The wars in Iraq and Afghanistan have become known for the enemy’s reliance on improvised explosive devices (IEDs). It has been estimated that explosive weaponry accounts for 75% of all US military casualties.1 Since 2001, about 1,380 US soldiers in the Afghanistan War have been killed in action and 9,813 wounded in action because of IEDs. From March 2003 to November 2011, about 2,209 US soldiers in the Iraq war have been killed in action and 21,743 wounded in action due to IEDs.2,3 Note that those numbers reflect only service members who have been killed or wounded in action; it is likely that many others are exposed to blast in the combat environment but do not require immediate medical attention and, therefore, are not reflected in the numbers reported.
Explosions may cause five major patterns of injury—primary, secondary, tertiary, quaternary, and quinary. Primary blast injury is caused by the blast wave itself, secondary injury is caused by fragments of debris propelled by the explosion, tertiary injury is due to the acceleration of the body or part of the body by the blast wave or blast wind, quaternary injuries include all other injuries directly caused by a blast but not classified by another mechanism (for example, burns, toxic-substance exposures,
1Belmont, P. J., A. J. Schoenfeld, and G. Goodman. 2010. Epidemiology of combat wounds in Operation Iraqi Freedom and Operation Enduring Freedom: Orthopaedic burden of disease. Journal of Surgical Orthopaedic Advances 19(1):2-7.
3Global War on Terrorism Casualties by Reason. http://siadapp.dmdc.osd.mil/personnel/CASUALTY/gwot_reason.pdf (accessed September 1, 2013).
and psychologic trauma), and quinary injuries are illnesses or diseases that result from chemical, biologic, or radiologic substances released by a bomb.
The Department of Veterans Affairs (VA) is concerned about the long-term health effects of exposure to blast. Therefore, it asked that the Institute of Medicine (IOM) conduct a study to assess the relevant scientific information and draw conclusions regarding the strength of the evidence of an association between exposure to blast and health effects. The IOM also was asked to make recommendations for future research on the topic. The IOM appointed the Committee on Gulf War and Health: Long-Term Effects of Blast Exposures to address that task. The specific charge to the committee states that
the IOM shall comprehensively review, evaluate, and summarize the available scientific and medical literature associated with the multisystem response to blast exposures and subsequent acute and long-term health consequences among Gulf War Veterans. In making determinations, the committee shall consider
a. The strength of scientific evidence, the replicability of results, the statistical significance of results, and the appropriateness of the scientific methods used to detect the association;
b. In any case where there is evidence of an apparent association, whether there is reasonable confidence that the apparent association is not due to chance, bias, or confounding;
c. The increased risk of illness among human or animal populations exposed to blast injuries;
d. Whether a plausible biological mechanism or other evidence of a causal relationship exists between exposure to blast and long-term systemic adverse health effects;
e. Whether type of blast (for example, shaped blast wave vs diffuse) is associated with injury pattern; and
f. Whether improvements in collective and personal blast protection are associated with diminished blast injury.
In evaluating the long-term health effects of blast exposures among Gulf War Veterans, the committee should look broadly for relevant information. Information sources to pursue could include but are not limited to
a. Published peer-reviewed literature related to blast injuries among the 1991 Gulf War Veteran population;
b. Published peer-reviewed literature related to blast injuries in active-duty service members and veterans who served in the Iraq and Afghanistan wars, and other conflicts as appropriate;
c. Published peer-reviewed literature related to blast injuries among similar populations such as allied military personnel; and
d. Published peer-reviewed literature related to blast injuries in other populations.
