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Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations Committee on the Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations Board on Population Health and Public Health Practice Health and Medicine Division A Consensus Study Report of

THE NATIONAL ACADEMIES PRESS  500 Fifth Street, NW  Washington, DC 20001 This activity was supported by Contract Order No. 36C24E18C0068 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: 978-0-309-67910-7 International Standard Book Number-10: 0-309-67910-9 Digital Object Identifier: https://doi.org/10.17226/25837 Additional copies of this publication are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, W ­ ashington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu. Copyright 2020 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2020. Respiratory health effects of airborne hazards exposures in the Southwest Asia Theater of Military Operations. Washington, DC: The National Academies Press. https://doi.org/10.17226/25837.

The National Academy of Sciences was established in 1863 by an Act of ­ongress, signed by Presi- C dent Lincoln, as a private, nongovernmental institution to advise the nation on issues related to sci- ence and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine. www.­nationalacademies.org. Learn more about the National Academies of Sciences, Engineering, and Medicine at ­­­

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on informa- tion gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task. Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies. For information about other products and activities of the National Academies, please visit www. nationalacademies.org/about/whatwedo.

COMMITTEE ON THE RESPIRATORY HEALTH EFFECTS OF AIRBORNE HAZARDS EXPOSURES IN THE SOUTHWEST ASIA THEATER OF MILITARY OPERATIONS MARK J. UTELL (Chair), Professor of Medicine and Environmental Medicine, Director of Occupational and Environmental Medicine, former Director of Pulmonary and Critical Care Medicine, University of Rochester Medical Center LUNG-CHI CHEN, Professor, Department of Environmental Medicine, New York University Grossman School of Medicine ELLEN A. EISEN, Professor, School of Public Health, University of California, Berkeley MEREDITH FRANKLIN, Associate Professor, Division of Biostatistics, Keck School of Medicine, University of Southern California; Director of MS Programs in Biostatistics, Health Data Sciences, and Epidemiology KIRK D. JONES, Clinical Professor, University of California, San Francisco MEREDITH C. McCORMACK, Associate Professor of Medicine and Medical Director, Pulmonary Function Laboratory, Johns Hopkins University; Vice Chair, American Thoracic Society Committee for Proficiency Standards in Pulmonary Function Testing CECILE S. ROSE, Professor of Medicine, National Jewish Health, Division of Environmental and Occupational Health Sciences, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine FRANK E. SPEIZER, Professor of Environmental Science, Harvard T.H. Chan School of Public Health, Edward H. Kass Distinguished Professor of Medicine, Harvard Medical School ELAINE SYMANSKI, Professor, Center for Precision Environment Health, Department of Medicine, Baylor College of Medicine SVERRE VEDAL, Professor Emeritus, Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington JODY WIREMAN, Environmental Health Advisor, Defense Health Agency Study Staff DAVID A. BUTLER, Scholar and Study Director ELIZABETH BARKSDALE BOYLE, Program Officer CHRISTINA R. SAMUEL, Research Associate REBECCA F. CHEVAT, Senior Program Assistant ANNE N. STYKA, Senior Program Officer KRISTIN E. WHITE, Associate Program Officer ROSE MARIE MARTINEZ, Senior Director, Board on Population Health and Public Health Practice v

Reviewers This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspec- tives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, 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 thank the following individuals for their review of this report: GEORGIANA BROOKE ANDERSON, Colorado State University VICTORIA CASSANO, Performance Medicine Consulting, LLC CAROLYN COMPTON, Arizona State University SARAH C. R. ELGIN, Washington University in St. Louis DIANE GOLD, Harvard University PHILIP I. HARBER, University of Arizona HOWARD KIPEN, Rutgers University School of Public Health PETROS KOUTRAKIS, Harvard University CARRIE A. REDLICH, Yale School of Medicine RICHARD B. SCHLESINGER, Pace University Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report, nor did they see the final draft before its release. The review of this report was overseen by SANDRO GALEA, Boston University School of Public Health, and DAVID A. SAVITZ, Brown University. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies. vii

