Associations of Outdoor Ozone Concentration with Thyroid Function and the Mediated Role of Serum Metabolites: A Panel Study of Healthy Children

Abstract

Epidemiological evidence linking air pollution to children’s thyroid function is inconsistent, and the role of metabolites remains unknown. We conducted a panel study with 3 repeated visits among 143 children aged 4-12 years. The outdoor levels of ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and fine particulate matter were estimated 3 consecutive days preceding blood draw. Exposure to ozone was linearly associated with the reduction of free thyroxine (FT4) only at lag 0 day. Bayesian kernel machine regression and weighted quantile sum regression indicated that exposure to air pollution mixture linked to reduced FT4 at lag 0 day, with ozone being the primary contributor. Untargeted metabolomics were measured in 48 children, revealing that 27 serum metabolites were associated with ozone, primarily involving ether lipid and glycerophospholipid metabolism pathways. Casual inference tests showed that eight glycerophospholipid metabolites were identified as mediators of ozone's effect on FT4, seven of which were involved in ether lipid pathway. The integrated analysis identified a cluster of children with reduced FT4, characterized by increased ozone and decreased phosphatidylethanolamine plasmalogen and alkyl-phosphatidylcholine. Our findings suggested that short-term exposure to outdoor ozone in children may disrupt glycerophospholipid levels within the ether lipid metabolic pathway, leading to reduced FT4.