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 the Southwest Asia theater—which for the purposes of this report is defined as Iraq, Kuwait, Saudi Arabia, the neutral zone between Iraq and Saudi Arabia, Bahrain, Gulf of Aden, Gulf of Oman, Oman, Qatar, the United Arab Emirates, and the waters of the Persian Gulf, the Arabian Sea, and the Red Sea—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.
During and after the initial Gulf conflict, veterans began reporting a variety of health problems. In response to the concerns raised, Congress has passed laws mandating the study of health outcomes in theater veterans, and the Department of Defense (DoD) and the Department of Veterans Affairs (VA) have undertaken their own initiatives to address outstanding questions.
In September 2018, VA requested the National Academies of Sciences, Engineering, and Medicine to form an expert committee to undertake a study of the evidence regarding respiratory health outcomes in veterans of the Southwest Asia conflicts and to identify gaps in this evidence, 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 VA might partner with to accomplish this work. Its full Statement of Task is reproduced as Box S-1. This report, prepared by the Committee on the Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations, provides responses to the elements of that task.
The committee formed to address VA’s charge comprised 11 experts in epidemiology, pulmonology, pathology, exposure assessment, military and veterans’ health, and toxicology. It held five in-person meetings between March 2019 and February 2020; additional, later meetings were conducted remotely. One meeting included a workshop where the investigators involved in the epidemiologic studies named in the Statement of Task were invited to give updates on their work and other experts presented the latest scientific and medical developments regarding
respiratory health, airborne exposure assessment, and exposure characterization research. Veterans and veteran service organization representatives also presented their views.
Several other activities were undertaken to develop the scientific foundation for the report’s findings, conclusions, and recommendations. These included detailed searches of the published peer-reviewed literature dating back to 1991, requests for information from VA and from authorities in the fields under consideration, and examination of additional pertinent publicly available literature, including relevant National Academies reports. This report builds on earlier literature reviews published as part of the Gulf War and Health series of National Academies reports—in particular, Volume 4: Health Effects of Serving in the Gulf War; Volume 8: Update of Health Effects of Serving in the Gulf War; and Volume 10: Update of Health Effects of Serving in the Gulf War, 2016—as well as two related reports: Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan and Assessment of the Department of Veterans Affairs Airborne Hazards and Open Burn Pit Registry.
THE COMMITTEE’S APPROACH TO ANALYZING THE AVAILABLE INFORMATION
The committee’s literature review was a targeted examination of epidemiologic studies of respiratory health outcomes—including excess mortality due to respiratory disease—in military and veteran populations potentially exposed to airborne hazards in the Southwest Asia theater. It was focused on studies of these populations that had not been previously summarized in earlier National Academies reports. The committee considered whether there were any other non-military population groups that might provide supplemental information but concluded that the differences in the airborne exposures encountered by such groups—specifically, differences in the composition
of the chemical agents and particulates and in the duration, intensity, and other circumstances of exposure—were too great to justify their use in evaluations of the health effects of military service in Southwest Asia.
Toxicologic studies, which include studies of laboratory animals and cell cultures, focus on mechanisms rather than clinical outcomes. As such these studies were included as supplemental sources of information where relevant, but they were not reviewed in a comprehensive manner as the epidemiologic literature was.
The committee’s evaluation of the evidence considered the extent to which a particular study was well designed and methodologically sound. This included whether it specifically examined respiratory health outcomes; identified an appropriate comparison group; had an adequate sample size and power to detect an effect if one existed; characterized the airborne exposure(s) it considered as thoroughly as the available data permitted; performed rigorous health outcome assessment based, to the extent possible, on objective measures and tests over an appropriate time period; ascertained and factored known and potential confounders; and used appropriate statistical analyses. All of these considerations were taken in account when weighing how much a study should contribute to the committee’s overall evaluation of the literature base.
