Military burn pit exposure and airway disease: implications for our Veteran population

Abstract

Millions of Veterans have been exposed to burn pit smoke during combat deployments throughout the last three decades. Toxic compounds present in burn pit fumes that may cause or exacerbate upper and lower airway disease include dioxins, polyaromatic hydrocarbons (PAHs), particulate matter (PM) among others. There have been several observational studies assessing a potential role of burn pit exposure in the development of a multitude chronic health conditions and the Veterans Administration has established the Airborne Hazards and Open Burn Pit Registry in 2014. However, specific causality of airway disease from burn pits has been difficult to prove and there are multiple barriers toward etiologic research. Preclinical models have demonstrated airway dysfunction and inflammation but modeling human exposures remains challenging. Here, we review the current literature on the potential impact of burn pit exposure on chronic airway disease.

Introduction

Almost three and half million members of the US military have been exposed to smoke and fumes from open burn pits. Those deployed in the Middle East have been exposed to smoke from oil well fires, as well as sand and dust. Others have been exposed to air pollution and mechanical fumes from the engines of aircraft, vehicles, and ships. In 2021, Congress passed the Veterans Burn Pits Exposure Recognition Act followed by the PACT Act in 2022 extending healthcare benefits to veterans with burn pit exposure. This has garnered national attention to the potential health consequences of burn pit exposure.

Burn pits contain human and food waste, plastics, electronics, rubber, wood, fuels, metals, munitions, and chemicals. Simulations of burn pit smoke using combustion of wood, plastics, diesel fuel have shown that polycyclic aromatic hydrocarbons (PAHs), dioxins, volatile organic compounds (VOCs) are released.^1–3 Particulate matter (PM) less than 2.5 μm is also produced that has significant increased lung injury in mice.^{1, 4} Environmental air sampling near burn pits and incinerators at Bagram Airfield in Afghanistan showed high levels PM2.5 as well as the toxic acrylic acid intermediate acrolein.⁵ Sampling at Joint Base Balad, the 2^nd largest US base in Iraq in 2007 identified burn-pit related emissions as the single most important source of dioxins and furans (76%) while engine emissions were the largest sources of polyaromatic hydrocarbons.⁶

Open combustion of waste products was particularly common in Iraq, Afghanistan, and areas of Southwest Asia. A study of over four hundred thousand Veterans deployed during 2001 – 2014 across 109 US bases across the world found that 85 percent of personnel were deployed to bases with burn pits and a median duration of days deployed was over one year.⁷ As the health hazards of such exposures became evident, the US Department of Defense released regulations on burn pits in 2009 that required segregation of hazardous and medical waste and established limitations on items that could be disposed in burn pits. However, despite these regulations, forty percent of bases still had burn pits in use in 2014.⁷ It is unclear whether these regulations have had any impact on health, as comparative studies on health outcomes before and after these changes were made, or on air sampling for emissions, have not been done.

The impact of burn pits exposure on lower and upper airway disease

Deployed personnel to Middle East are variably exposed to burn pits, sandstorms, exhaust fumes, among other potential toxic exposures that could increases the risk of lung diseases including asthma. Analysis of 75,770 military personnel from 2001 to 2013 in the Millennium Cohort Study found that up to 5% developed new-onset asthma and combat exposure increased the risk by 24–30%.⁸ Specifically, deployment to Iraq and Afghanistan, which represents the largest cohort of current Veterans, significantly increased the risk of new-onset asthma with an incidence of up to 14%.^{9, 10} Between 2003 and 2011, the prevalence of asthma nearly tripled (1.1% to 3.1%) in 760,621 Veterans, more so than chronic obstructive pulmonary disease (COPD) and interstitial lung disease.¹¹

A few prospective studies exist that have assessed potential airway complications related deployment exposures. The STAMPEDE study investigated 50 returning military personnel with no pre-deployment history of pulmonary or cardiac disease who reported new-onset pulmonary symptoms. Most of these patients had exposures to dust/sand, burn pits, and vehicle exhaust. After undergoing pulmonary function testing, chest tomography, impulse oscillometry, and methacholine challenge, 36% of patients showed airway hyperreactivity, 16% met criteria for asthma based bronchodilator response or methacholine challenge, and 8% had reduced diffusing capacity of carbon monoxide (DLCO) without other findings.¹² The follow up STAMPEDE II study prospectively examined pre- and post-deployment pulmonary function testing in the general military population. Of the 1693 patients examined pre-deployment and 843 examined post-deployment, the authors found no significant change in spirometry values pre and post-deployment. The authors also performed subgroup analysis based on patients with smoking history, BMI greater than 30, and those with self-reported asthma and again found no significant change in spirometry values among these subgroups.¹³ Thus it is unclear whether pulmonary symptoms that develop post-deployment can be truly attributed to obstructive lung disease or other lung pathology. Overall, from the limited data, there appears to be mixed heterogenous lower airway tract syndromes that may be related to deployment.

