TESTIMONY OF DRUE H. BARRETT, PH.D.

BEFORE THE
SUBCOMMITTEE ON LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION
COMMITTEE ON APPROPRIATIONS
U.S. SENATE

Mr. Chairman, thank you for the opportunity to update the Subcommittee on the Centers for Disease Control and Prevention=s (CDC) research programs pertaining to Gulf War veterans= illnesses. I am Dr. Drue Barrett, Chief of the Veterans= Health Activity Working Group in the Division of Environmental Hazards and Health Effects of the National Center for Environmental Health (NCEH). I serve as CDC=s liaison to the Department of Health and Human Services (HHS) on Gulf War issues. I a member of the Research Working Group that serves the Persian Gulf Veterans Coordinating Board and the Military and Veterans Health Coordinating Board. NCEH has been designated as the lead Center at CDC for addressing Gulf War veterans= health concerns, however other Centers within CDC have also been involved in this effort, most notably, the National Center for Infectious Diseases.

The purpose of my testimony is to provide the Subcommittee with background information on what is currently known about illnesses among Gulf War veterans and the possible relationship between these illnesses and environmental hazards encountered during the Gulf War. My testimony will include a discussion of the recent Institute of Medicine (IOM) report on depleted uranium, sarin, pyridostigmine bromide, and vaccines, a review of CDC=s Gulf War research activities, and an assessment of the Federal research effort to address the health concerns of Gulf War veterans.

Shortly after the end of the Gulf War, reports began to emerge that veterans were experiencing a variety of somatic symptoms generally not accompanied by physical signs or laboratory abnormalities. The most commonly reported symptoms include complaints of chronic fatigue, headache, muscle and joint aches and pains, and cognitive disturbances.

In 1994, the findings of a National Institutes of Health Technology Assessment Workshop established the priority of conducting controlled epidemiologic research to determine the prevalence of symptoms among Gulf War veterans and a number of such studies have been completed. This research effort has included population-based studies, including cross-sectional and longitudinal cohort studies; cluster and cross-sectional studies of specific military units, commands, or branches of service; and studies of U.S. and other coalition forces. Importantly, control subjects have been assessed in order to compare prevalence rates across groups. These control groups have included military personnel activated during the time of the Gulf War who remained stateside, troops deployed to other regions during the Gulf War, and military participants in other conflicts. Assessment approaches have included mail and telephone surveys, in person questionnaires and interviews, and physical examinations. The number of respondents participating in these studies have ranged from a few hundred to over 20,000. Response rates have ranged from poor (31%) to very good (76%).

The findings of these studies have been remarkably consistent, regardless of the study methodology employed. Active duty and reserve personnel deployed to the Gulf War report nearly all assessed symptoms at a higher rate than comparison groups. Gulf War veterans are also more likely to rate their overall health status since the Gulf War as poorer than their non-deployed peers. The most useful or generalizable studies of symptom prevalence have been population-based, have used a comparable control group of military era personnel not deployed to the Gulf, and have used at least some standardized or validated instruments to allow comparisons to other populations or studies.

A number of environmental exposures have been mentioned in relation to Gulf War veterans= health concerns. These have included environmental and occupational pollutants (e.g., sand, petroleum products, pesticides, Chemical Agent Resistant Coating paint, smoke from oil-well fires), medical prophylaxes (e.g., anthrax and botulinum toxin vaccines and pyridostigmine bromide), depleted uranium munitions, and biologic and chemical warfare agents. Several studies have explored the relationship between exposures during the Gulf War and subsequent health outcomes. However, as noted by the IOM in their recent report, this research has been hampered by a lack of objective exposure data. Since most studies have examined the association between retrospective recall of exposures and self-reported health outcomes, it has been difficult to eliminate the impact of potential recall bias. To date, no specific exposure has been identified as responsible for the various health complaints of Gulf War veterans.

