More than 2 decades have passed since the 1990–1991 conflict in the Persian Gulf. During the intervening years, many Gulf War veterans have experienced various unexplained symptoms that many associate with service in the gulf region, but no specific exposure has been definitively associated with symptoms. Research has been hampered by a lack of exposure measurements and a lack of objective measures of health outcomes in the veterans.
Numerous researchers have described the pattern of signs and symptoms found in Gulf War veterans and noted that veterans deployed to the gulf report unexplained symptoms at higher rates than nondeployed veterans or veterans deployed elsewhere during the same period. Gulf War veterans have consistently shown a higher level of morbidity than the nondeployed, in some cases with severe and debilitating consequences.
On August 2, 1990, Iraqi armed forces invaded Kuwait; within 5 days, the United States had begun to deploy troops to Southwest Asia in Operation Desert Shield. Intense air attacks against the Iraqi armed forces began on January 16, 1991, and opened a phase of the conflict known as Operation Desert Storm. Those two operations, although brief, exposed US and coalition forces to an array of biologic and chemical agents; for example, oil-well fires became visible in satellite images as early as February 9, 1991. The ground war began on February 23; by February 28, 1991, the war was over; and an official cease-fire was signed in April 1991. The oil-well fires were extinguished by November 1991. The last troops to participate in the ground war returned home on June 13, 1991. In all, about 697,000 US troops had been deployed to the Persian Gulf area during the two operations.1
Although the military operations were considered successful, with few battle injuries and deaths, veterans soon began reporting numerous health problems that they attributed to their participation in the Gulf War. Most of the men and women who served in the Gulf War returned to normal activities without serious health problems, but many experienced an array of unexplained symptoms, such as fatigue, muscle and joint pain, loss of concentration,
1Henceforth, the two operations—Desert Storm and Desert Shield—will be referred to as the Gulf War.
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1 INTRODUCTION More than 2 decades have passed since the 1990–1991 conflict in the Persian Gulf. During the intervening years, some Gulf War veterans have experienced various unexplained symptoms that many associate with service in the gulf region, but no specific exposure has been definitively associated with symptoms. Research has been hampered by a lack of exposure measurements and a lack of objective measures of health outcomes in the veterans. Numerous researchers have described the pattern of signs and symptoms found in Gulf War veterans and noted that veterans deployed to the gulf report unexplained symptoms at higher rates than nondeployed veterans or veterans deployed elsewhere during the same period. Gulf War veterans have consistently shown a higher level of morbidity than the nondeployed, in some cases with severe and debilitating consequences. BACKGROUND On August 2, 1990, Iraqi armed forces invaded Kuwait; within 5 days, the United States had begun to deploy troops to Southwest Asia in Operation Desert Shield. Intense air attacks against the Iraqi armed forces began on January 16, 1991, and opened a phase of the conflict known as Operation Desert Storm. Those two operations, although brief, exposed US and coalition forces to an array of biologic and chemical agents; for example, oil-well fires became visible in satellite images as early as February 9, 1991. The ground war began on February 23; by February 28, 1991, the war was over; and an official cease-fire was signed in April 1991. The oil-well fires were extinguished by November 1991. The last troops to participate in the ground war returned home on June 13, 1991. In all, about 697,000 US troops had been deployed to the Persian Gulf area during the two operations.1 Although the military operations were considered successful, with few battle injuries and deaths, veterans soon began reporting numerous health problems that they attributed to their participation in the Gulf War. Most of the men and women who served in the Gulf War returned to normal activities without serious health problems, but many experienced an array of unexplained symptoms, such as fatigue, muscle and joint pain, loss of concentration, forgetfulness, headache, respiratory complaints, rashes, sleep disturbances, and gastrointestinal distress. 