Modeling Airborne Hazard Exposures Using an Airway-on-a-Chip Platform to Elucidate Common Pathophysiological Mechanisms and Medical Countermeasure Targets
Abstract
Objectives and Rationale: Burn pits are a common way to eliminate waste in war zones. Exposure to smoke emitted from burn pits in military bases has been linked with lung disease among military and civilian personnel returning from war zones. Over 2 million U.S. military personnel have been deployed in war zones in the past 20 years; therefore there is a growing concern that a significant number of Veterans have been exposed to hazardous emissions from burn pits during military service. The objective of our proposal is to better understand how different burn pit fuels (such as plywood, cardboard, plastic, and mixtures) and different combustion conditions (such as smoldering and flaming burning) impacts the toxicity of burn pit smoke and the potential health impact on exposed Service Members. To achieve this objective, our collaborator (Dr. Yong Ho Kim, see letter of support) has generated burn pit smoke condensates representing different military burn pit conditions based on the waste stream data from U.S. military bases. Our team at Wake Forest has developed an in vitro airway exposure testing system, known as airway Organ Tissue Equivalents (OTEs), which are miniature lab- grown human airway tissues that closely reproduce the function and responses of human airway tissue. In this proposed collaborative study, we will expose airway OTEs to different types of burn pit smoke, characterize the toxicity each of the different conditions, and identify the chemicals most likely to cause lung injury and disease. Ultimate Applicability of the Research: A long-term goal of this project is to advance the development of therapeutics, treatments, and strategies to mitigate the adverse effects of burn pit smoke exposure. This will include development of diagnostic biomarkers, guidance to minimize future exposures, and development of therapeutics and treatments for Service Members with burn pit exposure related lung disease. Relevance to the TERP: This proposal directly addresses the FY22 TERP Topic Area, Airborne Hazards and Burn Pits, and the Focus Area, Identify toxicants associated with airborne hazards and elucidate mechanisms of associated effects on human health. Our proposal also has broad relevance for multiple FY22 TERP Program Goals. Generating a better understanding of how toxic exposures to burn pit emissions result in adverse effects addresses Program Goal 1. This proposal also addresses Program Goals 2, 3, and 4, with potential applications of this work in identifying exposure biomarkers to guide diagnosis and treatment, for the prediction and prevention of future toxic exposures, and by advancing the development of therapeutics, treatments, and strategies to mitigate the adverse effects of exposures. Potential Clinical Applications, Benefits, and Risks: We expect one early clinical application of this would be as diagnostic screen to identify disease risk for those Service Members exposed to different types of burn pit smoke emissions. We expect to identify biomarkers that could be used to for diagnosis of burn pit-related lung disease and potentially guide treatment. The proposal also has potential to predict and prevent toxic exposures by preventing burning of different types of hazardous waste. These approaches are all very low risk as they represent laboratory-based testing to provide new data, guidelines, and treatments for Service Members. Projected Timeline: We will perform burn pit smoke exposures and dose/toxicity studies in Year 1 of the proposal. Characterization of tissue function and disease mechanisms will be performed in both Years 1 and 2. Data analysis to identify burn pit chemicals associated with toxicity and injury will be performed in Year 3. Contributions to Advancing Knowledge: The health effects of air pollution remain a public health concern worldwide. Combustion of solid fuels is a major source of air pollutants and vary with fuel type, location, seasons, and
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310896
Entities
People
- Sean V Murphy
Organizations
- United States Army
- Wake Forest University