Risk of respiratory diseases associated with long-term ozone exposure: a nationwide population-based cohort study

• This study estimates the risk of respiratory diseases (COPD and asthma) by 5-year ozone exposure from 2006 to 2019 in almost all Koreans. • Individual 5-year cumulative O3 exposure was estimated based on monthly averages of daily maximum 8-hour moving concentrations using residential area. • Higher O3 exposure was associated with increased COPD and asthma incidence after adjustment for confounding factors including PM2.5. Short-term exposure to ozone (O 3 ) has been linked to respiratory diseases, but evidence on long-term effects remains limited. This study evaluated the association between cumulative O 3 exposure and the incidence of chronic obstructive pulmonary disease (COPD) and asthma. This is a nationwide retrospective cohort study using Korean National Health Insurance data covering the entire Korean population from 2006 to 2019. Nine overlapping 5-year cumulative O 3 exposure cohorts were created, and disease incidence in the subsequent year was identified using NHI data. Monthly averages of daily maximum 8-hour moving O 3 concentrations were linked to residential areas to estimate cumulative exposure. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using negative binomial generalized linear models with a log link to account for overdispersion, adjusting for demographics, socioeconomic status, residential area, and fine particulate matter (PM₂.₅); calendar year was modeled with spline functions to flexibly control for nonlinear temporal trends. The logarithm of person-years was included as an offset, and cluster-robust (sandwich) standard errors were used to account for within-stratum correlation. Higher O 3 exposure was associated with increased COPD incidence, with adjusted RRs of 1.042 (95% CI 1.033–1.051) for Q2, 1.164 (1.155–1.174) for Q3, and 1.216 (1.205–1.227) for Q4 versus Q1 (p<0.001). Asthma risk also increased (Q4 vs Q1: RR 1.070 [1.065–1.075]; p<0.001). Associations persisted across PM 2.5 strata and were strongest among women aged ≥65 years in urban area (Q4: COPD, 1.189 [1.156–1.223]; asthma, 1.102 [1.088–1.116]). This large population-based study provides robust evidence that long-term O 3 exposure contributes to COPD and asthma incidence. As ambient O 3 levels continue to rise in East Asia, reducing ozone precursors and strengthening protection for vulnerable groups should be prioritized in environmental and public health policy.