In an effort to further examine the health effects associated with exposures encountered during the Gulf War, the IOM reviewed the scientific and medical literature on depleted uranium, sarin, pyridostigmine bromide, and vaccination against botulinum toxin and anthrax. Because of the lack of data on actual exposures among Gulf War veterans, the committee was not able to assess the likelihood that Gulf War veterans= health problems are associated with or caused by these agents. Instead most of the conclusions in the report are based on occupational and clinical exposures. The committee did find sufficient evidence for some transient acute health effects associated with high doses of pyridostigmine bromide (such as those used in treatment of myasthenia gravis) and with anthrax and botulinum toxoid vaccinations. They found sufficient evidence of a causal relationship between exposure to sarin and a dose-dependent acute cholinergic syndrome that develops in seconds to hours subsequent to sarin exposure and resolves in days to months and limited/suggestive evidence of an association between exposure to sarin at doses sufficient to cause acute cholinergic effects and subsequent long-term health effects. Other than the findings for sarin, the committee concluded that there was inadequate or insufficient evidence to make a determination that the exposures would result in long-term adverse health effects. The IOM based their conclusions on an exhaustive review of 1,000 peer reviewed journal articles. Although the IOM findings cannot provide conclusive answers about the health impact of these exposures on Gulf War veterans, this report may provide some reassurance that among other populations there does not seem to be strong evidence that in the absence of acute effects these exposures are associated with long term health effects.

In order to further explore what is known about Gulf War veterans= health concerns, I would like to review CDC=s research activities in this area. CDC=s initial efforts were to examine the health impact of the oil well fires. Researchers from the NCEH and several other Federal agencies conducted cross-sectional surveys of workers in Kuwait City in May 1991 and of firefighters in the oil fields in October 1991. Blood samples were tested for 31 volatile organic compounds (VOCs) and compared to a referent group of persons living in the United States collected as part of the third National Health and Nutrition Examination Survey (NHANES III). The median concentration of VOCs among the firefighters was quite elevated. However, among the non-firefighting personnel, VOC concentrations were equal to or lower than the levels found among the reference group.

NCEH also collaborated with the Department of Defense (DoD) in a study of 30 members of an Army Unit located in Germany. Blood from these military personnel was tested for VOCs at three points in time, prior, during and after their deployment to Kuwait. Only one compound, tetrachloroethylene, was found to be elevated. This is a compound found in degreasing agents used to clean equipment.

In 1994, CDC collaborated with the Mississippi Department of Health and the Department of Veterans Affairs (VA) on an assessment of reports of adverse birth outcomes among members of two Mississippi National Guard Units that served in the Gulf War. This investigation found no increase above expected rates in the total number of birth defects, or the frequency of premature birth and low birth weight. The frequency of other health problems such as respiratory infections, gastroenteritis, and skin diseases among children born to these veterans also did not appear to be elevated. Due to the small sample size, this investigation was unable to assess individual categories of birth defects.

In 1994, CDC initiated an epidemiologic study of Gulf War veterans from Iowa. The Iowa study, conducted in collaboration with the Iowa Department of Public Health and the University of Iowa, was one of the first population-based epidemiologic studies to document that Gulf War veterans are reporting more medical and psychiatric conditions than their non-deployed military peers. In fact, this study was recently described by IOM as Aperhaps the strongest study on Gulf War veterans= experience of symptoms related to deployment in the Gulf.@ The 3,695 subjects who completed this study were selected from a larger population of almost 29,000 military personnel who listed Iowa as their home of record. Furthermore, the subjects in this study were specifically selected to represent individuals from all four branches of the military, and include both regular military personnel and National Guard and reservists. Seventy-six percent of the eligible study subjects completed the detailed telephone interviews. This study is also one of the first controlled epidemiological studies to evaluate the health consequences of the Gulf War. The study included a carefully selected comparison group of military personnel who were not deployed to the Persian Gulf but who served during the time of the Gulf War. The Iowa study found that the Gulf War military personnel were more likely than those who did not serve in the Gulf War to report symptoms suggestive of cognitive dysfunction, depression, chronic fatigue, post-traumatic stress disorder, and respiratory illness (asthma and bronchitis). The conditions identified in this study appear to have had a measurable impact on the functional activity and daily lives of these Gulf War veterans. Among Gulf War veterans, minimal differences were observed between the National Guard or reserve troops and the regular military personnel. The results of the Iowa study were published in the Journal of the American Medical Association in 1997.

