GULF WAR and HEALTH

VOLUME 10

Update of Health Effects of
Serving in the Gulf War, 2016

Committee on Gulf War and Health, Volume 10:
Update of Health Effects of Serving in the Gulf War

Board on the Health of Select Populations

Institute of Medicine

Deborah Cory-Slechta and Roberta Wedge, Editors

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

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This study was supported by Contract No. VA241-P-2024 between the National Academy of Sciences and the Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-38041-6
International Standard Book Number-10: 0-309-38041-3
Digital Object Identifier: 10.17226/21840

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Gulf War and health: Volume 10: Update of health effects of serving in the Gulf War, 2016. Washington, DC: The National Academies Press. doi: 10.17226/21840.

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COMMITTEE ON GULF WAR AND HEALTH, VOLUME 10: UPDATE OF HEALTH EFFECTS OF SERVING IN THE GULF WAR

DEBORAH A. CORY-SLECHTA (Chair), Professor of Environmental Medicine, University of Rochester, NY

ROBERT H. BROWN, JR., Chair and Professor of Neurology, University of Massachusetts Medical School

ALBERTO CABAN-MARTINEZ, Assistant Professor, University of Miami Miller School of Medicine, FL

JAVIER I. ESCOBAR, Associate Dean for Global Health, Professor of Psychiatry and Family Medicine, Rutgers Robert Wood Johnson Medical School, NJ

SCOTT FISHMAN, Professor of Anesthesiology and Pain Medicine, Professor of Psychiatry and Behavioral Medicine, Chief, Division of Pain Medicine in Department of Anesthesiology and Pain Medicine, University of California, Davis, School of Medicine

MARY A. FOX, Assistant Professor, Bloomberg School of Public Health, Johns Hopkins University, MD

HERMAN J. GIBB, Consultant, Gibb Epidemiology Consulting, LLC, VA

ROGENE F. HENDERSON, Senior Biochemist and Toxicologist Emeritus, Lovelace Respiratory Research Institute, NM

CLIFFORD JACK, Professor, Diagnostic Radiology, Mayo Clinic, MN

HOWARD M. KIPEN, Professor and Chair (Interim) of Environmental and Occupational Medicine, Acting Associate Director at Environmental and Occupational Health Sciences Institute, and Director of Clinical Research and Occupational Medicine Division at Rutgers School of Public Health, NJ

KENNETH W. KIZER, Director, Institute for Population Heath Improvement, University of California, Davis, Health System, and Distinguished Professor, University of California, Davis, School of Medicine and the Betty Irene Moore School of Nursing

JOEL KRAMER, Professor of Neuropsychology, University of California, San Francisco, School of Medicine

FRANCINE LADEN, Professor of Epidemiology, Harvard School of Public Health, MA

JAMES M. NOBLE, Assistant Professor of Neurology at Columbia University Medical Center, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain and the G.H. Sergievsky Center, Columbia University, NY

ANBESAW SELASSIE, Associate Professor, Department of Public Health Sciences, Medical University of South Carolina

NANCY F. WOODS, Professor of Biobehavioral Nursing and Dean Emeritus, School of Nursing, University of Washington

Study Staff

ROBERTA WEDGE, Study Director

CARY HAVER, Associate Program Officer

ANNE STYKA, Program Officer (from January 2015)

NICOLE FREID, Senior Program Assistant

CHRISTIE BELL, Financial Officer

FREDERICK ERDTMANN, Director, Board on the Health of Select Populations

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Reviewers

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. 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 individuals for their review of this report:

Katie M. Applebaum, George Washington University

F. DuBois Bowman, Columbia University

Patricia A. Janulewicz-Lloyd, Boston University School of Public Health

Kevin C. Kiley, Albany Medical Center

Kurt Kroenke, Indiana University

Carol S. North, University of Texas Southwestern Medical Center

Martin Philbert, University of Michigan School of Public Health

Marguerite R. Seeley, Gradient Corporation

Lawrence Steinman, Stanford University

Simon Wessley, King’s College London

Christina Wolfson, McGill University

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 Harold C. Sox, Patient-Centered Outcomes Research Institute, and Maryellen L. Giger, University of Chicago. They were 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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Preface

The last nine Institute of Medicine committees that prepared the Gulf War and Health series of reports have diligently assessed the evidence for possible health effects associated with exposures experienced by veterans during the Gulf War. All the prior committees, as well as the current committee, have sought to identify diseases and health conditions caused by Gulf War exposures to help the Department of Veterans Affairs (VA) care for those veterans who were harmed. Several volumes in this series have recommended carefully designed research endeavors in the hope of finally understanding the long-term health effects caused by the war.

Unfortunately, all of the Gulf War and Health committees have faced similar challenges in their attempts to identify the health effects that are clearly the result of deployment to the Gulf War. Foremost among these is the ever unknowable impact of the various chemical exposures that occurred during the 1990–1991 Gulf War, whether alone or in combination with other environmental, chemical, and/or genetic factors. Objective exposure data gathered during and after the war have been, and are expected to continue to be, unavailable.

Studies of Gulf War illness specifically, the most frequently reported health outcome in these veterans, have been hampered by the relatively amorphous nature of the disorder and its multiple definitions over the past two decades, including chronic multisymptom illness, Gulf War syndrome, and multiple unexplained physical symptoms. Even though the evidence base for Gulf War illness has increased over the past few years, it has provided little new information that has increased our understanding of the disease or how to effectively treat or manage it.

