Pulmonary Vascular Dysfunction after Deployment-Related Exposures

在伊拉克和阿富汗，军事环境暴露是普遍存在的，包括颗粒空气污染水平 是美国城市的10倍。虽然因果关系尚不清楚， 在部署期间和部署后经常报告呼吸道症状，部署到伊拉克或 阿富汗与呼吸系统疾病的风险增加有关。尽管存在症状， 大多数退伍军人具有正常的肺容量和气流，如通过肺活量测定法检测的。然而，在这方面， 肺活量测定法在这一人群中可能不敏感，并且不能评估肺的主要功能， 气体交换通过测量肺碳弥散量来评估静息时的气体交换 一氧化碳（DLCO），我们的初步数据表明，DLCO通常减少退伍军人，尽管正常 肺活量测定法肺容量和气流正常但DLCO低的模式-即，DLCO的单独减少 - 提示早期肺血管或肺实质疾病。DLCO的孤立减少 先前在呼吸道相关细支气管疾病中报告，包括一个现役 运动时呼吸困难的士兵。我们假设在部署期间暴露于颗粒空气污染 导致小颗粒在远端气道中沉积，导致局灶性肺血管损伤，释放 血管活性介质和全身血管功能障碍，表现为呼吸道症状， 运动时呼吸困难。我们的目标是：目标1）非侵入性地评估静息和运动气体交换， 以及肺血流动力学对递增和最大运动的反应，目的2）识别 血管损伤的全身标志物，包括血管活性介质和全身血管活性介质的循环水平， 反应性退伍军人事务部和国防部的肺病学家已经认识到， 评估部署后呼吸道症状的挑战是肺功能正常的个体; 所以呢我们就把重点放在九一一之后的这一批老兵身上。具体来说，我们将招募两组退伍军人 肺容量和气流正常，但有（正常PFT）和无DLCO降低（低DLCO）。通过 根据肺功能模式（正常PFT与低DLCO）将退伍军人分组，我们将 能够辨别DLCO的孤立减少是一种不寻常的变体还是部署的预兆- 相关的肺病。为了补充我们的目标，我们将进行探索性后续评价（每年一次 在奖励的持续时间内）对退伍军人的子集，以确定肺血管功能和 亚临床肺血管疾病的全身标志物随时间进展。通过这些研究，我们 期望发现有关部署相关呼吸道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.