Despite the potential link to deployment-related lower airway disease in soldiers, early studies of Veterans did not find a specific association between burn pit exposure and respiratory outcomes.¹⁴ Corollary studies have suggested links between burn pit exposure and the development of malignancy, cardiovascular disease, and airways disease^{15, 16}, though there is a lack of high-quality data to demonstrate a strong correlation. A recent retrospective study examined 31 non-smoking soldiers who were healthy pre-deployment but developed respiratory symptoms during and post-deployment.¹⁷ The authors were able to detect the presence of burned oxidized metals, carbonaceous materials, and polycyclic aromatic hydrocarbons (present in burn pit fumes) in lung biopsies. Histologically there was evidence of fibrosis and constrictive bronchiolitis in biopsy tissue, which correlated clinically with a reduction in respiratory muscle strength and abnormal impulse oscillometry with 21 out of 31 patients showing airway hyperresponsiveness. Interestingly, 26 out of the 31 patients had normal spirometry, 3 had evidence of restrictive lung disease, and none had an obstructive pattern. These findings suggest a poorly defined heterogeneous respiratory syndrome, though a majority demonstrated airway hyperresponsiveness which may mimic asthma.

There are fewer studies that have looked at the association of burn pit exposure with upper airway disease. A systematic review published in 2021 of nine articles, four prospective cohort, one cross-sectional, and four retrospective cohort studies found a paucity of data directly linking burn pit exposure to upper respiratory symptoms. Most studies were limited by small sample size, recall bias due to survey use, failure to account for confounders, and limited follow up time.¹⁸ A more recent cross-sectional study of 186 patients based on self-reported deployment and burn pit exposure showed a higher rate of sinus and nasal disease among patients with exposure.¹⁹ The rate of CRS with nasal polyposis was 27.8% in patients with exposure compared to 8.5% in those were deployed without exposure, which also correlated with higher SNOT-22 scores. Lung-Kennedy endoscopy scores were also significantly higher in those who had exposure compared to those who did not have exposure. There was also a significantly higher rate of allergic rhinitis symptoms in deployed patients with exposure (61.1%) compared to those without exposure (23.9%). Interestingly there was no significant difference in the rates of CRS without nasal polyposis. However, the nature of self-reporting leads to recall bias and there was no information to quantify duration of deployment between the groups being compared or duration of burn pit exposure.

In summary, while there are studies investigating the potential role of burn pit exposure with pulmonary symptoms, the conclusions are difficult to interpret given the different methodology (lung function testing versus biopsy) and potential for recall biases. Moreover, due to a lack of well powered and designed studies looking at upper airway symptoms, no definitive conclusions can be drawn between burn pit exposure with the development of rhinosinusitis symptoms.

Utility of centralized burn pit registries

Though the relationship between burn pit exposure and health has not been fully established, creating a central database is one important step towards launching epidemiologic research into this area of respiratory disease research. The VA established the Airborne Hazards and Open Burn Pit Registry (AHOBPR) in 2014, which consists of an online questionnaire with an optional in-person health evaluation. As of March 2022, over 300,000 veterans completed the online questionnaire with about a third declining the health evaluation.²⁰ However, an assessment of the AHOBPR by the National Academies of Sciences (NAS) identified several critical limitations of the AHOBPR. Among these are self-selection bias due to the voluntary self-enrollment process, recall bias and self-report bias due to the dependency of questionnaires, and lack of follow up. Specifically, the questionnaire does not contain questions about non-burn pit exposures, composition of burn pits, so exposure data was of insufficient quality. As a result of the lack of an appropriate control population, inadequate exposure assessment, failure to assess for potential confounders, or lack of representative sample population due to possible sampling bias, the NAS concluded that the AHOBPR was not an appropriate resource for etiologic research on the association of airborne hazard exposure and health outcomes.^{21, 22} Instead, they refer to the Millennium Cohort Study⁸, which is a large epidemiologic study started by the Department of Defense in 2001 as more appropriate for etiologic research due to its regular follow up and standardized surveys. However, the number of questions about exposure history would need to be expanded for this study to be useful in studying the health outcomes with burn pit exposure. These large cohort studies have significant limitations toward being appropriate to assess clear link specifically with burn-pit exposures and health outcomes. Thus, improving burn-pit related disease research is greatly needed and proposed steps are highlighted in Figure 1.

