Epithelial Repair Dysfunction in the Pathogenesis of Deployment-Related Lung Disorders (DLD)
Abstract
The proposed research directly addresses two of the FY21 PRMRP Topic Areas: Burn Pit Exposure and Respiratory Health. While respiratory disease among troops who have deployed to Afghanistan and Iraq and been exposed to burn pits and other inhaled noxious compounds has been widely described, the underlying biologic basis of this is not understood. We propose to address this critical deficit by comparing deployers with and without respiratory disease using an approach based in cell and molecular biology. The lining cells of the airways, termed epithelial cells, are the first to come in contact with inhaled irritants and have been shown to orchestrate responses that can lead to repair or disease. Thus, a focus on epithelial cell function and inflammation is logical. We anticipate that these investigations will help to better diagnose respiratory disease in deployers and potentially lead to rational treatment strategies. Almost 3 million American troops have deployed to Southwest Asia post-9/11 to support conflicts in Afghanistan and Iraq. A large proportion of these individuals have experienced exposure to inhalational hazards that include burn pit/trash burning emissions, sand storms, combat dust, diesel particulates, vapors and gases from industrial fires (e.g., sulfur dioxide from the Al Misraq sulfur mine fire) and from explosive blasts (e.g., chlorine containing improvised explosive devices). Upon return from combat, many of these deployers exhibit a wide range of respiratory disorders, from chronic dyspnea, cough, wheeze, chest tightness, to sinusitis, asthma, bronchiolitis, as well as conditions with overlapping phenotypes, collectively called Deployment Related Lung Disorders or DLD. The diagnosis of DLD has been challenging because the Pulmonary Function Test (PFT) is often near normal. Surgical biopsies from DLD patients showed distal lung pathology characterized by peribronchiolar metaplasia, chronic inflammation, and hyperinflation/emphysema as major pathological phenotypes. Some of the inhaled agents are potent carcinogens, raising the concern for the future development of lung cancer, an outcome that often takes 20 years or more to present clinically. The Department of Veterans Affairs (VA) has designated DLD as an area of research emphasis, confirming its significance. However, we have very little insight into the underlying mechanisms of this emerging lung disease. Furthermore, biological differences in symptomatic and asymptomatic deployers remain unknown. A number of reports have supported the increased frequency of respiratory complaints and disorders in deployers compared to controls. In 2009, the Millennium Cohort Study team reported questionnaire data on 46,077 participants, with a focus on respiratory symptoms such as cough or shortness of breath, chronic bronchitis or emphysema, and asthma. Deployers had a higher rate of reporting respiratory symptoms (14%) than did non-deployers (10%). Increased respiratory symptoms were seen in both Army and Marine Corps deployers, independent of smoking status, and were linearly associated with deployment length. Land-based deployment was associated with increased symptom reporting compared to sea-based deployment. A smaller study reported in 2010 of 6,233 patients seen at the Northport NY VA Medical Center (VAMC) found an increased risk of new onset asthma in deployers compared to stateside Veterans (6.6% vs. 4.3%), which persisted after stratification by gender and age. The Millennium Cohort Study has recently confirmed this association in a survey study of 75,770 participants in which a 24%-30% increased likelihood of developing asthma for deployers compared to non-deployers was reported. Combat experience among deployers was a critical feature in risk for new onset asthma compared to non-deployers. A narrowing of small airways, termed constrictive bronchiolitis, was reported in a case series of 80 soldiers from Fort Campbell, KY in 2011. Forty-nine (49) und
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210424
Entities
People
- Moumita Ghosh
Organizations
- United States Army
- University of Colorado Denver