Analysis of Postdeployment Serum Samples Identifies Potential Biomarkers of Exposure to Burn Pits and Other Environmental Hazards

Thatcher, Thomas H.; Woeller, Collynn F.; Thakar, Juilee; Khan, Atif Ali; Hopke, Philip K.; Smith, M. R.; Uppal, Karan; Walker, Douglas I.; Go, Young‐Mi; Jones, Dean P.; Krahl, P; Mallon, Timothy M.; Sime, Patricia J.; Phipps, Richard P.; Utell, Mark J.

doi:10.1097/jom.0000000000001715

Cited by 9 publications

(5 citation statements)

References 67 publications

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“…Multiple toxicant and chemical stressors may contribute to the etiology of GWI, including potential sources such as burn pits in forward operating bases, nerve agents from destroyed munition sites, organophosphates insecticides and PB used prophylactically against potential nerve agent exposure [ 26 , 40 , 65 ]. Indeed, burn pits remain a potential source of toxicant exposure for Veterans involved in more recent operations including Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) and among Military personnel serving after September 11, 2001 [ 60 ]. Additional research is needed to understand the long-term health outcomes for Veterans with r-mTBI and how environmental exposures, such as burn pits and other toxic chemicals, are associated with chronic disease mortality [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of gulf war toxic exposures after mild traumatic brain injury

Ferguson

McCartan

Browning

et al. 2022

acta neuropathol commun

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Chemical and pharmaceutical exposures have been associated with the development of Gulf War Illness (GWI), but how these factors interact with the pathophysiology of traumatic brain injury (TBI) remains an area of study that has received little attention thus far. We studied the effects of pyridostigmine bromide (an anti-nerve agent) and permethrin (a pesticide) exposure in a mouse model of repetitive mild TBI (r-mTBI), with 5 impacts over a 9-day period, followed by Gulf War (GW) toxicant exposure for 10 days beginning 30 days after the last head injury. We then assessed the chronic behavioral and pathological sequelae 5 months after GW agent exposure. We observed that r-mTBI and GWI cumulatively affect the spatial memory of mice in the Barnes maze and result in a shift of search strategies employed by r-mTBI/GW exposed mice. GW exposure also produced anxiety-like behavior in sham animals, but r-mTBI produced disinhibition in both the vehicle and GW treated mice. Pathologically, GW exposure worsened r-mTBI dependent axonal degeneration and neuroinflammation, increased oligodendrocyte cell counts, and increased r-mTBI dependent phosphorylated tau, which was found to colocalize with oligodendrocytes in the corpus callosum. These results suggest that GW exposures may worsen TBI-related deficits. Veterans with a history of both GW chemical exposures as well as TBI may be at higher risk for worse symptoms and outcomes. Subsequent exposure to various toxic substances can influence the chronic nature of mTBI and should be considered as an etiological factor influencing mTBI recovery.

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Section: Discussionmentioning

confidence: 99%

Impact of gulf war toxic exposures after mild traumatic brain injury

Ferguson

McCartan

Browning

et al. 2022

acta neuropathol commun

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“…25,27 In particular, increased risk of homicide for military veterans is strongly associated with substance use disorders, including both drugs and alcohol, 28 which have high prevalence in the military veteran population. 29 Environmental exposures, such as burn pits and other toxic chemicals, 30,31 may help explain the higher cancer mortality rates observed in the post-9/11 military veteran population.…”

Section: Jama Network Open | Public Healthmentioning

confidence: 99%

Association of Traumatic Brain Injury With Mortality Among Military Veterans Serving After September 11, 2001

et al. 2022

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IMPORTANCE Emerging evidence suggests that harmful exposures during military service, such as traumatic brain injury (TBI), may contribute to mental health, chronic disease, and mortality risks. OBJECTIVETo assess the mortality rates and estimate the number of all-cause and cause-specific excess deaths among veterans serving after the September 11, 2001, terrorist attacks (9/11) with and without exposure to TBI.