1 Henceforth, the two operations—Desert Storm and Desert Shield—will be referred to as the Gulf War. 15
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16 CHRONIC MULTISYMPTOM ILLNESS IN GULF WAR VETERANS The men and women who served in the Persian Gulf region potentially were exposed to a wide variety of environmental, biologic, and chemical agents—including sand, smoke from oil- well fires, paints, solvents, insecticides, petroleum fuels and their combustion products, organophosphate nerve agents, pyridostigmine bromide (PB), depleted uranium (DU), anthrax and botulinum toxoid vaccines, and infectious diseases—in addition to psychologic and physiologic stress. In the more than 20 years that have passed since the Gulf War, veterans of that war have suffered numerous health consequences that might be related to exposure to those agents, conditions, and circumstances, although none of them has been causally linked to the Gulf War veterans’ symptoms. Numerous studies and reports have investigated possible causes of Gulf War veterans’ symptoms (e.g., the Institute of Medicine’s Gulf War and Health series, Volumes 1 , 2 , and 3 ; Brown, 2006; King’s College, 2010). In response to concerns about Gulf War veterans’ ill health, two laws were passed: the Persian Gulf War Veterans Act of 1998 (Public Law 105-277) and the Veterans Programs Enhancement Act of 1998 (Public Law 105-368). Each law mandated studies by the National Academy of Sciences’ Institute of Medicine (IOM) to examine the biologic and chemical hazards experienced in the gulf that might have been associated with the illnesses of Gulf War veterans. In the intervening years, the IOM, research organizations, and independent researchers have studied the many exposures in the gulf region and their potential for causing the array of symptoms reported by Gulf War veterans. THE GULF WAR SETTING2 The pace of the buildup for the war was unprecedented. In the first 3 months, the rapid deployment of US forces by sea and air exceeded that of any previous initial US period of war. Within 5 days of the Iraqi invasion of Kuwait, the United States and other coalition countries had begun to move troops into the region. By September 15, 1990, within 6 weeks of the invasion of Kuwait, deployed American service members numbered 150,000, including nearly 50,000 reservists. Within the next month, another 60,000 troops arrived in Southwest Asia; in November, an additional 135,000 reservists and National Guard members were called up (DOD, 1992). The Gulf War differed from previous wars in the demographic composition of military personnel and the uncertain conditions for many reservists. Of the total number deployed, almost 7% were women and about 17% were from National Guard and reserve units. Military personnel were, overall, older than those who had participated in previous wars, with a mean age of 27 years, as of 1991 (Joseph et al., 1997). Rapid mobilization exerted substantial pressures on those who were deployed, disrupting lives, separating families, and, for reserve and National Guard units, creating uncertainty about whether jobs would be available when they returned to civilian life. 2 Adapted from Gulf War and Health, Volume 1: Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccines (IOM, 2000); Gulf War and Health, Volume 2: Insecticides and Solvents (IOM, 2003); Gulf War and Health, Volume 3: Fuels, Combustion Products, and Propellants (IOM, 2005).
