Abstract
BACKGROUND: Environmental contaminants, especially volatile organic compounds (VOCs) and their metabolites (mVOCs), are of significant interest for treating autoimmune diseases due to their potential immunomodulatory effects. This study aimed to assess the association between urinary mVOCs and the risk of rheumatoid arthritis (RA) in U.S. adults. METHODS: A total of 4,622 adults, including 296 participants with RA, were included in the present study utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2020. Sixteen mVOCs were selected for the analysis while controlling for potential confounders. Weighted logistic regression models were employed to assess the association between individual mVOCs and RA risk. Least absolute shrinkage and selection operator (LASSO) regression was used to select mVOCs and covariates most pertinent to the prevalence of RA for further analyses. Then, weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) models were used to estimate associations between the mVOC mixture and RA. Mediation analyses were performed to examine the effect of inflammatory indices on these relationships. RESULTS: In single-pollutant models, levels of most mVOCs were greater in the RA patients than in the patients without arthritis. Furthermore, multi-pollutant models unveiled a positive effect of the mVOC mixture on the risk of RA in both WQS regression (OR: 1.37; 95% CI: 1.12, 1.68; P = 0.002) and qgcomp (OR: 1.23; 95% CI: 1.07, 1.49; P = 0.034) models. This effect was notably stronger for female participants. The lymphocyte-to-monocyte ratio (LMR), a surrogate for inflammatory markers, mediated the association between the mVOC mixture and the prevalence of RA with a mediated proportion of 4.65%. CONCLUSIONS: This study supports the substantial connection between VOC co-exposure and the risk of RA, with inflammation potentially acting as a mediator in this relationship.