4.2. Existing Literature on Long-Term and Persistent Effects of Exposure
Like military personnel deployed to Operations Desert Shield and Desert Storm
, Veterans of OIF were exposed to a multitude of hazardous agents and psychologic stressors and have since reported symptoms in multiple body systems [19
]. The effect of these exposures has been both acute and long-lasting. In some cases, the presentation and reporting of symptoms is delayed for many months to years, only first coming to the attention of medical providers when coupled with other life-course events, comorbidities and aging [4
Several underlying mechanisms have been postulated for the long-term deleterious health effects of Veterans who were deployed to the Gulf region. Biologic evidence comes from a study of mitochondrial DNA damage of Veterans exposed approximately 25 years in the past and now exhibiting >3 domains of moderate-severe illness (i.e., fatigue, pain, neurologic, cognitive, mood, skin, gastrointestinal, and respiratory) [20
]. Compared with an unexposed military population, exposed Veterans manifested 20% higher levels of mtDNA damage (p
= 0.015) along with non-significant increases in nuclear DNA lesion frequency. Greater mtDNA damage is consistent with mitochondrial dysfunction (secondary to environmental and chemical toxicants) and offers supporting pathophysiologic evidence for the persistence of illness over time. Independent of smoking history, subsequent effects also are believed to impact the efficiency of electron transport chain complexes to clear reactive oxygen species from the body.
A range of chemicals and toxins are thought to impair mitochondrial and basic cellular functions for days to years after exposure, impeding the body’s ability to detoxify these agents [21
]. Coenzyme Q10 (CoQ10) is a potent antioxidant that aids mitochondrial energy production. In a randomized, double-blind trial of Veterans with symptoms thought to be the result of their service-related exposures during deployment to the Gulf region (e.g., muscle weakness, fatigue with exertion, cognitive impairment, gastrointestinal ailments, and skin problems), those who received CoQ10 versus placebo had improved physical function (summary performance scores) [23
]. Furthermore, the level of benefit was correlated with increasing concentrations of CoQ10 in the bloodstream.
DNA damage and mitochondrial repair, especially in the context of inductive-adaptive protection, remain a complex topic. The persistent clinical symptoms associated with deployment may reflect an inability to return to an uninduced hormetic state after the elimination of putative exposures, resulting in a “long-term metabolic shift” [24
]. This process likely is a function of the extent and duration of exposure in combination with endogenous genetic regulation, with some Veterans effected more severely than others.
In another study postulating long-term effects of deployment to the Gulf region, Veterans had increased Bacteroidetes, but decreased Firmicutes in their microbiota, compared with a non-effected referent group [25
]. In general, as noted by the authors, imbalances in the human microbiome have been associated with neurologic disorders, inflammatory bowel disease, metabolic disorder, liver disease, and cancer. Furthermore, experimental results conducted by the same team in a murine model reinforced human findings. Animals had altered enteric viral populations in the gut, indicative of inflammatory phenotype and neuronal immunotoxicity [26
]. While these initial results are provocative, more definitive studies with a larger cohort and adjustment for antibiotic use history are needed to validate long-term alterations in gut-microbiome among this group of Veterans, especially given their higher documented rate of infection [25
The constellation of health issues experienced by Iraq War Veterans appears similar in many respects to the earlier cohort of Gulf War I Veterans, consistent with chronic multisymptom illness (CMI) (personal communication with Dr. Steven C. Hunt, Director, Deployment Health Clinic, VA Puget Sound Health Care Systems). In a prospective longitudinal study, approximately half of Operations Iraqi Freedom/Enduring Freedom
(OIF/OEF) Veterans met the criteria for mild to moderate CMI. Additionally, 11% fulfilled the case definition for severe CMI, while 90% of those with chronic musculoskeletal pain met the criteria for CMI [27
]. Nonetheless, the symptoms most common to OIF/OEF Veterans were not necessarily those most often observed among the Gulf War I cohort, suggesting overlapping but not equivalent conditions. For example, while nearly all Veterans who served in Iraq and Afghanistan experienced at least one environmental hazard, the most common exposure was to air pollution and pesticides, precipitated by sandstorms and burn pits [28
]. In the case of airborne hazards, many of the deployed military personnel to OIF/OEF were exposed to levels that far exceeded safe exposure guidelines [29
]. CMI is a highly nonspecific diagnosis and to some extent discordant characterization for the illnesses reported by Veterans who were deployed to the Gulf region. Nonetheless, this term remains a basic starting point when assessing the varying and multiple exposures experience by Veterans deploy to this region.
The Millennium Cohort reported increased odds of CMI (odds ratio = 1.70) among those who were deployed to combat duty in Iraq and Afghanistan compared with pre-deployment assessment [30
]. While the prevalence of symptom reporting increased across all Millennium Cohort Study groups during the second time interval between surveys (2004–2007), suggesting a persistence of symptoms, this trend could alternatively be attributable to multiple deployments by the end of the second time interval.
