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Gulf War and Health: Volume 2: Insecticides and Solvents (2003)

Chapter: Appendix A: Overview of Illnesses in Gulf War Veterens

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Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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APPENDICES

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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A
OVERVIEW OF ILLNESSES IN GULF WAR VETERANS

Miriam Davis, PhD1

A decade after the Gulf War, questions persist about illnesses reported by veterans. About 20% of Gulf War-deployed veterans receive some form of disability compensation.2 A sizable number of veterans report having fatigue, rash, headache, muscle and joint pain, and loss of memory (Joseph, 1997; Murphy et al., 1999). An increased prevalence of those symptoms has been borne out by large controlled studies of deployed and nondeployed military personnel3 from four countries—the United States, the United Kingdom, Denmark, and Canada. That so many Gulf War veterans report unexplained4 symptoms and disability has prompted concerns about their exposure to potentially hazardous agents during the Gulf War. The US government has invested substantially in health research to understand veterans’ illnesses, search for their causes, and find effective treatments (CDC, 1999; IOM, 2001; Research Working Group, 1999).

This appendix describes the research that has addressed three fundamental questions about illnesses in Gulf War veterans:5 What are the nature and prevalence of veterans’ symptoms and illnesses? Do their unexplained symptoms warrant classification as a new syndrome? Are exposures to specific biologic, chemical, and radiologic agents during the Gulf War associated with veterans’ symptoms and illnesses? Those questions are designed to guide the reader through a complex body of research. The appendix summarizes studies of Gulf War veterans’ symptoms, diagnosable illnesses, mortality, and hospitalizations; and it provides a brief overview of the Gulf War veterans registry programs established by the Department of Veterans Affairs (VA) and the Department of Defense (DOD). The

1  

Department of Epidemiology and Biostatistics, School of Public Health and Health Services, George Washington University, and independent medical writer.

2  

About 155,000 of the more than 700,000 Gulf War veterans receive various degrees of disability compensation or a disability pension from the Department of Veterans Affairs (Sullivan, P, personal communication, Dec. 14, 2001).

3  

Many studies have compared the health of military personnel deployed to the Gulf War with that of military personnel who were not deployed to the Gulf War but served during the same period (Gulf War era). Some studies have a comparison cohort of military personnel who served in another deployment (such as Bosnia).

4  

Unexplained symptoms or unexplained illnesses mean that health complaints cannot be accounted for or explained by current medical diagnoses.

5  

This appendix uses the term Gulf War veterans in the broadest sense. Unless otherwise specified, the term denotes all military personnel who served in the Gulf War theater between August 2, 1990, and June 13, 1991, regardless of whether they later continued on active duty, returned to the reserves or National Guard, or left military service.

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

information presented here offers background for the reader and offers context for members of the IOM committee.

This appendix updates a previous chapter on Gulf War illnesses contained in the first volume (IOM, 2000). Some studies of Gulf War veterans covered here are also discussed more thoroughly in the body of this volume because they are relevant to understanding the health effects of insecticides and solvents. There, they are incorporated into the body of evidence evaluated by the committee to reach its conclusions about the health effects of insecticides and solvents.

REGISTRY PROGRAMS

Some 700,000 US servicemen and servicewomen were deployed in the Gulf War in 1990 and 1991 (PAC, 1996). The demographic composition of the deployment was more diverse than that of previous deployments; there were greater racial and ethnic diversity, more women, and more reserves and National Guard troops (Table A.1).

TABLE A.1 Demographic Characteristics of US Gulf War Troops

Characteristic

Percentage of Troopsa

Sex

Male

93

Female

7

Age (mean) in 1991 (years)

27

Race or ethnicity

Non-Hispanic/White

70

Black

23

Hispanic

5

Other

2

Rank

Enlisted

90

Officer

10

Military branch

Army

50

Navy

23

Marines

15

Air Force

12

Military Status

Active DutyReserves or

83

National Guard

17

SOURCE: Joseph, 1997

aTotal about 697,000 US military personnel.

Soon after the war ended in 1991, veterans began to seek medical treatment for a variety of symptoms and illnesses (PAC, 1996). DOD and VA responded to veterans’ health concerns by establishing programs for veterans to voluntarily receive clinical examinations largely for diagnostic purposes. By 1994, those registry programs had been revised and renamed the Comprehensive Clinical Evaluation Program (hereinafter called the DOD registry) and the Persian Gulf Registry and Uniform Case Assessment Protocol (hereinafter called the VA registry). The programs are similarly structured. They begin with an initial physical examination, including patient and exposure history and screening laboratory tests, which are followed by an opportunity for referral to more-specialized testing and

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

consultation if needed (Joseph, 1997; Murphy et al., 1999).6 About 125,000 Gulf War veterans underwent registry health examinations through March 1999 (IOM, 1999a), most conducted under VA auspices. The programs continue to register participants.

The symptoms most commonly reported in 1992–1997 by the 52,835 participants in the VA registry were fatigue, rash, headache, muscle and joint pain, and loss of memory (Table A.2) (Murphy et al., 1999). An almost identical set of symptoms was reported most frequently among the roughly 20,000 participants in the DOD registry (CDC, 1999). Veterans classified in the DOD registry as having “symptoms, signs, and ill-defined conditions” complained most frequently of fatigue, headache, and memory loss (Roy et al., 1998). Clinicians were able to arrive at a primary diagnosis for about 82% of symptomatic DOD registry participants (Joseph, 1997) and for a similar fraction of VA registry participants (Murphy et al., 1999) (Table A.2).

TABLE A.2 Most Frequent Symptoms and Diagnoses 53,835 Participants in VA Registry (1992–1997).

Symptoms or Diagnoses

Frequency, %

Self-Reported Symptoms

 

Fatigue

20.5

Skin rash

18.4

Headache

18.0

Muscle and joint pain

16.8

Loss of memory

14.0

Shortness of breath

7.9

Sleep disturbances

5.9

Diarrhea and other gastrointestinal symptoms

4.6

Other symptoms involving skin

3.6

Chest pain

3.5

No complaint

12.3

Diagnosis (ICD-9-CM)

 

No medical diagnosis

26.8

Musculoskeletal and connective tissue

25.4

Mental disorders

14.7

Respiratory system

14.0

Skin and subcutaneous tissue

13.4

Digestive system

11.1

Nervous system

8.0

Infectious diseases

7.1

Circulatory system

6.4

Injury and poisoning

5.3

Genitourinary system

3.0

Neoplasm

0.4

 

SOURCE: Murphy et al., 1999.

A registry program established by the United Kingdom Ministry of Defence for UK Gulf War veterans found similar types and frequencies of symptoms and diagnoses (Coker et al., 1999). The most recent publication from the British registry found 20% to be unwell, predominantly with psychiatric diagnoses, especially posttraumatic stress disorder (Lee et al., 2001). Across the registries, musculoskeletal disease; mental disorder; and symptoms, signs, and ill-defined conditions7 were the three most common diagnostic categories,

6  

Several independent advisory committees have reviewed these programs and made recommendations for their refinement (NIH, 1994; IOM, 1995, 1996, 1997, 1998; PAC, 1996).

7  

“Symptoms, signs, and ill-defined conditions” refers to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 780–799, which are reserved for 160 subclassifications of ill-defined common conditions not coded elsewhere in ICD-9-CM or lacking distinct physiologic or psychologic basis (US DHHS, 1998).

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

together accounting for more than 50% of primary diagnoses (CDC, 1999). Registries are self-selected case series of veterans who presented for care, so they cannot and were not intended to be representative of the symptoms and illnesses of the entire group of Gulf War veterans. Nor were registries designed with control groups or with diagnostic standardization across the multiple sites at which examinations took place (Joseph, 1997; Roy et al., 1998). Finally, owing to their reliance on standard diagnostic classifications, registries were not designed to probe for novel diagnoses8 or to search for biologic correlates. Thus, because of their methodologic limitations, registry studies cannot stand alone as a basis of conclusions or of the conduct of research.

Registry programs, do, however, provide a glimpse into veterans’ symptoms and the difficulties of fitting them into standard diagnoses. Registry programs are a valuable source of information for generating hypotheses. The hypotheses can be tested in rigorous epidemiologic studies with control groups to estimate the population prevalences of symptoms among Gulf War veterans and compare them to rates among otherwise similar troops who were not deployed to the Gulf War.

EPIDEMIOLOGIC STUDIES OF VETERANS’ SYMPTOMS AND GENERAL HEALTH STATUS

A number of epidemiologic studies have been conducted on the health status of Gulf War veterans. The driving issues behind many of the studies have been to determine the nature of symptoms and symptom clusters, whether symptom clusters constitute a new and unique syndrome, and what types of exposures might have produced the symptoms. The second issue—the quest to define a new syndrome—requires some explanation. The question is whether unexplained symptoms constitute a syndrome and, if so, whether they are best studied and treated as a unique, new syndrome or a variant form of a known syndrome (IOM, 2000). The finding of a new set of unexplained symptoms in a group of patients does not automatically mean that a new syndrome has been found. Rather, it constitutes the beginning of a process to demonstrate that the patients are affected by a unique clinical entity distinct from established clinical diagnoses.

