Association of Agricultural, Occupational, and Military Inhalants With Autoantibodies and Disease Features in US Veterans With Rheumatoid Arthritis

Our plain-English summary of Association of Agricultural, Occupational, and Military Inhalants With Autoantibodies and Disease Features in US Veterans With Rheumatoid Arthritis, by A.V. Ebel, G. Lutt, J.A. Poole, et al (Arthritis & Rheumatology, 2021).

The study

• Authors: A.V. Ebel, G. Lutt, J.A. Poole, G.M. Thiele, J.F. Baker, G.W. Cannon, A. Gaffo, G.S. Kerr, A. Reimold, P. Schwab, N. Singh, J.S. Richards, D.P. Ascherman, T.R. Mikuls, B.R. England
• Journal: Arthritis & Rheumatology
• Published: 2021;73(3):392-400
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: To determine the association of inhalant exposures with rheumatoid arthritis (RA)-related autoantibodies and severity in US veterans.

Methods: Participants in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were mailed surveys assessing occupational, agricultural, and military inhalant exposures. Demographic characteristics, disease activity, functional status, and extraarticular features were obtained from the VARA registry, while HLA-DRB1 shared epitope (SE) status, anti-cyclic citrullinated peptide (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, and extraarticular features) were assessed using multivariable linear and logistic regression models adjusted for age, sex, race, and tobacco use and stratified by SE status. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results: Questionnaires were returned by 797 of 1,566 participants (50.9%). Survey respondents were older, more often White or male, and less frequently smokers, and had lower disease activity compared to nonrespondents. 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 participants who were positive for SE alleles, burn pit exposure (OR 5.69 [95% CI 2.73, 11.87]) and military waste disposal exposure (OR 5.05 [95% CI 2.42, 10.54]) were numerically more strongly associated with anti-CCP positivity. Several inhalant exposures were associated with the presence of chronic lung disease, but not with the presence of RF or the level of disease activity.

Conclusion: Military burn pit exposure and military waste disposal exposure 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.

© 2020, American College of Rheumatology.

In plain English

This study looked at US veterans who already had rheumatoid arthritis (RA) and were enrolled in the Veterans Affairs Rheumatoid Arthritis registry. Surveys about past farm, job and military inhalant exposures were returned by 797 of 1,566 participants (50.9%). The researchers compared the answers with stored blood tests for RA-related antibodies (anti-CCP and rheumatoid factor), with a genetic risk marker called the shared epitope, and with disease features. After adjustment for age, sex, race and tobacco use, veterans reporting military burn pit exposure (OR 1.66, 95% CI 1.02-2.69) or military waste disposal exposure (OR 1.74, 95% CI 1.04-2.93) had higher odds of being anti-CCP positive. Occupational asbestos (reported by 31.1%) and military asbestos (25.6%) were among several exposures associated with chronic lung disease. Other exposures were not associated with anti-CCP, and no exposure was associated with rheumatoid factor. The authors concluded that burn pit and waste disposal exposures were associated with anti-CCP positivity. They noted several limits. The timing of each individual exposure was not collected, so some exposures may have occurred after RA began. The design was cross-sectional, and there was no comparison group without RA.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Nested cross-sectional study using a mailed exposure survey within an existing registry (cohort) of veterans with RA
• Who was studied: 797 of 1,566 surveyed US veterans with rheumatoid arthritis (50.9% response) from the VARA registry, at nine VA sites (Omaha, Iowa City, Portland, Dallas, Birmingham, Salt Lake City, Washington D.C., Pittsburgh, Philadelphia). Respondents were mostly male (86.7%) and white (82.1%), with a mean age of 69.5.
• Exposure: Self-reported agricultural, occupational, military and household inhalant exposures. These included occupational dust, gasoline, adhesives, metal grinding, occupational asbestos, pesticides, organic solvents, military gasoline, military asbestos, Agent Orange, burn pits, waste disposal, industrial solvents and air pollution. Occupational asbestos was reported by 31.1% and military asbestos by 25.6%. Fiber type was not specified.
• Main results:
  • Among all respondents, after adjustment for age, sex, race and tobacco use, military burn pit exposure (OR 1.66, 95% CI 1.02-2.69) and military waste disposal exposure (OR 1.74, 95% CI 1.04-2.93) were associated with higher odds of anti-CCP positivity.
  • Participants with both burn pit exposure and shared epitope alleles had an OR of 5.69 (95% CI 2.73-11.87) for anti-CCP positivity, compared with participants who had neither.
  • Participants with both military waste disposal exposure and shared epitope alleles had an OR of 5.05 (95% CI 2.42-10.54) for anti-CCP positivity.
  • The test for an additive interaction between burn pit exposure and shared epitope (RERI 2.55, 95% CI -1.45 to 6.54) was not statistically significant.
  • When the analysis was also adjusted for shared epitope, the burn pit odds ratio was unchanged (OR 1.66), but its 95% confidence interval included 1 (0.98-2.80).
  • Occupational asbestos and military asbestos, along with occupational dust, pesticides and military burn pits, were independently associated with the presence of chronic lung disease (COPD, ILD, asthma, farmer's lung disease or bronchiectasis).
  • Inhalant exposures other than burn pits and waste disposal were not associated with anti-CCP. No agricultural, occupational or military exposure was associated with rheumatoid factor.
  • No inhalant exposure was significantly associated with the extra-articular features of interstitial lung disease or subcutaneous nodules.
  • Exposures were not significantly associated with disease activity or functional status. The one exception was Agent Orange, which was associated with higher MDHAQ (functional status) scores (B 0.09, 95% CI 0.01-0.18, p 0.03) but not with disease activity. The authors stated this did not support a causal interpretation.
• The authors' conclusion: The authors concluded that burn pit and military waste exposure were specifically associated with anti-CCP positivity in these veterans with RA, particularly in those positive for the HLA-DRB1 shared epitope. They said the findings support emerging evidence that various inhalant exposures may contribute to the generation of RA autoantibodies, and that prospective studies are needed.
• Limitations the authors state:
  • The questionnaire did not collect deployment site, proximity to burn pits, or duration of burn pit exposure.
  • Only 19% of those reporting burn pit exposure served during periods characterized by classical open-air burn pits.
  • Beginning and ending dates of farm and military exposure periods were collected. However, the timing of individual exposures was not collected, and some exposures may have occurred after RA onset.
  • The design was cross-sectional, in a homogeneous veteran population who all had RA, and there was no comparison group without RA.
  • Because several exposures were examined at the same time, some findings may have been due to chance.
  • Most respondents reported several exposures, which may have led to underestimation of associations with specific exposures.
  • Because most participants were men, associations could not be evaluated separately for men and women.

Topics

Medical terms in this study, explained in our Lexicon: Odds Ratio, confidence interval.

Related studies

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• Living with mesothelioma: A qualitative study of the experiences of male military veterans in the UK — S. Ejegi-Memeh, L. Darlison, et al. (2021)
• Occupations and exposures in the work environment as determinants for rheumatoid arthritis — A.R. Olsson, T. Skogh, et al. (2004)
• Asbestos plaques in a typical Veteran's hospital population — J.A. Miller, J.V. Zurlo (1996)
• Is Male Rheumatoid Arthritis an Occupational Disease? A Review — D. Murphy, D. Hutchinson (2017)
• Asbestos exposure and mesothelioma mortality among atomic veterans — J.E. Till, H.L. Beck, et al. (2022)

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