More recently the Iowa data has been examined to determine whether the health complaints of Gulf War veterans represent a novel illness unique to service in the Persian Gulf. We assumed that if there was a Gulf War syndrome, the symptom pattern would vary between the deployed veterans and the non-deployed controls. Although Gulf War veterans reported nearly every symptom more often than those who did not deploy to the Gulf, we found that Gulf War veterans and non-deployed controls had the same patterns of symptoms suggesting that the health complaints of Gulf War veterans are similar to those of the general military population and are not consistent with the existence of a unique Gulf War syndrome. This study was published earlier this year in the American Journal of Medicine.

Also in 1994, CDC initiated a study of Air Force personnel. This study organized symptoms reported by Air Force Gulf War veterans into a case definition, characterized clinical features, and evaluated risk factors. The cross-sectional questionnaire was sent to 3,723 currently active volunteers from four Air Force populations. Clinical evaluations were performed on 158 Gulf War veterans from one unit, irrespective of health status. A case was defined based on reporting one or more chronic symptoms from at least 2 of 3 categories (fatigue, mood-cognition and musculoskeletal) and was further characterized as mild-to-moderate or severe depending on the severity of the reported symptoms. The prevalence of mild-to-moderate and severe cases were 39% and 6%, respectively, among 1,155 Gulf War veterans versus 14% and 0.7% among 2,520 non-deployed veterans. Fifty-nine (37%) clinically evaluated Gulf War veterans were non-cases, 86 (54%) were mild-to-moderate cases and 13 (8%) were severe cases. The key observation of the study was that Air Force Gulf War veterans were significantly more likely to meet criteria for severe and mild-to-moderate illness than were non-deployed personnel. There was no association between the chronic multisymptom illness and risk factors specific to combat in the Gulf War (month of season of deployment, duration of deployment, duties in the Gulf War, direct participation in combat, or locality of Gulf War service). The finding that 15% of non-deployed veterans also met illness criteria was equally important and suggests that the multisymptom illness observed in this population is not unique to Gulf War service. The clinical evaluation component of the study found that neither mild-to-moderate nor severe cases were associated with clinically significant abnormalities on physical examination or routine laboratory tests. However, Gulf War veterans classified as having mild-to-moderate and severe illness had a significant decrease in functioning and well-being compared with non-cases. The results from this study were published in CDC=s Morbidity and Mortality Weekly Report in 1995 and in the Journal of the American Medical Association in 1998.

Subsequent analyses of data from the Air Force study have examined the association between physical, chemical, and emotional deployment stressors reported by Gulf War veterans and the development of chronic multisymptom illness following the war. The illness defined in this study was found to be related to reporting pyridostigmine bromide use, insect repellent use, injuries that required medical attention, and a belief that biological or chemical weapons had been used. These findings were published earlier this year in the Journal of Nervous and Mental Disorders.

CDC is currently funding a follow-up to the Iowa study focusing on evaluating self-reported symptoms of asthma. This study involves a detailed clinical evaluation of a sample of subjects who completed the initial telephone survey. This evaluation includes a physical examination; tests of lung functioning; questions regarding medical, occupational, and exposure history; assessment of functional status and quality of life; and assessment of psychiatric history and personality functioning. The examinations are being conducted at the University of Iowa Hospitals and Clinics in Iowa City, Iowa. This study is in its final phases of data collection.

The University of Iowa has also been funded by DoD to conduct validation studies of additional health outcomes among participants of the telephone survey. These include validation of depression, cognitive dysfunction, and fibromyalgia. CDC is providing technical assistance to DoD and the University of Iowa for this study.