Categories of Association
A system of four categories of association was used to classify the strength of scientific evidence of respiratory health outcomes following exposure to airborne hazards in the Southwest Asia theater. These categories were adapted from a system used by the International Agency for Research on Cancer. They have gained wide acceptance by Congress, VA, researchers, and veterans groups and have been used in several previous National Academies reports addressing health issues for veterans of the Southwest Asia theater conflicts and Vietnam. The criteria for each of the four categories of association define a degree of confidence with which a conclusion can be drawn based on the extent to which bias and other sources of error could be reduced and thus on the quality of the evidence. Implicit in these categories is the idea that “the absence of evidence is not evidence of absence.” That is, based on the currently available literature that met the committee’s criteria for inclusion, a lack of informative data does not mean that there is no increased risk of a specific adverse event, only that the available evidence does not allow a conclusion to be drawn regarding an association.
The committee considered the full body of available information, including supplemental evidence, when reaching a judgment about association for a given outcome. Where the literature base allowed, separate conclusions were made for 1990–1991 Gulf War veterans and post-9/11 veterans. Four categories of association were used to classify outcomes.
For effects to be classified as having “sufficient evidence of an association,” a positive association between one or more in-theater airborne exposures and a respiratory health outcome in humans must have been observed in studies in which chance, bias, and confounding can be ruled out with reasonable confidence.
For health outcomes in the category of “limited or suggestive evidence of an association,” the evidence must suggest an association between an in-theater exposure and a respiratory outcome in studies of humans, but it can be limited by an inability to confidently rule out chance, bias, or confounding. Because there are a number of agents of concern whose toxicity proﬁles are not expected to be uniform—speciﬁcally, the many airborne hazards that may be encountered in theater—apparent inconsistencies can be expected among study populations that have experienced different exposures.
By default, any health outcome is placed in the category of “inadequate or insufﬁcient evidence to determine an association” unless enough reliable scientiﬁc data have accumulated to categorize it elsewhere. In this category, the available human studies of exposure to airborne hazards in the Southwest Asia theater and respiratory conditions may have inconsistent ﬁndings or be of insufﬁcient quality, validity, consistency, or statistical power to support a conclusion regarding the presence of an association. Such studies might have failed to control for confounding factors (such as smoking) or might have had an inadequate assessment of exposure. In some cases, the body of evidence is too small to permit firm conclusions, such as when there are no available studies to validate or corroborate the findings of a single study. In other cases, some evidence from human studies exists, but the heterogeneity of exposures, outcomes, and methods leads to inconsistent findings that preclude a more
definitive conclusion. If a respiratory condition or outcome is not addressed specifically in this report, then it can be considered to be in this category.
The category of “limited or suggestive evidence of no association” is used for health outcomes for which several adequate studies covering the full range of human exposure were consistent in showing no association or a reduced risk with an exposure to airborne hazards encountered in the Southwest Asia theater at any concentration, with the studies having relatively narrow conﬁdence intervals. A conclusion of “no association” is inevitably limited to the conditions, exposures, and observation periods covered by the available studies, and the possibility of a small increase in risk related to the magnitude of exposure studied can never be excluded.
AIRBORNE HAZARDS ENCOUNTERED IN THE SOUTHWEST ASIA THEATER
Southwest Asia theater veterans were exposed to a broad range of potentially hazardous airborne agents. These include such regional environmental exposures as air pollution from dusts; local point and area sources such as traffic, waste management, and local industries; and the aeroallergens and microbial agents present in the theater. Exposures related to military operations are also contributors, such as exhaust from heaters, military vehicles, and aircraft as well as smoke from structural fires, explosions, burning oil wells, or burn pits. One of these exposures, particulate matter, has received special attention because a growing body of literature suggests that it is associated with a number of adverse respiratory and other health effects. Additionally, some service members had occupations, job duties, or tasks that exposed them to a variety of vapors, gases, dusts, and fumes. Exposures differed by conflict and varied by location and over time. For example, 1990–1991 Gulf War veterans are more likely to have been exposed to smoke from oil-well fires, which were set by Iraqi forces as they retreated. In 2003 a fire ignited at the Mishraq State Sulfur Mine Plant near Mosul, Iraq, and burned for almost 1 month, releasing high concentrations of sulfur dioxide and hydrogen sulfide into the surrounding area. Veterans of the post-9/11 conflicts are more likely to have been exposed to emissions from burn pits, which were in operation for extended periods on bases where large numbers of personnel worked and lived.