The toxic exposures experienced by Veterans of the Wars in Iraq and Afghanistan appear to have lasting effects, and for nearly 40% of Veterans, it is a syndrome that is similar in presentation to CMI [28
]. Notably, this finding appears to hold even after accounting for key confounding variables known to be associated with post-deployment somatic symptoms. Given the cascade of symptoms reported after deployment to the Gulf region, independent of the year period, researchers have hypothesized that CMI is not attributable to a single stressor but rather is the consequence of exposure to several different types of exposures over a relatively brief time window [31
]. In retrospect, the illnesses associated with the above-mentioned military conflicts likely mirror similar chronic conditions such as fibromyalgia and chronic fatigue syndrome, which also are believed to have abstruse (and possibly multiple) etiologies [31
]. While definitive supporting evidence is lacking, idiopathic environmental intolerance may possibly explain the equivocal nature of such conditions. Under this unifying framework, both acute and long-lasting symptoms of nonspecific but multiple organ systems, are hypothesized to be the result of subtoxic exposure to an amalgamation of chemicals and/stressors [32
], resulting in chemical sensitivities [34
]. The accumulated body burden of the latter may underlie why certain Veterans do not have uniquely high exposure levels of a single toxin or single event-related exposure, but rather they represent a complex mixture of xenobiotics and genetic predisposition [35
]. Interestingly, in a systematic review, Veterans of the Gulf War were approximately three and a half times more likely to report multiple chemical sensitivity or CMI as defined by the Centers for Disease Control (CDC) [36
Another potential mechanism underlying the persistent CMI symptoms experienced by OIF Veterans is a primed inflammatory response vis-à-vis insecticide exposure [37
]. Various insecticides, including agents obtained on the local market (such pet tick-and-flea collars), were used in OIF to combat sand flies [38
]. In many cases, the compounds in the form of liquid were regularly applied to the skin or included as waste in burn pits and have been hypothesized as the basis for ‘sickness behavior-like symptoms’ reported in the literature [37
4.4. Unknown Threats to Health and Perceived Barriers to Care
Combat casualty rates were at an all-time high in 2004, 2005, and 2007 in Iraq [39
]. Most respondents in our survey reported deploying in 2004, 2005, and 2007, respectively. During deployment to a combat zone, service members do not focus solely on environmental exposures and airborne toxins, but more so on the combat environment itself and resulting injuries. Secondly, understanding that military guidelines and regulations are exact and authoritative, it is perplexing that such activities would occur that would place the service member at risk. Awareness briefings and literature; appropriate pre-deployment training related to the matter; attention to risks and enforcement of risk reduction (through protective measures, e.g., appropriate clothing and masks/filters/respiratory equipment) were minimal. Personal protective equipment (PPE) as evidenced by the questionnaire was either not issued or not used by service members. Utilizing respirator masks while working in the immediate area(s) of burn pits would decrease service members’ potential exposure to environmental toxins. However, and understandably, when deployed to a combat zone, consideration of environmental exposures and airborne toxins are generally sidelined. Service members have other more critical issues to focus on such as life-threatening injury and survival.
Perceived barriers to care post-deployment includes risk of loss of job (military) and risk of medically related military discharge (IAW AR 40-501: Standards of Medical Fitness, AR 600-60: Physical Performance Evaluation System, AR 635-40: Physical Evaluation for Retention, Retirement and Separation). Most respondents fell into the 25–34-year-old range and 30% are still currently serving in the military. Often Veterans assume that if they seek treatment for chronic symptoms they may become “flagged” and removed from their military job or discharged from service which would have directly impacted many respondents. This includes disincentive or negative incentive aspects (sociologic/psychologic factors) for resisting treatment. In addition, our average age group did not fall into the “common” health concern cohort, i.e., those chronic conditions more commonly seen in the older population versus a previously healthy, physically fit service member. One example is the earlier onset of acute myeloid leukemia in the Iraq War Veteran population resulting in death before age 40, compared with the national average age for this specific cancer of 70 years [40
]. Because of this, some service members may avoid seeking medical treatment. Additional barriers of care include those who utilize civilian healthcare facilities versus the Department of Veterans Affairs Medical Centers. When an Iraq War Veteran is seen at a civilian hospital for respiratory-like symptoms, the civilian providers, unfamiliar with the toxicity of burn pit exposure, may attribute the symptoms to tobacco use, lack of exercise, allergies, or bacterial and viral infections. However, if the same Iraq War Veteran is seen at the Department of Veterans Affairs Medical Center, the respiratory-like symptoms may be viewed differently; the possibility of toxic exposures during deployments is a known entity.
