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

<bold>Aim:</bold> In the UK, an estimated 15% of asthma patients have a concurrent COPD diagnosis. This study aims to investigate the roles of both air pollution and genetic susceptibility in the progression from asthma to COPD. <bold>Methods:</bold> The study included 46,832 participants with asthma who were recruited into the UK Biobank cohort during baseline years 2006-2010. Adjusted covariates including age, sex, ethnicity, Townsend deprivation score, education level, economic status, smoking, alcohol consumption and body mass index (BMI) were obtained from questionnaire and physical measurement. Air pollutants (PM2.5 and NO2) were estimated at baseline address using land-use regression models. Genetic risk score (low, moderate, high) was derived for each participant using novel genetic signals identified for asthma-COPD overlap. Cox proportional hazards regression analysis was employed to quantify the risks of both air pollution and genetic scores on incident COPD among asthmatics. <bold>Results:</bold> During a median 8.1 years of follow-up, 3,759 (8%) participants with asthma at baseline had developed COPD. For each 10 µg/m3 increase in PM2.5 and NO2, the hazard ratio (HR) of developing COPD among asthmatics was 1.56 (95%CI: 1.12, 2.17) and 1.10 (95%CI: 1.04, 1.15) respectively. There was an evident dose-response relationship identified for NO2, whilst the significant association was found only in the highest exposure group of PM2.5. For both pollutants, significant associations were observed only among those with a high genetic risk score. <bold>Conclusion:</bold> Traffic-related air pollution is clearly linked to the progression from asthma to asthma-COPD, particularly among those with a moderate-to-high genetic risk score.