Steps to improving burn pit research

Pre-clinical burn pit models

In the laboratory setting, several preclinical models have been developed to mimic aspects of burn pit exposure (summarized in Table 1).^{1, 23–29} One model used an automated combustion system of burn materials consisting of plywood, cardboard, plastics, which are some of the components in burn pits.²⁹ The authors found higher levels of volatile organic compounds (VOCs) in smoldering fires rather than flaming fires. Mice that were exposed to the fumes for 2 days did not show any histopathologic changes in lung sections or a significant change in inflammatory cytokines from BAL fluid. This could be due to inadequate dose/duration of exposure. The authors also point out that their model does not contain other components of burn pit smoke including biologic waste, electronics, munitions, and fuels.

Table 1.

Burn pit related pre-clinical mouse models

Reference	Compounds	Protocol	End Points	Major Findings
Szema, A. M., et al. (2014)23	Iraq Dust	Euthanized 1mo post single instillation	1. Lung inflammation 2. Pro-inflammatory cytokines	1.Crystals, septate thickening, and inflammation post exposure 2. Increased IL-2 and reduced Tregs
Lin, D., et al. (2018)24	1. PM 2. PM + RuX	1.Euthanized 4 or 3 weeks post single instillation	1.Lung inflammation in response to drug treatment (Rux)	Rux decreases lung injury with upregulation of Tregs
Berman, R., et al. (2020)25	1.Afghanistan Particulate matter (APM)	24hr post single inhalation APM.	1.Airway inflammation and AHR	1. APM induced AHR and neutrophilic inflammation 2. AHR is IL-33/ST2 dependent
Kim, Y. H., et al. (2021)1	Plywood, cardboard Plastic, diesel	4h and 24h post single aspiration.	1. Lung inflammation, LDH, cytokines 2. Respiratory parameters	Increased neutrophils and pro-inflammatory cytokines (IL-6 and macrophage inflammatory protein-2 (MIP-2)) in bronchoalveolar lavage fluid (BALF) at 4h.
Berman, R., et al. (2021)26	1. APM 2. House Dust Mite (HDM)	APM for 12 days, followed by HDM exposure	1.single cell RNA sequencing 2. Pulmonary inflammation and AHR	1. Monocyte population induced by combined PM and HDM treatment and expressing ALOX15 2. PM+HDM increased airway resistance
Trembley, J. H., et al. (2022)27	Carbon Black nanoparticles	24h after 6h exposure.	Pro-inflammatory biomarkers in arteries, brain, lung, and plasma	1. Increased IFN-$\gamma$ and TNF-$\alpha$ in multiple tissue samples 2. Increased CV injury markers
Aslaner, D. M., et al. (2022)28	1. PM<2.5$\mu$M 2. PM<2.5$\mu$M /psychological stress	Inhalation for 6h/day for 5 days/week for three weeks	1. Pulmonary function 2. goblet cell hyperplasia 3. Cardiac function	1. Reduced lung function 2. Increased AHR, goblet cell hyperplasia
Vance, S. A., et al. (2023)29	Plywood, cardboard, mixed plastics	Exposed for 1h for two days and euthanized 4h later	1. Respiratory parameters 2. Lung inflammatory cells, cytokines	1. Reduced breathing frequency and minute volumes 2. No acute effects on lung inflammation

Another model assessed mice exposed to 4–10X ambient PM2.5 levels for 3 weeks using an aerosol concentration enrichment system in combination with or without concomitant stress simulation using a social defeat model.²⁸ The mean PM2.5 exposure in this model was reported to be equivalent to a deployment length of 1.4 years. Controls were exposed to air passed through a HEPA filter. Mice exposed to PM showed increased lung resistance to methacholine challenge and slightly higher mucin staining on lung sections without obvious changes in lung pathology. Others have looked at exposure to carbon black nanoparticles (CB) as a surrogate for burn pit exposure, given carbon is a significant component of burn pit emissions.²⁷ Exposure of mice to 6 hours of CB aerosol led to elevated inflammatory cytokines including Th2 cytokines such as IL-4, IL-5, and IL-13 in both blood and lung tissue compared to control mice exposed to HEPA filtered air. The target of 6 mg/m3 is reported to mimic long term exposures.

