Pulmonary Vascular Dysfunction after Deployment-Related Exposures

部署相关暴露后的肺血管功能障碍

• 批准号: 9892976
• 负责人: Michael J. Falvo
• 金额: --
• 依托单位: VA NEW JERSEY HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-10-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892976
• 关键词: Acute; Address; Afghanistan; Air Movements; Air Pollutants; Air Pollution; Attention; Award; Behavior; Biopsy; Blood Circulation; Blood Vessels; Blood flow; Blood specimen; Bronchiolitis; Carbon Monoxide; Cardiopulmonary; Case Series; Characteristics; Chronic; Chronic lung disease; Cities; Clinic; Clinical; Clinical Data; Complement; Data; Deposition; Diffuse; Diffusion; Disease; Distal; Doppler Echocardiography; Dose; Dyspnea; Early Diagnosis; Early Intervention; Early treatment; Endothelin-1; Endothelium; Environmental Exposure; Etiology; Evaluation; Exercise; Exercise Test; Exertion; Exhibits; Exposure to; Family; Frequencies; Future; Gases; Goals; Guidelines; Health; Heart; Impairment; Individual; Intervention; Iraq; Knowledge; Location; Lung; Lung diseases; Measurement; Mediating; Mediator of activation protein; Membrane; Methods; Military Personnel; Nature; Nitric Oxide; Occupational; Particulate; Particulate Matter; Pattern; Peripheral; Physiological; Plasma; Population; Positioning Attribute; Procedures; Provider; Pulmonary function tests; Reporting; Resistance; Respiratory Signs and Symptoms; Rest; Right ventricular structure; Risk; Secondary to; Soldier; Spirometry; Suggestion; Symptoms; Techniques; Testing; Time; Ultrasonography; United States; United States Department of Veterans Affairs; Variant; Vascular Diseases; Veterans; active duty; base; brachial artery; burn pit; constriction; endothelial dysfunction; epidemiology study; experience; follow-up; hemodynamics; lung volume; medical specialties; novel; particle; post 9/11; pressure; pulmonary function; recruit; respiratory; respiratory health; response; symptom treatment; vascular injury

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.

军事环境暴露在伊拉克和阿富汗都普遍存在，包括特定的空气污染水平 比美国城市城市高10倍。尽管因果关系尚不清楚，但 经常在部署期间和之后报告呼吸道症状，并部署到伊拉克或 阿富汗与增加呼吸系统疾病的风险增加有关。尽管存在症状，但 大多数退伍军人具有正常的肺体积和气流，如肺活量测定法所示。然而， 肺活量测定法在该人群中可能不敏感，并且无法评估肺的主要功能 汽油交换。通过测量碳扩散能力来评估气体交换 一氧化碳（DLCO），我们的初步数据表明，在退伍军人目的地正常情况下，DLCO通常会降低 肺活量测定法。正常肺部体积和气流的模式，但DLCO低 - 即DLCO孤立的还原 - 建议早期肺血管或副肺疾病。 DLCO的孤立减少具有 以前在与暴露相关的支气管疾病中报道了一系列现役的细支气管疾病 士兵劳累时患有呼吸困难。我们假设暴露于部署期间的空气污染 导致远端气道中的小颗粒沉积，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，表现为呼吸道症状和 呼吸困难。我们的目标是：目标1）非侵入性评估休息和行使气体交换为 以及肺血液动力学对增量和最大运动的反应，目标2） 血管损伤的全身标志物，包括血管活性介质的循环水平和全身血管 反应性。退伍军人事务和国防部的肺科医生已经认识到最大的 评估病后呼吸道症状的挑战是患有正常肺活量的个体。 因此，我们将专注于这组9/11名退伍军人。具体来说，我们将招募两组退伍军人 具有正常的肺部体积和气流，但具有（正常的PFT），而没有降低DLCO（低DLCO）。经过 根据肺功能模式（正常的PFT与低DLCO）将退伍军人分为组，我们将是 可以辨别DLCO的孤立减少是不寻常的变体还是部署的预兆 - 相关肺部疾病。要完成我们的目标，我们将进行探索性后续评估（每年 在奖励的持续时间内）在退伍军人的一部分中，以确定肺血管功能和 亚临床肺血管疾病的全身标记随着时间的流逝而发展。通过这些研究，我们 期望发现有关部署相关呼吸疾病以及短期和长期的新知识 军事环境暴露的期限后果，这可能有助于早期诊断和治疗 有症状的9/11名退伍军人。