The health effects of these airborne hazards were likely influenced by factors common to military operations in Southwest Asia. These effect modifiers include temperature extremes, psychosocial stress, sleep deprivation, and noise.
CONCLUSIONS REGARDING THE ASSOCIATION BETWEEN IN-THEATER AIRBORNE HAZARDS AND RESPIRATORY HEALTH OUTCOMES
The committee formulated a list of 27 health outcomes for their literature review, delineated in Box S-2. The list included the conditions explicitly listed in the Statement of Task and those that the committee believed to be “of great concern to veterans.”
Of these outcomes, none met the criteria for sufficient evidence of an association. The evidence for respiratory symptoms—which included chronic persistent cough, shortness of breath (dyspnea), and wheezing—met the criteria for limited or suggestive evidence of an association for both veterans who served in the 1990–1991 Gulf War and those who served in the post-9/11 conflicts. Studies considered in previous National Academies reports were relatively consistent in reporting associations between deployment and more prevalent self-reported respiratory symptoms in theater veterans, and outcomes from more recent studies are largely in line with those findings. Importantly, a recent study that compared symptom reporting before, during, and after deployment found that the self-reported frequency of symptoms was increased both during and after deployment relative to pre-deployment.1 Many of the studies considered, however, were weakened by bias induced by the self-selection of their participants (which may have led to people being more likely to participate if they had respiratory symptoms than if they did not) and by the lack of control for cigarette smoking, which is known to exacerbate symptoms. These concerns, while serious, were consistent with a classification in the limited or suggestive category. Lastly, the committee
1 Morris, M. J., A. J. Skabelund, F. A. Rawlins III, R. A. Gallup, J. K. Aden, and A. B. Holley. 2019. Study of Active Duty Military Personnel for Environmental Deployment Exposures: Pre- and Post-Deployment Spirometry (STAMPEDE II). Respiratory Care 64(5):536–544.
concluded that there is limited or suggestive evidence of no association between deployment to the 1990–1991 Gulf War and changes in lung function.
The committee found that there was inadequate or insufficient information to evaluate the association between service in the Southwest Asia theater and all of the remaining respiratory health outcomes it examined. While there are a variety of reasons for this that vary by the outcome under consideration, one prominent cause was the lack of good exposure characterization. Many studies used deployment to the theater as their only metric of exposure, and this undoubtedly led to people with widely different exposure experiences being grouped together for analysis purposes. Such grouping would be expected to diminish the possibility of observing an effect if one existed if there were large numbers of those with relatively low exposure compared with those with relatively high exposure.
Another reason for conclusions of inadequate or insufficient evidence of associations was the widespread use of self-reported health outcomes and exposures. In the military deployment setting, this can be an issue if, for example, those who have a respiratory health problem are more likely to recall airborne exposures than those who do not or, alternatively, if those who experienced airborne exposures are more likely to report a respiratory health problem.
CHALLENGES AND OPPORTUNITIES FOR ADVANCING THE UNDERSTANDING OF RESPIRATORY HEALTH ISSUES IN SOUTHWEST ASIA THEATER VETERANS
The committee’s Statement of Task requested it to “pay particular attention to hazards associated with burn pit exposures” and to use the results of its comprehensive review to “identify knowledge gaps, research that could feasibly be conducted to inform the field and generate answers, newly emerging technologies that could aid in these efforts, and organizations that VA might partner with to accomplish this work.” Its information-gathering efforts included extensive efforts to develop information that would inform responses to these queries.
