Association of Agricultural, Occupational, and Military Inhalants with Autoantibodies and Disease Features in U.S. Veterans with Rheumatoid Arthritis

OBJECTIVE To determine the association between inhalant exposures with RA-related autoantibodies and severity in U.S. Veterans. METHODS Participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry were mailed surveys assessing occupational, agricultural, and military inhalant exposures. Demographics, disease activity, functional status, and extra-articular features were obtained from the VARA registry while HLA-DRB1 shared epitope (SE) status, anti-CCP antibodies, and rheumatoid factor (RF) were measured using banked DNA/serum from enrollment. Associations between inhalant exposures and RA-related factors (autoantibodies, severity, extra-articular features) were assessed using multivariable linear and logistic regression models adjusting for age, sex, race, and tobacco use and stratified by SE status. RESULTS Questionnaires were returned by 797 of 1566 participants (50.9%). Responders were older, more often white or male, less frequent smokers, and had lower disease activity. Anti-CCP positivity was more common among veterans exposed to burn pits (OR 1.66; 95% CI 1.02-2.69) and military waste disposal (OR 1.74, 95% CI 1.04-2.93) independent of other factors. Among those positive for SE alleles, burn pit (OR 5.69, 95% CI 2.73-11.87) and military waste disposal (OR 5.05, 95% CI 2.42-10.54) exposures were numerically more strongly associated with anti-CCP positivity. Several inhalant exposures were associated with the presence of chronic lung disease but not RF or disease activity. CONCLUSION Military burn pit and military waste disposal exposures were independently associated with the presence of anti-CCP antibodies in RA patients. These findings are consistent with emerging evidence that various inhalant exposures influence autoantibody expression and RA risk.