More than 15 years have passed since the Iraqi invasion of Kuwait in August 1990 and the offensive by coalition troops in January 1991. Oil-well fires became visible in satellite images as early as February 9, 1991; the ground war began on February 24; and by February 28, 1991, the war was over. The military operation in the gulf was brief: an official cease-fire was signed in April 1991, and 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 during the conflict.
Although the Persian Gulf War was considered a successful military operation with few injuries and deaths among coalition forces, many returning veterans soon began to report numerous health problems that they believed were associated with their service in the gulf. Although most Gulf War veterans returned to normal activities, some have had a wide array of symptoms and unexplained illnesses. This volume summarizes the overall health effects in veterans and notes which health outcomes are more evident in Gulf War veterans than in their nondeployed counterparts.
An impressive body of literature details the veterans’ symptoms and illnesses. At the request of the Department of Veterans Affairs (VA), the Institute of Medicine (IOM) appointed a committee (the Committee on Gulf War and Health: A Review of the Medical Literature Relative to Gulf War Veterans’ Health) to review that body of literature and to summarize what is known about the current status of the veterans’ health.
Previous IOM committees and their reports focused on associations between biologic or chemical agents to which veterans might have been exposed in the gulf and health outcomes. Those committees typically relied on studies of occupational groups exposed to the putative agents and, when available, included studies of veterans. The present committee, however, did not use occupational groups as surrogates of exposure to the putative agents that might have been found in the gulf, but rather reviewed the research on Gulf War veterans themselves that details their symptoms and illnesses. The numerous studies that have been conducted in the intervening years since the war have typically compared Gulf War veterans with their nondeployed counterparts. Thus, within the limitations of each study, it is possible to determine which symptoms and illnesses are associated with deployment to the Persian Gulf.
In 1998, in response to the growing concerns of ill Gulf War veterans, Congress passed two laws: PL 105-277, the Persian Gulf War Veterans Act, and PL 105-368, the Veterans Programs Enhancement Act. Those laws directed the secretary of veterans affairs to enter into a contract with the National Academy of Sciences (NAS) to review and evaluate the scientific and medical literature regarding associations between illness and exposure to toxic agents,
environmental or wartime hazards, or preventive medicines or vaccines associated with Gulf War service and to consider the NAS conclusions when making decisions about compensation. The study was assigned to the IOM.
The Persian Gulf War legislation directs IOM to study diverse biologic, chemical, and physical agents. Exposures to most of the Gulf War agents have been extensively studied and characterized, primarily in occupational settings (for example, exposure to pesticides, solvents, and fuels), but exposures to others have not been as well studied and characterized in human populations (for example, exposure to nerve agents and vaccines).
Given the large number of agents to study, IOM divided the task into several reviews, which are now complete: 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); and Gulf War and Health: Updated Literature Review of Sarin (IOM 2004). Three other studies are underway: one examining the long-term sequelae of infectious diseases that are endemic to the Persian Gulf, another reviewing the long-term health effects that might be associated with deployment-related stress, and a third reviewing whether there is an increased risk of amyotrophic lateral sclerosis in all veteran populations. The present report summarizes health effects in veterans deployed to the Persian Gulf irrespective of specific exposures.
THE GULF WAR SETTING1
Although the committee’s charge was not to review the scientific evidence on the possible health effects of various agents to which Gulf War veterans were potentially exposed, the committee recognized that it needed to have as complete an understanding of the Gulf War experience as possible. Furthermore, information on the likelihood or magnitude of specific exposures might be helpful in interpreting epidemiologic studies that are reviewed in detail in Chapters 4 and 5. It should be noted, that in addition to reviewing studies from the United States, the committee reviewed studies from Australia, Canada, Denmark, and the United Kingdom.
The information in this section provides a context for the many scientific articles that the committee reviewed and an appreciation (albeit limited) of the collective experience of Gulf War veterans. It is compiled from many sources (Gunby 1991) and from presentations by veterans and other speakers at the committee’s public meeting (Hyams et al. 1995; IOM 1995; IOM 1996; IOM 1999; Joellenbeck et al. 1998; Lawler et al. 1997; NIH Technology Assessment Workshop Panel 1994; PAC 1996; PAC 1997; Persian Gulf Veterans Coordinating Board 1995; U.S. Department of Veterans Affairs 1998; Ursano and Norwood 1996).