The process of defining a new syndrome usually begins with a case definition that lists classification criteria to distinguish the potentially new patient population from patients with known clinical diagnoses. Development of the first case definition is a vital milestone intended to spur research and surveillance. More like a hypothesis than a conclusion, it is an early step in the process; it is often revised as more evidence comes to light. Case definitions usually are a mixture of clinical, demographic, and laboratory criteria. Clinical criteria are signs (physical-examination findings) and symptoms (subjective complaints of patients). Demographic criteria refer to age, sex, ethnicity, or other individual characteristics or exposure-related variables. Laboratory criteria refer to biologic measures of pathology or etiology (such as x-ray pictures and blood test results).

One method of developing an operational case definition is a statistical technique known as factor analysis (Ismail et al., 1999). Factor analysis is useful in identifying a small number of correlated variables from among a much larger number of observed variables, such as the symptoms that are reported in a survey of veterans. Factor analysis

8  

Registries rely on the ICD-9-CM (Joseph, 1997; Murphy et al., 1999).

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

aggregates survey responses into statistical groupings of factors that might or might not have biologic plausibility or clinical relevance. Several researchers have used factor analysis in their studies (described later in this appendix) of the health of Gulf War veterans. When factor analysis is used in studies of veterans, the observed variables are measurements of veterans’ symptoms, and the fundamental factors are symptom groupings that might represent a potential new syndrome. Any new syndrome (defined by factor analysis or other means) can have a distinct, albeit often unknown, etiology and pathogenesis (Taub et al., 1995). It is recognized that factor analysis has the potential to generate syndromes that might not be reproduced when a new population is examined.

When evidence is presented that the case definition—defined by factor analysis or other methods—successfully singles out a new patient population from comparison groups, the case definition may gain recognition by the medical establishment as a new syndrome (IOM, 2000). There are many advantages to defining and classifying a new syndrome, among them the creation of a more homogeneous patient population, which is a crucial step for determining prevalence and improving diagnosis and treatment. A potential disadvantage is the mislabeling or misclassification of a condition, which can thwart progress for years, if not decades (Aronowitz, 1991). Classification of a new patient population also stimulates further understanding of the natural history of a disease, risk factors, and ultimately etiology and pathogenesis. As more knowledge unfolds about etiology and pathogenesis an established syndrome can rise to the level of a disease. The renaming of a syndrome as a disease implies that the etiology or pathology has been identified.

Population-Based Studies

This section summarizes findings of population-based studies of Gulf War veterans. The next section summarizes findings of other types of epidemiologic studies. A population-based study is a methodologically robust type of epidemiologic study because its goal is to obtain information that is representative of the population of interest, in this case Gulf War veterans. The cohort may be the entire population of interest or a random selection from the population of interest. Population-based studies of Gulf War veterans sample a cohort of veterans by contacting them where they live, as opposed to where they seek treatment or where they serve in the military (such as a particular base or a particular branch of the service). Studies of military units or other military subgroups are less representative of the broader Gulf War veteran population than are population-based studies.

Large population-based studies of Gulf War veterans have been conducted in several countries that participated in the Gulf War coalition (the United States, Canada, Denmark, and the United Kingdom). They have shown consistent findings in the nature of unexplained symptoms and in their deleterious effects on functioning. Summary features of the studies appear in Table A.3 with those of other major epidemiologic studies.

Virtually all epidemiologic studies of Gulf War veterans, regardless of study design, rely on self-reports of symptoms and exposures. As discussed in Chapter 2, studies based on self-reports have inherent limitations because of potential inaccuracies in recall of past events and difficulty in verifying the reports. Most of the larger epidemiologic studies described here were conducted through mail or telephone surveys, which precluded clinical examination and diagnosis. Comparison groups were veterans of the same era who were not deployed to the Gulf War.

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

TABLE A.3 Major Studies of Gulf War Veterans’ Symptoms and Syndromes

Reference

Subjects/Controls (n)

Study Design

Military Branch and Status

Response Rate (%)

Major Findings

Population-Based Studies

Iowa Persian Gulf Study Group, 1997;

Doebbeling et al., 2000

1896/1799

Population-based survey, factor analysis

All US branches and duty status

76

Symptoms (subjects vs control

Fibromyalgia: 19.2% vs 9.6% Cognitive dysfunction: 18.7% 7.6%

Depression: 17.0% vs 10.9%

Three factors (somatic distress, psychological distress, and panic) higher in prevalence but not unique to Gulf War veterans

Kang et al., 2000, 2002

11,441/9476

Population-based survey, factor analysis

All US branches and duty status

70

All 48 symptoms significantly more common in deployed vs non-deployed (p<0.05) Numerous chronic medical conditions reported twice as often

(see Table A.5); possible neurological syndrome requiring further evidence

Goss Gilroy Inc., 1998

3113/3439

Survey

All Canadian Gulf War veterans

64.5

Symptoms

Chronic fatigue (OR=5.27)

Cognitive dysfunction (OR=4.36)

Multiple chemical sensitivity (OR=4.01)

Unwin et al., 1999;

Ismail et al., 1999

2961/2620, 2614a

Population-based survey, factor analysis

UK Gulf War veterans (U. London)

65.1

Symptoms

Fatigue (OR=2.2)

Posttraumatic stress (OR=2.6

Psychological distress (OR=1.6)

Three factors (mood, respiratory system, peripheral nervous system) higher in prevalence, but not unique to Gulf War veterans

Cherry et al., 2001a;

Cherry et al., 2001b

9585/4790b

Population-based survey, factor analysis

UK Gulf War veterans (U. Manchester)

85.5

Symptoms

Almost all 95 symptoms were more common in deployed versus nondeployed. Numbness and tingling and widespread panic were about two times more prevalent

Five factors (psychological, peripheral, respiratory, gastrointestinal, and concentration) higher in prevalence, but not unique to Gulf War veterans

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

Reference

Subjects/Controls (n)

Study Design

Military Branch and Status

Response Rate (%)

Major Findings

Ishoy et al., 1999b;

Suadicani et al., 1999

821/400

Population-based survey, multivariate analysis

Danish peacekeeping veterans

58–84

Symptoms

Greater prevalence of neuropsychological, gastrointestinal and dermatological symptoms, but not musculoskeletal, among deployed versus nondeployed

About 21 percent of veterans reported a clustering of 3–5 neuropsychological symptoms vs 6.2 percent of controls (p<0.001)

Other Epidemiologic Studies

Haley et al., 1997b

249/no controls

Survey, factor analysis

Navy reserve

41

25% have one of six syndromes: impaired cognition, confusion-ataxia, arthro-myo-neuropathy, phobia-apraxia, fever-adenopathy, weakness-incontinence

Fukuda et al., 1998

1163/2538

Survey, clinical exam, factor analysis

Air Force National Guard and 3 other Air Force units

35–70

31 of 33 symptoms significantly more prevalent in Gulf War veterans; defined case as 1 or more symptoms from 2 of 3 categories: fatigue, mood-cognition, musculoskeletal; case not unique to Gulf War veterans

Proctor et al., 1998

300c/48

Survey or clinical interview

All US branches and duty status

38–62

PTSD diagnosis: 5, 7% vs 0%

Dermatological symptoms (OR =9.6, 6.9)c

Gastrointestinal symptoms (OR =8.0, 5.8)c

Neuropsychological symptoms (OR=6.4, 5.2)c

NOTE: OR=odds ratio; PTSD=posttraumatic stress disorder.

aTwo comparison groups (Bosnia, Gulf era).

bThe deployed group consisted of a main cohort (n=4795) and a validation cohort (n=4790).

cThe 300 Gulf War veterans came from two study groups—one from Ft. Devens and the other from New Orleans. The control group was deployed to Germany.

The Iowa Study

The “Iowa study,” a major population-based study of US Gulf War veterans, was a cross-sectional survey of a representative sample of 4886 military personnel who listed Iowa as their home of record at the time of enlistment (Iowa Persian Gulf Study Group, 1997). The study examined the health of military personnel in all branches of service who were still serving or had left service. The sample was randomly selected from and representative of about 29,000 military personnel. Of the eligible study subjects, 3695 (76%) completed a telephone interview. Study subjects were divided into four groups, two that had been deployed to the Gulf War and two that had not been. Trained examiners using standardized questions,

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

instruments, and scales interviewed the subjects.9 The two groups of Gulf War military personnel reported roughly twice the prevalence of symptoms suggestive of the following conditions: fibromyalgia, cognitive dysfunction, depression, alcohol abuse, asthma, posttraumatic stress disorder (PTSD), sexual discomfort, and chronic fatigue (Table A.4).10 Furthermore, on a standardized instrument for assessing functioning (the Medical Outcome Study’s 36-item questionnaire known as the Short Form-36, or SF-36), Gulf War veterans displayed significantly lower scores in all eight subscales for physical and mental health. The subscales profile aspects of quality of life. The subscales for bodily pain, general health, and vitality showed the greatest absolute differences between deployed and nondeployed veterans. In short, this large, well-controlled study demonstrated that some sets of symptoms were more frequent and quality of life poorer among Gulf War veterans than among nondeployed military controls.