4.5. Nursing Implications
Professional nurses play an important role in the interprofessional health care team particularly with patient assessment, education and navigation. As discussed above, when a person enters the healthcare system, assessment frequently starts with a general knowledge of typical age-related concerns and patterns. The healthcare provider would see a younger, fit adult and may assume the underlying cause of respiratory symptoms is an acute infection or an irritation from lifestyle factors such as smoking or seasonal allergies. However, triage and/or assigned nurses who include the simple question “Are you a Veteran”, the initial algorithm related to respiratory symptoms diagnosis and patient care would have a different interpretation. The healthcare team could consider the potential cause for respiratory symptoms as one that is related to chronic respiratory difficulties associated with toxic environmental exposure to burn pits while deployed, especially in Iraq. Professional development for nurses and other healthcare providers on the toxic effects of burn pit exposure in Veterans who have served in Iraq is the responsibility of healthcare administrators, in both civilian and military hospitals.
Military nurses perform a significant role in educating service members about the potential risks associated with deployment to another country or region of the world. Educating soldiers and other military personnel about burn pits and hazardous exposures could start with emphasis on the use of personal protective equipment (PPE), and the benefit of decreased exposure risk. Pre-deployment briefings before deployment to zones that utilize burn pits would increase awareness of the potential exposures as well as post-discharge/retirement and Veteran screenings. Theoretical support for this approach is supported by the Health Belief Model (HBM), as described below.
In general, they have more frequent and intense engagement, both in theater and post-deployment, in serving the healthcare needs of Veterans. Nurses with military field experience especially have the greatest impact (i.e., most important in preventive aspects as well as identification and treatment) and serve a critical role in helping to resolve problems, finding practical solutions, and improving the operational effectiveness of post-deployment healthcare. They also are best positioned to aid the mission of the U.S. Army Training and Doctrine Command (TRADOC) to ensure the safety and battlefield fitness of our warfighters and their healthcare needs afterwards.
Most respondents served in one military branch (Army) and were enlisted, “non-commissioned officers”. Accordingly, our results may not generalize to all Iraq War Veterans or to other military populations. The study relied on “self-reported
” data, with a potential increased risk of biases, attribution, exaggeration, and selective memories. We also are unable to rule out that sicker Veterans may have responded to our survey. While exposures to certain toxic substances, even at low levels or for brief periods, may increase disease risk, information pertaining to the level, intensity, and mode of contact with such putative agents was not collected in this study. The unique genetic vulnerability of a Veteran to a particular risk factor was unknown, as was the exact etiology and pathobiology of symptoms many years after the putative exposure(s). Inconsistencies regarding CMI symptom reporting for burn pit exposures across studies may have limited the generalizability of findings [38
]. Some ambiguity exists in how physical fitness was assessed in our survey. Further versions will benefit by being able to differentiate if observed decreases in physical fitness were attributable to time spent or shortness of breath during exercise.
As is the case for a single-point-in-time survey, Veterans who died were not included in the analysis suggesting that the rates for some outcomes may be underreported. However, our sample was not restricted to participants who only used Veteran Administration facilities for their health care. Previous assessments of this specific cohort were not available for comparison.
The key authors of this manuscript are Veterans who were deployed to Iraq in support of OIF. In establishing the non-profit HunterSeven Foundation, they hoped to provide an independent resource for fellow Veterans to express their experiences. The initial survey information collected by the Foundation was not intended to be a research project but rather a means to acknowledge and explore potential exposures associated with their deployment and a vehicle for encouraging Veteran engagement and communication. While it lacks a certain degree of epidemiologic rigor, the participants were more candid and willing to provide insights that often are missing in more formal surveys conducted by the Veterans Administration (VA) or the Department of Defense (DoD). In the future, it is hoped that the HunterSeven Foundation will serve as a recruitment resource for difficult to reach Veterans of this conflict. In every sense, the data collected thus far by the HunterSeven Foundation is preliminary in nature. The sample size is small, and resources have not been available for follow-up data cleaning or to recontact Veterans regarding incomplete or inconsistent survey responses. Because of the before and after deployment context for several survey questions, there are many cases of missing values. If the sample size was larger it would be feasible to impute or model the missing data. Accordingly, traditional statistical tests for comparing correlated (before-after) data and obtaining p-values were not performed but rather only simple percentages were reported. Nonetheless, it is hoped that the information presented will be helpful in planning the future recruitment of this population. For interested readers, the data reported as percentages (p) follow a binomial distribution and the standard deviations may be estimated as the square root of p(1 − p)/N. For crude comparisons of before and after groups, one may use these standard deviations, keeping in mind that the underlying data is correlated and that such comparisons will not be statistically rigorous (and thus are not provided in the manuscript).