Longitudinal associations between metabolites and long-term exposure to ambient air pollution: Results from the KORA cohort study.

• Longitudinal study in the general population with a large sample size. • The repeated measurements of metabolites strengthened statistical power. • Soot, coarse particles and NO 2.were negatively associated with some phosphatidylcholines. • Physically inactive participants were more susceptible. Long-term exposure to air pollution has been associated with cardiopulmonary diseases, while the underlying mechanisms remain unclear. To investigate changes in serum metabolites associated with long-term exposure to air pollution and explore the susceptibility characteristics. We used data from the German population-based Cooperative Health Research in the Region of Augsburg (KORA) S4 survey (1999–2001) and two follow-up examinations (F4: 2006–08 and FF4: 2013–14). Mass-spectrometry-based targeted metabolomics was used to quantify metabolites among serum samples. Only participants with repeated metabolites measurements were included in the current analysis. Land-use regression (LUR) models were used to estimate annual average concentrations of ultrafine particles, particulate matter (PM) with an aerodynamic diameter less than 10 μm (PM 10), coarse particles (PM coarse), fine particles, PM 2.5 absorbance (a proxy of elemental carbon related to traffic exhaust, PM 2.5abs), nitrogen oxides (NO 2 , NO x), and ozone at individuals' residences. We applied confounder-adjusted mixed-effects regression models to examine the associations between long-term exposure to air pollution and metabolites. Among 9,620 observations from 4,261 KORA participants, we included 5,772 (60.0%) observations from 2,583 (60.6%) participants in this analysis. Out of 108 metabolites that passed stringent quality control across three study points in time, we identified nine significant negative associations between phosphatidylcholines (PCs) and ambient pollutants at a Benjamini-Hochberg false discovery rate (FDR) corrected p -value < 0.05. The strongest association was seen for an increase of 0.27 μg/m3 (interquartile range) in PM 2.5abs and decreased phosphatidylcholine acyl-alkyl C36:3 (PC ae C36:3) concentrations [percent change in the geometric mean: −2.5% (95% confidence interval: −3.6%, −1.5%)]. Our study suggested that long-term exposure to air pollution is associated with metabolic alterations, particularly in PCs with unsaturated long-chain fatty acids. These findings might provide new insights into potential mechanisms for air pollution-related adverse outcomes. [ABSTRACT FROM AUTHOR]