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INTRODUCTION 17 Living Conditions Combat troops were crowded together in warehouses and tents on arrival and then often moved to isolated desert locations with limited protection from the environmental elements. Most troops lived in tents and slept on cots lined up side by side, which afforded virtually no privacy or quiet. Sanitation was often primitive, with strains on latrines and communal washing facilities. Hot showers were infrequent, the interval between launderings of uniforms was sometimes long, and desert flies, scorpions, and snakes were a constant nuisance. Military personnel worked long hours and had few outlets for relaxation. Troops were ordered not to fraternize with local people, and alcohol was prohibited in deference to religious beliefs in the host countries. A mild, traveler’s type of diarrhea affected more than 50% of the troops in some units. Fresh fruits and vegetables from neighboring countries were identified as the risk factor and were removed from the diet. Thereafter, the diet consisted mostly of packaged foods and bottled water. For the first 2 months of troop deployment (August and September), temperatures were extremely high, as high as 115°F, with sand temperatures upwards of 150°F. Except for coastal regions, the relative humidity was less than 40%. Troops had to drink large quantities of water to prevent dehydration. Although the summer months were hot and dry, temperatures in winter (December through March) were low; wind-chill temperatures at night dropped to well below freezing. Wind and blowing sand made protection of skin and eyes imperative. Troops were not allowed to wear contact lenses except in air-conditioned areas that were protected from sand. Environmental and Chemical Exposures The most visually dramatic environmental event of the Gulf War was the smoke from more than 750 oil-well fires. Smoke rose and formed giant plumes that could be seen for hundreds of kilometers. There were other potential sources of exposure to petroleum-based products. Kerosene, diesel, and leaded gasoline were used in unvented tent heaters, cooking stoves, and portable generators. Petroleum products, including diesel fuels, were used to suppress sand and dust, and petroleum fuels were used for burning waste and trash. Pesticides, including dog flea collars, were widely used by troops in the gulf to combat the region’s ubiquitous insect and rodent populations. Permethrin was provided in spray cans for treating uniforms, and DEET in liquid or stick form was used as a personal mosquito and fly repellent. Other pesticides used by military personnel included methyl carbamates, organophosphates, and chlorinated hydrocarbons. Insecticides were used to control insects that are vectors of infectious diseases, such as leishmaniasis, sand fly fever, and malaria. Many possible exposures were related to particular occupational activities in the Gulf War. Most of the occupational chemical exposures appear to have been related to repair and maintenance activities, including battery repair (corrosive liquids), cleaning or degreasing (solvents, such as chlorinated hydrocarbons), sandblasting (abrasive particles), vehicle repair (asbestos, carbon monoxide, and organic solvents), weapon repair (lead particles), and welding or cutting (chromates, nitrogen dioxide, and heated metal fumes). Troops painted vehicles and equipment used in the gulf with chemical-agent–resistant coatings either before they were shipped to the gulf or in ports in Saudi Arabia. Working conditions in the field were not ideal, and recommended occupational-hygiene standards might not have been followed at all times.
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18 CHRONIC MULTISYMPTOM ILLNESS IN GULF WAR VETERANS Exposure of US personnel to DU occurred as the result of friendly-fire incidents, cleanup operations, and accidents (including fires). Others may have inhaled DU dust through contact with DU-contaminated tanks or munitions. DU is 67% denser than lead, has a high melting point, is highly pyrophoric, has a tensile strength comparable with that of most steels, and is chemically highly reactive. Because of those characteristics, the US military used a layer of DU for protection in heavy-armor tanks and in weapons. Threat of Chemical and Biologic Warfare When US troops first arrived in the gulf, they had no way of knowing whether they would be exposed to biologic and chemical weapons. Iraq had used such weapons in fighting Iran and in attacks on the Kurdish minority in Iraq. Military leaders feared that the use of such weapons in the gulf could result in the deaths of tens of thousands of Americans. Therefore, in addition to the standard vaccinations given before military deployment, about 150,000 troops received anthrax vaccine and about 8,000 received botulinum toxoid vaccine. Troops were also given blister packs of 21 tablets of PB to protect against possible chemical warfare; they were to take PB on the orders of a commanding officer when chemical-warfare attack was believed to be imminent. Chemical sensors and alarms were distributed throughout the region to warn of such attacks. The alarms were extremely sensitive and could be triggered by many substances, including