Hazards Associated with Burn Pit Exposures
Concerns have long been raised over the hazards associated with exposure to emissions from the open burn pits used in theater for waste management. These exposures have been the primary topic of earlier National Academies reports and are the focus of VA’s Airborne Hazards and Open Burn Pit Registry effort, which had more than 200,000 participants as of spring 2020. Concern over burn pit exposures is understandable, given their prominence as a source of smoke and fumes in military facilities where large numbers of service members were present and the known toxic effects of the byproducts of combustion of the materials that were burned in them. However, an examination of the literature on the topic reveals that there is very little evidence addressing how hazards associated with burn pit exposures may result in adverse respiratory health outcomes, and the epidemiologic literature to date has not found an association. The committee believes that existing research efforts on the health of theater personnel are inadequate to shed light on this question and that bringing resolution to the issue will require new research addressing the existing efforts’ deficiencies—such as the study approach for evaluating the health effects of burn pit exposures at the former Joint Base Balad in Iraq proposed in the 2011 Institute of Medicine report Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan—in combination with various advances such as the identification and use of biomarkers of burn pit exposures.
Knowledge Gaps and Research That Could Feasibly Be Conducted to Address Them
The committee identified a large number of gaps in the current information base regarding respiratory health outcomes in the population of veterans who served in the Southwest Asia theater. These can be grouped as gaps in knowledge concerning adverse respiratory health outcomes in theater veterans, gaps in knowledge concerning in-theater airborne exposures, and gaps in knowledge about the biologic and toxicologic effects of in-theater airborne exposures. There are three circumstances where the committee offers recommendations for actions by VA.
The first concerns constrictive bronchiolitis, a disorder that includes several small airway diseases that are defined by the presence of bronchiolar inflammation, fibrosis, or both. The interpretation of lung biopsies for constrictive bronchiolitis has proven to be controversial, leading to uncertainty over the diagnoses of veterans exposed to airborne agents encountered in the Southwest Asia theater. Given the interest surrounding the question of whether in-theater exposures may be responsible for an increase in the prevalence of constrictive bronchiolitis in veterans of these conflicts, the committee concludes that actions to resolve this issue should be given a high priority by VA. Much of the current debate regarding the prevalence of constrictive bronchiolitis is the result of uncertainty and disagreement over the interpretation of the pathologic findings in symptomatic individuals. In order to better manage these circumstances, the committee recommends that VA establish an expert panel to advise it on issues related to the diagnosis of constrictive bronchiolitis in veterans and its possible relationship to military service. This panel should be external to VA and should include members with a range of expertise, including expertise in such areas as pulmonary medicine, toxicology, epidemiology, exposure assessment, and radiology, but with the primary membership consisting of experienced pulmonary pathologists. Veterans should also be part of the panel.
The expert advisory panel would be charged with developing specific guidelines for the evaluation of symptomatic Southwest Asia theater–deployed veterans in whom the differential diagnosis includes constrictive bronchiolitis. Its short- and longer-term tasks would include
- Determination of the adequacy of various lung biopsy approaches for the diagnosis of constrictive bronchiolitis and recommendations for best practices.
- Development of recommendations for consistently processing, handling, and storing lung biopsy materials.
- Development of consistent histologic/pathologic criteria to be used for confirming a diagnosis of constrictive bronchiolitis in theater veterans with suspected cases who present at a VA facility or who apply for disability compensation for the disease.
- Review—by the pathology working group within the panel—of biopsy slides from cases in which the issue of a diagnosis of constrictive bronchiolitis related to service has been raised. This review should not be limited to controversial cases but instead be applied to all such cases that fall under VA’s areas of responsibility. The working group should be charged with providing a written summary report of each case in a timely manner.
- Establishment of criteria for the evidence base for determining whether an association exists between a veteran’s military service and constrictive bronchiolitis, including the types and sources of information that could be considered.
- Recommendations for the research that would help resolve outstanding questions regarding constrictive bronchiolitis in veterans.
- Revision of the guidelines as new evidence becomes available.
The committee recognizes that the creation of this advisory committee and its role in peer review is not without controversy or cost, but it believes that such a committee is critical to ensuring that VA has a consistent approach in establishing or denying a diagnosis and evaluating its possible service connection. The presence of such a committee should also reassure veterans that they are receiving a fair review that uses the best science.
