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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 GULF WAR and HEALTH VOLUME 4 HEALTH EFFECTS OF SERVING IN THE GULF WAR Committee on Gulf War and Health: A Review of the Medical Literature Relative to the Gulf War Veterans’ Health Board on Population Health and Public Health Practice INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This study was supported by Contract V101(93)P-2155 between the National Academy of Sciences and the Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project. International Standard Book Number-10: 0-309-10176-X International Standard Book Number-13: 978-0-309-10176-9 Library of Congress Control Number: 2006934960 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at www.iom.edu. Copyright 2006 by the National Academy of Sciences. All rights reserved. Printed in the United States of America. The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 “Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Advising the Nation. Improving Health.
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 THE NATIONAL ACADEMIES Advisers to the National on Sciences, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 COMMITTEE ON GULF WAR AND HEALTH: A REVIEW OF THE MEDICAL LITERATURE RELATIVE TO GULF WAR VETERANS’ HEALTH LYNN R. GOLDMAN, MD, MPH, (chair) Professor, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD MARCIA ANGELL, MD, Senior Lecturer on Social Medicine, Department of Social Medicine, Harvard Medical School, Boston, MA W. KENT ANGER, PhD, Associate Director for Occupational Research, Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR MICHAEL BRAUER, ScD, Professor, School of Occupational and Environmental Hygiene, University of British Columbia, Vancouver, British Columbia DEDRA S. BUCHWALD, MD, Director, Harborview Medical Center, University of Washington, Seattle, WA FRANCESCA DOMINICI, PhD, Associate Professor, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD ARTHUR L. FRANK, MD, PhD, Professor, Chair, Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, PA FRANCINE LADEN, ScD, Assistant Professor of Medicine, Channing Laboratory, Harvard Medical School, Boston, MA DAVID MATCHAR, MD, Director, Center for Clinical Health Policy Research, Duke University Medical Center, Durham, NC SAMUEL J. POTOLICCHIO, MD, Professor, Department of Neurology, George Washington University Medical Center, Washington, DC THOMAS G. ROBINS, MD, MPH, Professor, Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI GEORGE W. RUTHERFORD, MD, Professor, Vice-Chair, Department of Epidemiology and Biostatistics, Division of Preventive Medicine and Public Health, School of Medicine, University of California, San Francisco, CA CAROL A. TAMMINGA, M.D., Professor, Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas, TX
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 STAFF CAROLYN FULCO, Senior Program Officer ABIGAIL MITCHELL, Senior Program Officer DEEPALI PATEL, Senior Program Associate MICHAEL SCHNEIDER, Senior Program Associate JUDITH URBANCZYK, Senior Program Associate HOPE HARE, Administrative Assistant PETER JAMES, Research Associate DAMIKA WEBB, Research Assistant RENEE WLODARCZYK, Intern NORMAN GROSSBLATT, Senior Editor ROSE MARIE MARTINEZ, Director, Board on Population Health and Public Health Practice CONSULTANTS MIRIAM DAVIS, Independent Medical Writer, Silver Spring, MD ANNE STANGL, Tulane School of Public Health and Tropical Medicine, New Orleans, LA
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 REVIEWERS This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following for their review of this report: ARTHUR K. ASBURY, MD, Department of Neurology, University of Pennsylvania, Philadelphia, PA SHARON COOPER, PhD, Professor and Chair, Department of Epidemiology and Biostatistics, Texas A & M University School of Rural Public Health, College Station, TX PETER J. DYCK, MD, Director, Peripheral Nerve Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN DAVID GAYLOR, PhD, MS, President, Gaylor & Associates, LLC, Eureka Springs, AR JACK M. GORMAN, MD, President and Psychiatrist in Chief, McLean Hospital, Belmont, MA PHILIP GREENLAND, MD, Executive Associate Dean for Clinical and Translational