THE GULF WAR AND HEALTH SERIES
The present volume is part of an IOM series on health effects related to military service during wartime. The series began in 1998 when, in response to the growing concerns of ill Gulf War veterans, Congress passed two laws: Public Law (PL) 105-277, the Persian Gulf War Veterans Act, and PL 105-368, the Veterans Programs Enhancement Act. Those laws directed the secretary of veterans affairs to enter into a contract with the National Academy of Sciences to review and evaluate the scientific and medical literature regarding associations between illness and exposure to toxic agents, environmental or wartime hazards, and preventive medicines or vaccines associated with Gulf War service and to consider the resulting conclusions when making decisions about compensation. The study was assigned to the IOM, and eight volumes have been published.4
The legislation did not preclude an IOM recommendation or a VA request for additional studies, particularly as subjects of concern arise. For example, VA’s request that the IOM consider whether there is an increased risk of amyotrophic lateral sclerosis in all veteran populations resulted in the report Amyotrophic Lateral Sclerosis in Veterans; an examination of all health effects in veterans deployed to the 1991 Persian Gulf War irrespective of specific exposures resulted in Gulf War and Health, Volume 4: Health Effects of Serving in the Gulf War; and another VA request regarding the long-term effects of traumatic brain injury resulted in Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury. The present volume grew out of discussions with VA over concern about blast injuries and the potential long-term effects of being exposed to a blast.
HOW THE COMMITTEE APPROACHED ITS CHARGE
The committee was charged with conducting a review of the scientific literature on the association between blast and long-term health effects. The charge did not specify the type of blast injury—primary, secondary, tertiary, quaternary, and quinary—and, therefore, the committee did not attempt to limit its review to any mechanism of blast injury. In fact, many of the studies reviewed by the committee, particularly epidemiologic studies,
4Casualties. 20134 Gulf War and Health, Volume 1: Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccine; Gulf War and Health, Volume 2: Insecticides and Solvents; Gulf War and Health, Volume 3: Fuels, Combustion Products, and Propellants; Gulf War and Health, Volume 4: Health Effects of Serving in the Gulf War; Gulf War and Health, Volume 5: Infectious Diseases; Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress; Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury; and Gulf War and Health, Volume 8: Update of Health Effects of Serving in the Gulf War.
did not specify the mechanism of exposure (that is, the reported exposure was to blast generally). The review included all relevant studies of blast in any population (military, occupational, and other) and health outcomes. Thus, the committee reviewed all papers that provided information on blast and health outcomes. By examining the full array of evidence of health outcomes in different populations, the committee asked the question, Can sustaining a blast be associated with a specific health outcome?
Several literature searches were performed in 2012 and 2013 in an effort to keep current with the relevant science. The committee reviewed more than 12,800 titles and abstracts of scientific and medical articles related to blast and health outcomes. It also reviewed the full text of about 400 peer-reviewed journal articles, many of which are described in this report.
After obtaining the full-text articles, the committee needed to determine which studies to include in its evaluation. To accomplish that task, the committee developed inclusion guidelines. Studies were categorized as primary or supportive or were excluded from further examination. Primary studies had greater methodologic rigor and so provided the strongest evidence on health outcomes of blast exposure. For many health outcomes, no primary studies were identified; in these cases, supportive studies necessarily guided the committee’s determinations. Many of the studies reviewed by the committee had limitations that are commonly encountered in epidemiologic studies, including a lack of representative sample, selection bias, lack of control for potential confounding factors, self-reports of exposure and health outcomes, and outcome misclassification. Because of the inadequacy of epidemiologic literature that can inform understanding of long-term outcomes of exposure to blast, the committee relied heavily on the literature to assess the strength of the evidence on acute effects and on the collective clinical knowledge and expertise of the committee members to draw conclusions regarding the plausibility of the long-term outcomes. Some of the long-term outcomes are obvious and well documented as consequences of the acute injuries; others will require additional research studies to understand the long-term consequences of exposure specifically to blast.
To express its judgment of the available data clearly and precisely, the committee agreed to use the categories of association that have been established and used by previous committees on Gulf War and health and other IOM committees that have evaluated vaccine safety, effects of herbicides used in Vietnam, and indoor pollutants related to asthma. Those categories of association have gained wide acceptance over more than a decade by Congress, government agencies (particularly VA), researchers, and veterans’ groups. The five categories in Box S-1 describe different levels of association and sound a recurring theme: the validity of an association is likely to vary to the extent to which common sources of spurious associations can
The Categories of Association
Sufficient Evidence of a Causal Relationship
Evidence is sufficient to conclude that there is a causal relationship between blast exposure and a specific health outcome in humans. The evidence fulfills the criterion of sufficient evidence of an association (below) and satisfies several of the criteria used to assess causality: strength of association, dose–response relationship, consistency of association, temporal relationship, specificity of association, and biologic plausibility.
