Short-term exposure to air pollutant mixtures and seasonal acute exacerbations of chronic obstructive pulmonary disease: A time-stratified case-crossovecr study

Although ambient air pollution triggers acute exacerbation of chronic obstructive pulmonary disease (AECOPD), pollutants are commonly evaluated individually and mixture and lagged effects are often overlooked. Using the Korean National Health Insurance Service-National Sample Cohort (2006-2019), the short-term effects of air pollution on AECOPD incidence were investigated. A time-stratified case-crossover design matched each case day to control days from the same year, season, and weekday. Conditional Poisson regression with distributed lag nonlinear models (DLNMs) estimated lag-specific and cumulative relative risks for single pollutants, while quantile g-computation (Qgcomp) evaluated mixture effects. Lag structures up to 7 d were analyzed, adjusting for meteorological factors and public holidays. Stratified analyses were conducted by age, sex, income level, smoking status, and body mass index (BMI). In total, 5981 AECOPD events were identified. Short-term ambient pollutant exposure increased AECOPD risk, especially during winter and spring. In season-stratified DLNMs, pollutant effects strengthened across longer lags and moving-average windows, whereas O₃ showed opposite patterns in winter. Multiple pollutants exerted combined effects on AECOPD, with early peaks in spring (lags 0-2), the highest estimate at lag 0 (odds ratio [OR] = 1.19, 95% CI: 1.04-1.34), and persistent associations across lag structures in winter (ORs: 1.20-1.28). Stronger effects were observed among men, adults aged ≥ 65 years, current smokers, and individuals with BMI ≥ 25. Short-term ambient air pollutant exposure increased AECOPD risk during winter and spring, especially in men and the elderly, underscoring the importance of targeted measures to reduce pollution exposure among vulnerable populations.