The Associations of Air Pollution Mixture Exposure with Plasma Proteins in an Elderly U.S. Panel

The impact of air pollution exposure on circulating proteins remains underexplored, particularly in vulnerable elderly populations. This study investigated the individual and joint effects of air pollutants on circulating proteins in 208 elderly participants from the Cancer Prevention Study-II Nutrition Cohort. Prediagnostic plasma samples were collected (1998-2001), and 484 proteins were measured using the Olink platform. Annual average exposures to six air pollutants in the calendar year of blood draw were estimated. We used linear regression for individual pollutants and quantile g-computation for mixture effects, adjusting for confounders, considering multiple comparison correction, and testing interactions with smoking status. Pathway enrichment and protein-protein interaction analyses were conducted for the associated proteins. We identified 167 distinct proteins associated with individual pollutants or mixtures (<i>p</i> < 0.05), including 15 meeting a false discovery rate <0.2. IL32, ADAM15, and IL8 demonstrated consistent negative associations with ≥4 exposure metrics. Twenty proteins were associated with both mixtures and individual air pollutants with consistent effect directions. These proteins were enriched in pathways linked to immunity and signaling. Stratified analyses revealed differing associations with 99 proteins between current and former smokers. The findings offer valuable insight into the chronic biological response in plasma protein levels to air pollution exposure.