The committee’s discussions also included the potential significance of both time and aging, both of which can present substantial difficulties for research efforts. Specifically, the time that has elapsed since the war—25 years—brings with it the potential to impact veterans’ recall of events, including the frequency, duration, and intensity of their exposures during their service. At the same time, advancing age can provoke new health concerns and the development of new diseases long after the war. In any population, it can be difficult to distinguish aging-related effects from those caused by a war many years ago. The committee emphasized that some health consequences with a long latency period, such as some cancers and neurodegenerative conditions, may not yet be fully described or be characterized

by Gulf War illness. While the symptoms of Gulf War illness are expected to have developed soon after the deployment, similar symptoms, such as headache or cognitive problems, appearing 20 years after the war are unlikely to be related to Gulf War service but may be caused by other exposures or conditions that are entirely unrelated to the Gulf War. Thus, it is ever more important that any future research endeavors use well-designed protocols to minimize the effects of time and aging on the interpretation of Gulf War veterans’ health.

The committee did take note of research focused on the determination of potential biomarkers for Gulf War illness; this focus highlights the importance of exploring all avenues of research that might prove fruitful in diagnosing and treating veterans with this debilitating illness. Critical to both the diagnosis and treatment of Gulf War illness, however, is acknowledging the brain–body continuum. This committee concurs with the findings of previous Gulf War and Health committees in that Gulf War illness is not a psychosomatic illness, and it is cognizant of the residual stigma associated with having a mental health disorder and veterans’ frustration of being told that their persistent and disabling symptoms are “all in their heads.” Nevertheless, as the committee has tried to emphasize, there is a requisite interconnectedness of the physiological systems of the body and the brain, such that dysfunctions of either have consequences that can extend to both. In the same context, the committee has also tried to reiterate that although Gulf War illness should not be called a psychosomatic disorder, this does not mean that it or any chronic disease, including cancer, diabetes, and heart disease, does not have psychological components that might be amenable to mental health therapies as well as other treatments. For example, many investigations into biomarkers of Gulf War illness acknowledge this brain–body continuum by looking for explanations of the illness in brain functioning. The committee believes it would be a disservice to Gulf War veterans to ignore treatments that might address the mental health and neurocognitive components of Gulf War illness.

The committee would like to acknowledge and give sincere thanks to Dr. Ralph Loren Erickson and Dr. Robert Bossarte of VA; Dr. Beatrice Golomb and Dr. Roberta White from the VA Research Advisory Committee on Gulf War Veterans’ Illnesses (RAC); Ronald Brown and James Bunker from the National Gulf War Resource Center, Mr. James Binns and Dr. Lea Steele, former RAC members; Anthony Hardie, David Hatfield, Remington Nevin, Denise Nichols, Daniel Sullivan, Peter Sullivan, and the other Gulf War veterans for their presentations to the committee which it found both illuminating and moving. The committee would also like to thank Dr. Carolyn Clancy, Under Secretary for Health of VA, for her informative remarks.

The committee gained valuable insight and context from the many veterans who attended the committee’s first and second meetings or participated by phone. Their experiences and concerns echoed the seriousness of their health conditions even 25 years after the Gulf War. Their needs and concerns resonated with the committee as it endeavored to review the evidence objectively. The committee sincerely thanks the many individual veterans and veteran service organization representatives who took the time and made the effort to inform the committee’s deliberations.

I would like to express my sincere gratitude to the expert committee members for their thoughtfulness, insights, and hard work. I know I speak for the entire committee in expressing many thanks to Roberta Wedge for efficiently guiding the report through its various stages and keeping the committee organized and moving forward; to Cary Haver and Anne Styka for their research efforts; to Nicole Freid for her administrative support, and to the National Academies Research Center’s Daniel Bearss for creating and executing the literature search strategy and Ellen Kimmel for fact checking.

Deborah A. Cory-Slechta, Chair

Committee on Gulf War and Health, Volume 10: Update of Health Effects of Serving in the Gulf War

Contents

PREFACE

ACRONYMS AND ABBREVIATIONS

SUMMARY

Charge to the Committee

The Committee’s Approach

Major Cohort Studies

Health Outcomes

Animal Studies

Findings and Recommendations

Moving Forward

1 INTRODUCTION

The Gulf War Setting

The Gulf War Aftermath

Charge to the Committee

Committee’s Approach to Its Charge

Organization of the Report

2 CONSIDERATIONS IN IDENTIFYING AND EVALUATING THE LITERATURE

Identification of the Literature

Evaluation Process

Individual Variability

Exposure Assessment

Categories of Association

Conclusions

3 HUMAN COHORT STUDIES AND THEIR DERIVATIVES

Organization of This Chapter

U.S. Veteran Cohorts

United Kingdom Veteran Studies

Australian Veteran Studies

Danish Peacekeeper Studies

Canadian Veterans Studies

Summary

4 EVALUATION OF HEALTH CONDITIONS

Gulf War Illness

Cancer

Blood and Circulatory System Conditions

Endocrine and Metabolic Conditions

Mental and Behavioral Health Conditions

Neurologic Conditions

Respiratory System Conditions

Gastrointestinal System Conditions

Chronic Skin Conditions

Pain-Related Conditions

Genitourinary System Conditions

Adverse Reproductive and Perinatal Outcomes

Causes of Mortality

Health Conditions Related to Depleted Uranium Exposure

5 ANIMAL STUDIES

Animal Models of Gulf War Illness

Blood–Brain Barrier Permeability, Brain Histopathology, and Brain Metabolism and Function

Behavioral Effects

Organ System Effects

Conclusions

6 FINDINGS AND RECOMMENDATIONS

Summary of Findings

Gulf War Illness

Neurological Conditions

Lung and Brain Cancer

Other Health Conditions

Exposure Assessments

Sex, Race, and Ethnicity

Moving Forward

7 REFERENCES

APPENDIX: COMMITTEE BIOGRAPHIES

Acronyms and Abbreviations