some organic solvents, vehicle exhaust fumes, and insecticides. Although followup analysis by the Department of Defense (DOD) found no evidence of the use of chemical-warfare agents, the alarms sounded often; troops responded by donning confining protective gear and ingesting PB as an antidote to the effects of nerve gas. In addition to the alarms, there were widespread reports of dead sheep, goats, and camels, and troops were taught that those could indicate the use of chemical or biologic weapons. The sounding of the alarms, the reports of dead animals, and rumors that other units had been hit by chemical-warfare agents caused the troops to be concerned that they would be or had been exposed to the agents. After the war, there was the potential for exposure to additional chemicals, such as sarin and cyclosarin. Unbeknownst to the troops at the time, US demolition of munitions stored in a complex in Khamisiyah, Iraq, liberated stores of sarin and cyclosarin. DOD conducted dispersion modeling to estimate exposure, but none of the models found any troops to have been exposed to concentrations above “first-noticeable-effects levels,” that is, concentrations that would have been high enough to set off chemical alarms or to produce visible symptoms of acute cholinergic syndrome3 among troops. No medical reports by the US Army Medical Corps at the time of the release were consistent with signs and symptoms of an acute exposure to sarin or cyclosarin. That is consistent with the absence of reports of symptoms of acute cholinergic syndrome by medical personnel or veterans. However, as noted in a 2004 General Accounting Office report (GAO, 2004), epidemiologic studies that use the DOD models incorporate substantial exposure misclassification because of errors in estimation of troop locations combined with uncertainty regarding plume locations. Low-level exposure could have occurred without producing acute cholinergic syndrome. 3 Acute cholinergic syndrome is evident seconds to hours after exposure and usually resolves in days to months. Symptoms may include copious respiratory and oral secretions, diarrhea, vomiting, sweating, altered mental status, autonomic instability, and generalized weakness that can progress to paralysis and respiratory arrest.
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INTRODUCTION 19 CHARGE TO THE COMMITTEE The Department of Veterans Affairs (VA) provided the charge to the committee, which is presented below: An ad hoc committee will develop a case definition for chronic multisymptom illness (CMI)4 as it pertains to the 1990–1991 Gulf War Veteran population. The committee will comprehensively review, evaluate, and summarize the available scientific and medical literature regarding symptoms for CMI among the 1991 Gulf War Veterans. The committee will look broadly for relevant information, including, but not limited to: • Published peer-reviewed literature describing the symptomatology for CMI; • Published peer-reviewed literature concerning existing case definitions for CMI among the 1990–1991 Gulf War Veteran population; • Published peer-reviewed literature concerning existing case definitions of CMI among similar populations such as Allied military personnel; and • Published peer-reviewed literature concerning case definitions for other populations with a similar constellation of symptoms. • Discussions with researchers involved with developing case definitions for CMI in 1990–1991 Gulf War Veterans. • Discussions with clinicians who treat Veterans of the 1990-1991 Gulf War. In addition to reviewing and summarizing the available scientific and medical literature regarding symptoms and case definitions for CMI among Gulf War Veterans, the committee will: • Establish a consensus case definition along with guidelines for its use. • Evaluate existing case definitions in relation to priorities identified by the committee and determine whether an existing case definition is adequate, an existing case definition needs to be revised, or a new case definition needs to be established. • Consider issues such as specificity (the degree to which the definition applies to 1990–1991 Gulf War Veterans), sensitivity (the degree to which the case definition captures the excess symptomatology in 1990–1991 Gulf War Veterans), reliability (the degree to which Veterans’ symptoms are determined in a consistent manner), and portability (the degree to which the case definition is suitable for use in different study designs) in evaluating case definitions.5 • Consider the potential for the case definition, optimized for research purposes, to be used in clinical practice. • Consider other case definition characteristics deemed important. • Recommend additional areas of research or study that may be required to more adequately develop a consensus definition for CMI in 1990–1991 Gulf War Veterans. • Evaluate the terminology currently used in referring to CMI in Gulf War Veterans and recommend appropriate usage. 4 The committee uses the term chronic multisymptom illness throughout the report, as defined in the statement of work, when referring to the symptom complex in Gulf War veterans. 5 In completing its analysis, the committee clarified the definitions of sensitivity and specificity in Chapter 2.
