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

Abstract

BACKGROUND AND AIM: Long-term exposure to air pollution is associated with a vast number of adverse health outcomes, while the underlying mechanisms remain unclear. Therefore, this study aimed to investigate changes in serum metabolites associated with long-term exposure to air pollution in a longitudinal study design. METHODS: 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 current analysis. Land-use regression models were used to estimate annual average concentrations of ultrafine particles, particles with a diameter < 10 µm, coarse particles (PMcoarse), fine particles, PM2.5 absorbance (a proxy of elemental carbon related to traffic exhaust, PM2.5abs), nitrogen oxides (NO2, NOx), and ozone at individuals’ residences. We applied covariate-adjusted linear mixed-effects regression models to examine associations between long-term exposure to air pollution and metabolites. RESULTS: 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 among these study waves, we identified nine significant negative associations between phosphatidylcholines (PCs) and PM2.5abs, PMcoarse, and NO2, 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 PM2.5abs 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%)]. CONCLUSIONS: 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 health outcomes. KEYWORDS: long-term air pollution, targeted metabolomics, phosphatidylcholine