Innate Immunity and Deployment-Related Lung Diseases
Abstract
Objectives and Rationale: Since 2001, over 3 million United States military personnel and contractors have been deployed to Southwest Asia and Afghanistan where they have been exposed to airborne particulate matter (PM) arising from a combination of sandstorms, explosive blasts, and combat-related dust that is contaminated with toxic pollutants from local industries, burn pit combustion products, and diesel exhaust. An unknown number of military personnel have returned from deployment with persistent respiratory symptoms that limit their ability to meet physical fitness requirements of active-duty service and contribute to long-term disability. This application will examine the role of immune cells of the respiratory system in causing deployment-related lung disease. We will use existing (banked) biological samples obtained from military personnel previously deployed to Southwest Asia and Afghanistan who have ongoing respiratory symptoms after deployment. We will analyze the samples using sophisticated molecular (single cell RNA analysis) and protein level (CyTOF mass cytometry) techniques to characterize specific populations of immune cells in the lung and how these differ between previously deployed military personnel and healthy subjects. Once we learn the cellular signaling pathways that are linked to these alterations, we will experimentally test their importance in a culture system being thin slices of human lung obtained from organ donor s unused for transplant. In the system, we can test the effects of drugs and also gene therapies to try and prevent the damage to the lung. The ultimate goal of this proposal is to identify novel therapeutic targets in order to diminish injury to the lung and the long-term respiratory consequences of deployment-related lung disease. Relation to Original Funded Research: The primary objective of the parent FY16 Focused Program Award is to determine how respiratory exposure to airborne PM in combination with exposures to chemical toxicants, blast overpressure lung injury, and infections damages the epithelial cells that line the conducting and gas exchange surfaces of the lung. The current Expansion Award application builds on key discoveries and the clinical and research infrastructure and resources developed under the parent Focused Program Award and will focus on the role of specific types of immune cells in the lung in causing the untoward effects of respiratory exposures to airborne PM and other toxicants. The current proposal will leverage the resource of banked biological samples from the cohort of over 325 military personnel previously deployed to Southwest Asia and Afghanistan with persistent respiratory symptoms who have undergone comprehensive clinical evaluation at the National Jewish Health Deployment Lung Disease Clinic. The goal of the current application is to characterize specific populations of immune cells in the lung and how these differ between previously deployed military personnel and health subjects. The long-term goal is to determine the role of specific types (subsets) of respiratory immune cells in causing damage to the lung from deployment-related exposures that will allow us to develop therapies to prevent this damage. Relevance to FY20 PRMRP Topic Areas: This grant proposal is in response to the PRMRP Expansion Award opportunity in the area of Respiratory Health and addresses the following FY020 PRMRP Areas of Encouragement: development of improved methods for assessing and treating lung injury due to chemical, smoke, inhalation burn … and research on airborne chemical and pollution hazards that affect lung function associated with specific acute health outcomes for … deployed Service Members. This proposal stems from knowledge generated from a FY16 Focused Program Award (10/2016-09/2021) titled, “Mechanisms and Treatment of Deployment-Related Lung Injury: Repair of the Injured Epithelium” (PR150109; G. Downey PI). Applicability and Impact of Rese
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110666
Entities
People
- Gregory P. Downey
Organizations
- National Jewish Health
- United States Army