ILD were identified among patients with autoimmune diseases, including 39 with SLE, 135 with RA, and 98 with primary SS. We found that the duration of exposure to PM 2.5 higher than modest level was associated with the risk of ILD development in patients with SS (adjOR 1.07, 95% CI 1.01–1.13), and similar trends were also found in patients with SLE (adjOR 1.03, 95% CI 0.95–1.12) and RA (adjOR 1.03, 95% CI 0.99–1.07). Intriguingly, we observed an inverse correlation between the duration of exposure to O3 and the development of ILD in patients with SS (adjOR 0.83, 95% CI 0.70–0.99); however, the finding was not found in patients with SLE (adjOR 1.13, 95% CI 0.92–1.37) and RA (adjOR 0.98, 95% CI 0.87–1.11).Conclusion:In conclusion, we identified that longer exposure to PM2.5 higher than modest level tended to be associated with the development of ILD in patients with autoimmune diseases, mainly SS.

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