To paraphrase Winston Churchill, Gulf War Illness (GWI) is a mystery wrapped in an enigma—a complex interplay of multiple symptoms, caused by a variety of environmental and chemical hazards. To make things more difficult, there are no diagnostic biomarkers or objective laboratory tests with which to confirm a GWI case. Instead, clinicians rely on patients’ reports of symptoms and the absence of other explanations for the symptoms.
Looking to provide more information on the epidemiology and biology of GWI, US Department of Veterans Affairs (VA) researchers analyzed data from the VA Cooperative Studies Program 2006/Million Veteran Program 029 cohort, the largest sample of GW-era veterans available for research to date: 35,902 veterans, of whom 13,107 deployed to a post 9/11 Persian Gulf conflict.
The researchers used the Kansas (KS) and Centers for Disease Control and Prevention (CDC) definitions of GWI, both of which are based on patient self-reports. The KS GWI criteria for phenotype KS Sym+ require ≥ 2 mild symptoms or ≥ 1 moderate or severe symptoms in at least 3 of 6 domains: fatigue/sleep problems, pain, neurologic/cognitive/mood, gastrointestinal, respiratory, and skin. The criteria for phenotype KS Sym+/Dx- also exclude some diagnosed health conditions, such as cancer, diabetes mellitus, and heart disease. The researchers examined both of these phenotypes.
They also used 2 phenotypes of the CDC definition: CDC GWI is met if the veteran reports ≥ 1 symptoms in 2 of 3 domains (fatigue, musculoskeletal, and mood/cognition). The second, CDC GWI severe, is met if the veteran rates ≥ 1 symptoms as severe in ≥ 2 domains.
Of the veterans studied, 67.1% met the KS Sym+ phenotype; 21.5% met the KS Sym+/Dx– definition. A majority (81.1%) met the CDC GWI phenotype; 18.6% met the severe phenotype. The most prevalent KS GWI domains were neurologic/cognitive/mood (81.9%), fatigue/sleep problems (73.9%), and pain (71.5%).
Although their findings mainly laid a foundation for further research, the researchers pointed to some potential new avenues for exploration. For instance, “Importantly,” the researchers say, “we consistently observed that deployed relative to nondeployed veterans had higher odds of meeting each GWI phenotype.” For both deployed and nondeployed veterans, those who served in the Army or Marine Corps had higher odds of meeting the KS Sym+, CDC GWI, and CDC GWI severe phenotypes. Among the deployed, Reservists had higher odds of CDC GWI and CDC GWI severe than did active-duty veterans.
Their findings also revealed that older age was associated with lower odds of meeting the GWI phenotypes. “[S]omewhat surprisingly,” they note, this finding held in both nondeployed and deployed samples, even after adjusting for military rank during the war. The researchers cite other research that has suggested younger service members are at greater risk for GWI (because they’re more likely, for example, to be exposed to deployment-related toxins). Most studies, the researchers note, have shown GWI and related symptoms to be more common among enlisted personnel than officers. Biomarkers of aging, such as epigenetic age acceleration, they suggest, “may be useful in untangling the relationship between age and GWI case status.”