Sufficient Evidence of an Association
Evidence is sufficient to conclude that there is a positive association; that is, a consistent association has been observed between blast exposure and a specific health outcome in human studies in which chance and bias, including confounding, could be ruled out with reasonable confidence as an explanation for the observed association.
Limited/Suggestive Evidence of an Association
Evidence is suggestive of an association between blast exposure and a specific health outcome in human studies but is limited because chance, bias, and confounding could not be ruled out with reasonable confidence.
Inadequate/Insufficient Evidence of an Association
Evidence is of insufficient quantity, quality, consistency, or statistical power to permit a conclusion regarding the existence of an association between blast exposure and a specific health outcome in humans.
Limited/Suggestive Evidence of No Association
Evidence from several adequate studies is consistent in not showing a positive association between blast exposure and a specific health outcome. A conclusion of no association is inevitably limited to the conditions and length of observation in the available studies. The possibility of a very small increase in risk of the health outcome after exposure to blast cannot be excluded.
be ruled out as the reason for the observed association. Accordingly, the criteria for each category express a degree of confidence that is based on the extent to which sources of error were reduced. The committee discussed the evidence and reached consensus on the categorization of the evidence on each health outcome.
SUMMARY OF CONCLUSIONS
The committee’s conclusions on human health outcomes of exposure to blast and on the effectiveness of blast protection are summarized below. It is important to note that although the information here is presented by individual organ systems and other specific outcomes, exposure to blast often leads to polytrauma (multiple traumatic injuries) and a multisystem response.
Human Health Outcomes
The committee focused its formal conclusions (below) on long-term adverse health outcomes, particularly those not necessarily caused by a severe or obvious acute injury. Acute injuries to each organ system from exposure to blast are summarized in Chapter 4.
Sufficient Evidence of a Causal Relationship
- Penetrating eye injuries resulting from exposure to blast and permanent blindness and visual impairment (visual acuity of 20/40 or worse).
- Some long-term effects on a genitourinary organ—such as hypogonadism, infertility, voiding dysfunction, and erectile dysfunction—associated with severe injury, which is defined as a complete structural and functional loss that cannot be reconstructed.
Sufficient Evidence of an Association
- Development of posttraumatic stress disorder (PTSD). The association may be related to direct experience of blast or to indirect exposure, such as witnessing the aftermath of a blast or being part of a community affected by a blast.
- Endocrine dysfunction (hypopituitarism and growth hormone deficiency) in cases of severe or moderate blast-related traumatic brain injury (TBI).
- Postconcussive symptoms and persistent headache in cases of mild blast TBI.
- In non-blast severe or moderate TBI, permanent neurologic disability, including cognitive dysfunction, unprovoked seizures, and headache. These associations also are known outcomes in TBI studies that included blast and non-blast mechanisms considered together. It is plausible that severe or moderate blast TBI is simi-
- larly associated with permanent neurologic disability even though studies that specifically addressed blast TBI are lacking.
- Long-term dermal effects, such as cutaneous granulomas.
Limited/Suggestive Evidence of an Association
- Chronic traumatic encephalopathy with progressive cognitive and behavioral decline in cases of recurrent blast TBI.
- Long-term effects on the tympanic membrane and auditory thresholds.
- Major limb injuries, including amputations, resulting from exposure to blast and long-term outcomes for the affected limb and for the cardiac system.
- Acute gastrointestinal perforations and hemorrhages, and solid-organ laceration, all of which can have long-term consequences.
- Long-term consequences for the musculoskeletal system, including heterotopic ossification in amputated limbs and osteoarthritis.
- Long-term complications of burns.
Inadequate/Insufficient Evidence of an Association
- Tinnitus and long-term effects on central auditory processing.
- Long-term effects on balance dysfunction and vertigo.
- Long-term effects on vision in cases of acute nonpenetrating eye injuries.