Research, Northwestern University Feinberg School of Medicine, Chicago, IL HOWARD KIPEN, MD, MPH, Director, Clinical Research and Occupational Medicine Division, Environmental & Occupational Health Sciences Institute, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ JOSEPH LADOU, MD, Editor, International Journal of Occupational and Environmental Health, Professor, Division of Occupational and Environmental Medicine, University of California, San Francisco, CA ELLEN REMENCHIK, MD, MPH, Assistant Professor, Occupational and Environmental Medicine, The University of Texas Health Center, Tyler, TX KATHERINE S. SQUIBB, PhD, Associate Professor & Head, Division of Environmental Epidemiology & Toxicology, University of Maryland School of Medicine, Baltimore, MD Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by David J. Tollerud, Professor and Chair, Department of Environmental and Occupational Health Sciences, University of Louisville and by Harold Sox, editor, Annals of Internal Medicine, American College of Physicians of Internal Medicine. Appointed by the National Research Council, Dr. Sox was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 PREFACE The 1990-1991 Persian Gulf War was brief and entailed few US casualties in comparison with other wars, and yet it had a profound impact on the lives of many of the troops. Among the 700,000 US military personnel deployed in the battle theater, many veterans have reported chronic symptoms and illnesses that they have attributed to their service in the gulf. Numerous studies have been conducted to characterize the long-term adverse health consequences of deployment to the Persian Gulf. Potential exposures to numerous hazardous substances have been identified in association with the Gulf War. Most alarming are the smoke from oil-well fires that were set by Iraqis as they retreated at the end of the war and the potential exposures arising from the US military bombing of a poison-gas munitions dump at a location called Khamisiyah. Military personnel have also been reported to have had other exposures, such as to fuels, vaccines, pharmaceuticals, and pathogens. Most recently, the Department of Defense published a report documenting a large amount of pesticide use in the war theater. For most of those exposures, it is difficult or impossible to reconstruct doses because of lack of exposure measurements on either the individual or group level. The situation is compounded by the stress experienced by many veterans during deployment and in some cases after deployment. Stress is known to have serious acute and chronic health effects, but at the time of the Gulf War relatively little attention was given to reduction of stress and its consequences. The Department of Veterans Affairs (VA) and the US Congress have secured the assistance of the Institute of Medicine (IOM) in evaluating the scientific literature regarding possible health outcomes associated with exposures that might have occurred in the Gulf War, IOM has published several volumes that review the clinical diseases that might be associated with exposures, such as exposure to sarin gas, depleted uranium, pesticides, solvents, rocket propellants, fuels, and combustion products. Such reviews continue and will provide information about illnesses related to exposure to pathogens, stress, and chemical agents. The congressional request regarding the possible association between illness and exposures in the gulf is similar to the approach Congress took after the Vietnam War to address the potential adverse health effects of exposure to Agent Orange. The current report, however, takes a different approach, which is to identify the adverse health effects, if any, that are occurring among Gulf War veterans and thus might warrant further attention, either on the individual level or for the Gulf War veterans as a whole. Many of the relevant studies are limited by the lack of objective exposure information. Although there is a blood test that can provide an indication of exposure to Agent Orange and dioxin that occurred many years ago, there is not biological measure that can be employed today to assess exposures during the Gulf War. Another limitation is that most studies have relied on self-reports of symptoms and symptom-based case definitions to determine whether rates of diseases were increased among Gulf War veterans. Nonetheless, some studies do point to psychiatric disorders and neurologic end points that might be associated with Gulf War service and for which it might be possible to develop new approaches to prevention and clinical treatment that could benefit not only Gulf War veterans but also veterans of later conflicts. Our committee does not recommend