A second knowledge gap that could be filled by appropriate research concerns the question of whether Southwest Asia theater veterans are experiencing excess mortality from respiratory diseases. The committee’s review of the literature found that the most recently published mortality study of 1990–1991 Gulf War veterans, which included death due to chronic obstructive pulmonary disease and from respiratory system diseases in general, used 2004 as its cutoff date, while the last salient study of post-9/11 veterans who had been deployed to the theater was generated using data from 2011 and offered no breakout of respiratory disease mortality. It is important to revisit this issue in order to identify whether there are respiratory health outcomes that warrant more intense study or surveillance of this population. Therefore, the committee recommends that an updated analysis of mortality in Southwest Asia theater veterans be conducted. Future mortality studies need to be based on analyses that compare higher- and lower-exposed veterans, rather than analyses comparing all veterans to the general population. This in turn will require that a retrospective exposure assessment be included so that the study can produce useful estimates of exposure-related mortality risk. An informative new study to determine whether there is excess mortality in deployed veterans should also consider not just the cause of death and contributing causes of death but also other underlying health conditions that might not be listed as a cause or contributing cause of death but that might confound an association as well as detailed demographic and service information on the veterans and their circumstances of deployment.
The third area where action by VA could fill a knowledge gap involves taking advantage of existing DoD and VA health record integration efforts. DoD and VA have been working toward a modernized and interoperable electronic health record (EHR) since at least 2013, and those efforts are scheduled to come to fruition in summer 2020 when such a system will be rolled out at some initial test sites. An integrated system such as this—in addition to its primary goal of facilitating a secure and seamless transfer of the medical records of active-duty service members as they transition to veteran status—has the potential to enable investigators, with proper human subjects assurances, to far more easily access these data for research purposes. An integrated EHR system would also simplify the monitoring of respiratory health status (including lung function) over time, which is needed for investigations of outcomes that have long latency periods.
In order to accomplish these objectives, the committee recommends that VA and DoD explicitly integrate research access considerations into their planning as they refine the implementation of their new interoperable electronic health record system. The committee further suggests that, as part of this effort, VA and DoD commit resources to developing a database of research study data derived from the integrated records. Data integration is still at a relatively early stage, and it is important for VA to be planning now for how it might use the information derived from EHRs so that it can properly configure the system for access.
In addition, the committee identified a number of more general opportunities for advancing knowledge regarding respiratory outcomes in theater veterans for VA’s consideration as it establishes its overall health research agenda. Among these are opportunities for promoting research on biomarkers of effect, exposure, and susceptibility, which would allow better characterization of exposures and health status by establishing objective measures. Recent advances in the analysis of satellite data are allowing retrospective estimates of airborne particulates concentrations that may in turn make possible more accurate estimates of exposures of deployed personnel. VA is already sponsoring some work in these areas and will benefit from the information derived from it.
Newly Emerging Technologies to Address Knowledge Gaps
In addition to the aforementioned newly emerging technologies related to biomarker discovery and measurement and advances in remote measurement and estimation of airborne pollutants via satellites, the committee thought it appropriate to touch on some of the new technologies that might be brought to bear to gather information during active duty that would aid in the future evaluation of airborne exposures and health outcomes by VA. In particular, the committee points to three efforts. The first is silicone wristbands for exposure detection, a nascent technology that might allow for individual-level exposure information derived from an easily worn device. There have already been proof-of-concept studies suggesting that these wristbands may have utility. Second, DoD is in the initial stages of sponsoring research on low-cost technologies that could be used to support real-time health risk assessment and mitigation decision making and to generate data that could be made a part of individual longitudinal exposure records. Third, a separate DoD effort is aimed at developing a field-deployable epigenome “reader” for the real-time evaluation of exposures.
