Clinical Markers and Monitoring for Post-9-11 Deployment Lung Diseases

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The overall goals of this project are to recruit and characterize a VA-based cohort of veterans with post- 9/11 southwest Asia, Afghanistan, and Djibouti (SWAAD) deployment with and without deployment-related lung diseases (DLD) such as asthma, bronchiolitis, and other small airways/distal airways disease and to identify clinical markers to accurately diagnose and monitor longitudinal lung function and health outcomes. This approach will lay the groundwork for future research efforts to identify treatment/management strategies to improve the health of United States veterans, understand and reduce disability, and avoid costly and unnecessary medical testing. Nearly three million military men and women have deployed to Iraq, Afghanistan, and other southwest Asia locations since 2001 as a part of several major military operations. The major ones include Operation Enduring Freedom (OEF) and Operation Freedom's Sentinel (OFS) in Afghanistan as well as Operation Iraqi Freedom (OIF), Operation New Dawn (OND) and Operation Inherent Resolve (OIR) in Iraq. Deployment to these regions is associated with exposure to complex inhalational hazards that may include burn pit/trash- burning emissions, desert dust, diesel particulates, and combat dust. Previous studies have demonstrated links between these exposures and post-9/11 deployment-related asthma and small airways/distal lung diseases such as bronchiolitis. Several studies have shown that DLD diagnosis often is challenging using conventional diagnostic tools, and long-term prognosis of DLD is unknown. Previously, our deployment lung disease research team demonstrated that newer techniques such as the lung clearance index (LCI) test may have a role in disease detection as a noninvasive marker of deployment-related distal lung disease. LCI testing may be more sensitive in detection of deployment-related distal lung diseases (DDLD) such as bronchiolitis than traditional diagnostic testing that includes pulmonary function testing, cardiopulmonary exercise testing, and chest imaging with computerized tomography. Thus, LCI also may be a more sensitive test to monitor longitudinal lung function in those with DLD that was missed by traditional lung function testing but detected by lung biopsy (the goal-standard diagnostic method for lung disease). Our study hypothesis is that post-9/11 southwest Asia and Afghanistan veterans with DLD will have longer deployment duration, lower diffusion capacity (e.g. abnormal diffusion/possible gas exchange abnormalities) on lung function testing, exhibit clinical biomarkers of increased cell activation and inflammation, and have worse longitudinal respiratory health outcomes (decline in lung function) compared to post-9/11 southwest Asia and Afghanistan veterans without DLD. We anticipate that LCI testing will be a useful early marker of distal lung injury in deployers and will correlate with abnormalities on surgical lung biopsy better than spirometry. We also hypothesize that LCI will be more sensitive in detecting abnormal lung function decline than conventional pulmonary function testing (PFT) in deployers with DLD. This study should help inform a standardized approach to managing symptomatic post-9/11 veterans in the larger VA system, where consistent evaluation and care is currently lacking. The clinical characterization of DLD in veterans and the establishment of a biorepository of blood and lung tissue in a cohort that is clinically phenotyped will lay the groundwork for evidence-based treatment and care. Furthermore, assembling this well- characterized cohort of post-9/11 veterans with and without DLD will provide a foundation for future clinical translational studies that will include clinical trials/interventions as well as longitudinal health outcomes research that may yield novel and accurate methods of diagnosis and treatment for veterans with DLD.