Association of air pollution with chronic obstructive pulmonary disease: anemia-related outcomes and exploratory...

Air pollution contributes to chronic obstructive pulmonary disease (COPD), but its associations with anemia-related outcomes in COPD and the modifying role of genetic susceptibility remain unclear.

To examine the associations of ambient air pollution with COPD and anemia-related outcomes, and to assess the potential modifying role of genetic susceptibility.

This Taiwan Biobank case-control study included 7,566 cases and 22,698 age- and sex-matched controls. COPD was defined by presence of airflow obstruction or self-reported emphysema/chronic bronchitis, and anemia by World Health Organization hemoglobin cutoffs. Residential 1-, 3-, 6-, and 12-month exposures to particulate matter with an aerodynamic diameter ≤10 µm (PM₁₀) and ≤2.5 µm (PM_2.5), nitrogen dioxide (NO₂), nitric oxide (NO), nitrogen oxides (NOx), sulfur dioxide (SO₂), carbon monoxide (CO), and ozone (O₃) were estimated at recruitment. Logistic regression was used for binary outcomes, and linear regression for spirometric and hematologic traits. Models were adjusted for age, sex, body mass index, smoking experience, and genetic principal components in genetic analyses.

Higher PM₁₀, PM_2.5, NO₂, NO, NOx, SO₂, and CO exposures were associated with higher COPD risk. Each 10 µg/m³ increase in PM_2.5 was associated with COPD at 1 month [odds ratio (OR) = 1.252, 95% confidence interval (CI): 1.222-1.283] and 12 months (OR = 1.642, 95% CI: 1.588-1.699). Positive associations were observed when participants with COPD and anemia were compared with controls with anemia, whereas the within-COPD anemia analysis showed no consistent positive association between ambient air pollution and anemia status. Hemoglobin polygenic risk score showed nominal interactions with SO₂ for anemia risk in COPD across all exposure periods (interaction ORs = 1.062-1.093). In the COPD genome-wide association study, rs4808295-A in ZNF100 was associated with lower COPD risk (OR = 0.865, p = 1.63 × 10^-10) and remained stable in sensitivity analysis.

Residential air pollution exposure across the evaluated pre-recruitment averaging periods was associated with COPD. The nominal HGB PRS-SO₂ interaction suggests heterogeneity in hematologic responses according to genetic susceptibility, whereas the within-COPD anemia analysis did not show a consistent positive association between ambient air pollution and anemia status.