Acknowledgments The committee could not have written this report without the help of a number of people. We wish to par- ticularly thank the presenters and participants in our October 2019 workshop—listed in Appendix A—who shared their expertise and perspectives on respiratory health issues in veterans and the research that might allow a better understanding of them. Drs. R. Loren Erickson and Eric Shuping of the Department of Veterans Affairs also briefed the committee and responded to our follow-up questions. The committee members are very appreciative of the outstanding efforts of the staff of the National Acad- emies of Sciences, Engineering, and Medicine’s Health and Medicine Division, who supported us in our work, David Butler, who served as study director; and Elizabeth Boyle, Christina Samuel, Anne Styka, Kristin White, and Stephanie Hanson, who had a daunting task of identifying and culling the large and complex literature we reviewed and more generally guiding and assisting the committee in its mission. We are also very grateful to Rebecca Chevat for capably providing logistical support. Finally, we would like to acknowledge Jorge Mendoza, a senior research librarian who conducted the literature searches for the committee, and Misrak Dabi, the financial business partner for the project. Mark J. Utell, Chair Committee on the Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations ix

Contents ACRONYMS AND ABBREVIATIONS xiii SUMMARY 1 1 INTRODUCTION 11 U.S. Deployments to the Southwest Asia Theater, 12 Aftermath of Southwest Asia Theater Deployment, 14 Charge to the Committee, 18 Committee’s Approach to Its Charge, 18 Organization of the Report, 19 References, 20 2 AIRBORNE HAZARDS IN SOUTHWEST ASIA 23 Exposures Associated with Military Operations in the Southwest Asia Theater, 25 Regional Environmental Exposures, 29 Occupational Exposures, 36 Exposure Tracking by the Department of Defense, 36 Factors That May Lead to Increased Vulnerability to Airborne Hazards, 36 Final Observations on Airborne Hazards, 38 References, 38 3 EVALUATION OF THE EVIDENCE BASE AND BACKGROUND OF MAJOR STUDIES AND COHORTS 43 Identification and Screening of Literature, 43 Evaluation Process, 48 Background on Epidemiologic Studies and Populations, 52 References, 74 xi

xii CONTENTS 4 EVALUATION OF RESPIRATORY OUTCOMES 81 Respiratory Symptoms, 82 Upper Airway Disorders, 98 Pulmonary Function Testing, 107 Lower Airway Disorders, 116 Respiratory Cancers, 170 Mortality, 174 Final Observations, 181 References, 181 5 CHALLENGES AND OPPORTUNITIES FOR ADVANCING THE UNDERSTANDING OF RESPIRATORY HEALTH ISSUES IN SOUTHWEST ASIA THEATER VETERANS 193 Issues Identified for the Committee’s Attention, 193 Hazards Associated with Burn Pit Exposures, 194 Knowledge Gaps, 199 Research That Could Feasibly Be Conducted, 202 Newly Emerging Technologies to Address Knowledge Gaps, 216 Organizations That the Department of Veterans Affairs Might Partner with to Address Knowledge Gaps, 218 References, 224 APPENDIXES A PUBLIC MEETING AGENDAS 235 B NATIONAL ACADEMIES REPORTS RELATED TO GULF THEATER VETERANS’ HEALTH 239 C EPIDEMIOLOGIC STUDIES OF RESPIRATORY HEALTH OUTCOMES IN SOUTHWEST ASIA THEATER VETERANS NEWLY REVIEWED BY THE COMMITTEE 243 D COMMITTEE MEMBER AND STAFF BIOGRAPHICAL SKETCHES 249

Acronyms and Abbreviations AEP acute eosinophilic pneumonia AFRL Air Force Research Laboratory AH&OBP Airborne Hazards and Open Burn Pit AHBPCE VA Airborne Hazards and Burn Pits Center of Excellence AHCE Airborne Hazards Center of Excellence ARDS acute respiratory distress syndrome ATS American Thoracic Society BALF bronchoalveolar lavage fluid BMI body mass index CARC chemical agent resistant coating CBRNE Chemical, Biological, Radiological, Nuclear, and high yield Explosives CDC Centers for Disease Control and Prevention CDMRP Congressionally Directed Medical Research Programs CHAI Comparative Health Assessment Interview CHPPM U.S. Army Center for Health Promotion and Preventive Medicine CI confidence interval CMS Centers for Medicare & Medicaid Services COPD chronic obstructive pulmonary disease CT computed tomography DARPA Defense Advanced Research Projects Agency DECAMP Detection of Early Lung Cancer Among Military Personnel DHA Defense Health Agency DHB Defense Health Board DL/VA the ratio of DLCO to alveolar volume DLCO diffusing capacity of the lung to carbon monoxide DMDC Defense Manpower Data Center xiii

