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

该项目的总体目标是招募和描述一个基于VA的退伍军人队列， 9/11西南亚、阿富汗和吉布提（SWAAD）部署，有和没有部署相关 肺部疾病（DLD），如哮喘、细支气管炎和其他小气道/远端气道疾病，以及 识别临床标志物，以准确诊断和监测纵向肺功能和健康结果。 这一方法将为今后确定治疗/管理策略的研究工作奠定基础 改善美国退伍军人的健康，了解和减少残疾，避免昂贵的， 不必要的医疗检查 近300万名男女军人被部署到伊拉克、阿富汗和其他西南地区。 自2001年以来，作为几次重大军事行动的一部分，主要包括： 持久自由（OEF）和自由哨兵行动（OFS）以及伊拉克行动 新黎明行动（OND）和内在决心行动（OIR）。部署到 这些区域与暴露于复杂的吸入性危害有关，可能包括燃烧坑/垃圾- 燃烧排放物、沙漠灰尘、柴油微粒和战斗灰尘。之前的研究已经证明了 这些暴露与9/11后部署相关的哮喘和小气道/远端肺部疾病之间的关系 例如细支气管炎。几项研究表明，DLD诊断通常具有挑战性， DLD的诊断工具和长期预后尚不清楚。此前，我们的部署肺病 一个研究小组证明，新的技术，如肺清除指数（LCI）测试，可能有一个新的方法， 在疾病检测中的作用，作为部署相关远端肺疾病的非侵入性标志物。LCI测试可 在检测部署相关远端肺部疾病（DDLD）（如细支气管炎）方面比 传统诊断测试，包括肺功能测试、心肺运动测试，以及 胸部计算机断层扫描因此，LCI也可能是一个更敏感的测试，以监测 DLD患者的纵向肺功能被传统肺功能检测遗漏，但被 肺活检（肺部疾病的目标标准诊断方法）。 我们的研究假设是，9/11后，患有DLD的西南亚和阿富汗退伍军人将有 展开持续时间较长，扩散能力较低（例如，异常扩散/可能的气体交换 异常），表现出增加的细胞活化和炎症的临床生物标志物， 与9/11后相比，纵向呼吸健康结果（肺功能下降）更差 没有DLD的西南亚和阿富汗退伍军人。我们预计，LCI测试将是一个有用的早期 展开器远端肺损伤的标志物，与手术肺活检异常的相关性优于 肺活量测定法我们还假设LCI在检测异常肺功能下降方面更敏感 与DLD部署人员的常规肺功能测试（PFT）相比。 这项研究应该有助于提供一种标准化的方法来管理有症状的9/11后退伍军人， 更大的VA系统，目前缺乏一致的评估和护理。的临床特征 退伍军人中的DLD以及在临床上 表型分析将为循证治疗和护理奠定基础。此外，组装这一良好- 一个特征性的9/11后退伍军人队列，有和没有DLD将为未来的临床研究提供基础。 转化研究，包括临床试验/干预措施以及纵向健康结局 这项研究可能为DLD退伍军人提供新的准确的诊断和治疗方法。

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.