VA RESEARCH ON GULF WAR VETERANS' HEALTH

June 1998

VA is committed to a thorough investigation of the health consequences of exposure to potential environmental hazards, including chemical warfare agents, during the Gulf War through carefully controlled scientific studies. A key question is why early studies have shown Gulf veterans are experiencing a greater prevalence of symptoms in comparison with control populations. Comparisons of symptoms and illnesses between Gulf veterans and appropriate controls is a priority echoed in the interagency Annual Report to Congress: Federally Sponsored Research on Gulf Veterans' Illnesses. (The interagency report is available electronically on the Internet at
http://www.va.gov/resdev/pgrpt97.htm.)

The federal research commitment in this area by VA and other departments has now reached $115 million cumulatively in support of 121 research projects. VA is addressing these Gulf veteran health questions through targeted protocols funded through VA's hospital-based intramural research program, and through environmental hazards research centers that were selected through scientific competition. Each center coordinates a collection of integrated study protocols and specialized core laboratories with research directors holding faculty appointments at affiliated universities.

 

MAJOR VA EPIDEMIOLOGICAL STUDIES

Health Survey: VA's National Health Survey of Gulf War veterans is designed to determine the prevalence of symptoms and illnesses among a random sampling of Gulf War veterans from across the nation. The survey is being conducted in three phases:

Phase I was a population-based mail survey of the health of 30,000 selected veterans of the Gulf War era. About half of these veterans served in the theater of operations. The data collection is completed and analyses are in progress.

Phase II consisted of a telephone interview of 8,000 non-respondents from Phase I (4,000 veterans from each group) to examine factors that may have made a difference in whether or not a veteran participated. Additionally, 4,000 veterans who responded to the Phase I mail survey and the Phase II telephone survey (2,000 from each group) were selected for a medical record review to validate their responses from the survey. Phase II is nearing completion.

Phase III involves 2,000 of the veterans who responded to the postal survey and underwent a telephone interview who will be invited, along with their families, to participate in a comprehensive physical examination program. These examinations will be conducted at 17 VA medical centers nationwide and will involve specialized examinations, including neurological, rheumatological, psychological, and pulmonary evaluations. Completion of data collection is anticipated in late 1999.

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Mortality Study: VA's Environmental Epidemiology Service has analyzed cause-of-death data gathered from death certificates for its Mortality Followup Study of Gulf Veterans, comparing non-combat deaths of Gulf-deployed veterans with a control group of troops never deployed to the Gulf. The first phase of the study, covering deaths through September 1993, found that veterans of the Gulf War have experienced a higher rate of death due to accidents, as has been observed after other wars.

When these deaths due to external causes are excluded, Gulf veterans have not experienced a higher mortality rate due to disease-related causes. Both the Gulf theater and non-deployed control group veterans had a lower death rate than Americans their age in general, according to the study report published Nov. 14, 1996, in the New England Journal of Medicine. An analysis of new data through December 1995 revealed results similar to the previously published study.

 

ENVIRONMENTAL HAZARDS RESEARCH CENTERS

The Boston Environmental Hazards Research Center, in conjunction with Boston University, is conducting six Gulf-related research projects aimed at determining health effects of environmental exposure to potential hazardous agents, with a particular emphasis on behavioral toxicology, immunotoxicology, cancer epidemiology, and behavioral psychopathology. This interdisciplinary work extends current Gulf-related research at the Boston VA Medical Center, which includes assessment of health, psychological well-being, and neuropsychological function of selected Gulf War veterans.

Data shared among projects allow investigators to examine such hypotheses as whether exposures (self-reported and otherwise) in the Gulf can be related to health symptoms, performance on psychological tests, alterations in immune function, or alterations in pulmonary function tests.

One project is examining the possible relationship between the experience of multiple symptom-based health complaints and such clinical phenomena as chemical sensitivities, chronic fatigue syndrome, organic brain syndromes resulting from toxicant exposures, post-traumatic stress disorder (PTSD), and somatization disorders. Other studies are investigating the central and peripheral nervous system in a group of veterans with possible environmentally related disorders, while another is assessing pulmonary and immune system function in the same study cohort.

Additional approaches at the Boston Environmental Hazards Research Center include a rodent model of immunologic changes related to petroleum product exposure, a registry of cancer incidence among Gulf veterans, and a study of cellular receptors as a susceptibility biomarker for polycyclic aromatic hydrocarbon (a component of incomplete petroleum combustion) exposure. Researchers at the Boston Environmental Hazards Research Center also are collaborating with Danish and Japanese scientists on related studies.