Symptom clustering. The Iowa study was the first major population-based study to group sets of symptoms into categories suggestive of existing syndromes or disorders, such as fibromyalgia or depression. Its finding of considerably higher prevalence among Gulf War veterans of symptom groups suggestive of fibromyalgia, depression, and cognitive dysfunction (see Table A.4) motivated other researchers to examine—through factor analysis—the potential for a new syndrome that would group and classify veterans’ symptoms. Several years later, the same team of investigators performed a factor analysis on the Iowa cohort (Doebelling et al., 2000). They identified three symptom factors in deployed veterans—somatic distress, psychologic distress, and panic—but the factors were not exclusive to deployed veterans. Thus, the study did not support the existence of a new syndrome.

Exposure-symptom relationships. The Iowa study assessed exposure-symptom relationships by asking veterans to report on their exposures in the Gulf War. Researchers found that many of the self-reported exposures were significantly associated with health conditions. For example, symptoms of cognitive dysfunction were found to have been associated with self-reports of exposure to solvents or petrochemicals, smoke or combustion products, lead from fuels, pesticides, ionizing or nonionizing radiation, chemical-warfare agents, use of pyridostigmine, infectious agents, and physical trauma. A similar set of exposures was associated with symptoms of depression or fibromyalgia. The study concluded that no exposure to any single agent was related to the conditions that the authors found to be more prevalent in Gulf War veterans (Iowa Persian Gulf Study Group, 1997).

9  

Sources of questions included the National Health Interview Survey, the Behavioral Risk Factor Surveillance Survey, the National Medical Expenditures Survey, the Primary Care Evaluation of Mental Disorders, the Brief Symptom Inventory, the CAGE questionnaire, the PTSD (Posttraumatic Stress Disorder) Checklist—Military, the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Questionnaire, the Chalder Fatigue Scale, the American Thoracic Society questionnaire, and the Sickness Impact Profile.

10  

The conditions listed were not diagnosed, because no clinical examinations were performed. Rather, before conducting their telephone survey, researchers grouped sets of symptoms from their symptom checklists into a priori categories of diseases or disorders. After a veteran identified himself or herself as having the requisite set of symptoms, researchers analyzing responses considered the veteran as having symptoms “suggestive” of or consistent with a particular disorder but not as having a formal diagnosis of the disorder.

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

TABLE A.4 Results of the Iowa Study

Symptoms (in order of frequency)a

Prevalence in Gulf War Veterans (%)

Prevalence in Non-Gulf War Veterans (%)

Fibromyalgia

19.2

9.6

Cognitive dysfunction

18.7

7.6

Alcohol abuse

17.4

12.6

Depression

17.0

10.9

Asthma

7.2

4.1

PTSD

1.9

0.8

Sexual discomfort

1.5

1.1

Chronic fatigue

1.3

0.3

SOURCE: Iowa Persian Gulf Study Group, 1997.

aBased on survey instrument designed by investigators to incorporate structured instruments and standardized questions.

VA Study

A major population-based study of US veterans was mandated by Public Law 103–446. It is a retrospective cohort study conducted by VA. Its purpose is to estimate the prevalence of symptoms and other health outcomes in Gulf War veterans versus non-Gulf War veterans.11 This population-based survey had three phases. The first phase was a questionnaire mailed to 30,000 veterans. The second phase validated self-reported data with medical-record review and analyzes characteristics of those who did not respond to the mailed survey. The third phase is a comprehensive medical examination and laboratory testing of a random sample of 2000 veterans drawn from both the Gulf War and the comparison group (Research Working Group, 1998). The purpose of the third phase is to establish diagnoses that will make it possible to see what proportion of self-reported symptoms are due to established diseases rather than unexplained illnesses. The findings of only the first two phases have been published.

The study was designed to be representative of the nearly 700,000 US veterans sent to the Persian Gulf and 800,680 non-Gulf veterans of the same era. Questionnaires were mailed to a stratified random sample of 15,000 Gulf War and 15,000 non-Gulf War veterans identified by DOD and representing various military branches and units. The questionnaires contained a list of 48 symptoms and questions about chronic medical conditions, functional limitations, and other items from the National Health Interview Survey. A questionnaire about exposures was also included. The response rate was about 70%.

The investigation found significantly higher symptom prevalence of all 48 symptoms among Gulf War veterans (Kang et al., 2000). Four of the 10 most frequently reported symptoms are runny nose, headache, unrefreshing sleep, and anxiety (Table A.5). Numerous chronic medical conditions—such as sinusitis, gastritis and dermatitis—were reported more frequently among Gulf War veterans; many were reported twice as often. Ten symptoms and 12 medical conditions were remarkably similar in prevalence to those in a UK cohort (Unwin et al., 1999). Finally, Gulf War veterans reported significantly higher rates of functional impairment (27.8% versus 14.2%), limitations of employment (17.2% versus 11.6%), and health-care use, as assessed by clinic visits (50.8% versus 40.5%) or hospitalizations (7.8% versus 6.4%). In a randomly selected subset of veterans, medical-record reviews verified more than 90% of self-reported reasons for clinic visits or hospitalizations.

11  

Health outcomes include reproductive outcomes in spouses and birth defects in children.

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

Symptom clustering. The VA study searched for potentially new syndromes through factor analysis. A separate article by Kang and colleagues (2002) found that 47 symptoms reported by veterans yielded six factors, only one of which contained a cluster of neurologic symptoms that did not load on any factors in the non-Gulf War deployed veterans. The symptoms in the cluster were 1) loss of balance/dizziness; 2) speech difficulty; 3) blurred vision; and 4) tremors/shaking. A group of 277 deployed veterans (2.4 percent) versus 43 non-deployed veterans (0.45 percent) met a case definition subsuming all four symptoms. The authors interpreted their findings as suggesting a possible unique syndrome related to Gulf War deployment that requires objective supporting clinical evidence.

TABLE A.5 Results of the VA Study

10 Most Common Self-Reported Symptomsa

Prevalence in Gulf War Veterans (%)

Prevalence in Non-Gulf War Veterans (%)

Runny nose

56

43

Headache

54

37

Unrefreshing sleep

47

24

Anxiety

45

28

Joint pain

45

27

Back pain

44

30

Fatigue

38

15

Ringing in ears

37

23

Heartburn

37

25

Difficulty sleeping

37

21

5 Most Common Self-Reported Chronic Medical Conditionsa

Prevalence in Gulf War Veterans (%)

Prevalence in Non-Gulf War Veterans (%)

Sinusitis

38.6

28.1

Gastritis

25.2

11.7

Dermatitis

25.1

12.0

Arthritis

22.5

16.7

Frequent diarrhea

21.2

5.9

SOURCE: Kang et al., 2000.

aFor symptoms, subjects were asked whether symptoms were recurring or persistent during the previous 12 months. The differences in prevalence all are statistically significant (p<0.05).

Exposure-symptom relationships. A nested case-control analysis was performed on those who met the case definition to determine which of 23 self-reported exposures were more common among cases versus controls (Kang et al., 2002). Of nine exposures that were at least three times higher among deployed cases, two were solvent-related: CARC paint (51.2 percent in cases vs 16.3 percent in controls) and chemically contaminated food (73.4 percent in cases vs 20.6 percent in controls). No pesticide-related exposures were reported three or more times more frequently in cases versus controls. Dose-response was not studied because of the nature of the dataset regarding self-reported exposure.

The article covering the large cohort (Kang et al., 2000) did not assess exposure-symptom relationships. It reported on exposures only by compiling the percentages of veterans who reported each of 23 environmental exposures and nine vaccine or prophylactic exposures (such as to pyridostigmine bromide). The five most common environmental exposures reported by more than 60% of survey participants were to diesel, kerosene, or other petrochemical fumes; to local food other than that provided by the armed forces; to chemical protective gear; to smoke from oil-well fires; and to burning trash or feces. Table

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

A.6 lists the percentages of veterans reporting pesticide or solvent-related exposures of interest to the committee.

TABLE A.6 VA Study Percent Distribution of Self-Reported Exposures (n=11,441)

Self-Reported Exposures

Percentage

Personal pesticides, including creams, sprays and flea collars

48.4

Contact with prisoners of wara

32.8

Food contaminated with smoke, oil, or other chemicals

30.2

Other paint or solvent or petrochemicals substances

29.7

Chemical Agent Resistant Compound Paint

21.7

SOURCE: Kang et al., 2000

aLindane used as delousing agent (Cecchine et al., 2000)

Oregon and Washington Veterans

Veterans from Oregon or Washington were studied in a series of analyses by investigators of the Portland Environmental Hazards Research Center (McCauley et al., 1999). A questionnaire was sent to a random sample (n=2343) of 23,711 Gulf War veterans listing Oregon or Washington as their home state of record at the time of deployment. The response rate was 56%. The study found high rates (20–60%) of self-reported symptoms, including cognitive-psychologic symptoms, unexplained fatigue, musculoskeletal pain, gastrointestinal complaints, and rashes. However, among the first 225 participants who later came for a clinical examination, there were significant differences between their self-reported symptoms on questionnaires and their symptoms reported at clinical examination. Significantly fewer veterans reported symptoms at clinical examination.