The challenge is that any technology, no matter how effective or well-intentioned it is, will take a back seat to the exigencies of operating in the field. It will not gain acceptance unless it can be seamlessly incorporated into operations, can be used in a way that does not encumber or otherwise limit personnel, and does not compromise their security. That said, there appear to be multiple technologies that hold the promise of developing information on active-duty personnel that would later aid VA in its evaluation of the health effects of military exposure to airborne agents. While it will be the responsibility of DoD to develop and deploy these technologies and to gather and maintain the information they generate, VA has a role to play in defining the type and form of that information that would be most useful, fostering studies that take advantage of the information to better understand health outcomes in veterans, and keeping abreast of advancements in domains that they do have responsibility for, such as patient care that might feed into exposure technology development.
Organizations That the Department of Veterans Affairs Might Partner with to Address Knowledge Gaps
A number of federal agencies, investigators in the United States and abroad, and other governmental and private-sector organizations are currently conducting research relevant to theater veterans’ health or else have information that could improve the conduct of such work. The committee offers one specific recommendation for VA regarding partnering. It identifies a broad range of organizations that have potentially useful exposure or health information that VA should consider collaborating with in order to address specific needs and pursue new research opportunities.
The specific recommendation concerns DoD, an organization that VA already partners extensively with on issues related to the effects of occupational and environmental exposures on military and veteran health. The partnerships include VA’s work with the Defense Health Agency, with which VA collaborates on the individual
longitudinal exposure record, a web-based application that provides DoD and VA with the ability to link information on an individual to military exposures and health information. DoD maintains or supports a number of biorepositories that store materials of potential utility to studies of respiratory health outcomes in theater veterans, including biomarkers research. And two research organizations—the Air Force Research Laboratory and the Defense Advanced Research Projects Agency—conduct or support research relevant to the evaluation of the effects of airborne exposures. VA’s existing collaborations with DoD are yielding benefits for both service members and veterans in the form of information that can be used to identify, manage, and cope with potentially harmful exposures. The committee recommends that VA continue and expand its partnership with DoD on environmental health issues, focusing on the free flow of information on exposures encountered during military service and on the health of personnel before, during, and after deployment and after transition to veteran status. This partnership should include cooperation on identifying which respiratory health status information should be gathered during active duty for later use as baseline data in evaluating veterans’ health for treatment, benefits, and research purposes.
The committee also notes that other federal agencies, including the National Aeronautics and Space Administration, National Oceanic and Atmospheric Administration, National Institute of Environmental Health Sciences, and National Institute for Occupational Safety and Health, hold data and conduct research on airborne exposures. Much of this work addresses particulate matter, a well-established airborne hazard.
Although most of the committee’s conclusions regarding health outcomes fall under the category of “inadequate or insufﬁcient evidence to determine an association,” it wishes to emphasize that this should not be interpreted as meaning that there is no association between respiratory health outcomes and deployment to Southwest Asia, but rather that the available data are, on the whole, of insufficient quality to make a scientific determination. Existing studies suffer from limitations in
- exposure estimation;
- the availability of pertinent health, physiologic, behavioral, and biomarker data, especially data collected both pre- and post-deployment;
- the amount of time that has passed since exposure; and
- the use of additional or alternate sources of data that might enrich analyses.
Given these limitations, the committee concludes that a new approach is needed that will allow researchers to better examine and answer the question of whether certain respiratory outcomes are associated with deployment. This new approach is not one that is intended to reprise the common theme of “more research is needed” or to suggest that the only alternative is to undertake work that will take many years to bear fruit. Rather, well-conducted epidemiologic studies are possible today using retrospective designs that better account for confounding factors such as smoking habits, combine and analyze existing data in innovative ways, standardize outcome ascertainment methods to allow for better comparability of results, and improve the estimation of exposure.
While burn pit–related research will certainly be a part of this work, it will likely be challenging to attribute specific respiratory effects to this exposure alone. The more important question is whether deployment to the Southwest Asia theater—with all of the hazardous airborne exposures it entailed—may be responsible for adverse respiratory outcomes. The report’s observations, conclusions, and recommendations identify not just the existing knowledge gaps but the many means that VA and the organizations that it can partner with inside and outside the government have for addressing them and providing veterans with the health information they need.
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