The pace of the buildup for the Gulf War was unprecedented. Within 5 days after Iraq invaded Kuwait, the United States began moving troops into the region as part of Operation Desert Shield. By September 15, 1990, the number of American service members reached 150,000 and included 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. By February 24, 1991, more than 500,000 US troops had been deployed to the Persian Gulf region. In addition to the US troops, a coalition force of 34 member countries was eventually assembled.
The Gulf War reflected many changes from previous wars, particularly in the demographic composition of military personnel and the uncertainty of conditions for many reservists. Of the nearly 700,000 US troops who fought in Operation Desert Shield and Operation Desert Storm, 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 28 years. Seventy percent of the troops were non-Hispanic/White; 23% were black, and 5% were Hispanic (Joseph 1997). Rapid mobilization exerted substantial pressure 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.
Combat troops were crowded into warehouses and tents on arrival and then often moved to isolated desert locations. Most troops lived in tents and slept on cots lined up side by side, affording virtually no privacy or quiet. Sanitation was often primitive, with strains on latrines and communal washing facilities. Hot showers were infrequent, the interval between laundering uniforms was sometimes long, and desert flies were a constant nuisance, as were scorpions and snakes. Military personnel worked long hours and had narrowly restricted outlets for relaxation. Troops were ordered not to fraternize with local people, and alcoholic drinks were prohibited in deference to religious beliefs in the host countries. A mild, traveler’s type of diarrhea affected more than half of the troops in some units. Fresh fruits and vegetables from neighboring countries were identified as the cause 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 1990) the weather was extremely hot and humid, with air temperatures as high as 115°F and sand temperatures reaching 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 summers were hot and dry, temperatures in winter (December-March) were low, with wind-chill temperatures at night dropping to well below freezing. Wind and blowing sand made protection of skin and eyes imperative. Goggles and sunglasses helped somewhat, but visibility was often poor.
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 plumes from individual fires rose and combined to form giant plumes that could be seen for hundreds of kilometers. There were additional potential sources of exposure to petroleum-based combustion products. Kerosene, diesel, and leaded gasoline were used in unvented tent heaters, cooking stoves, and portable generators. Exposures to tent-heater emissions were not specifically documented, but a simulation study was conducted after the war to determine exposure (see Chapter 2). Petroleum products, including diesel fuels, were also used to suppress sand and dust, and petroleum fuels were used to aid in the burning of waste and trash.
Pesticides, including dog flea collars, were widely used by troops in the Persian Gulf to combat the region’s ubiquitous insect and rodent populations; and although guidelines for use were strict, there were many reports of misuse. The pesticides used included methyl carbamates, organophosphates, pyrethroids, and chlorinated hydrocarbons. The use of those pesticides is reported in numerous reports (e.g., RAND 2000), however objective information regarding individual levels of pesticide exposure is generally not available.
Many exposures could have been related to particular occupational activities in the Gulf War. The majority of occupational chemical exposures appear to have been related to repair and maintenance activities, including battery repair (corrosive liquids), cleaning and degreasing (solvents, including chlorinated hydrocarbons), sandblasting (abrasive particles), vehicle repair (asbestos, carbon monoxide, and organic solvents), weapon repair (lead particles), and welding and cutting (chromates, nitrogen dioxide, and heated metal fumes). In addition, troops painted vehicles and other equipment used in the gulf with a chemical-agent-resistant coating either before being shipped to the gulf or at 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.
Exposure of US personnel to depleted uranium (DU) occurred as the result of “friendly-fire” incidents, cleanup operations, and accidents (including fires). Others might have inhaled DU dust through contact with DU-contaminated tanks or munitions. DU exposure is discussed in more detail in Chapter 2. Assessment of DU exposure, especially high exposure, is considered to be more accurate than assessment of exposure to most other agents because of the availability of biologic monitoring information.
Threat of Chemical and Biologic Warfare
When US troops arrived in the gulf, they had no way of knowing whether they would be exposed to biologic and chemical weapons. Iraq previously 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 before military deployment, about 150,000 troops received anthrax vaccine and about 8,000 botulinum toxoid vaccine. In some cases, vaccination records were kept, and they provide an objective measure of exposure in addition to self-reporting by troops.