Symptom clustering. Investigators studied clusters of unexplained symptoms by creating a new case definition for unexplained illness (Storzbach et al., 2000). Cases were identified through questionnaires as meeting a threshold number, combination, and duration of fatigue, cognitive/psychologic, and musculoskeletal symptoms. Veterans whose symptom clusters remained unexplained at clinical examination (after exclusion of established diagnoses) were defined as constituting cases. Controls were those who at the time of clinical examination had no history of case-defining symptoms during or after their service in the Gulf War. In an analysis of the 241 cases versus 113 controls, investigators found small but statistically significant deficits in cases on some neurobehavioral tests of memory, attention, and response speed. Cases also were significantly more likely to report increased distress and psychiatric symptoms (Storzbach et al., 2000). A later analysis focused on a subgroup of 30 (of the 241) cases whose performance was slowest on the Oregon Dual Task Procedure (ODTP), a relatively new test of digit recognition that assesses motivation, attention, and memory (Storzbach et al., 2001). In comparison with other cases, the “slow ODTP” group performed more poorly on other neurobehavioral tests of memory, attention, and reaction time but not on psychologic tests. Investigators plan more-extensive imaging and EEG tests on this subgroup of cases.

Exposure-symptom relationships. Another nested case-control analysis of the population-based cohort examined whether cases of unexplained illness were more common in any of the three periods of Gulf War deployment: precombat, combat, and postcombat (Spencer et al., 1998). Subjects were not asked about specific exposures, but their period of deployment was used as a proxy for different combinations of environmental exposures. Of 14 potential exposures likely to be differentially encountered during deployment periods, two were of special interest to the committee: “insect repellent” and “pesticides.” Those two

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

exposures were more common in the precombat and postcombat periods than in the combat period. The sample consisted of 244 veterans with unexplained illness and 113 healthy controls. The vast majority of subjects with unexplained illness served in more than one of the three deployment periods. In the few cases with service in only one of the periods, there were no statistically significant differences in prevalence between periods, although there was a trend for cases to be more common in veterans who served in the postcombat period. Those findings suggest that cases do not readily fall into distinct deployment periods.

The Canadian Study

The findings of a 1997 survey (Goss Gilroy Inc., 1998) mailed to the entire cohort of Canadian Gulf War veterans were similar to those of the Iowa study. Respondents from Canada who had been deployed to the Gulf War (n=3113) were compared with respondents deployed elsewhere (n=3439) during the same period. Of the Gulf War veterans responding, 2924 were male and 189 were female. Deployed forces had significantly higher rates of self-reported chronic conditions and symptoms of a variety of clinical outcomes12—(chronic fatigue, cognitive dysfunction, multiple chemical sensitivities, major depression, PTSD, chronic dysphoria, anxiety, fibromyalgia, and respiratory diseases)—than controls. The greatest differences between deployed and nondeployed forces were in the first three outcomes. The symptom grouping with the highest overall prevalence was cognitive dysfunction, which occurred in 34–40% of Gulf War veterans compared with 10–15% of control veterans. Gulf War veterans also reported significantly more visits to health-care practitioners, greater dissatisfaction with their health status, and greater health-related reductions in recent activity than control veterans.

Symptom clustering. The Canadian study did not search for potentially new syndromes.

Exposure-symptom relationships. In Canadian Gulf War veterans, the greatest number of symptom groupings was associated with self-reported exposures to psychologic stressors and physical trauma. Several symptom groupings also were associated with exposure to chemical-warfare agents, nonroutine immunizations, sources of infectious diseases, and ionizing or nonionizing radiation. Nevertheless, a subset of Canadian veterans who could not have been exposed to many of the agents, because they were based at sea, reported symptoms as frequently as did land-based veterans.

The UK Studies

The UK sent 53,000 personnel to the Gulf War. The UK’s centralized health delivery systems enabled researchers to readily retrieve service records. From the pool of veterans, two teams of researchers each studied a separate, nonoverlapping, stratified random sample of Gulf War veterans. One team was from the University of London (Guy’s, King’s, and St. Thomas’s Medical School), and the other team was from the University of Manchester.

Unwin and collaborators (1999) at the University of London investigated the health of servicemen from the UK in a population-based study. The study used a random sample of the entire UK contingent deployed to the Gulf War13 and two comparison groups. One of the

12  

Several of the reported health conditions or symptoms were combined to define clinically meaningful outcomes (Goss Gilroy Inc., 1998).

13  

UK military personnel in the Gulf War were somewhat different from US personnel in demographics, combat experience, and exposures to particular agents (U.K. Ministry of Defence, 2000).

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

comparison groups was deployed to the conflict in Bosnia (n=4250); this made the study the only one to use a comparison population with combat experience during the time of the Gulf War. The second comparison group (n=4246) was deployed to other noncombat locations outside the UK in the same timeframe. Through a mailed questionnaire, the investigators asked about symptoms (50 items), medical disorders (39 items), functional capacity, and other topics. The findings for the Gulf War cohort and comparison cohorts were compared through calculation of odds ratios (ORs). The study controlled for potential confounding factors (including sociodemographic and lifestyle factors) by logistic regression analysis. Only male veterans’ results were analyzed, because female veterans’ roles and symptoms were distinct enough to warrant separate consideration.

The UK Gulf War-deployed veterans (n=4248) reported higher prevalence of symptoms and diminished functioning than did either comparison group. Gulf War veterans were 2–3 times more likely than comparison subjects to have met symptom-based criteria for chronic fatigue, posttraumatic stress reaction, and “chronic multisymptom illness,” the label for the first case definition14 developed by Centers for Disease Control and Prevention (CDC) researchers to probe for the existence of a potential new syndrome among Gulf War veterans (Fukuda et al., 1998). That the Bosnia cohort in the UK study, which was deployed to a combat setting, reported fewer symptoms than the Gulf War cohort suggests that combat deployment itself does not account for higher symptom reporting.

A separate analysis of this UK Gulf War cohort found that the prevalence of multiple chemical sensitivity (MCS)15 was 1.3%, a rate significantly greater than in the comparison groups. The prevalence of chronic fatigue syndrome at 2.1% was not significantly greater (Reid et al., 2001).

Symptom clustering. In a companion study using the UK data set, Ismail and colleagues (1999) set out to determine whether the symptoms that occurred with heightened prevalence in UK Gulf War veterans constituted a new syndrome. By applying factor analysis, they were able to identify three fundamental factors, which they classified as related to mood, respiratory system, and peripheral nervous system. The pattern of symptom reporting by Gulf War veterans differed little from the patterns by Bosnia and Gulf War-era comparison groups, although the Gulf War cohort had a higher frequency of symptom reporting. Furthermore, the study did not identify in this cohort the six factors characterized by Haley and colleagues (1997b) in their factor-analysis study described in the next section. The UK authors interpreted their results as evidence against the existence of a unique Gulf War syndrome. Nevertheless, in a later study of veterans’ beliefs, the authors found that 17.3% of UK Gulf War veterans believed that they had a condition known as Gulf War syndrome (Chalder et al., 2001).

Exposure-symptom relationships. In the UK Gulf War cohort, most self-reported exposures were associated with all of the health outcomes; that was also true for the two comparison cohorts (Unwin et al., 1999). The authors interpreted that finding as evidence that the exposures were not uniquely associated with Gulf War illnesses. Veterans with symptoms, regardless of deployment status, were more likely to report a wide variety of exposures than those without symptoms. Within the Gulf War cohort, two vaccine-related

14  

A case is defined as having one or more chronic symptoms in at least two of these three categories: fatigue, mood—cognition (for example, feeling depressed or difficulty in remembering or concentrating), and musculoskeletal (joint pain, joint stiffness, or muscle pain). This case definition was developed as a research tool to organize veterans’ unexplained symptoms into a potentially new syndrome.

15  

Based on criteria of Simon and colleagues (1993).

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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exposures—vaccination against biologic-warfare agents and receiving multiple vaccinations—were associated with the case definition of the chronic multisymptom illness developed by CDC researchers (Fukuda et al., 1998). A later analysis of the data on a subcohort of UK veterans found that receiving multiple vaccinations during deployment was associated with five of the six health outcomes examined, including multisymptom illness as defined by CDC (Hotopf et al., 2000). Analysis of the subgroup of veterans meeting case criteria for MCS found that they were significantly more likely to report several types of pesticide exposures (Reid et al., 2001). Veterans meeting case criteria for chronic fatigue syndrome were not more likely to report pesticide exposure but were more likely to report combat-related injury (Reid et al., 2001).

