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以退伍军人为基础的具有以下职位的退伍军人队列： 9/11西南亚、阿富汗和吉布提(斯瓦德)部署，与部署相关和不与部署相关 肺部疾病(DLD)，如哮喘、毛细支气管炎和其他小气道/远端呼吸道疾病，以及 确定临床标志物，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。 为了改善美国退伍军人的健康，了解和减少残疾，避免昂贵和 不必要的医疗检查。 近300万名男女军人被部署到伊拉克、阿富汗和其他西南部地区 自2001年以来，作为几项重大军事行动的一部分，该公司在亚洲设立了办事处。主要的业务包括运营 持久自由(OEF)和自由行动在阿富汗的哨兵(OFS)以及伊拉克行动 伊拉克的自由行动(OIF)、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危险有关，可能包括烧伤坑/垃圾- 燃烧废气、沙漠尘埃、柴油微粒和战斗尘埃。以前的研究已经证明了这种联系 这些暴露与9/11部署后相关哮喘和小气道/远端肺部疾病之间的关系 比如毛细支气管炎。多项研究表明，使用常规方法诊断DLD通常具有挑战性。 诊断工具方面，DLD的长期预后尚不清楚。此前，我们部署的肺部疾病 研究小组证明，较新的技术，如肺清除指数(LCI)测试可能会有 作为部署相关远端肺部疾病的非侵入性标记，在疾病检测中的作用。LCI测试可能 对毛细支气管炎等部署相关的远端肺部疾病(DDLD)的检测比 传统的诊断测试，包括肺功能测试，心肺运动测试，以及 胸部计算机断层扫描成像。因此，LCI也可能是一项更敏感的监测测试 DLD患者的纵向肺功能，传统的肺功能测试漏掉了这些功能，但通过 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事件后患有DLD的西南亚和阿富汗退伍军人将有 部署持续时间较长，扩散能力较低(例如异常扩散/可能的气体交换 肺功能测试的异常)，显示细胞活化和炎症增加的临床生物标志物， 与9/11事件后相比，纵向呼吸健康状况(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 部署人员远端肺损伤的标志物，并将与外科肺活检的异常更好地相关 肺活量测定法。我们还假设LCI在检测肺功能异常下降方面更敏感。 在患有DLD的部署者中进行常规肺功能测试(PFT)。 这项研究应该有助于提供标准化的方法来管理9/11事件后的退伍军人 较大的退伍军人制度，目前缺乏一致的评估和护理。多发性硬化症的临床特点 退伍军人的DLD以及在临床队列中建立血液和肺组织的生物库 表型将为循证治疗和护理奠定基础。此外，组装这口井- 患有和不患有DLD的9/11事件后退伍军人的特征队列将为未来的临床提供基础 将包括临床试验/干预以及纵向健康结果的转化性研究 可能为患有DLD的退伍军人提供新的和准确的诊断和治疗方法的研究。

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.