Air pollution, lung function and mortality: survival and mediation analyses in UK Biobank

Abstract

Background: Air pollution is associated with lower lung function, and both are associated with premature mortality and cardiovascular disease (CVD). Evidence remains scarce on the potential mediating effect of impaired lung function on the association between air pollution and mortality or CVD.

Methods: We used data from UK Biobank (n∼200 000 individuals) with 8-year follow-up to mortality and incident CVD. Exposures to particulate matter <10 µm (PM₁₀), particulate matter <2.5 µm (PM_2.5) and nitrogen dioxide (NO₂) were assessed by land-use regression modelling. Lung function (forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and the FEV₁/FVC ratio) was measured between 2006 and 2010 and transformed to Global Lung Function Initiative (GLI) z-scores. Adjusted Cox proportional hazards and causal proportional hazards mediation analysis models were fitted, stratified by smoking status.

Results: Lower FEV₁ and FVC were associated with all-cause and CVD mortality, and incident CVD, with larger estimates in ever- than never-smokers (all-cause mortality hazard ratio per FEV₁ GLI z-score decrease 1.29 (95% CI 1.24-1.34) for ever-smokers and 1.16 (95% CI 1.12-1.21) for never-smokers). Long-term exposure to PM_2.5 or NO₂ was associated with incident CVD, with similar effect sizes for ever- and never-smokers. Mediated proportions of the air pollution-all-cause mortality estimates driven by FEV₁ were 18% (95% CI 2-33%) for PM_2.5 and 27% (95% CI 3-51%) for NO₂. Corresponding mediated proportions for incident CVD were 9% (95% CI 4-13%) for PM_2.5 and 16% (95% CI 6-25%) for NO₂.

Conclusions: Lung function may mediate a modest proportion of associations between air pollution and mortality and CVD outcomes. Results likely reflect the extent of either shared mechanisms or direct effects relating to lower lung function caused by air pollution.

FIGURE 1

Directed acyclic graphs (DAGs) detailing the analyses in this paper. The aim of the paper is to understand the extent to which the relationship between air pollution and outcomes studied (all-cause mortality, cardiovascular disease (CVD) mortality and all incident CVD) may be mediated by lung function impairment (see DAG 1). a indicates the relationship between air pollution and lung function, which has already been studied in detail in Doiron et al. [2]. b indicates the relationship between lung function and the outcomes (see table 3; all-cause and CVD mortality have been previously studied in Gupta and Strachan [7], this analysis additionally studies fatal and non-fatal CVD events and extends analyses to smokers). The sum of a+b indicates the indirect effect of air pollution on the outcomes that passes via lung function. c′ indicates the direct effect of air pollution on the outcomes. The total effect of air pollution on the outcomes c is estimated in table 3. The mediated proportion is the indirect effect a+b divided by the total effect c and is given in table 4. PM₁₀: particulate matter <10 µm; PM_2.5: particulate matter <2.5 µm; NO₂: nitrogen dioxide; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity.

FIGURE 2

Flowchart detailing construction of the analysis sample in UK Biobank. CVD: cardiovascular disease.