Association of Gulf War Illness-Related Symptoms with Military Exposures among 1990–1991 Gulf War Veterans Evaluated at the War-Related Illness and Injury Study Center (WRIISC)

Abstract

Veterans with difficult-to-diagnose conditions who receive care in the Department of Veterans Affairs (VA) healthcare system can be referred for evaluation at one of three specialty VA War-Related Illness and Injury Study Centers (WRIISC). Veterans of the 1990–1991 Gulf War have long experienced excess rates of chronic symptoms associated with the condition known as Gulf War Illness (GWI), with hundreds evaluated at the WRIISC. Here we provide the first report from a cohort of 608 Gulf War Veterans seen at the WRIISC who completed questionnaires on chronic symptoms (>6 months) consistent with GWI as well as prominent exposures during Gulf War deployment. These included veterans’ reports of hearing chemical alarms/donning Military-Ordered Protective Posture Level 4 (MOPP4) gear, pesticide use, and use of pyridostigmine bromide (PB) pills as prophylaxis against the effects of nerve agents. Overall, veterans in the cohort were highly symptomatic and reported a high degree of exposures. In multivariable models, these exposures were significantly associated with moderate-to-severe chronic symptoms in neurocognitive/mood, fatigue/sleep, and pain domains. Specifically, exposure to pesticides was associated with problems with concentration and memory, problems sleeping, unrefreshing sleep, and joint pain. Use of MOPP4 was associated with light sensitivity and unrefreshing sleep and use of PB was associated with depression. We also evaluated the association of exposures with symptom summary scores based on veterans’ severity of symptoms in four domains and overall. In multivariable modeling, the pain symptom severity score was significantly associated with pesticide use (Odds ratio (OR): 4.13, 95% confidence intervals (CI): 1.78–9.57) and taking PB pills (OR: 2.28, 95% CI: 1.02–5.09), and overall symptom severity was significantly associated with use of PB pills (OR: 2.41, 95% CI: 1.01–5.75). Conclusion: Decades after deployment, Gulf War veterans referred to a VA tertiary evaluation center report a high burden of chronic symptoms, many of which were associated with reported neurotoxicant exposures during the war.

Pyridostigmine Bromide Pills and Pesticides Exposure as Risk Factors for Eye Disease in Gulf War Veterans

“…Both PB pills and pesticides exposures have been linked to other aspects of GWI in prior studies. A study of 604 GW veterans examined relationships between neurotoxin exposure and four GWI domains (neurocognitive/mood, gastrointestinal, fatigue/sleep, and pain) [ 10 ]. Exposure to both pesticides (OR = 4.13, 95% CI = 1.78–9.57) and PB pills (OR = 2.28, 95% CI = 1.02–5.09) were strongly associated with pain severity.…”

“…Pesticides were also associated with difficulties in concentrating (OR = 2.29, 95% CI = 1.04–5.02) and recall (OR = 2.18, 95% CI = 1.04–4.56), difficulty with sleep (OR = 3.06, 95% CI = 1.19–7.89), unrefreshing sleep (OR = 3.13, 95% CI = 1.09–8.98), and joint pain (OR = 2.46, 95% CI = 1.04–5.82). PB pill use was associated with depression (OR = 2.68, 95% CI = 1.28–5.60) [ 10 ]. In our study, we did not examine sleep quality but did find that individuals exposed to PB and pesticides were significantly more likely to be diagnosed with sleep apnea compared to their respective controls.…”

“…While GWI pathophysiology is not fully understood, researchers have hypothesized that some exposures may have acted as neurotoxins that, in combination with genetic predisposition and stress, led to the development of a chronic neuroinflammatory state and the symptoms of GWI [ 6 , 7 , 8 ]. Of the previously listed exposures, PB pills (given as prophylaxis against nerve gas) and pesticides are most closely studied in connection with GWI [ 9 , 10 ]. In a study of GW veterans who were in Iraq or Kuwait during the conflict, those who met the criteria for GWI (n = 101) were significantly more likely to have received PB pills (OR = 3.50, CI = 1.65 to 7.41, p < 0.05) and to have been exposed to pesticides on their skin (OR = 2.07, CI = 1.06 to 4.05, p < 0.05) compared to those who did not meet the criteria for GWI (n = 76) [ 11 ].…”

Association of Atherosclerotic Cardiovascular Disease, Hypertension, Diabetes, and Hyperlipidemia With Gulf War Illness Among Gulf War Veterans

“…More than 3 decades after the end of the 1990 to 1991 Gulf War, the complex medical challenges faced by Gulf War veterans (GWVs) persist. 1 , 2 Population studies indicate that about one‐third of the nearly 700 000 US military personal who served during the Gulf War may be affected by the chronic multisymptom illness commonly referred to as Gulf War illness (GWI). 2 There is no clinical case definition to diagnose GWI in health care settings, but research case criteria for GWI recommended by a 2014 report of the Institute of Medicine are based on veterans' symptoms, including persistent fatigue, neurocognition/mood difficulties, pain, and gastrointestinal, skin, and respiratory symptoms.…”

Advancing the Role of Neuroimmunity and Genetic Susceptibility in Gulf War Illness

“…Over the past 30 years since the war ended, an increasing body of research has accumulated on the pathobiology of this disorder. Overall, most evidence is suggestive of in-theater neurotoxicant exposures as a major underlying cause of chronic health symptoms [ 1 ]. As reflected in the titles of the two Special Issues, neuroimmune mechanisms are thought to be the primary targets of the neurotoxicant exposures that instigate the multiple symptoms modulated by underlying genetic susceptibility.…”