The University of Manchester study used a random sample of UK veterans’ years after the Gulf War (Cherry et al., 2001a). The cohort was separate from that studied by Unwin and colleagues (1999). Two groups of veterans deployed to the Gulf War (n=9585, a main cohort and a validation cohort) were compared with veterans who were not deployed but whose health would not have prevented deployment (n=4790). Veterans were sent a questionnaire about the extent to which they were burdened by 95 symptoms in the previous month. By asking them to mark their answers on a visual analogue scale, investigators sought to determine the degree of symptom severity. Investigators also sought to determine areas of peripheral neuropathy by asking veterans to shade body areas on two mannequins in which they were experiencing pain or numbness and tingling. On almost all 95 symptoms, deployed veterans reported higher symptom severity. The overall mean symptom severity score was similar in the two Gulf War cohorts and significantly greater than that for the non-Gulf War cohort. For 14 symptoms—including memory, concentration, and mood problems—the severity scores of deployed veterans were at least twice those of the nondeployed. Numbness and tingling were reported by about 14% of deployed and about 7% of nondeployed. Widespread pain was also reported more frequently (12.2% versus 6.5%).

Symptom clustering. Through factor analysis, the investigators identified seven factors, which accounted for 48% of the variance. Deployed veterans’ scores were significantly different on five of them: psychologic, peripheral, respiratory, gastrointestinal, and concentration factors. No difference was found in the neurologic factor, and appetite, the final factor, was significantly lower than in the non-Gulf War cohort. None of the factors was exclusive to Gulf War veterans, so the investigators concluded that their findings did not support a new syndrome (Cherry et al., 2001a).

Exposure-symptom relationships. The two UK Gulf War cohorts completed a second questionnaire with details of the dates when they were sent to each location and the exposures they had experienced. The exposure questionnaire contained 14 exposures. The main analysis involved a multiple regression of each of the seven factors on all exposures and other potential confounders. Many of the reported exposures correlated with one another. In the multivariate regression analysis, the number of days that veterans handled pesticides was related to the overall severity score and to the peripheral and neurologic factors. The number of days when they applied insecticide to their skin was related to severity and to the peripheral, respiratory, and appetite factors. The number of inoculations was associated with skin and musculoskeletal symptoms. There was a marked dose-response gradient for the association between insect repellents and the peripheral and respiratory

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

factors. A dose-response gradient for the association of handling pesticides with the peripheral factor was present but less robust. The handling of pesticides was associated with peripheral neuropathy (OR=1.26, p<0.001), and the use of insect repellent was associated with widespread pain (OR=1.15, p<0.001). Respraying vehicles and living in sprayed quarters were not associated with any health outcomes. Because the ORs were only slightly increased, the investigators interpreted weak relationships between symptoms and exposures (Cherry et al., 2001b).

The Danish Study

Troops from Denmark were primarily involved in peace-keeping or humanitarian roles after the end of the Gulf War. They were studied in a series of population-based studies (Ishoy et al., 1999b; Suadicani et al., 1999). A total of 821 veterans were eligible by virtue of having served any time in the period August 1990 to December 1997. Because Danish troops in the Gulf War were successively replaced every 6 months, most respondents were not there until years after the end of the war. About 60% were deployed from 1992 to 1994, and 20% after 1995. The Gulf War veterans were matched by age, sex, and profession to 400 members of the Danish armed forces who were not deployed to the Gulf War. Symptom and exposure questionnaires and health examinations were used. Findings of health examinations were not used in the study’s analysis of symptom-exposure relationships.

Of 22 neuropsychologic symptoms, 17 were significantly more prevalent among Gulf War veterans than among controls. Many of the symptoms were correlated with one another. Headache and fatigue-related symptoms were present in about 20% of deployed versus up to 10% of nondeployed. Gastrointestinal symptoms and diseases and symptoms related to the skin or allergy were more frequent in deployed veterans. The pattern of symptoms, except musculoskeletal symptoms (which were not more prevalent), was similar to the patterns seen in the UK, VA, and Canadian cohorts. The investigators concluded that the overlap of symptoms between veterans deployed during and after the war indicated the existence of common risk factors independent of exposure to war itself.

Symptom clustering. The authors did not use factor analysis, but they did use a multiple logistic regression analysis with adjustments for age and sex to find the most relevant neuropsychologic symptoms (Suadicani et al., 1999). Only five of the 17 symptoms remained significant after adjustment for the interrelationship of variables. About 21% of veterans reported a clustering of three to five of the relevant symptoms versus 6.2% of controls (p<0.001). Relevant symptoms included concentration or memory problems, repeated fits of headache, balance disturbances or fits of dizziness, abnormal fatigue not caused by physical activity, and problems in sleeping all night. The symptoms excluded from further analysis included numbness or tingling in hands and feet, suddenly diminished muscular power, and tingling or shivering of arms, legs, or other parts of the body.

Exposure-symptom relationships. One of the analyses investigated whether 22 neuropsychologic symptoms were associated with 18 self-reported environmental exposures16 (Suadicani et al., 1999). Most exposures were significantly associated with three to five relevant neuropsychologic symptoms in a univariate analysis. Four exposures, especially “bathing in or drinking contaminated water (fumes, oil, chemicals),” remained significant after adjustment in a multiple logistic model that adjusted for associations of

16  

Exposures did not include pyridostigmine bromide or vaccinations against chemical- or biologic warfare agents, because Danish veterans had a peace-keeping role and thus were not at risk for chemical or biologic warfare.

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

exposures with one another. The exposure-symptom findings are discussed further in the body of this report. A separate multivariate analysis of gastrointestinal symptoms found them to be associated with two exposures: burning of waste or manure and exposure to insecticide against cockroaches (Ishoy et al., 1999a).

Other Studies of Veterans’ Symptoms and General Health Status

One of the first epidemiologic studies of US Gulf War veterans was of more than 4000 active-duty and reserve personnel from Pennsylvania and Hawaii (Stretch et al., 1995). Veterans deployed to the Gulf War reported higher prevalence of 21 of 23 symptoms on a symptom checklist than nondeployed veterans (although the total response rate was only 31%). Overall, deployed veterans were about 2–4 times more likely than nondeployed veterans to report each symptom.

The symptom experience of two cohorts of Gulf War veterans from Massachusetts (Ft. Devens) and New Orleans was studied by Proctor and colleagues (1998). In comparison with veterans deployed to Germany during the Gulf War era, stratified random samples of both Gulf War cohorts had increased prevalence of 51 of 52 items on a health-symptom checklist. The greatest differences in prevalence of reported symptoms were for dermatologic symptoms (such as rash, eczema, and skin allergies), neuropsychologic symptoms (such as difficulty in concentrating and difficulty in learning new material), and gastrointestinal symptoms (such as stomach cramps and excessive gas). The study’s nearly 300 subjects represented a stratified random sample of 2949 troops from Ft. Devens and 928 troops from New Orleans; both groups consisted of active-duty, reserve, and National Guard troops. The cohorts were also the focus of several studies of stress-related disorders (discussed later in this appendix).

Female Air Force veterans were studied by Pierce (1997), who examined a stratified sample of 525 women (active-duty, National Guard, and reserve) drawn from all 88,415 women who served in the Air Force during the Gulf War era. Women deployed to the Gulf War reported rash, cough, depression, unintentional weight loss, insomnia, and memory problems more frequently than women deployed elsewhere. The pattern of symptom reporting was similar to that reported by men and women who participated in the Iowa study. In addition, women deployed to the Gulf War were more likely than controls to report sex-specific problems, such as breast cysts and lumps and abnormal cervical cytology.

The first published study to search for new syndromes was conducted by Haley and collaborators (1997b), who studied a battalion of naval reservists called to active duty for the Gulf War (n=249). More than half the battalion had left the military by the time of the study. Of those participating, 70% reported having had a serious health problem since returning from the Gulf War, and about 30% reported having no serious health problems. The study was the first to cluster symptoms into new syndromes by applying factor analysis. Through standardized symptom questionnaires and two-stage factor analysis, the investigators defined what they considered to be either six syndromes or six variants of a single syndrome, which they labeled impaired cognition, confusion-ataxia, arthromyoneuropathy, phobia-apraxia, fever-adenopathy, and weakness-incontinence. One-fourth of the veterans in this uncontrolled study (n=63) were classified as having one of the six syndromes. The first three syndromes had the strongest factor clustering of symptoms.

In a followup study of the same cohort, Haley and colleagues (1997a) used a case-control design to examine neurologic function. They chose as cases the 23 veterans who had

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

scored highest on the three syndromes with the strongest factor clustering. The results of extensive neurologic and neurobehavioral testing demonstrated that cases had significantly greater evidence of neurologic dysfunction when compared with two small groups of healthy controls from the same battalion.17 Investigators concluded that the three syndromes, derived from factor analysis of symptoms, may signify variant forms of expression of a generalized injury to the nervous system.18 In a later study, cases with one of the three syndromes were more likely than healthy controls to exhibit vestibular dysfunction (Roland et al., 2000). Related research on the same subset of veterans has found evidence of basal ganglia and brainstem neuronal loss via magnetic resonance spectroscopy (Haley et al., 2000).

