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BACKGROUND: The effect of long-term exposure to air pollution on the development of chronic obstructive pulmonary disease (COPD) is still controversial, and the role of the interactions of air pollution with genetic risk and lifestyle in COPD risk is unclear. METHODS: We included 452762 participants derived from the UK Biobank. Annual concentrations of air pollutions, including particle matter (PM2.5, PM10), nitrogen oxides (NOx), and nitrogen dioxide (NO2), were assessed using land-use regression model. We applied Cox proportional hazard model to evaluate the associations between air pollution and COPD risk. In addition, we constructed a polygenic risk score and a lifestyle score, and assessed whether genetic susceptibility and lifestyle modified the effect of air pollution on the COPD risk. FINDINGS: Each interquartile range (IQR) increase in annual concentrations of PM2.5, PM10, NOx, and NO2 was associated with 1.17 (95% CI: 1.15,1.19), 1.05 (95% CI: 1.03,1.06), 1.13 (95% CI: 1.11,1.14), and 1.19 (95% CI: 1.16,1.21) times the risk of COPD, respectively. We observed an additive interaction between PM2.5 and genetic risk (P-interact=0.095), and a negative interaction between PM2.5 and lifestyle (P-interact=0.062). The HRs for each IQR increase in PM2.5 were 1.21, (95% CI: 1.16-1.25) and 1.24, (95% CI: 1.21-1.26) in individuals with healthy and unfavourable lifestyle, respectively; and 1.16, (95% CI: 1.13-1.19) and 1.19, (95% CI: 1.16-1.22) in those with low genetic risk and high genetic risk, respectively. Participants with high air pollution exposure, high genetic risk and unfavourable lifestyle showed the highest risk of COPD. INTERPRETATION: Long-term exposure to air pollution was associated with increased risk of COPD, especially in those with high genetic risk and unfavourable lifestyle. FUNDING: None.

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Air pollution, Chronic obstructive pulmonary disease, Genetic susceptibility, Lifestyle