Invited Commentary: Unexplained Health Problems after Gulf War ServiceFinding Answers to Complex Questions
Lea Steele1
1 From the Kansas Commission on Veterans Affairs, 700 SW Jackson Street, Suite 701, Topeka, KS 66603.
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ABSTRACT
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Numerous studies have investigated the health problems reported by veterans of the Persian Gulf War, but important questions remain. Epidemiologic studies have consistently indicated that Gulf War veterans report unexplained symptoms at significantly higher rates than veteran comparison groups but that they have not experienced excess rates of disease-related mortality. Addressing unanswered questions surrounding post-Gulf-War health problems presents a complex challenge for researchers, but not an insurmountable one. Progress in understanding the role of potential etiologic factors can be made using epidemiologic approaches traditionally applied in the absence of individual exposure data, such as comparisons between veteran subgroups with differing illness profiles and deployment histories.
morbidity; mortality; pathological conditions, signs and symptoms; Persian Gulf syndrome; veterans
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INTRODUCTION
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In the decade since the Persian Gulf War, the health problems reported by returning veterans have been a source of contention and controversy (1

). Much of the controversy has related to questions about the nature and causes of these ailments. Early discussion focused on whether the conditions were organic or psychological, a result of stress or of toxic exposures (5
7
). More recently, debate has shifted to the existence of a unique "Gulf War syndrome" (8
, 9
) and whether these unexplained symptoms should be considered primarily part of a general phenomenon that occurs after every war or a consequence of events and exposures unique to the Gulf War (8
, 10
, 11
).
Epidemiologic investigations have made progress in identifying some of the "harder" post-Gulf-War health outcomesthat is, outcomes that can be objectively assessed and quantified, such as mortality and hospitalization rates. Less progress has been made in characterizing the "softer" endpointsthe many symptoms reported by Gulf War veterans that are often unaccompanied by observable signs or laboratory abnormalities.
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What do we know about the health of Gulf War veterans?
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The article by Kang and Bullman (12
) in this issue of the Journal compares mortality rates between Gulf War veterans and Gulf-War-era veterans who did not serve in the war. After 7 years of follow-up, no association was found between disease-related deaths and either Gulf War service overall or proximity to the Khamisiyah weapons demolition site in Iraq. Another key finding is that Gulf War veterans have not experienced excess rates of death due to cancer or amyotrophic lateral sclerosis, although this cohort will have to be followed for many more years to monitor mortality due to conditions that develop over longer latency periods. Higher rates of mortality from accidents but not from disease have been reported among Gulf War veterans in the United Kingdom (13
). In addition, studies have identified few differences in hospitalization rates between Gulf War veterans and non-Gulf veterans in the years since the war (14
16
).
A different picture of veterans' post-Gulf-War health status is provided by another body of epidemiologic research. Population-based studies have consistently shown that Gulf veterans have an unexpectedly high level of morbidity, as characterized by self-reported symptomatology and diagnosed medical and psychiatric conditions (17







26
). Overall, the types of symptoms reported by different veteran groups are strikingly similar, even though veterans in these studies came from different countries and served in different areas of the Persian Gulf theater. Gulf War veterans, as a group, are significantly more symptomatic than nondeployed Gulf-War-era veterans (17
, 19





26
), Gulf-War-era veterans deployed to other areas of the world (18
), and veterans who served in the war in Bosnia (22
). Among Gulf War veterans, the prevalences of symptoms and multisymptom complexes are frequently associated with specific self-reported wartime exposures (19
, 22
, 27



32
). Symptomatic Gulf veterans typically have few abnormalities on routine clinical examinations and laboratory tests (21
, 33
), although preliminary studies have identified group differences in neurologic and immune parameters (34