The three syndromes identified by Haley and colleagues (1997b) were the focus of a companion case-control study that examined their relationship to self-reported exposures to neurotoxicants. The study tested the hypothesis that exposure to organophosphates and related chemicals that inhibit cholinesterase is responsible for the three nervous system-based syndromes (Haley and Kurt, 1997). Each of the syndromes was associated with a distinct set of risk factors. The impaired-cognition syndrome was found, through multiple logistic regression, to be associated with jobs in security and the wearing of flea-and-tick collars. The confusion-ataxia syndrome was associated with self-reports of having been involved in a chemical-weapons attack and of having advanced adverse effects of pyridostigmine bromide.19 Finally, arthromyoneuropathy was associated with higher scores on the scale of advanced adverse effects of pyridostigmine bromide and with an index created by the investigators to enable veterans to self-report the amount and frequency of their use of government-issued insect repellent. The authors concluded that some Gulf War veterans had delayed, chronic nervous system syndromes as a result of exposure to combinations of neurotoxic chemicals (Haley and Kurt, 1997).

Another study by Haley and collaborators (1999) examined whether genetic susceptibility could play a role in placing some veterans at risk for neurologic damage by organophosphate chemicals. They hypothesized that neurologic symptoms in ill veterans might be explained by their having genetic polymorphisms (variations) in metabolizing enzymes. One set of polymorphisms could impair their ability to detoxify organophosphates (such as sarin, soman, and some pesticides) rapidly. The investigators studied 45 veterans, 25 with chronic neurologic symptoms as identified through their earlier factor-analysis study and 20 healthy controls from the same battalion. They measured blood butyrylcholinesterase and two types, or allozymes, of paraoxonase/arylesterase 1. The genotypes encoding the allozymes were also studied. The investigators found that veterans who were ill had blood butyrylcholinesterase levels similar to those of control subjects; however, ill veterans had lower type Q paraoxonase/arylesterase, the allozyme that hydrolyzes sarin rapidly. They also were more likely to have the type R genotype, which encodes the allozyme that has low hydrolyzing activity for sarin. The authors interpreted their findings as suggesting that

17  

One group of healthy controls (n=10) was deployed to the Gulf War; the other (n=10) was not.

18  

Neuropsychologic or neurologic impairments have been the focus of several smaller studies as well. Some found subtle changes in nerve-conduction velocity and cold sensation (Jamal et al., 1996) and in some tests of finger dexterity and executive functioning (Axelrod and Milner, 1997); others found no significant differences in measures of nerve conduction and neuromuscular functioning (Amato et al., 1997) or neuropsychologic performance (Goldstein et al., 1996).

19  

The scale for adverse effects of pyridostigmine bromide was developed by the investigators to measure less-common adverse effects, such as excessive sweating, tearing, chest tightness, nausea, muscle twitching, muscle cramps, headache, and pounding heartbeat.

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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reduced ability to detoxify environmental chemicals may have contributed to the onset of neurological symptoms in some Gulf War veterans.

A large study by Fukuda and colleagues (1998) used factor analysis and other methods to assess the health status of Gulf War veterans. By studying an Air Force National Guard unit from Pennsylvania and three comparison Air Force populations, the investigators aimed to organize symptoms into a case definition and to carry out clinical evaluations on a subset of veterans. Of 3701 veterans surveyed, those deployed to the Gulf War experienced higher prevalence of chronic symptoms (33 of 35 symptoms with more than 6-month duration were reported to be more prevalent) than nondeployed veterans. The authors then used two methods to derive a case definition: factor analysis and a clinical approach. The two approaches yielded similar case definitions, and the investigators chose the latter for its simplicity of application in research.

The authors defined a case of chronic multisymptom illness as having one or more chronic symptoms from at least two of three categories: fatigue, mood-cognition symptoms (for example, feeling depressed and difficulty in remembering or concentrating), and musculoskeletal symptoms (joint pain, joint stiffness, or muscle pain). According to that definition, 39% of Gulf War-deployed veterans and 14% of nondeployed veterans had mild to moderate cases, whereas 6% and 0.7%, respectively, had severe cases. On the basis of a total of 158 clinical examinations in one unit, there were no abnormal physical or laboratory findings among those who met the case definition. Cases reported significantly lower functioning and well-being.

A sizable fraction (14%) of nondeployed veterans also met the mild-to-moderate case definition. The investigators concluded that their case definition could not specifically characterize Gulf War veterans with unexplained illnesses (Fukuda et al., 1998). The study, however, had several limitations, the most important of which was its coverage of only active Air Force personnel (several years after the Gulf War), which limits its generalizability to other branches of service and to those who left the service possibly because of illness.

To assess risk factors, the authors performed clinical evaluations on a subset of veterans (n=158), all of whom volunteered for the evaluation and came from the index unit of the Pennsylvania Air Force National Guard. Of the members of this unit, 45% had been deployed to the Gulf War. Overall, there was a dearth of abnormal findings from blood, stool, and urine testing among those who met the case definition for chronic multisymptom illness. There were no differences between cases and noncases in the proportion that seroreacted to botulinum toxin, anthrax protective antigen, leishmanial antigens, and other antigens. This was among the few studies to have assessed exposures (mostly to infectious diseases) via laboratory testing, as opposed to self-reports, but the sample undergoing clinical evaluation was relatively small and restricted to Air Force National Guard members.

A nested case-control study of the same cohort (n=1002) sought to identify self-reported exposures associated with cases of chronic multisymptom illness (Nisenbaum et al., 2000). It found that meeting the case definition of severe and mild-to-moderate illness was associated with use of pyridostigmine bromide, use of insect repellent, and belief in a threat from biologic or chemical weapons. Having an injury requiring medical attention was also associated with having a severe case of chronic multisymptom illness.

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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EPIDEMIOLOGIC STUDIES OF SPECIFIC HEALTH END POINTS

Mortality Studies

A large mortality study of nearly all Gulf War-deployed veterans identified no excess postwar mortality, with the exception of a rise in death from motor-vehicle accidents (Kang and Bullman, 1996). The study examined mortality patterns through 1993 by using two databases, 1) the VA Beneficiary Identification and Records Locator Subsystem and 2) deaths reported to the Social Security Administration.20 It compared deployed veterans with a similarly sized cohort of veterans who did not serve in the Gulf War. The most recent publication by the authors found that by 1997 the excess mortality risk from motor-vehicle accidents had disappeared, a finding consistent with the mortality pattern after the Vietnam War (Kang and Bullman, 2001).

A second mortality study of US active-duty military personnel focused exclusively on the Gulf War period. It compared noncombat mortality among troops stationed in the Gulf War and troops on active duty elsewhere. There was no excess noncombat mortality in deployed veterans, except for unintentional injury (due to vehicle accidents and other causes; Writer et al., 1996). Similarly, a recently published study of UK veterans of the Gulf War in relation to contemporaneous controls found no increase in mortality other than an increase in accidental death (Macfarlane et al., 2001).

The principal limitation of published mortality studies is the short duration of their followup observation. More time must elapse before excess mortality would be expected from illnesses with long latency, such as cancer, or with a gradually deteriorating course, such as multiple sclerosis.21

Hospitalization Studies

The risk of hospitalization was the subject of two large studies of active-duty personnel discharged from DOD hospitals before and after the Gulf War. The first study compared almost 550,000 Gulf War veterans with almost 620,000 nondeployed veterans and found no significant and consistent differences in hospitalizations after the war (Gray et al., 1996). Before the Gulf War, from 1988 to 1990, those later deployed to the Persian Gulf were at lower risk for hospitalization than their nondeployed counterparts, probably because of the healthy-warrior effect. To permit valid before-after comparisons, the investigators used statistical methods to remove bias introduced by the “healthy-warrior effect” (also called the “healthy-worker effect”).

A second hospitalization study re-examined the same dataset of active-duty personnel discharged from DOD hospitals to search for excess hospital admissions for

20  

The degree of completeness of using these record systems was assessed with a validation study that used state vital-statistics data. Ascertainment was estimated at 89% of all deaths in the Gulf War cohort and comparison group.

21  

Critics assert that the mortality study by Kang and Bullman (1996) made errors in calculating confidence intervals around mortality and did not adequately account for the “healthy-warrior effect,” the possibility that troops mobilized to the Gulf War were healthier than nondeployed troops and thereby biased the study toward not finding a mortality difference (Haley, 1998). The study authors disagreed and demonstrated that other statistical techniques, recommended by critics, had negligible impact on their confidence intervals (Kang and Bullman, 1998). To counter the charge of selection bias, the study authors pointed out that effects of any potential selection bias were minimal inasmuch as they found no differences in mortality risk between troops mobilized to sites other than the Gulf War and troops not mobilized at all (Kang and Bullman, 1998).

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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unexplained illnesses. The authors reasoned that the first study might have missed hospitalizations for a new or poorly recognized syndrome. Hospital discharge coding might have inconsistently classified such hospitalizations by many diagnoses and masked an effect if one were present. The second study operationally defined unexplained illnesses as diagnoses falling into several catchall International Classification of Diseases, Ninth Revision—Clinical Modification (ICD-9-CM) diagnostic categories comprising nonspecific infections and other ill-defined conditions. After adjusting for hospitalizations only for evaluation (as opposed to treatment) in the DOD registry program, the authors found no significant differences between deployed and nondeployed active-duty military (Knoke and Gray, 1998).

