Association between volatile organic compound exposure and elevated total immunoglobulin E: Risk factor screening in mixed exposure scenarios and potential biological mechanisms.

Environmental pollutants are increasingly recognized as important modulators of immune function, yet the influence of volatile organic compound (VOC) exposure on immunoglobulin E (IgE) levels remains poorly characterized. Using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006, we systematically evaluated the association between VOC metabolites and total IgE levels through five statistical approaches combined with machine learning algorithms. Mediation analyses were conducted to examine the role of inflammatory markers in these associations. Finally, functional enrichment analyses were employed to identify potential pathways and key molecular targets. Our analyses consistently demonstrated significant positive associations between VOC exposure and elevated total IgE levels. 2-aminothiazoline-4-carboxylic acid (ATCA), N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), and N-Acetyl-S- (3-hydroxypropyl)-L-cysteine (HPMA) emerged as robust risk factors. Mediation analysis revealed that eosinophil (EOS) counts accounted for 15.89% to 29.03% of the observed associations between VOC metabolites and total IgE levels. TNF and IL-17 signaling pathways were significantly enriched (P_adjust < 0.05). Integrated analyses confirmed VOC exposure as a significant environmental risk factor for elevated total IgE levels, primarily driven by ATCA, CYMA, and HPMA, with inflammatory responses as a plausible mechanism.