40
). Additionally, Gulf veterans score lower than comparison groups on standardized tests assessing physical and psychological function (19
, 21
, 22
, 41
).
Studies have also indicated that, while some Gulf veterans are affected by psychiatric conditions, including posttraumatic stress disorder, the increased morbidity observed among Gulf War veterans cannot be adequately accounted for by deployment stress and psychiatric illness (28
, 42
, 43
). This is not surprising, given the brief and decisive nature of the Gulf War. Over 70 percent of veterans deployed to the region were not involved in combat and did not witness any deaths (24
).
To summarize, with respect to post-Gulf-War health problems, two facts have been consistently demonstrated: 1) Gulf War veterans, as a group, have not been unduly affected by adverse health outcomes associated with "hard" measures, such as rates of hospitalization and disease-related mortality; and 2) Gulf War veterans, as a group, have consistently been shown to be more symptomatic and debilitated than non-Gulf-War veterans. The obvious conclusion to draw from these two facts is that, whatever the nature of the health problems affecting Gulf War veterans, they do not currently appear to be of the type that generally results in hospitalization or premature death.
Beyond these main points, not much more is actually known about post-Gulf-War health problems. Most other essential information regarding these problems remains unknown or unverified. At the population level, basic epidemiologic parameters, including prevalence, population distribution, and etiologic and risk factors have yet to be clearly elucidated. Clinically, pathophysiologic mechanisms and diagnostic markers have not been identified, nor have efficacious medical therapies been demonstrated, although two clinical trials are currently under way. Why has so little progress been made, despite numerous studies and a federal research investment that now exceeds $155 million (44
)? There are several reasons, some obvious, others less so.
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Complex illnesses are difficult to study
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The most obvious reason for the lack of progress in identifying the basic epidemiologic parameters of post-Gulf-War health problems is the challenge inherent in investigating illness that is identified almost solely on the basis of subjective symptoms. Moreover, many believe that "Gulf War illness" would more accurately be termed "Gulf War illnesses" (45
), since symptom profiles vary from person to person. Add to that the appearance that these problems are multifactorial in originthat is, that they may have been precipitated by several factors, either alone or in different combinationsand the situation is enough to give an epidemiologist pause.
The less obvious impediments to progress may include blind alleys generated in attempts to make sense out of this complex illness phenomenon. As with any new area of medical inquiry, useful answers can emerge only when we are able to ask the right questions.
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Is there a Gulf War syndrome?
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"Is there a unique Gulf War syndrome?" has been identified as the central health question following Operation Desert Storm (46
) and has been the subject of a number of research articles and commentaries (4
, 8
, 11
, 33
, 40
, 47
49
). While this question is worth answering, it is not the fundamental question at issue. Addressing it as the primary question, in effect, puts the cart before the horse. The more essential question can be phrased "Are veterans of the Gulf War affected by chronic health problems associated with their service in the war?" If that question can be clearly answered and if, as population studies have suggested, the answer appears to be yes, the most immediate follow-up questions would relate to the symptomatic, physiologic, and psychological characteristics of these health problems and to factors associated with their etiology. Only after these questions have been addressed can we begin to determine whether we are looking at one syndrome or more and whether these syndromes are distinct from previously identified conditions.
Recent observations on whether post-Gulf-War health problems constitute a unique syndrome have relied on the results of exploratory factor analyses. In these analyses, general lists of symptoms reported by large, heterogeneous groups of Gulf War veterans have been found to load onto factors similar to those found in non-Gulf veterans (47
49
). The question remains, however, as to whether factor analysis is a suitable tool for determining the presence or absence of a unique syndrome in a given population.
It would be appealing to simply subject all the symptoms reported by a population to a relatively straightforward analysis that would allow any "new" syndromes to reveal themselves as constructs. Unfortunately, this is not what one would expect from an exploratory factor analysis of symptoms. The explanation as to why this is so requires an understanding of what factor analysis is and what the factors in a given analysis actually represent. An excellent description of these considerations was provided by renowned psychometrician Dr. Stanley Mulaik in his presentation at the 1998 Conference on Federally Sponsored Gulf War Veterans' Illnesses Research (50
). Pointing out that "factors are not syndromes," he cautioned investigators that exploratory factor analyses are unlikely to reveal novel symptom patterns, especially when relying exclusively on first-order factors.