Those hospitalization studies provide some reassurance that excess hospitalizations did not occur among veterans of the Gulf War who remained on active duty through 1993. Like the mortality studies, however, they did not capture illnesses that might have longer latency, such as cancer, or illnesses in people separated from the military and admitted to nonmilitary (VA and civilian) hospitals (Haley, 1998). The studies did not measure the use of outpatient treatment and thus only detected illnesses that required hospitalization (Gray et al., 1996; Knoke and Gray, 1998).

Studies of Birth Defects and Reproductive Outcomes

Several studies failed to identify an excess of birth defects in offspring of deployed versus nondeployed veterans. A small study of two Mississippi National Guard units (n=282) deployed to the Gulf War found no excess rate of birth defects in National Guard members’ children compared with rates expected on the basis of surveillance systems and previous surveys (Penman et al., 1996). A much larger study of all live births in military hospitals (n=75,000), from 1991 to 1993, included a comparison population of births to nondeployed personnel. The risk of birth defects in children of Gulf War personnel was the same as in the control population (Cowan et al., 1997). This important study, the largest to date on birth defects, was limited to military hospitals and thereby excluded persons ineligible for care in military hospitals (members of the National Guard, reserves, and those who left the military over the course of study). National Guard and reserve troops, as noted earlier, constituted a relatively high percentage of US troops deployed to the Gulf War (Table A.1). Anecdotal reports of an excess of Goldenhar syndrome, a rare congenital anomaly that affects the development of facial structures, prompted another study of birth defects. The syndrome is not specifically coded for in reporting birth defects, so the study reviewed medical records of all listings in several more inclusive birth defect categories that would have subsumed it. Araneta and colleagues (1997) found too few cases of Goldenhar syndrome from which to draw definitive conclusions.

The recently published population-based VA study of US Gulf War veterans found that male veterans reported a significantly higher rate of miscarriage than did controls, and both male and female veterans reported significantly higher birth defects among liveborn infants. Concerned about reporting bias, the investigators suggested that the observation needs to be confirmed by a review of medical records (Kang et al., 2001).

Several ongoing studies are addressing the limitations of previous studies. Population-based studies to capture births in all hospitals—both military and civilian—are under way in the United States and the UK. A large US study will pool birth-defect data from several states by matching statewide birth certificates with military records (Araneta et

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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al., 1999). Another UK study is probing the prevalence of birth defects, problems in reproduction and fertility, and cancer in children; this study covers all UK Gulf War veterans and Gulf War-era controls, a total of 106,000 veterans (Doyle et al., 1999).

Studies of Stress-Related Disorders

Two population-based epidemiologic studies of Gulf War veterans described earlier detected a significant increase in the self-reported prevalence of symptoms of PTSD and depression (Goss Gilroy Inc., 1998; Iowa Persian Gulf Study Group, 1997).22 In the Iowa study, 17% of Gulf War veterans reported symptoms of depression and 1.9% reported symptoms of PTSD.23 Those figures were significantly higher than those for nondeployed controls, whose prevalences were 11% and 0.8%, respectively (Table A.4). The third population-based study found that UK Gulf War veterans were about 2.5 times more likely than controls to have symptoms of PTSD; there were no significant differences in the levels of depression between deployed veterans and controls (Unwin et al., 1999). The large, population-based VA study did not survey veterans for PTSD or depression (either symptoms or diagnoses).

The rates of PTSD and depression in less-representative military units also have been studied. In a study of military personnel (n=16,167) from Pennsylvania and Hawaii (described earlier), 8–9% of deployed veterans met criteria for PTSD symptoms on the basis of self-reported symptom checklists compared with 1–2% of nondeployed veterans (Stretch et al., 1996). Similarly, a small study found higher PTSD scores in deployed than in nondeployed veterans (Perconte et al., 1993a).

Sutker and colleagues (1993) compared 215 National Guard and Army reserve veterans who were deployed to the Gulf War with 60 veterans from the same unit who were activated but not deployed overseas. None had sought mental health treatment. The investigators found that 16–24% of war zone-exposed troops had symptoms of distress that suggested depression or PTSD. Those who reported higher levels of stress had greater severity of PTSD and more health complaints than veterans who had low self-reported stress or no war-zone stress. Similarly, PTSD symptoms or diagnoses were more likely in groups of Gulf War veterans who had combat exposure or injury (Baker et al., 1997; Labbate et al., 1998; Wolfe et al., 1998), in women (Wolfe et al., 1993), in veterans who had been exposed to missile attack (Perconte et al., 1993b), and in those who had grave-registration duties (Sutker et al., 1994).

A study by Engel and colleagues (1999) is one of the few that used a clinician-administered diagnostic instrument rather than self-reported symptom scales to assess the presence of psychiatric disorders. Researchers compiled diagnoses from among all Gulf War veterans (n=13,161) who sought health examinations through the DOD registry during its first year of operation (1994–1995). The authors used the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III-R [SCID-NP]) to explore a range of possible psychiatric disorders and the Clinician-

22  

Most epidemiologic studies of veterans have assessed the prevalence of self-reported symptoms of PTSD by asking subjects to fill out validated psychometric scales, such as the Mississippi Scale for Combat-Related PTSD and the PTSD Checklist—Military. Psychometric scales of PTSD, useful as screening tools for approximating a PTSD diagnosis, are not deemed to be diagnostic by themselves (Keane et al., 1988; Kulka et al., 1991).

23  

A recent reanalysis of PTSD-symptom prevalence in the Iowa cohort found an adjusted OR of 2.02 for deployed versus nondeployed veterans, but the finding was of borderline significance (confidence interval, 0.97–4.23) (Barrett et al., 2002).

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

Administered PTSD Scale to explore PTSD. Both measures have been psychometrically validated on combat veterans, so this study is methodologically stronger than many of the previous investigations. However, the study did not use a control or comparison group and, in using a treatment-seeking population, was not, by design, representative of the Gulf War veteran population. The authors found that 37% of the veterans met criteria for at least one psychiatric disorder. About 13% of the entire sample met diagnostic criteria for mood disorders, 14% for somatoform disorders,24 and 6% for current PTSD. A study of a subset of this cohort (n=131) referred for specialty evaluation found that PTSD and somatoform disorders were associated with the reporting of traumatic events (such as handling dead bodies) (Labbate et al., 1998). The authors of the smaller study concluded that at least some veterans with unexplained physical symptoms might be suffering the consequences of combat trauma.

There is only one longitudinal study of PTSD in Gulf War veterans. The rates of PTSD symptoms, measured with a validated symptom questionnaire known as the Mississippi Scale for Combat-Related PTSD, showed an increase from 3% of deployed veterans immediately after the war to 8% in 1993–1994 (Wolfe et al., 1999). Women and veterans with the highest levels of combat exposure were at greatest risk for PTSD. Two years later, in 1994–1996, the same research team conducted an even more methodologically rigorous study via structured clinical interviews (in addition to PTSD questionnaires). They found a current diagnosis of PTSD in 5–7% of deployed veterans (n=206) compared with none in a control group deployed to Germany (n=48) (Wolfe et al., 1999). Regarding depression, the 1994–1996 wave of the study found similarly increased rates of current major depressive disorder and dysthymia (two distinct types of depression) but did not find increased rates of somatoform disorders. Yet nearly two-thirds of veterans who reported health symptoms in the moderate to high range had no current psychiatric diagnosis, such as PTSD or major depressive disorder.25 The authors concluded that although psychiatric diagnosis is associated with some Gulf War health complaints, such diagnoses do not account entirely for the full range and extent of Gulf War veterans’ symptom reporting.

Studies of Infectious Disease, Gastrointestinal Symptoms, and Testicular Cancer

During the Gulf War, the occurrence of infectious diseases was lower than expected (Hyams et al., 1995). The most common infectious disease among US troops was diarrheal disease caused by the bacterial pathogens Escherichia coli and Shigella sonnei, as detected by stool cultures (Hyams et al., 1991). Almost 60% of troops who responded to a questionnaire reported at least one episode of diarrheal disease within an average of 2 months in Saudi Arabia (Hyams et al., 1991). Upper respiratory infections also were frequent (Hyams et al., 1995). Finally, 19 cases of cutaneous leishmaniasis and 12 cases of a variant of visceral leishmaniasis have been reported among US Gulf War veterans.26 The latter is an unusual finding because the etiologic agent found in veterans’ tissue samples—

24  

This term encompasses a variety of disorders in which patients have multiple physical symptoms that are not explained by a known medical disease or condition, by the effects of a substance, or by another mental disorder. The symptoms cause clinically significant distress or impaired functioning (APA, 1994).

25  

About 40% also had no lifetime history of these disorders (Wolfe et al., 1999).