We are also funding the Boston University School of Public Health to conduct a study examining the relationship between cognitive function and symptom patterns among Gulf War veterans. In one component of this study, functional magnetic resonance imaging (fMRI) is being used to examine possible differences in brain activation patterns between Gulf War veterans and era controls with different levels of symptoms. A second component of the study is using a new data-driven mathematical technique, Logical Analysis of Data, to examine how Gulf War veterans= symptoms cluster together. This may provide useful information for determining etiology or for developing a case definition. Finally, this study also includes a component examining the neuropsychological functioning of a sample of Danish Gulf War troops. Investigators are currently in the data collection phase for the fMRI component of this study and in the data analysis phase for the other two components. We anticipate that this study will be complete by the end of this year.

Finally, CDC is funding the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School to conduct a study examining case definition issues. The study will assess the persistence and stability of Gulf War veterans symptoms over time, compare the performance of data-driven case definitions to existing definitions for medically unexplained symptoms, and examine the role of psychiatric conditions in Gulf War veterans= unexplained illnesses. We originally expected that this study would be completed in late 2000, however the process of protocol development and clearance took somewhat longer than we anticipated. Thus, we expect that this study will require an additional year to complete.

CDC is also collaborating with DoD and VA on a number of projects including a study of health outcomes among Saudi Arabia National Guard members and a study of Amyotrophic Lateral Sclerosis (ALS) among Gulf War veterans. This collaboration has included providing input on study protocols, reviewing human subjects issues, and assisting in laboratory assessments.

CDC, in collaboration with other HHS agencies, recently sponsored a conference to develop future Gulf War research recommendations. On February 28 through March 2, 1999, CDC brought together scientists, clinicians, veterans, veterans= service organizations, Congressional staff, and other interested parties to discuss and make recommendations regarding the direction of future research on undiagnosed illnesses among Gulf War veterans and their links with multiple chemical and environmental exposures.

Concurrent workgroups were convened in order to develop research recommendations in four areas: pathophysiology, etiology, and mechanisms of action; assessment and diagnosis of illnesses; treatment; and prevention of illnesses in future deployments. This conference highlighted the importance of including veterans in the process of planning and implementing research. Veterans and scientists alike expressed that they found the process useful and that future similar efforts should be encouraged. A report was released earlier this year that summarized the outcome of each of the four workgroup sessions. The recommendations developed at this conference have been shared with the interagency Research Working Group and need to be considered in light of the existing research portfolio in order to avoid unnecessary duplication of efforts. We are currently developing a call for research proposals that will build on the recommendations developed during the conference. We would specifically like to address the issue of health risk communication and the development of more effective methods for delivering deployment-related health information.

The Federal research portfolio on Gulf War veterans= illnesses has been managed by the Research Working Group of the Persian Gulf Veterans Coordinating Board and in the near future will be managed by the Military and Veterans= Health Coordinating Board. Various agencies within HHS have participated in the interagency effort to coordinate research, however the majority of this research has been funded by DoD and VA. To date there have been 192 federally-funded research projects on Gulf War veterans= illnesses. These projects represent a broad spectrum of research efforts, ranging from small pilot studies to large-scale epidemiology studies addressing mechanistic, clinical, and epidemiological issues. Similar efforts have been initiated in other coalition countries, most notably in the United Kingdom and Canada. Many of the projects are ongoing and we eagerly await the results of these studies. In addition to the Federal research effort, numerous independent review panels and expert committees, such as the IOM committees, have evaluated the available data on Gulf War veterans= illnesses. Despite these extensive research and review efforts, many questions remain regarding the health impact of the Gulf War. However, these remaining questions reflect the complexity of assessing and predicting the health impact of military deployments. Despite this complexity, the federal research effort continues in an effort to uncover the causes of illnesses among Gulf War veterans so that effective treatment approaches can be developed and similar illnesses in future deployments can be prevented.

Mr. Chairman, this concludes my testimony. I would be happy to answer any questions the Subcommittee may have.