Factors expected from such analyses would be those associated with pathology or distress in particular organs or systems. Such factors would probably be similar in any heterogeneous population, even those including individuals with different chronic diseases precipitated by different etiologic factors. In other words, comparing the results of exploratory factor analyses of symptoms endorsed by Gulf War and non-Gulf-War veterans would not be expected to identify a unique "Gulf War syndrome," regardless of whether veterans are affected by excess morbidity or distinct pathologies as a result of their Gulf War service.
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Can these questions be answered? Suggestions for epidemiologic research
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Because wartime exposure data are not available for individual veterans, there have been suggestions that we might never know what caused these problems or, by extension, their physiologic mechanisms (6
, 51
). However, epidemiologic methods are particularly well-suited to providing clues that generate specific hypotheses about disease etiology, even when individual exposure data cannot be obtained. It is therefore surprising that epidemiologic methods traditionally used to investigate unknown diseases potentially caused by environmental factors have scarcely been applied to the Gulf War illness question. Epidemiologists generally begin investigations of unknown diseases by first generating a description of the illness and then delineating its distribution in a given population according to characteristics of person, place, and time. This classic approach has proven useful in a study of Kansas Gulf War veterans, where a defined symptom pattern was found to be strongly associated with the places and time periods in which veterans had served in the Persian Gulf theater (25
).
Progress in understanding whether environmental exposures might have contributed to veterans' illnesses can be made by conducting epidemiologic studies that compare symptom profiles of well-defined veteran subgroups (52
, 53
). Veterans may be grouped in any number of ways (e.g., by unit or location). If, for example, veterans in Unit A have a high rate of a defined symptom complex but veterans in Unit B have a low rate, differences in deployment experiences and circumstances between the two groups should provide important insights about possible etiologic factors.
Associations between illness and location in the Persian Gulf theater have been described in unpublished studies conducted by researchers from the Department of Veterans Affairs (54
), in a Congressional report on in-theater locations of veterans filing disability claims (55
), and by Navy investigators (56
). In a study of 2,715 Marine Gulf veterans conducted in March 1991, Navy investigators defined three exposure groups according to unit locations in the preceding months. The study found that the group of veterans who had been closest to oil well fires for the longest period of time had significantly more respiratory symptoms (wheezing, cough, runny nose, sore throat) and gastrointestinal symptoms (diarrhea, stomach cramps, nausea, vomiting) than did veterans stationed in other locations (56
). This early study shows that differences in the frequencies and patterns of symptoms by time and place can be and have been identified and can provide useful information, even when individual exposure data are unavailable.
Another urgent requirement for progress in both epidemiologic and clinical investigations is a consensus definition of what constitutes a Gulf War illness "case." Arriving at such a definition may be a difficult challenge in a community of researchers divided about whether a Gulf War illness problem even exists; yet we know that Gulf War veterans, as a group, endorse symptoms in several categories at higher frequencies than do individuals in comparison populations. This excess morbidity can be described and quantified (57
). Without a standardized case definition, investigators will continue to identify different groups of symptomatic veterans as "cases," which will result in findings that are difficult to interpret and impossible to compare.
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Conclusions
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Answering fundamental questions about the health problems reported in the wake of Gulf War service poses a complex challenge for researchers, but not an insurmountable one. At this stage of our understanding, one of the plausible explanations for the Gulf War illness mystery is that, as one Gulf veteran put it, "Something happened to us out there in the desert" (58
). Whatever that something might have been, it is too early to pronounce these questions unanswerable. This is especially so when epidemiologic approaches that have the potential to provide basic etiologic information have yet to be fully utilized.
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ACKNOWLEDGMENTS
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The author thanks Dr. Jeff Levin for helpful suggestions on an earlier version of this commentary.
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NOTES
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Reprint requests to Dr. Lea Steele at this address
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Received for publication May 11, 2001.
Accepted for publication May 23, 2001.
Related articles in Am. J. Epidemiol.:
- Mortality among US Veterans of the Persian Gulf War: 7-Year Follow-up
- Han K. Kang and Tim A. Bullman
Am. J. Epidemiol. 2001 154: 399-405.
[Abstract]
[FREE Full Text]