title: 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: 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.
  
  
  
  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, NO2and 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).
  
  
  
  There were 10 discovery cohort associations, of which seven were lysophosphatidylcholines (LPCs); NO2was 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).
  
  
  
  LPCs are associated with short-term exposure to air pollutants, in particular NO2Further 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.
authors.affiliation: Institute of Epidemiology II.
authors.forename: Cavin K
authors.initials: CK
authors.lastname: Ward-Caviness
authors.affiliation: Institute of Epidemiology II.
authors.forename: Susanne
authors.initials: S
authors.lastname: Breitner
authors.affiliation: Institute of Epidemiology II.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wolf
authors.affiliation: Institute of Epidemiology II.
authors.forename: Josef
authors.initials: J
authors.lastname: Cyrys
authors.affiliation: Institute of Bioinformatics and Systems Biology, and.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Institute of Epidemiology II.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang-Sattler
authors.affiliation: Institute of Epidemiology II.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Institute of Epidemiology II, peters@helmholtz-muenchen.de.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D000397:Air Pollution / Q000009:adverse effects*; D000428:Alcohol Drinking / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005858:Germany; D006801:Humans; D016014:Linear Models; D008244:Lysophosphatidylcholines / Q000097:blood; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009585:Nitrogen Dioxide / Q000009:adverse effects*; D010126:Ozone / Q000032:analysis; D052638:Particulate Matter / Q000032:analysis; D011446:Prospective Studies; D012621:Seasons; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D013997:Time Factors
chemical_list: D005227:Fatty Acids; D008244:Lysophosphatidylcholines; D052638:Particulate Matter; D010126:Ozone; D009585:Nitrogen Dioxide
keywords: NO2; long-chain fatty acids; metabolomics; short-term air pollution