The New Jersey Environmental Hazards Research Center at the East Orange VA Medical Center, in conjunction with the Environmental and Occupational Health Sciences Institute of the University of Medicine and Dentistry of New Jersey, is undertaking four projects to

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gather information about illnesses among Gulf veterans for development of veterans' most characteristic symptom profiles. An epidemiological study is comparing two groups of Gulf veterans to collect and organize symptoms to define illness and identify risk factors through the case-control method. Study subjects will be divided into three groups based on symptom presentation -- chronic fatigue, chemical sensitivity, and asymptomatic -- to participate in a series of studies in such areas as immunological, neuropsychological and autonomic nervous system function. One project is examining chemical sensitivity through physiologic and cognitive reactivity to chemical challenges.

Those veterans whose response fulfills chronic fatigue criteria are being tested to determine physiologic and cognitive reactivity to exercise. An animal study is evaluating stress-related interactions with chemical exposure and pyridostigmine bromide. Investigators at the center also are coordinating the multicenter trial on treatment of chronic fatigue syndrome and fibromyalgia (see page 4).

The Portland Environmental Hazards Research Center, in conjunction with Oregon Health Sciences University's Center for Research on Occupational and Environmental Toxicology, is conducting research in four projects on the health effects associated with exposure to selected environmental chemical and biological hazards related to military service. The center is conducting a population-based, case-control study incorporating survey questionnaires on health status and exposure, followed by clinical evaluation and testing for subtle health effects associated with unexplained illness.

The center's research focus is on environmental factors encountered in military service that principally pose a threat to the neurological and musculoskeletal systems. Scientists from the center are exploring, at the whole organ and at the molecular level, key scientific issues involving epidemiology, neurobehavior, neuroendocrinology, neurotoxicology, dermatology and parasitology. Researchers hope to define more accurately relationships between illnesses in Gulf veterans and specific environmental, infectious and chemical warfare exposures. Researchers hope to elucidate mechanisms underlying health hazards associated with selected chemicals encountered in a combat environment to help prevent illness of future servicemembers.

The Center for the Study of Environmental Hazards to Reproductive Health, funded in late 1996, is a joint venture of the Louisville VA Medical Center and the University of Louisville's Kentucky Institute for the Environment and Sustainable Development. Its goal is to determine whether exposure to hazardous substances affects reproductive capacity and causes developmental abnormalities in the children of veterans. Although the center is primarily focused on Vietnam veterans' reproductive health, one project will be addressing reproductive outcomes in Persian Gulf veterans.

 

INTERAGENCY RESEARCH COORDINATION

Scientists at VA and the Departments of Defense (DoD) and Health and Human Services are collaborating on planning, management and conduct of Gulf War research projects. Federal research efforts are coordinated by the Research Working Group of the Persian Gulf Veterans Coordinating Board.

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OTHER INITIATIVES
Nerve Agent Exposure.
In early 1997, VA and DoD tasked the Medical Follow-Up Agency of the Institute of Medicine to undertake feasibility studies on the long-term health effects of exposure to chemical warfare nerve agents. In addition, the Research Working Group has developed a broad-based research strategy on this issue. Some studies have been funded and additional work in this area is expected in the future.

Chronic Fatigue Syndrome and Fibromyalgia. VA and DoD are planning a joint VA/DoD multi-center treatment trial for chronic fatigue syndrome and fibromyalgia in Gulf veterans as an outgrowth of efforts to seek possible treatments of clearly defined medical syndromes or illnesses among groups of Gulf veterans.

Other candidate treatments may be considered for additional randomized, multi-site treatment trials for Gulf War veterans' illnesses. For example, it may be possible to design and implement an antibiotic treatment trial for ill Gulf War veterans, and a planning committee for this study has been organized.

Neurocognitive Disorders. Another area of collaboration between VA and DoD is focused on the neurobiology of stress and stress-related disorders. Research proposals currently under review examine aspects of the wartime experience that create a confluence of cognitive, emotional and physical factors to produce chronic, non-specific symptoms and outcomes. Additional work is expected in such areas as the neurobiology of stress, the effectiveness of treatment involving trauma-based group therapy and other non-pharmacologic approaches to treatment.

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