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“…1 Schematic of possible NTA workflows that support three primary study objectives and corresponding study outputs discussed herein: classified samples, identified chemicals, and quantified chemi-cals. Note that for a given analysis, the number of features (N = i) is typically larger than the number of identified chemicals (N = j) military service members exposed to chemical contaminants during active duty [7].…”

Section: Sample Classificationmentioning

confidence: 99%

“…Targeted method performance criteria (i.e., thresholds for selectivity, sensitivity, accuracy, and precision) are well-defined, widely accepted, and adaptable to any given application, facilitating communication about results between analysts and stakeholders (i.e., any individuals with an interest in the data itself or data-driven decisions) [1][2][3]. Yet, in recent years, management agencies and supporting laboratories have been increasingly tasked with identifying new, unknown, or unexpected chemical stressors in complex samples (notable examples include novel per-and polyfluorinated alkyl substances [PFAS] in soil [4] and water [5,6], biomarkers of exposure to burn pits in serum [7], and discharged pharmaceuticals in wastewater [8]). Furthermore, researchers now routinely face the challenge of characterizing large classes of diverse chemicals (e.g., PFAS [9], illicit designer drugs [10,11] and steroids [12], and chemical warfare agents [13]) that may impact humans and/or ecological species.…”

Section: Introductionmentioning

confidence: 99%

“…These methods are highly versatile and capable of rapidly detecting known compounds (without the need for preliminary experimentation to develop and optimize targeted methods for specific analytes) [14,15], confidently identifying unknown/ unexpected contaminants [5,16], retrospectively assessing past exposures (via analysis of archived samples or data) [17,18], and efficiently classifying samples based on data patterns [19,20]. Moreover, NTA methods are amenable to virtually any sample medium, including air [21], water [5,6,14], sediment [22], soil [4,23], dust [24], food [25,26], consumer products [27], and biological specimens [7,28]. NTA research tools and approaches are being developed and applied at a staggering rate.…”

Section: Introductionmentioning

confidence: 99%

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Approaches for assessing performance of high-resolution mass spectrometry–based non-targeted analysis methods

et al. 2022

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Non-targeted analysis (NTA) using high-resolution mass spectrometry has enabled the detection and identification of unknown and unexpected compounds of interest in a wide range of sample matrices. Despite these benefits of NTA methods, standardized procedures do not yet exist for assessing performance, limiting stakeholders’ abilities to suitably interpret and utilize NTA results. Herein, we first summarize existing performance assessment metrics for targeted analyses to provide context and clarify terminology that may be shared between targeted and NTA methods (e.g., terms such as accuracy, precision, sensitivity, and selectivity). We then discuss promising approaches for assessing NTA method performance, listing strengths and key caveats for each approach, and highlighting areas in need of further development. To structure the discussion, we define three types of NTA study objectives: sample classification, chemical identification, and chemical quantitation. Qualitative study performance (i.e., focusing on sample classification and/or chemical identification) can be assessed using the traditional confusion matrix, with some challenges and limitations. Quantitative study performance can be assessed using estimation procedures developed for targeted methods with consideration for additional sources of uncontrolled experimental error. This article is intended to stimulate discussion and further efforts to develop and improve procedures for assessing NTA method performance. Ultimately, improved performance assessments will enable accurate communication and effective utilization of NTA results by stakeholders. Graphical abstract

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Analysis of Postdeployment Serum Samples Identifies Potential Biomarkers of Exposure to Burn Pits and Other Environmental Hazards

Cited by 9 publications

References 67 publications

Impact of gulf war toxic exposures after mild traumatic brain injury

Impact of gulf war toxic exposures after mild traumatic brain injury

Association of Traumatic Brain Injury With Mortality Among Military Veterans Serving After September 11, 2001

Approaches for assessing performance of high-resolution mass spectrometry–based non-targeted analysis methods

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