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 that more such studies be undertaken for the Gulf War veterans, but, there would be value in continuing to monitor the veterans for some health end points, specifically, cancer, especially brain and testicular cancers, neurologic diseases including Amyotrophic Lateral Sclerosis (ALS), and causes of death. Therefore, despite the serious limitations of the available studies as a group, they do point the way to actions that might benefit Gulf War and other combat veterans. I am deeply appreciative of the expert work of our committee members: Marcia Angell, W. Kent Anger, Michael Brauer, Dedra S. Buchwald, Francesca Dominici, Arthur L. Frank, Francine Laden, David Matchar, Samuel J. Potolicchio, Thomas G. Robins, George W. Rutherford, and Carol Tamminga. Although our committee developed conclusions independently of input from IOM and its staff, we deeply appreciate their hard work and attention to detail and the extensive research that they conducted to ensure that we had all the information that we needed from the outset. It has been a privilege and a pleasure to work with the IOM staff directed by Carolyn Fulco and with our consultant, Miriam Davis. Without them, this report would not have been possible. Most of all, our committee appreciates the veterans who served in the Gulf War and who have volunteered again and again to participate in the health studies that we reviewed. It is for them that we do this work. We hope this report will inform those who have given so much to our nation about what researchers have been able to learn about their health. LYNN R. GOLDMAN, MD, MPH PROFESSOR JOHNS HOPKINS UNIVERSITY
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 CONTENTS Summary 1 Charge to the Committee 1 Committee’s Approach to Its Charge 1 Limitations of the Gulf War Studies 2 Overview of Health Outcomes 2 Outcomes Based Primarily on Symptoms or Self-Reports 3 Outcomes with Objective Measures or Diagnostic Medical Tests 5 Recommendations 7 Predeployment and Postdeployment Screening 7 Exposure Assessment 7 Surveillance for Adverse Outcomes 8 Brief Summary of Findings and Recommendations 9 1 Introduction 11 Background 11 The Gulf War Setting 12 Deployment 12 Living Conditions 13 Environmental and Chemical Exposures 13 Threat of Chemical and Biologic Warfare 14 Charge to the Committee 15 Committee’s Approach to Its Charge 15 Inclusion Criteria 15 Complexities in Resolving Gulf War and Health Issues 16 Multiple Exposures and Chemical Interactions 16 Limitations of Exposure Information 16 Individual Variability 17 Unexplained Symptoms 17 Organization of the Report 18 References 18 2 Exposures in the Persian Gulf 21 Exposure Assessment in Epidemiologic Studies 21 Studies Assessing Exposures with Questionnaires 21 Exposure to Oil-Well Fire Smoke 22 Exposure to Vaccination 22
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Exposure to Pyridostigmine Bromide 23 Exposure to Depleted Uranium 24 General Cohort Studies (Prevalence Studies) 25 Studies Using Simulation to Assess the Potential Magnitude of Exposures 26 Tent Heaters 26 Khamisiyah Demolition and Potential Exposure to Sarin and Cyclosarin 26 Epidemiologic Studies Using Fate and Transport Models to Assess Exposure to Sarin and Cyclosarin 35 Studies Using Environmental Fate and Transport Models for Specific Exposures 37 Studies Using Biologic Monitoring for Specific Exposures 39 Depleted Uranium 39 Oil-Well Fire Smoke 40 Summary and Conclusions 41 References 41 3 Considerations in Identifying and Evaluating the Literature 45 Types of Epidemiologic Studies 45 Cohort Studies 45 Case-Control Studies 47 Cross-Sectional Studies 47 General Remarks 48 Defining a New Syndrome 48 Statistical Techniques Used to Develop a Case Definition 49 Inclusion Criteria 51 Additional Considerations 51 Bias 52 Confounding 52 Chance 52 Multiple Comparisons 52 Assignment of Causality 53 Limitations of Gulf War Veteran Studies 53 Summary 53 References 54 4 Major Cohort Studies 55 General Limitations of Gulf War Cohort Studies and Derivative Studies 56 Organization of This Chapter 58 Population-Based Studies 58 The Iowa Study 58 Department of Veterans Affairs Study 60 Oregon and Washington Veteran Studies 63 Kansas Veteran Study 64 Canadian Veteran Study 65 United Kingdom Veteran Studies 65
