Abstract
BACKGROUND: The biochemical dysregulation underlying the adverse health effects of exposure to air pollution (AP) remains unclear. OBJECTIVE: The objective of this study was to explore associations between long-term exposure to AP and the urinary metabolome. METHODS: In the Swedish birth cohort BAMSE (n = 4089), urine samples were collected from a subset of participants attending clinical examination at the 4-year follow-up and from all participants attending clinical examination at the 24-year follow-up. Among paired samples and children with diagnosis of asthma and/or low lung function, non-targeted screening using liquid chromatography high-resolution mass spectrometry was applied to 4-year samples (n = 612) and 24-year samples (n = 846) and metabolites were annotated based on standard matching to in-house compound libraries (n = 260 metabolites). Time-weighted average exposure to air pollutants (i.e., particulate matter with diameter ≤10μm (PM(10)), ≤2.5 μm (PM(2.5)), and nitrogen oxides (NO(x))) during the first year of life and the year prior to urine collection was estimated using validated dispersion models. The association between AP exposure and urine metabolites was estimated cross-sectionally using exponential regression. RESULTS: AP exposure was overall positively associated with metabolite abundance (p < 0.002). However, metabolite-specific associations exhibited variability. At the 4-year follow-up, the first-year-of-life and prior-year AP exposures were positively associated with 8 purine/pyrimidine derivative metabolites (e.g., an increase of 2.8 μg/m(3) (interquartile range) in PM(10) during the first year of life was associated with a 1.21-fold increase in 1,7-dimethylxanthine, p = 3.87E-05). We also observed interactions between AP exposures and metabolism-related genetic variants on metabolite levels. At the 24-year follow-up, prior year AP was negatively associated with levels of six long-chain fatty acids. IMPACT: Long-term exposure to air pollution alters urinary metabolites in children and young adults, revealing environmental impacts on systemic metabolism even at low levels of air pollution.