The mediating role of lung function on air pollution-induced cardiopulmonary mortality in elderly women: The SALIA cohort study with 22-year mortality follow-up

Abstract

Background: Air pollution exposure is associated with reduced lung function and increased cardio-pulmonary mortality (CPM).

Objectives: We analyzed the potential mediating effect of reduced lung function on the association between air pollution exposure and CPM.

Methods: We used data from the German SALIA cohort including 2527 elderly women (aged 51-56 years at baseline 1985-1994) with 22-year follow-up to CPM. Exposures to PM₁₀, PM_2.5, PM_2.5 absorbance, NO₂ and NO_x were assessed by land-use regression modelling and back-extrapolated to estimate exposures at baseline. Lung function (FVC, FEV₁) was measured by spirometry and transformed to GLI z-scores. Adjusted Cox proportional hazards and causal proportional hazards mediation analysis models were fitted.

Results: The survival analysis showed that reduced lung function (z-scores of FVC or FEV₁ below 5% predicted) reflected significantly lower survival probability from CPM (p < 0.0001). Longterm exposures to NO_x and NO₂ were associated with increased risks of CPM (eg. HR = 1.215; 95%CI: 1.017-1.452 for IQR increase in NO_x and HR = 1.209; 95%CI: 1.011-1.445 for IQR increase in NO₂) after adjusting for reduced lung function and additional covariates. The associations of PM_2.5 absorbance and CPM remained significant in models adjusted for FEV₁/FVC, but the associations with PM₁₀ and PM_2.5 were not significant. The mediation analysis showed significant indirect effects of NO₂ and NO_x on CPM mediated through reduced FEV₁ and FVC. The largest indirect effects were found for exposures to NO₂ (HR = 1.037; 95%CI: 1.005-1.070) and NO_x (HR = 1.028; 95%CI: 1.004-1.052) mediated through reduced FVC. The mediated proportion effect ranged from 13.9% to 19.6% in fully adjusted models.

Discussion: This study provides insights into the mechanism of reduced lung function in association between long-term air pollution exposure and CPM. The mediated effect was substantial for exposure to nitrogen oxides (NO_x and NO₂), but less pronounced for PM₁₀ and PM_2.5.

Keywords: Ambient air pollution; Cardiopulmonary mortality; Lung function; Mediation analysis; Survival analysis.