Why asthma progresses to COPD: environmental and genetic drivers

Xia, Y. — 2025-12-15T08:40:27-08:00

Asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic respiratory illnesses, with considerable overlap in older adults.1 Patients with features of both often face accelerated lung function decline, frequent exacerbations and poorer survival.2 Understanding why some patients with asthma progress to COPD has long been a challenge. In this issue of Thorax, Li and colleagues provide timely evidence implicating long-term air pollution exposure and genetic susceptibility in shaping this trajectory.3

Air pollution is a leading cause of respiratory morbidity worldwide.4 Particulate matter with a diameter of 2.5 µm (PM_2.5) and nitrogen dioxide (NO₂), largely from combustion sources, have been linked to COPD incidence and mortality in multiple cohorts.5 6 The WHO 2021 Air Quality Guidelines recommend annual concentrations below 5 μg/m³ for PM_2.5 and 10 μg/m³ for NO₂,7 yet most countries fail...

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

Li, G., Zhang, K., Yang, T., Jin, J., Guo, X., Cai, Y. S., Huang, J. — 2025-12-15T08:40:27-08:00

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 (NO₂) 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 NO₂, 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/m³ for PM_2.5 and 12 µg/m³ for NO₂. 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.

Thorax Environmental exposure

Why asthma progresses to COPD: environmental and genetic drivers

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