This investigation tests the hypothesis that military occupation-specific exposures to silica and other inorganic dusts are associated with the prospective development of rheumatoid arthritis (RA) and other rheumatic autoimmune diseases. There is ample support for this hypothesis from studies of civilian populations exposed to silica and other inorganic dusts, but this has never been studied in the military occupational context. The overarching Study Aim is to estimate the risk of rheumatoid arthritis (RA) and other rheumatic diseases associated with military service exposure to inorganic dust using an established roster of OEF/OIF/OND veterans who have had any Veterans Administration Health Care System (VAHCS) contact. We will define exposure by linking categorized (coded) military duties to a job exposure matrix developed for this study. The disease outcomes of interest will be defined by VAHCS visits coded for RA, systemic lupus erythematosus (SLE) and selected additional rheumatologic autoimmune conditions (such as systemic sclerosis, dermatomyositis, and vasculitis). Further diagnosis refinement will be supplemented by serologic data and natural language-based algorithms. We will analyze time until initial diagnosis for each target condition (Proportionate Hazards modeling) to estimate the risk of disease associated with military occupational exposure. We will adjust for key covariates, including sex, age, smoking, duration of service, and branch of service. We will limit study eligibility to full active duty military personnel (Reserve duty and National Guard members will not be included to better categorize exposure). After additional exclusions, we anticipate a cohort for analysis of 600,000 persons with approximately 2.4 million person years of VAHCS patient visits. Of the cohort, 25% will have had occupational assignments of higher; 18%, intermediate; and 57%, negligible exposure likelihood. In a preliminary logistic regression analysis in a subset of the cohort using RA as the outcome, we observed a 38% increased exposure-associated odds of disease (OR 1.38; 95% CI 1.05-1.80). Based on these data, we conservatively estimate that we will have sufficient study power (alpha 0.05; beta 0.20) to detect exposure-related increase risk as low as 1.3 for RA and below 1.5 for SLE. RA, SLE, and other autoimmune rheumatic diseases within the population served by the VAHCS are well recognized as an important source of morbidity. It is now well established that inorganic dust inhalation is a factor consistently associated with increased risk of such diseases among civilian populations. Yet these two independent and important phenomena never have been considered in relation to one another. In short, the question has not been asked, can military service itself be a contributor to such diseases? The answer to this question is critical to risk reduction, case identification, effective treatment, and potentially, and primary prevention.
This proposed project is directly relevant to program objectives and it will inform the health care of Veterans. By studying rheumatoid arthritis and other autoimmune conditions that may be related to past military occupational exposures, study findings can enhance primary, secondary, and tertiary disease prevention for this population. Using an epidemiologic approach is appropriate to the study question. Silica and related dusts in connection with military service are likely to be common but have not been well-studied. The diseases in question are associated with significant morbidity. Thus, this proposed study addresses a key knowledge gap with direct and relevant applications. Although well studied in civilian populations, the question has not been asked previously: can military service itself be a contributor to rheumatoid arthritis and other auto-immune rheumatic conditions? The answer to this question is critical to risk reduction, case identification, effective treatment, and disease prevention.