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20 CHRONIC MULTISYMPTOM ILLNESS IN GULF WAR VETERANS HOW THE COMMITTEE APPROACHED ITS CHARGE The IOM appointed a committee of 16 experts to carry out the task. The committee members have expertise in occupational medicine, biostatistics, psychometrics, epidemiology, basic science, clinical medicine, toxicology, psychiatry, neurology, gastroenterology, and sociology. Some of the committee members treated Gulf War veterans when they came to their clinics or practices, and one committee members’ practice is devoted solely to Gulf War and other veterans. The committee also consulted with an expert in brain imaging because that field was not represented on the committee. The committee members directed the staff to conduct an extensive search of the extant peer-reviewed literature. PubMed was searched for all references related to the 1990–1991 Gulf War. Initially, more than 5,000 papers were retrieved; after elimination of duplicates, 2,033 unique papers remained. The titles and abstracts of those papers were reviewed, and 718 were selected for more rigorous review. The committee members divided the work by reading papers related to their expertise. The papers that were reviewed included all health outcomes that have been noted in Gulf War veterans, for example, mortality, hospitalization, neurologic symptoms, respiratory symptoms, gastrointestinal symptoms, pain, birth defects and fertility, cancer, mental- health conditions, and overlapping syndromes. In an effort to characterize the symptomatology associated with CMI, the focus of the committee’s review is on studies of symptoms not associated with diagnosed medical or psychiatric conditions; the focus is on studies of symptom- reporting in Gulf War veterans. The committee agreed early on that a determination of the etiology of CMI was outside the scope of its charge. Thus, the committee did not consider toxicologic or exposure studies. The committee held one open meeting, in which members heard from veterans, government officials, researchers, clinicians who treat Gulf War veterans, and members of the VA Research Advisory Committee. The meeting increased the committee’s awareness of the variety of symptoms being experienced by the Gulf War veterans. In addition, the vigorous discussions with the veterans and researchers were invaluable for increasing the committee members’ understanding of the complexity of issues involved in its task. ORGANIZATION OF THE REPORT Chapter 2 introduces some of the issues that have made CMI so difficult to define and presents the general elements of case definitions. Chapter 3 summarizes the many cohort studies that focus on the Gulf War veterans’ symptomatology. It discusses how the cohorts were assembled, the limitations of the studies, and the array of symptoms identified. Chapter 4 provides a brief discussion of factor analysis and discusses previous efforts related to the use of factor analyses to detect a unique syndrome in Gulf War veterans. Finally, Chapter 5 presents the committee’s discussion of existing case definitions of CMI and its conclusions and recommendations. The report has two appendixes: Appendix A contains additional background information on statistical techniques used to identify a unique Gulf War syndrome, and Appendix B contains a graph depicting the range of percentages of symptoms endorsed by veterans.
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INTRODUCTION 21 REFERENCES Brown, M. 2006. Toxicological assessments of Gulf War veterans. Philosophical transactions of the Royal Society of London. Series B, Biological Sciences 361(1468):649-679. DOD (Department of Defense). 1992. TRADOC Support to Operations Desert Shield and Desert Storm: A Preliminary Study. Office of the Command Historian, US Army Training and Doctrine Command. GAO (Government Accounting Office). 2004. Gulf War Illnesses: DOD’s Conclusions about U.S. Troops’ Exposure Cannot Be Adequately Supported. Washington, DC: US Government Accountability Office. IOM (Institute of Medicine). 2000. Gulf War and Health, Volume 1: Depleted Uranium, Pyrodostigmine Bromide, Sarin, Vaccines. Washington, DC: National Academy Press. IOM. 2003. Gulf War and Health, Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. IOM. 2005. Gulf War and Health, Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. Joseph, S. C., R. R. Blanck, G. Gackstetter, R. Glaser, K. C. Hyams, S. Kinty, C. Magruder, J. Mazzuchi, F. L. O’Donnell, M. D. Parkinson, R. E. Patterson, and D. H. Trump. 1997. A comprehensive clinical evaluation of 20,000 Persian Gulf War veterans. Military Medicine 162(3):149-155. King’s College London. 2010. King’s Centre for Military Health Research: A Fifteen Year Report. What Has Been Achieved by Fifteen Years of Research into the Health of the UK Armed Forces? University of London.
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