Short-term NO2 exposure is associated with long-chain fatty acids in prospective cohorts from Augsburg, Germany: results from an analysis of 138 metabolites and three exposures

Abstract

Background: Short-term exposure to air pollution is associated with morbidity and mortality. Metabolites are intermediaries in biochemical processes, and associations between air pollution and metabolites can yield unique mechanistic insights.

Methods: We used independent cross-sectional samples with targeted metabolomics (138 metabolites across five metabolite classes) from three cohort studies, each a part of the Cooperative Health Research in the Region of Augsburg (KORA). The KORA cohorts are numbered (1 to 4) according to which survey they belong to, and lettered S or F according to whether the survey was a baseline or follow-up survey. KORA F4 (N = 3044) served as our discovery cohort, with KORA S4 (N = 485) serving as the primary replication cohort. KORA F4 and KORA S4 were primarily fasting cohorts. We used the non-fasting KORA F3 (N = 377) cohort to evaluate replicated associations in non-fasting individuals, and we performed a random effects meta-analysis of all three cohorts. Associations between the 0-4-day lags and the 5-day average of particulate matter (PM)_2.5, NO₂ and ozone were modelled via generalized additive models. All air pollution exposures were scaled to the interquartile range, and effect estimates presented as percent changes relative to the geometric mean of the metabolite concentration (ΔGM).

Results: There were 10 discovery cohort associations, of which seven were lysophosphatidylcholines (LPCs); NO₂ was the most ubiquitous exposure (5/10). The 5-day average NO₂-LPC(28:0) association was associated at a Bonferroni corrected P-value threshold (P < 1.2x10^-4) in KORA F4 [ΔGM = 11.5%; 95% confidence interval (CI) = 6.60, 16.3], and replicated (P < 0.05) in KORA S4 (ΔGM = 21.0%; CI = 4.56, 37.5). This association was not observed in the non-fasting KORA F3 cohort (ΔGM = -5.96%; CI = -26.3, 14.3), but remained in the random effects meta-analysis (ΔGM = 10.6%; CI = 0.16, 21).

Conclusions: LPCs are associated with short-term exposure to air pollutants, in particular NO₂ Further research is needed to understand the effect of nutritional/fasting status on these associations and the causal mechanisms linking air pollution exposure and metabolite profiles.

Keywords: NO2; long-chain fatty acids; metabolomics; short-term air pollution.