Sphingolipids as indicators of exposure to long-term air pollution: a targeted metabolomics approach

Metabolomic changes related to air pollution have been previously reported, including sphingolipid metabolism; however, evidence from long-term exposures assessed with long-term exposure using targeted metabolomics remains limited. We profiled plasma sphingolipids and amino acids in 188 individuals from the chronic obstructive pulmonary disease (COPD) in Dusty Areas cohort. Annual average concentrations of particulate matter ≤ 10 μm (PM₁₀, µg/m³) and nitrogen dioxide (NO₂, ppb) were estimated for each participant's residence using a national-scale universal kriging model integrating regulatory monitoring data and geographic predictors across South Korea. Multiple linear regression models, adjusting for demographic, clinical, and environmental covariates, evaluated associations between exposures and metabolites. Long-term PM₁₀ exposure was nominally associated with higher sphingomyelins [SM(d18:1/18:0), SM(d18:1/18:1), and SM(d18:1/24:1)], whereas NO₂ exposure was nominally associated with Cer(d18:1/24:0) and glutamate. PM₁₀ was not significantly associated with amino acids. No main associations remained significant after false discovery rate (FDR) correction. In subgroup analyses, particularly among patients with COPD, SM(d18:1/16:0), SM(d18:1/18:1), SM(d18:1/24:1), and SM(d18:1/18:0) met the FDR threshold, highlighting robust and subgroup-specific associations. Although results provide novel insights into pollutant-specific metabolic pathways, confirmation in larger cohorts is needed.