In summary, a variety of animal models have been developed to study the effects of burn pits. Although none can perfectly replicate exposures of soldiers due the heterogenous nature of their environment, these models are important tools to identify key lung immune and structural pathways that may be important in human burn pit exposures.

Biomarkers of burn pit exposure

Identification of biomarkers of burn pit exposure could be useful clinically and for future investigations. One group assessed polyaromatic hydrocarbon and dioxin levels in serum samples from military personnel pre- and post-deployment.³⁰ The majority of samples had undetectable levels of PAH, dioxins, and furans. Levels of some PAHs such as naphthalene were decreased post-deployment while no statistical significance was found for other PAH compounds. The authors attributed this finding to possible changes in smoking habits though no smoking history was available for comparison. There was limited detection of dioxins in most of the samples, and some were elevated pre-deployment while others were not elevated pre-deployment. Thus, it is not clear from this study whether measuring PAH or dioxin levels would be useful as a biomarker of burn pit exposure.

A later report by the same group examined serum microRNAs in 200 personnel who were deployed compared to those who were never deployed.³¹ They identified several microRNAs which may be important for the regulation of gene expression, as well as metabolites involved in the tryptophan pathway and cytokines that were associated with dioxin or furan exposure and deployment. While these results are interesting and open up questions about possible pathogenic mechanisms, it is important to note that samples were collected from healthy patients, and is thus unclear if these markers are relevant to actual disease or simply exposure without disease.

Concomitant sandstorm exposures

One of the challenges with burn pit airway research is the presence of numerous toxic, irritant, and potentially inflammatory exposures during Middle East deployments such as dust and sand storms. Increased exposure to dust storms positively correlates with asthma incidence (18% for high exposure vs. 14% for moderate). In addition to inorganic and particulate matter, dust storms contain high levels of aerosolized bacteria as well as fungi including the allergen Alternaria alternata which is associated with severe asthma.^32–34 Notably, agar cultures during sandstorms have shown the presence of 40% more fungi, respectively, compared to without sandstorms.³² Thus, airway exposures other than to burn pits including sandstorms could either primarily cause or act in an adjuvant fashion to promote burn bit related disease.

Conclusion

Studies of the effect of burn pit exposure on airway disease have enormous implications for millions of Veterans. However, there are significant challenges which we have briefly reviewed here including lack of a concise database for exposure history. While the VA AHOBPR contains useful demographic information, the NAS review has found critical shortcomings that limit its utility in epidemiologic and etiologic research. Another challenge regarding etiologic research is the heterogeneous nature of burn pits and the numerous environmental exposures of deployed military personnel. Dust, sand, military ordnance, and exhaust fumes also likely play an important role in disease pathogenesis and are very difficult to separate from burn pits. There have been few high-quality studies demonstrating a clear link between exposure and pulmonary disease and even fewer studies looking at sinonasal disease outcomes.

Several immune pathways have been proposed to link burn pit exposure with the development of chronic upper and lower airway disease. Among these include activation of innate immune signaling and activation of type 2 inflammatory pathways.³⁵ However, mechanistic immunologic studies are currently lacking. Importantly, future investigations into the role of environmental exposures in the development of disease in active-duty soldiers and Veterans is not only relevant to our soldiers and Veterans, but may also have important implications for the general population given the links between air pollution and other occupational exposures to airway diseases.

Key Messages.

1. With millions of veterans exposed to burn pit pits while in service, the potential health impacts of this exposure may be significant.

2. The research to date has been conflicting on these health impacts, though the research itself has also been limited.

3. Development and expansion of registries such as the Airborne Hazards and Open Burn Pit Registry (AHOBPR), preclinical models mimicking burn pit exposure, and biomarkers for burn pit exposure provide a multitude of potential areas of research.

4. Improved modeling and mechanistic studies are necessary for prevention and treatment of burn pit related airway disease.

Abbreviations/Acronyms:

PM

Particulate matter

PAH

Polyaromatic hydrocarbons

VOC

Volatile organic compounds

CRS

Chronic rhinosinusitis