- Long-term effects on cardiovascular function, such as accelerated atherosclerosis.
- Long-term effects on pulmonary function, respiratory symptoms, and exercise limitation.
- Long-term effects after acute blast lung injury.
- Long-term gastrointestinal outcomes in the absence of serious acute injury.
- Long-term effects associated with partial injury (defined as incomplete structural and functional loss that can be reconstructed) to a genitourinary organ.
- Long-term effects of infections.
On the basis of its evaluation, the committee drew several additional conclusions related to adverse health effects of exposure to blast:
- There is sufficient evidence of a substantial overlap in the symptoms of mild TBI and PTSD exposure to blast, and there is limited/ suggestive evidence that most of the shared symptoms are accounted for by PTSD and not a direct result of TBI alone.
- There is inadequate/insufficient evidence to assess the direct contribution of blast to depression, substance-use disorders, and chronic pain; however, the association of PTSD with these disorders is well established.
- There is limited/suggestive evidence that diffuse brain injury with swelling may be more likely after blast than in relation to other mechanisms that lead to TBI.
The committee was asked to consider whether improvements in collective and personal blast protection are associated with diminished blast injuries. After evaluating the literature on this topic, the committee concludes
- That there is sufficient evidence of an association between the use of personal protective equipment, including interceptive body armor and eye protection, and prevention of blunt and penetrating injuries caused by exposure to blast.
- That there is inadequate/insufficient evidence to determine whether there is an association between the use of current personal protective equipment and prevention of primary blast-induced (non-impact-induced) injuries.
As the committee evaluated the available evidence on health effects of exposure to blast, it identified a number of gaps in the evidence base. Filling the data gaps is important for advancing the understanding of how blast affects humans in the short term and the long term. A fundamental feature of exposure to blast is that it can result in complex, multisystem injuries. Attention to those complexities has often been lacking in research studies. It is important that research on blast emphasize multisystem injury patterns and seek to understand the clinical importance of cross-system interactions.
Below are the committee’s recommendations for research that it believes is most likely to provide VA with knowledge that can be used to inform decisions on how to prevent blast injuries, how to diagnose them effectively, and how to manage, treat, and rehabilitate victims of battlefield traumas in the immediate aftermath of a blast and in the long term.
VA can begin to improve the diagnosis of and treatment for blast inju-
ries, particularly in the case of health outcomes of which there is at least sufficient evidence of an association with exposure to blast (see above). The first step for VA should be to evaluate approaches that are already in place to detect, treat for, and rehabilitate after blast injuries.
Recommendation 5-1. The Department of Veterans Affairs should conduct a rigorous evaluation to determine whether current approaches for detecting, treating for, and rehabilitating after health outcomes of blast exposure are adequate.
A limitation of nearly all the studies evaluated by the committee was inadequate information about the exposure to blast. Most of the studies used self-reported exposure data rather than objective measures. Obtaining accurate, objective measurement of exposure to blast is essential for understanding the mechanisms of injury from blast.
Recommendation 5-2. The Department of Defense should develop and deploy a system that measures essential components of blast and characteristics of the exposure environment, that records and stores the collected information, and that links individual blast-exposure databases with self-reported information and with demographic, medical, and operational data.
Identifying blast injuries in service members, particularly injuries that are not acutely severe and may go undetected for long periods, poses a major challenge in both clinical and research settings. The ability to define biomarkers of blast injury that could serve as surrogates of exposure would constitute a substantial advance in the study of long-term outcomes of exposure to blast.
Recommendation 5-3. The Department of Veterans Affairs should conduct epidemiologic and mechanistic studies to identify biomarkers of blast injury.
The committee identified substantial gaps in much of the published research on blast injuries. The gaps include inadequately powered data sets, incomplete control populations, and poor study designs; an absence of combat-relevant expertise in blast on the research team; and a need to refine and advance preclinical models so that they can predict long-term multisystem effects of blast injuries in humans adequately. Greater collaboration within and among institutions will expand the expertise of research teams and help to fill the gaps, and this approach should be considered a strength, not a limitation, with respect to VA funding priorities.
