Occupational exposure to military burn pits and waste disposal sites were associated independently with the presence of anti-cyclic citrullinated peptide (CCP) antibodies in veterans with rheumatoid arthritis (RA), according to study results published in Arthritis & Rheumatology.

Questionnaires regarding exposures to agricultural, occupational, military, and household inhalants were mailed to participants from the Veterans Affairs Rheumatoid Arthritis (VARA) registry. Data to determine the timeframe and length of exposure were collected, including dates of farm and/or military exposures, as well as a detailed history of tobacco use, alcohol intake, and chronic lung disease diagnoses.

The primary study outcomes were RA-related autoantibody positivity/concentration and RA disease severity.  In total, 1566 survey were mailed with a 50.9% response rate (797 respondents). Respondents were most likely to be older White men (mean age, 69.5 years; 82.1% white, 86.7% men), but less likely to be current smokers (20.4%). Inhalant exposures were common among survey respondents: 72.2% reported occupational dust exposure, 31.1% reported occupational asbestos exposure, and 25.6% reported military asbestos exposure; nearly half (44.8%) of respondents lived or worked on a farm.


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After adjusting for age, sex, race, and tobacco use, exposures to military burn pits and military waste disposal were associated with higher odds of anti-CCP positivity (odds ratio [OR], 1.66; 95% CI, 1.02-2.69 and OR 1.74; 95% CI, 1.04-2.93, respectively) and higher anti-CCP concentrations (log-transformed B, 0.41; 95% CI, 0.03-0.80 and log-transformed B, 0.20; 95% CI, -0.20 to 0.61, respectively). Tobacco use was also strongly associated with anti-CCP positivity (OR, 1.78 and 3.48, respectively), and adjustments for smoking pack-years led to consistent results to primary analyses.

Other inhalant exposures were not associated with anti-CCP positivity or concentrations, and agricultural, occupational, and military inhalant exposures were not associated with rheumatoid factor positivity or concentration. Several types of inhalant exposures — occupational dust or asbestos, pesticides, and military asbestos or burn pits — were independently associated with the presence of chronic lung disease.

Researchers further investigated the gene-environment interaction between smoking and shared epitope (SE) alleles for seropositive RA. Specifically, the associations between military burn pit and/or waste disposal exposures and anti-CCP antibodies in conjunction with SE alleles were evaluated. Those with burn pit exposure and SE alleles had an OR of 5.69 (95% CI, 2.73-11.83) for anti-CCP positivity compared with respondents who were SE negative and not exposed. The association was stronger than for either risk factor in isolation (SE OR, 2.86; burn pit OR, 1.28). Similar findings were observed for waste disposal.

These findings are consistent with evidence suggesting that exposures to various inhalants, including occupational, agricultural, military, and household, influence both autoantibody expression and RA risk

The researchers reported several study limitations, including a lack of collection of extensive data regarding the specific site of deployment, proximity to burn pits, or self-reported duration of exposure. Additionally, the study was limited by the cross-sectional design, the homogenous population of veterans, and the lack of a non-RA comparator group.

“These findings support emerging evidence that various inhalant exposures may contribute to the generation of RA autoantibodies such as ACPA,” the researchers concluded. “Prospective cohort studies comprehensively evaluating the impact of inhalant exposures, including military burn pits and waste disposal, and genetic risk factors on RA risk are needed.”

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Ebel AV, Lutt G, Poole JA, et al. Association of agricultural, occupational, and military inhalants with autoantibodies and disease features in U.S. veterans with rheumatoid arthritis. Arthritis Rheumatol. Published online October 15, 2020. doi: 10.1002/art.41559