26  

Leishmaniasis is a variety of diseases affecting the skin (cutaneous leishmaniasis), mucous membranes, and internal organs (visceral leishmaniasis), caused by infection with single-celled parasites of the genus Leishmania. It is transmitted from infected animals or people to new hosts by the bites of sand flies (Clayman, 1989).

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

the protozoan parasite Leishmania tropica, transmitted by sand flies—is not endemic to the Persian Gulf area and is usually associated with cutaneous leishmaniasis (CDC, 1992; Hyams et al., 1995; Magill et al., 1993). Because veterans’ symptoms (such as fever, lymphadenopathy, and hepatosplenomegaly) were milder than symptoms of classic visceral leishmaniasis, the condition was given the name viscerotropic leishmaniasis. Even though visceral leishmaniasis and its variants are chronic infectious diseases, the cases were considered too few and classic signs and symptoms too readily detectable at physical examination to account for the much more frequent occurrence of unexplained illnesses in veterans (Hyams et al., 1995; PAC, 1996). Furthermore, in the controlled study of Gulf War veterans by Fukuda and colleagues (1998), none of the eight participants who seroreacted to leishmanial antigens met the study’s case definition of a severe case of unexplained illness; that suggests that viscerotropic leishmaniasis is distinct from veterans’ unexplained illnesses. However, some people with visceral or viscerotropic leishmaniasis can present with nonspecific symptoms (fatigue, low-grade fever, and gastrointestinal symptoms) that are consistent with those seen in veterans who have unexplained illnesses. Further research is required (NIH, 1994).

Gastrointestinal complaints, as noted earlier, are somewhat common among veterans in the DOD and VA registries (Joseph, 1997; Murphy et al., 1999, Table A.2). In the study noted earlier by Proctor and colleagues (1998), gastrointestinal symptoms were among the symptoms with greatest prevalence differences between deployed and nondeployed veterans. One study investigated a host of gastrointestinal symptoms in a National Guard unit (n=136). Excessive gas, loose stool, incomplete rectal evacuation, and abdominal pain were more prevalent during and after the war in deployed than in nondeployed veterans from the same unit (Sostek et al., 1996). The results were based on a 64-item questionnaire administered after the war. Subjects reported that their gastrointestinal complaints began while in the Persian Gulf area and persisted after return to the United States. A population-based study of Danish peacekeeping troops who were sent to the Persian Gulf after the war had significantly higher prevalence of gastrointestinal symptoms among deployed (9.1%) than nondeployed (1.7%) veterans (Ishoy et al., 1999a). The population-based study of US veterans found up to 25% of veterans reporting medical conditions of gastritis and frequent diarrhea (Kang et al., 2000, Table A.6).

Over the last 5 months of 1991, hospitalizations for testicular cancer were slightly increased in a large study of active-duty deployed versus nondeployed veterans (Gray et al., 1996). In a followup study, the investigators extended their analysis through 1996. They replicated their earlier finding but found that by 4 years after the war the cumulative risk of testicular cancer was similar in the two groups of veterans (Knoke et al., 1998). They attributed the transient increase in testicular cancer immediately after the war to regression to the mean because of the healthy-soldier effect and to deferral of care during deployment (during which time they would not have had the opportunity for diagnosis and treatment).

LIMITATIONS OF PAST AND CURRENT STUDIES

The epidemiologic studies of Gulf War veterans summarized above have contributed greatly to our understanding of veterans’ symptoms, but they are beset by limitations commonly encountered in epidemiologic studies. A major limitation is representativeness;

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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most studies focus on groups that are not representative of all Gulf War veterans with respect to their military duties and location during deployment, their military status during the war (active duty, reserves, or National Guard), their military status after the war (active duty, reserves, or discharged), their branch of service (Army, Navy, Air Force, or Marines), or ease of ascertainment (IOM, 1999a). The VA study, with its population-based design, is the most representative of US veterans. The findings of population-based studies in Canada (Goss Gilroy Inc., 1998) and the UK (Unwin et al., 1999; Cherry et al., 2001a) are generally consistent with the VA and other large US studies.

Other limitations of epidemiologic studies include small samples, low participation rates that could result in selection bias in some studies, and recall bias.27 The potential for recall bias is particularly important because most studies rely on self-reporting of symptoms and exposures years after the event rather than on biologic measures (Joellenbeck et al., 1998). Veterans with more symptoms are more likely to report more exposures (Unwin et al., 1999). Outcome misclassification is also a concern. One study found disparities between veterans’ symptom reporting on questionnaires and later clinical examination (McCauley et al., 1999). Studies might also be too narrow in their assessment of health status. The measurement instruments might have been too insensitive to detect abnormalities that affect deployed veterans. Finally, the period of investigation has, of necessity, been too brief to detect health outcomes that have a long latency or require many years to progress to the point where disability, hospitalization, or death occurs. Virtually all US studies are cross-sectional, and this limits the opportunity to learn about symptom duration and chronicity, latency of onset (especially for health conditions with a long latency, such as cancer), and prognosis.

A major problem for most epidemiologic studies of Gulf War veterans is the lack of biologic measures of exposure to potentially harmful agents. Reliance on self-reported exposures, which often took place years earlier, lacks external verification and is subject to recall bias, a problem that potentially affects many retrospective epidemiologic studies. Furthermore, self-reports of exposure may be complicated by recall of perceived—rather than actual—exposures (for example, because of the sensitivity of the monitors, many false alarms may have been perceived as chemical-warfare agent exposure). Enhanced record keeping and monitoring of the environment during and after the Gulf War would have averted this problem. Indeed, many expert panels have recommended efforts to improve record-keeping and environmental monitoring in future deployments (e.g., IOM, 1999b; NRC, 2000a,b,c).

CONCLUSION

This appendix provides an overview of the body of published studies on the health of Gulf War veterans. Gulf War veterans report more symptoms than do their nondeployed counterparts, according to methodologically robust studies from several countries (Goss Gilroy Inc., 1998; Kang et al., 2000; Iowa Persian Gulf Study Group, 1997; Unwin et al., 1999). Symptoms related to cognition, the musculoskeletal system, and fatigue are more prevalent among Gulf War veterans than controls. Many symptoms and their clustering do

27  

Selection bias would occur if Gulf War veterans who were symptomatic chose to participate in a study more frequently than those who were not symptomatic. Recall bias would occur if Gulf War veterans who were symptomatic tended to overestimate their exposures compared with veterans who were not symptomatic.

Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
×

not appear to fit conventional diagnoses. The question is whether these unexplained symptoms constitute a syndrome and, if so, whether they are best studied and treated as a unique new syndrome or as a variant form of an existing syndrome (IOM, 2000). Although one uncontrolled study reported several unique new syndromes through factor analysis (Haley et al., 1997), four controlled studies did not uncover a unique syndrome (Doebbeling et al., 2000; Fukuda et al., 1998; Ismail et al., 1999; Knoke et al., 2000). Since then, a new factor analysis study has been reported by the VA on a population-based sample of Gulf War deployed versus nondeployed veterans (Kang et al., 2002). The authors found a unique neurologic factor marked by dizziness/balance-related symptoms. They interpreted their findings as suggesting a possible syndrome related to Gulf War deployment that requires objective supporting clinical evidence.

The very lack of definition or classification of veterans’ unexplained symptoms and illnesses has made it difficult to diagnose and treat many Gulf War veterans (IOM, 2001). The commonality of the symptoms in the general population (Kroenke and Mangelsdorff, 1989), coupled with their nonspecific nature and lack of biologic markers, has made it difficult to determine which, if any, exposures or sets of exposures during the Gulf War are responsible.

The health studies reviewed in this appendix have found little or no excess mortality, hospitalizations, or birth defects in the children of veterans, although the studies have some limitations. Deployment to the Gulf War is associated with stress-related disorders, such as PTSD and depression, but a sizable number of veterans with unexplained symptoms do not have any psychiatric diagnoses.

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Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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Research Working Group of the Persian Gulf Veterans Coordinating Group. 1999. Annual Report to Congress: Federally Sponsored Research on Gulf War Veterans’ Illnesses for 1998. Washington, DC: Department of Veterans Affairs.

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Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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Suggested Citation:"Appendix A: Overview of Illnesses in Gulf War Veterens." Institute of Medicine. 2003. Gulf War and Health: Volume 2: Insecticides and Solvents. Washington, DC: The National Academies Press. doi: 10.17226/10628.
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Gulf War and Health, Volume 2, is the second in a series of congressionally-mandated studies by the Institute of Medicine that provides a comprehensive assessment of the available scientific literature on potential health effects of exposure to certain biological, chemical, and environmental agents associated with the Gulf War. In this second study, the committee evaluated the published, peer-reviewed literature on exposure to insecticides and solvents thought to have been present during the 1990-1991 war.

Because little information exists on actual exposure levels – a critical factor when assessing health effects – the committee could not draw specific conclusions about the health problems of Gulf War veterans. However, the study found some evidence, although usually limited, to link specific long-term health outcomes with exposure to certain insecticides and solvents.

The next phase of the series will examine the literature on potential health effects associated with exposure to selected environmental pollutants and particulates, such as oil-well fires and jet fuels.

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