Troops were also given blister packs of 21 tablets of pyridostigmine bromide (PB) to protect against agents of chemical warfare, specifically nerve gas. Troops were to take PB on the orders of a commanding officer when a 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. Alarms sounded often and troops responded by donning the confining protective gear and ingesting PB as an antidote to nerve gas. In addition to the alarms, there were widespread reports of dead sheep, goats, and camels, which troops were taught could be indication of 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 such agents.
Despite the small numbers of US personnel injured or killed during combat in the Gulf War, the troops, as in any war, faced the fear of death, injury, or capture by the enemy. After the
war, there was the potential for other exposures, including US demolition of a munitions storage complex at Khamisiyah, Iraq, which—unbeknownst to demolition troops at the time—contained stores of sarin and cyclosarin. The potential exposures to sarin and cyclosarin from the Khamisiyah incident are discussed in Chapter 2 and have been the subject of specific studies.
It has been documented from the Civil War to the Gulf War that a variety of physical and psychologic stressors have placed military personnel at high risk for adverse health effects (Engel et al. 2004; Hyams et al. 1996; Jones et al. 2002; Soetekouw et al. 2000). In addition to the threat or experience of combat, the Gulf War involved rapid and unexpected deployment, harsh living conditions, and anticipation of exposure to chemical and biologic agents, environmental pollution from burning oil fires, and family disruption and financial strain.
CHARGE TO THE COMMITTEE
The charge to this IOM committee is different from charges to previous IOM Gulf War committees in that this one does not associate health outcomes with specific biologic or chemical agents believed to have been present in the gulf, but rather it examines health outcomes related to deployment. For that reason, the committee did not review toxicologic or experimental studies. Thus, the committee has limited its review to epidemiologic studies of health outcomes in Gulf War veterans to determine their health status. The specific charge to the committee, as requested by the VA, was to review, evaluate, and summarize peer-reviewed scientific and medical literature addressing the health status of Gulf War veterans.
COMMITTEE’S APPROACH TO ITS CHARGE
The committee began its evaluation by presuming neither the existence nor the absence of illnesses associated with deployment. It sought to characterize and weigh the strengths and limitations of the available evidence. The committee did not address policy issues, such as decisions regarding compensation, potential costs of compensation, or any broader policy implications of its findings.
Extensive searches of the epidemiologic literature were conducted and over 4000 potentially relevant references were retrieved. After an assessment of the titles and abstracts of the initial searches, the committee focused on some 850 potentially relevant epidemiologic studies for review and evaluation.
The committee adopted a policy of using only peer-reviewed published literature as the basis for its conclusions. The process of peer review by fellow professionals increases the likelihood of high quality but does not guarantee the validity of a study or the ability to generalize its findings. Accordingly, committee members read each study critically and considered its relevance and quality. The committee did not collect original data, nor did it perform any secondary data analysis (except to calculate response rates for consistency among studies).
The committee’s next step, after securing the full text of the epidemiologic studies it would review, was to determine which studies would be considered primary or secondary
studies. The committee developed inclusion criteria for studies (Chapter 3). Primary studies provide the basis of the committee’s findings. For a study to be included in the committee’s review as a primary study it had to meet specified criteria. For example, it would have to include information about specific health outcomes; demonstrate rigorous methods, such as being published in a peer-reviewed journal; include details of its methods; include a control or reference group; have the statistical power to detect effects; and include reasonable adjustments for confounders. A secondary study provides background information or context for this report. Secondary studies, although mentioned, are not written-up in detail and typically are not included in tables.
COMPLEXITIES IN RESOLVING GULF WAR AND HEALTH ISSUES
Investigations of the health effects of past wars have often focused on narrowly defined hazards or health outcomes, such as infectious diseases (for example, typhoid and malaria) during the Civil War, specific chemical hazards (for example, mustard gas in World War I and Agent Orange and other herbicides in Vietnam), and combat injuries. A discussion of the possible health effects of Gulf War service, however, involves many complex issues, some of which are explored below. They include exposure to multiple biologic and chemical agents, limitations of exposure information, individual variability factors, and illnesses that are often nonspecific and lack defined medical diagnoses or treatment protocols. The committee was not tasked with addressing those issues, but it presents them in this introductory chapter to acknowledge the difficulties faced by veterans, researchers, policymakers, and others in reaching an understanding about the veterans’ ill health.
