Pulmonary Vascular Dysfunction after Deployment-Related Exposures

在伊拉克和阿富汗，军事环境暴露无处不在，包括颗粒物空气污染水平。 这是美国城市的10倍。尽管因果关系尚不清楚， 在部署期间和部署到伊拉克或之后经常报告呼吸道症状 阿富汗与呼吸道疾病的风险增加有关。尽管有症状存在， 通过肺活量测定仪检测，大多数退伍军人的肺容量和气流正常。然而， 肺活量测定在这一人群中可能不敏感，也不能评估肺的主要功能 气体交换。通过测量肺内碳弥散能力来评估静态气体交换。 一氧化碳(DLCO)，我们的初步数据表明，尽管退伍军人正常，但DLCO通常减少 肺活量测定法。肺容量和气流正常但DLCO低的模式--即孤立的DLCO减少 -提示早期肺血管或肺实质疾病。DLCO的单独减少已经 以前曾报告过与暴露相关的细支气管病，包括一系列现役病例 患有呼吸困难的士兵们正在劳累。我们假设在部署期间暴露在颗粒物空气污染中 结果小颗粒沉积在远端呼吸道，导致局灶性肺血管损伤，释放 血管活性物质和全身血管功能障碍，表现为呼吸道症状和 劳累时呼吸困难。我们的目标是：目标1)非侵入性评估休息和锻炼气体交换 以及对递增负荷和最大运动的肺血流动力学反应，目的2)确定 血管损伤的系统性标记物，包括血管活性物质和全身血管循环水平 反应性。退伍军人事务部和国防部的肺病学家认识到最大的 评估部署后呼吸道症状的挑战是肺活量正常的个体； 因此，我们将重点关注这群9·11后的退伍军人。具体来说，我们将招募两批退伍军人 肺容量和气流正常，但(PFT)正常，DLCO降低(低DLCO)。通过 根据肺功能模式(正常PFT与低DLCO)对退伍军人进行分组，我们将 能够辨别DLCO的孤立减少是一个不寻常的变种还是部署的先兆- 相关的肺部疾病。为了补充我们的目标，我们将进行探索性后续评估(每年 在获奖期间)，以确定肺血管功能和 亚临床肺血管疾病随时间进展的系统标志物。通过这些研究，我们 预计将发现与部署相关的呼吸系统疾病以及短期和长期- 军事环境暴露的长期后果，这可能有助于早期诊断和治疗 有症状的9/11后退伍军人。

Military environmental exposures are pervasive in Iraq and Afghanistan, including particulate air pollution levels that are 10 times higher than urban cities in the United States. Although a causal relationship is unclear, respiratory symptoms are frequently reported both during and following deployment, and deployment to Iraq or Afghanistan is associated with an increased risk of respiratory conditions. Despite the presence of symptoms, the majority of Veterans have normal lung volumes and airflows as detected by spirometry. However, spirometry may be insensitive in this population and does not assess the primary function of the lung which is gas-exchange. Gas-exchange is assessed at rest via the measurement of lung diffusing capacity of carbon monoxide (DLCO), and our preliminary data suggest that DLCO is commonly reduced in Veterans despite normal spirometry. The pattern of normal lung volumes and airflows but low DLCO – i.e., an isolated reduction in DLCO – suggests early pulmonary vascular or parenchymal lung disease. An isolated reduction in DLCO has previously been reported in exposure-related bronchiolar disorders, including a case series of active duty soldiers with dyspnea on exertion. We hypothesize that exposure to particulate air pollution during deployment results in deposition of small particles in the distal airways, resulting in focal pulmonary vascular injury, release of vasoactive mediators and systemic vascular dysfunction which manifests as respiratory symptoms and dyspnea on exertion. Our aims are: Aim 1) To non-invasively assess resting and exercise gas-exchange as well as the pulmonary hemodynamic response to incremental and maximal exercise, and Aim 2) To identify systemic markers of vascular injury, including circulating levels of vasoactive mediators and systemic vascular reactivity. Pulmonologists in the Departments of Veterans Affairs and Defense have recognized the biggest challenge in evaluating post-deployment respiratory symptoms is the individual with normal spirometry; therefore, we will focus on this group of post-9/11 Veterans. Specifically, we will recruit two groups of Veterans with normal lung volumes and airflows, but with (Normal PFT) and without reduced DLCO (Low DLCO). By classifying Veterans into groups based on pulmonary function patterns (Normal PFT vs. Low DLCO), we will be able to discern whether an isolated reduction in DLCO is an unusual variant or a harbinger of deployment- related lung disease. To complement our aims, we will conduct exploratory follow-up evaluations (annually over the duration of the award) on a subset of Veterans to determine how pulmonary vascular function and systemic markers of subclinical pulmonary vascular disease progress over time. Through these studies, we expect to uncover new knowledge about deployment-related respiratory disease as well as the short- and long- term consequences of military environmental exposures, which may facilitate earlier diagnosis and treatment of symptomatic post-9/11 Veterans.