Cardiopulmonary mortalityLung functionAmbient air pollutionMediation analysisSurvival analysis

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, PM2.5, PM2.5 absorbance, NO2 and NOx 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 NOx and NO2 were associated with increased risks of CPM (eg. HR =1.215; 95%CI: 1.017–1.452 for IQR increase in NOx 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 PM2.5 absorbance and CPM remained significant in models adjusted for FEV1/FVC, but the associations with PM10 and PM2.5 were not significant. The mediation analysis showed sig-nificant indirect effects of NO2 and NOx 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 NOx (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. 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 (NOx and NO2), but less pronounced for PM10 and PM2.5.