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普遍存在，包括颗粒物空气污染水平 是美国城市的 10 倍，尽管因果关系尚不清楚， 在部署期间和之后以及部署到伊拉克或其他地区时，经常报告呼吸道症状 尽管存在症状，阿富汗仍与呼吸道疾病的风险增加有关。 通过肺活量测定法检测，大多数退伍军人的肺容量和气流均正常。 肺活量测定法对该人群可能不敏感，并且不能评估肺的主要功能 通过测量肺碳扩散能力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，尽管正常，退伍军人中 DLCO 通常会减少 肺量和气流正常但 DLCO 较低的模式——即 DLCO 单独减少。 – 表明存在早期肺血管或实质肺疾病。 之前曾报道过与暴露相关的细支气管疾病，包括一系列现役病例 我们捕捉到了士兵在部署期间暴露在颗粒物空气污染中的情况。 导致小颗粒沉积在远端气道，造成局灶性肺血管损伤，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 我们的目标是： 目标 1) 以非侵入方式评估休息和运动时的气体交换。 以及肺血流动力学对增量和最大运动的反应，目标 2) 确定 血管损伤的全身标志物，包括血管活性介质和全身血管的循环水平 退伍军人事务部和国防部的肺科医生已经认识到最大的反应性。 评估部署后呼吸道症状的挑战是肺量测定正常的个体； 因此，我们将重点关注这批9/11后的退伍军人，具体来说，我们将招募两组退伍军人。 肺容量和气流正常，但具有（正常 PFT）且 DLCO 不减少（低 DLCO）。 根据肺功能模式（正常 PFT 与低 DLCO）将退伍军人分类，我们将 能够辨别 DLCO 的孤立减少是异常变体还是部署的先兆 为了补充我们的目标，我们将进行探索性随访评估（每年一次） 在奖励期间）对一部分退伍军人进行研究，以确定肺血管功能和 通过这些研究，我们发现了亚临床肺血管疾病随全身时间进展的标志物。 期望发现有关与部署相关的呼吸系统疾病以及短期和长期疾病的新知识 军事环境暴露的长期后果，这可能有助于早期诊断和治疗 9/11 后有症状的退伍军人。