xiv ACRONYMS AND ABBREVIATIONS DMSS Defense Medical Surveillance System DoD Department of Defense DoDSR Department of Defense Serum Repository DOEHRS-IH Defense Occupational and Environmental Health Readiness System–Industrial Hygiene DSRR directly standardized relative risk DU depleted uranium ECG electrocardiogram ECRHS European Community Respiratory Health Survey EHR electronic health record EPA Environmental Protection Agency EPMSP Enhanced Particulate Matter Surveillance Program ERS European Respiratory Society ESA European Space Agency FEF forced expiratory flow FEV forced expiratory volume FEV1 forced expiratory volume in 1 second FOT forced oscillation technique FRC functional residual capacity FVC forced vital capacity GINA Global Initiative for Asthma GM-CSF granulocyte-macrophage colony-stimulating factor GOLD Global Initiative for Chronic Obstructive Lung Disease HR hazard ratio HYSPLIT Hybrid Single Particle Lagrangian Integrated Trajectory ICD-9-CM International Classification of Diseases, Ninth Edition, Clinical Modification IgA immunoglobulin A IIP idiopathic interstitial pneumonia ILER Individual Longitudinal Exposure Record IOM Institute of Medicine IOS impulse oscillometry IPF idiopathic pulmonary fibrosis IR incidence rate IRB institutional review board IRR incidence rate ratio JPC Joint Pathology Center LCI lung clearance index LLN lower limit of normal LTBI latent tuberculosis infection MAIA Multi-Angle Imager for Aerosols MeSH medical subject heading miRNA micro RNA MISR Multi-angle Imaging SpectroRadiometer

ACRONYMS AND ABBREVIATIONS xv MODIS Moderate Resolution Imaging Spectroradiometer MOS military occupational specialty MRE meals, ready-to-eat MRR mortality rate ratio n population size NAAQS National Ambient Air Quality Standards NAS National Academy of Sciences NASA National Aeronautics and Space Administration n.d. no date NewGen National Health Study for a New Generation of U.S. Veterans NF-κB nuclear factor kappa B NHANES National Health and Nutrition Examination Survey NHLBI National Heart, Lung, and Blood Institute NHS National Health Survey of Gulf War Veterans and Their Families NIEHS National Institute of Environmental Health Sciences NIH National Institutes of Health NIOSH National Institute for Occupational Safety and Health NOAA National Oceanic and Atmospheric Administration NRC National Research Council OEF Operation Enduring Freedom OIF Operation Iraqi Freedom OMI Ozone Mapping Instrument OND Operation New Dawn OR odds ratio p p-value PAH polycyclic aromatic hydrocarbon PAP pulmonary alveolar proteinosis PCB polychlorinated biphenyl PCDD/F polychlorinated dibenzo-p-dioxin and dibenzo-p-furan PDF portable document format PET positron emission tomography PFT pulmonary function test pIgR polymeric immunoglobulin receptor PIR proportional incidence ratio PL Public Law PM particulate matter POEMS periodic occupational and environmental monitoring summary PTSD posttraumatic stress disorder RAC Research Advisory Committee on Gulf War Veterans’ Illnesses Raw airways resistance RD rate difference RFI request for information RR rate ratio RV residual volume SHADE Service and Health Among Deployed Veterans

xvi ACRONYMS AND ABBREVIATIONS SIR standardized incidence ratio SMR standardized mortality ratio SPIROLA Spirometry Longitudinal Data Analysis SSIC signs, symptoms, and ill-defined conditions STAMPEDE Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures TB tuberculosis TBI traumatic brain injury TLC total lung capacity TSP total suspended particles VA Department of Veterans Affairs VHA Veterans Health Administration VO2 volume of oxygen (O2) VOC volatile organic compound WHO World Health Organization WRIISC VA War Related Illness and Injury Study Center

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More than 3.7 million U.S. service members have participated in operations taking place in the Southwest Asia Theater of Military Operations since 1990. These operations include the 1990-1991 Persian Gulf War, a post-war stabilization period spanning 1992 through September 2001, and the campaigns undertaken in the wake of the September 11, 2001, attacks. Deployment to Iraq, Kuwait, Saudi Arabia, Bahrain, Gulf of Aden, Gulf of Oman, Oman, Qatar, the United Arab Emirates, and Afghanistan exposed service members to a number of airborne hazards, including oil-well fire smoke, emissions from open burn pits, dust and sand suspended in the air, and exhaust from diesel vehicles. The effects of these were compounded by stressors like excessive heat and noise that are inevitable attributes of service in a combat environment.

Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations reviews the scientific evidence regarding respiratory health outcomes in veterans of the Southwest Asia conflicts and identifies research that could feasibly be conducted to address outstanding questions and generate answers, newly emerging technologies that could aid in these efforts, and organizations that the Veterans Administration might partner with to accomplish this work.

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