Multiple Exposures and Chemical Interactions
Although Operation Desert Shield and Operation Desert Storm were relatively brief, military personnel were potentially exposed to numerous harmful agents. They include agents administered as preventive measures (such as, PB, vaccines, pesticides, and insecticides), hazards of the natural environment (such as, sand and endemic diseases), job-specific agents (such as, paints, solvents, and diesel fumes), war-related agents (such as, smoke from oil-well fires and DU), and hazards from cleanup operations (such as, sarin and cyclosarin). Thus, military personnel might have been exposed to various agents at various doses for various periods. Many of the exposures are not specific to the Gulf War, but the number and combination of agents to which the veterans might have been exposed make it difficult to determine whether any agent or combination of agents is the cause of Gulf War veterans’ illnesses.
Limitations of Exposure Information
Determining whether Gulf War veterans face an increased risk of illness because of their exposures during the war requires extensive information about each exposure (such as the actual agents, the duration of exposure, the route of entry and the internal dose) and documentation of adverse reactions. But very little is known about most Gulf War exposures. After the ground war, an environmental-monitoring effort was initiated primarily because of concerns related to smoke from oil-well fires and exposure to sarin and cyclosarin rather than for the other agents to which
the troops might have been exposed. Consequently, exposure data on other agents are lacking or are severely limited.
Various exposure assessment tools are being used in research to fill gaps in exposure information, but there are limitations in reconstruction of past exposure events. For example, veterans are surveyed to obtain recollections about agents to which they might have been exposed, although survey results might be limited by recall bias (see Chapter 3). Models have been refined to estimate exposures to sarin and cyclosarin, but it is difficult to incorporate intelligence information, meteorologic data, transport and dispersion data, and troop-unit location information accurately (see Chapter 2). Extensive efforts have been made to model and obtain information on potential exposures to DU, smoke from oil-well fires, and other agents. Although modeling efforts are important for discerning the details of exposures of Gulf War veterans, they require external review and validation. Furthermore, even if there were accurate troop location data, the location of individual soldiers would be very uncertain. Because of the limitations in the exposure data, it is difficult to determine the likelihood of increased risk for disease or other adverse health effects in Gulf War veterans that are due specifically to biologic and chemical agents.
Differences among people in their genetic, biologic, psychologic, and social vulnerabilities add to the complexities in determining health outcomes related to specific agents. Sensitive people will exhibit different responses to the same agents than people without the susceptibility. For example, a person who is a poor metabolizer of a particular substance, depending on his or her genetic makeup, might be at higher or lower risk for specific health effects due to exposure to the substance. Researchers are investigating the genotypes that code for two forms of an enzyme that differ in the rate at which they hydrolyze particular organophosphates (including sarin). Lower hydrolyzing activity would mean that despite identical exposure to sarin, more sarin would be bioavailable in people who are poor metabolizers and could result in increased anticholinesterase effects.
Many Gulf War veterans suffer from an array of health problems and symptoms (for example, fatigue, muscle and joint pain, memory loss, gastrointestinal disorders, and rashes) that are not specific to any disease and are not easily classified with standard diagnostic coding systems. Population-based studies have found a higher prevalence of self-reported symptoms in Gulf War veterans than in nondeployed Gulf War-era-veterans or other control groups (see Chapters 4 and 5; Goss Gilroy Inc. 1998; Iowa Persian Gulf Study Group 1997; Unwin et al. 1999). That Gulf War veterans do not all experience the same array of symptoms has complicated efforts to determine whether there is a “Gulf War syndrome” or overlap with other symptom-based disorders. The nature of the symptoms suffered by many Gulf War veterans does not point to an obvious diagnosis, etiology, or standard treatment.
ORGANIZATION OF THE REPORT
Chapter 2 is a background chapter that details many of the specific biologic and chemical agents in the gulf and provides a context for the rest of the committee’s report. Chapter 3 provides a brief background in epidemiology and describes the committee’s methods for choosing the epidemiologic studies that are reviewed in later chapters. Chapter 4 describes the major Gulf War cohorts and provides information about the numerous studies that have been derived from them; the chapter includes a summary table that lists all the original cohorts and their derivative studies. Chapter 5 describes and analyzes the studies of health outcomes in Gulf War veterans; it also provides the basis for the committee’s conclusions and recommendations, which are presented in Chapter 6.
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