Air pollution, genetic susceptibility and risk of progression from asthma to COPD

Background In the UK, an estimated 15% of asthma patients have concurrent chronic obstructive pulmonary disease (COPD), yet the underlying causes and mechanisms remain largely unexplored. This study aimed to investigate the roles of both ambient air pollution and genetic susceptibility in the progression from asthma to COPD. Methods 46 832 participants with asthma were recruited from the UK Biobank during the baseline period (2006–2010). Particulate matter with a diameter of 2.5 μm (PM 2.5 ) and nitrogen dioxide (NO 2 ) were estimated at baseline address using land-use regression models. Air pollution score reflected joint exposure to air pollution. Polygenic risk score was calculated using novel genetic signals identified for coexistence of asthma+COPD. Cox proportional hazards regression analysis was employed to quantify the risks of both ambient air pollution and genetic scores on incident COPD among asthmatics, adjusting for covariates. Results Over a median follow-up of 10.84 years, 3759 participants with asthma at baseline developed COPD. For an IQR increase in PM 2.5 and NO 2 , the HR for developing COPD was 1.07 (95% CI: 1.02 to 1.11) and 1.10 (95% CI: 1.04 to 1.15), respectively. Adverse effects could be observed at concentrations as low as 8 µg/m 3 for PM 2.5 and 12 µg/m 3 for NO 2 . A significant multiplicative interaction was identified between ambient air pollution and genetic susceptibility. Individuals with the highest genetic risk score exhibited the greatest risk, with an HR of 1.13 (95% CI: 1.05 to 1.22) per IQR increase in air pollution score (P interaction <0.05). Conclusions Ambient air pollution is strongly associated with progression from asthma to comorbidity COPD, particularly among individuals with high genetic risk.