IntroductionRheumatoid arthritis (RA) is an autoimmune disease and closely associated with both genetic and environmental factors. Volatile organic chemicals (VOC), a common environment pollutant, was associated with some autoimmune diseases, while whether VOC exposure or which VOC leads to RA is yet clarified.MethodsA cross-sectional study using data from the 6 survey cycles (2005-2006, 2011-2012, 2013-2014, 2015-2016, 2017-2018, 2017-2020) of NHANES program was performed. The RA or non-arthritis status of participant was identified through a questionnaire survey. The quantile logistic regression method was used for correlation analysis between VOC metabolites (VOCs) in urine and RA. The covariates included age, gender, race, educational level, marital status, total energy intake, physical activity, smoking, hypertension, diabetes, urine creatinine, albumin and marihuana use.ResultsA total of 9536 participants (aged 20 to 85) with 15 VOCs, comprising 618 RA and 8918 non-arthritis participants, was finally included for analysis. Participants in the RA group showed higher VOCs in urine than that in the non-arthritis group. A positive association between 2 VOCs (AMCC: Q4: OR=2.173, 95%CI: 1.021, 4.627. 3HPMA: Q2: OR=2.286, 95%CI: 1.207 - 4.330; Q4: OR=2.663, 95%CI: 1.288 -5.508.) and RA was detected in the model 3, which was independent of all the covariates. The relative parent compounds of the two VOCs included N,N-Dimethylformamide and acrolein.DiscussionThese findings suggested that the VOC exposure significantly associated with RA, providing newly epidemiological evidence for the establishment that environmental pollutants associated with RA. And also, more prospective studies and related experimental studies are needed to further validate the conclusions of this study.