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Danish Peacekeeper Studies 68 Australian Veteran Studies 69 Military-Unit-Based Studies 70 Ft. Devens and New Orleans Cohort Studies 70 Seabee Reserve Battalion Studies 71 Larger Seabee Cohort Studies 73 Pennsylvania Air National Guard Study 74 Other Cohort Studies 75 Hawaii and Pennsylvania Active Duty and Reserve Study 76 New Orleans Reservist Studies 76 Air Force Women Study 76 Connecticut National Guard 77 References 105 5 Health Outcomes 115 Cancer (ICD-10 C00-D48) 115 Primary and Secondary Studies 116 Summary and Conclusion 118 Mental and Behavioral Disorders (ICD-10 F00-F99) 122 Primary Studies 123 Secondary Studies 127 Summary and Conclusion 127 Neurobehavioral and Neurocognitive Outcomes (ICD-10 F00-F99) 131 Neurobehavioral Tests and Confounding Factors 131 Studies That Respond to Question 1 (Outcomes in Gulf War-Deployed Veterans vs Veterans Deployed Elsewhere or Not Deployed) 132 Studies That Respond to Question 2 (Symptomatic vs Nonsymptomatic Veterans) 135 Related Findings: Malingering and Association of Symptoms with Objective Test Results 140 Summary and Conclusion 140 Diseases of the Nervous System (ICD-10 G00-G99) 153 Amyotrophic Lateral Sclerosis 153 Summary and Conclusion 155 Peripheral Neuropathy and Other Neurologic Outcomes 157 Summary and Conclusion 159 Chronic Fatigue Syndrome 161 Primary Studies 162 Secondary Studies 162 Summary and Conclusion 163 Diseases of the Circulatory System (ICD-10 I00-I99) 166 Primary Studies 166 Secondary Studies 167 Summary and Conclusion 168 Diseases of the Respiratory System (ICD-10 J00-J99) 170 Associations of Respiratory Outcomes with Deployment in the Gulf War Theater 170
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Associations of Respiratory Outcomes with Specific Exposures Experienced by Gulf War Veterans During Their Deployment 172 Summary and Conclusion 174 Diseases of the Digestive System (ICD-10 K00-K93) 180 Primary Studies 180 Secondary Studies 181 Summary and Conclusion 181 Diseases of the Skin and Subcutaneous Tissue (ICD-10 L00-L99) 183 Primary Studies 183 Secondary Studies 183 Summary and Conclusion 183 Diseases of the Musculoskeletal System and Connective Tissue (ICD-10 M00-M99) 185 Arthritis and Arthralgia 185 Summary and Conclusion 186 Fibromyalgia 188 Primary Studies 188 Secondary Studies 189 Summary and Conclusion 190 Birth Defects and Adverse Pregnancy Outcomes (ICD-10 O00-Q99) 192 Birth Defects 192 Summary and Conclusion 194 Adverse Pregnancy Outcomes 195 Summary and Conclusion 195 Male Fertility Problems and Infertility 196 Symptoms, Signs, and Abnormal Clinical and Laboratory Findings (ICD-10 R00-R99) 202 Unexplained Illness 202 Hospitalizations for Unexplained Illness 202 Factor-Analysis Derived Syndromes 203 Cluster Analysis 212 Summary and Conclusion 213 Injury and External Causes of Morbidity and Mortality (ICD-10 S00-Y98) 219 Primary Studies 219 Secondary Studies 220 Summary and Conclusion 220 All-Cause Hospitalization Studies 223 Primary Studies 223 Summary and Conclusion 224 Multiple Chemical Sensitivity 227 Primary Studies 227 Secondary Studies 228 Summary and Conclusion 229 References 232
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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 6 Conclusions and Recommendations 247 Quality of the Studies 247 Overview of Health Outcomes 247 Outcomes Based Primarily on Symptoms and Self-Reports 248 Outcomes with Objective Measures or Diagnostic Medical Tests 251 Recommendations 254 Predeployment and Postdeployment Screening 254 Exposure Assessment 254 Surveillance for Adverse Outcomes 254 References 255 Index 261
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