Recommendation 5-4. To support innovation and improve the state of blast science, the Department of Veterans Affairs should develop opportunities for multidisciplinary research collaborations that cross institutional barriers between the Veterans Health Administration, the Department of Defense, and other institutions.
To assist VA and other researchers in improving the design of future studies, the committee offers several additional recommendations. It also notes that it is important that all studies use a standardized definition of blast exposure once it has been developed.
Recommendation 5-5. The Department of Veterans Affairs should conduct research on acute and long-term consequences of blast injury involving all service members and veterans, not only users of the Veterans Health Administration.
Recommendation 5-6. The Department of Veterans Affairs should create a registry of blast-exposed (not only blast-injured) service members to serve as a foundation for long-term studies.
Recommendation 5-7. The Department of Veterans Affairs should use existing military records to identify a cohort of service members who served in the Iraq and Afghanistan wars to enroll in a prospective study of the long-term effects of blast on health and rehabilitation. The cohort should not be limited to service members who are known to have been exposed to blast.
Recommendation 5-8. The Department of Veterans Affairs should identify and use as a resource existing longitudinal cohort studies on populations that include blast-exposed service members and veterans. This resource may include information from existing ancillary studies of these cohorts to improve the detection and measurement of adverse long-term health outcomes of blast exposure.
Recommendation 5-9. The Department of Veterans Affairs should create a database that links Department of Defense records (particularly records that identify blast-injured service members) to records in the Veterans Health Administration, active-duty military treatment facilities, and TRICARE (the Department of Defense health care program) to facilitate identification of long-term health care needs after blast injury.
Recommendation 5-10. The Department of Veterans Affairs should conduct case-control studies of select adverse outcomes to test for the potential contribution of blast to them.
Knowledge of predictors of increased risk of health conditions associated with blast exposure makes it possible for service members who are at increased risk to be assigned to duties that avoid or minimize particular exposures or to receive prophylactic treatment and rehabilitation. Screening tests conducted on entry into the military (not only before deployment) should be helpful in gathering information on predictors of increased risk of blast injury.
Recommendation 5-11. The Department of Defense should determine whether existing screening tests administered during the physical examination conducted on enlistment can be used to measure susceptibility to blast injury, and if additional screening tests might be helpful in determining whether a service member has an increased susceptibility to blast injury.
As part of its charge, the committee was asked to provide recommendations on disseminating information about the health effects of blast exposure throughout VA for the purpose of improving care and benefits provided to veterans.
Recommendation 5-12. The Department of Veterans Affairs should build on its existing educational and communications infrastructure to educate its clinicians and other health care team members further about the health effects of blast exposure. Specific actions should be taken to
- Develop clinical practice guidelines for blast-related injuries other than traumatic brain injury and posttraumatic stress disorder. The guidelines should be developed in collaboration with the Department of Defense and ideally would be used by both departments.
- Expand the focus of the Polytrauma and Blast-Related Injuries Quality Enhancement Research Initiative to include injuries other than traumatic brain injury and posttraumatic stress disorder. Blast injuries and rehabilitation after them should be viewed through a wide clinical lens.
- Offer continuing education credit courses on blast injury through the Simulation Learning, Education and Research Network and other relevant educational forums.
- Convene periodic state-of-the-science conferences (for example, every 2 or 3 years) on the health effects of blast injuries. Such conferences would be convened ideally in collaboration with the Department of Defense, and possibly with selected professional associations, and the conference proceedings would be published (for example, in special issues or supplements of professional journals).
- Establish a blast-injury literature clearinghouse or information repository that could be used as a resource for clinicians and researchers. It should be a joint effort of the Department of Veterans Affairs and the Department of Defense.
- Use such mechanisms as the Patient Aligned Care Team, clinical champions, and learning networks to educate Department of Veterans Affairs health care teams about the health effects of blast exposure.
- Encourage clinicians to ask veterans specifically about exposure to blasts. Develop standard screening questions specific to veterans’ exposures to blast for integration into the Department of Veterans Affairs electronic health record and as part of veterans’ military histories. The screening questions should be listed on the military health history pocket card.