The Pulmonary Vasculature and Platelets in Emphysema and COPD

肺气肿和慢性阻塞性肺病中的肺血管和血小板

基本信息

批准号：
9916800
负责人：
Carrie L Pistenmaa
金额：
$ 19.65万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9916800
关键词：
Accounting Acute Lung Injury Adult Alveolar wall Animal Model Animals Apoptosis Area Aspirin Biological Biological Response Modifier Therapy Biological Testing Biology Blood Platelets Blood Vessels Blood capillaries Blood flow Cardiac Cardiovascular system Cause of Death Cessation of life Chest Chronic Chronic Obstructive Airway Disease Clinical Investigator Clinical Research Clinical Trials Clinical Trials Design Coronary Arteriosclerosis Critical Care Cross-Over Studies Cross-Sectional Studies Data Data Analyses Defect Development Disease Disease Progression Distal Endothelium Environment Epidemiology Future Goals Health Care Costs Heterogeneity Hospitalization Hospitals Human Image Imaging Techniques Individual Intervention Learning Link Lung Lung diseases Magnetic Resonance Imaging Master&apos s Degree Measures Mediating Mentorship Morbidity - disease rate Morphology Multi-Ethnic Study of Atherosclerosis Outcome Outcome Measure Oxygen Participant Pathology Pathway interactions Patients Perfusion Persons Pharmacology Phase Physicians Placebos Platelet Activation Process Production Prostaglandin-Endoperoxide Synthase Publishing Pulmonary Emphysema Pulmonary vessels Randomized Research Research Personnel Resources Risk Risk Factors Role Sampling Scanning Short-Term Course Skin Smoker Structure Testing Thromboxane A2 Thromboxane B2 Thromboxanes Training Translational Research United States Variant Visual Woman Work X-Ray Computed Tomography airway obstruction alpha 1-Antitrypsin Deficiency base career development clinical center clinical investigation clopidogrel contrast enhanced improved in vivo insight instructor lung imaging medical schools mortality multidisciplinary novel operation patient oriented programs recruit serial imaging small airways disease success urinary

项目摘要

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are the major components of chronic lower respiratory disease, the 4th leading cause of death in the United States and the world. Despite this, there are no disease-modifying pharmacologic therapies for COPD. Thus, there are opportunities to advance treatment of COPD by identifying and testing biological therapies that alter disease progression. Candidate: As a pulmonary-critical care-trained physician and Instructor at Brigham and Women's Hospital (BWH) and Harvard Medical School (HMS), the PI has conducted preliminary research identifying platelet activation as a potential risk factor for COPD and emphysema. The PI's long term goal is to become an independent clinical investigator with a focus on strategies that impact the development and progression of emphysema and COPD. Career Development: The PI's short term goals are to complete a Master's Degree in Epidemiology, to learn about imaging analysis, measures of platelet activation and clinical trial design and operations, which she will do with the guidance of the assembled multi-disciplinary mentorship team. Environment: BWH and HMS have a track-record of success in research career development and has committed significant resources to support this proposal including use of the BWH Center for Clinical Investigation. Research: The proposed research aims will evaluate the vascular hypothesis of emphysema and a specific related biological pathway (platelet activation) in sequential steps. Aim 1 will assess the association between pulmonary vascular morphology and the progression of percent emphysema on CT. Aim 2 will measure urinary 11-dehydro-thromboxane B2, a measure of in vivo platelet activation, in a sample of 1,537 participants in the Subpopulations and Intermediate Outcomes Measured in COPD Study (SPIROMICS) to test whether platelet activation is associated with emphysema and pulmonary vascular morphology in cross- sectional analyses, and whether it predicts longitudinal progression of emphysema. Aim 3 will recruit 20 novel participants with visual emphysema on CT and mild-moderate COPD for a crossover study to determine whether dual antiplatelet therapy improves pulmonary microvascular perfusion on dual-energy CT scan compared to placebo. Together, these aims link the pulmonary vasculature, platelet activation and emphysema progression, and will test whether inhibiting platelet activation impacts our measures of microvascular pulmonary perfusion. Improvement in pulmonary perfusion with dual antiplatelet therapy would suggest that these therapies may impact long-term progression of emphysema, a hypothesis I would propose to test in a future R01/phase IIb RCT. In completing these research objectives, the PI aims to identify a potential novel pathway related to emphysema and COPD, and gain the expertise to establish an independent research program that identifies and tests therapies that impact the progression of emphysema and COPD.

理由：慢性阻塞性肺病（COPD）和肺气肿是慢性阻塞性肺病的主要组成部分。慢性下呼吸道疾病是美国和世界第四大死因。尽管因此，目前还没有针对慢性阻塞性肺病的疾病缓解药物疗法。因此，有机会通过识别和测试改变疾病进展的生物疗法来推进慢性阻塞性肺病的治疗。候选人：布莱根妇女医院接受过肺部重症监护培训的医生和讲师 (BWH) 和哈佛医学院 (HMS)，PI 已进行了识别血小板的初步研究激活是慢性阻塞性肺病和肺气肿的潜在危险因素。 PI 的长期目标是成为独立的临床研究者，专注于影响疾病发展和进展的策略肺气肿和慢性阻塞性肺病。职业发展：PI 的短期目标是完成以下领域的硕士学位：流行病学，了解影像分析、血小板活化测量和临床试验设计以及她将在组建的多学科指导团队的指导下进行操作。环境：BWH 和 HMS 在研究职业发展方面拥有成功的记录，并且投入了大量资源来支持该提案，包括使用 BWH 临床中心调查。研究：拟议的研究目标将评估肺气肿的血管假说和连续步骤中的特定相关生物途径（血小板激活）。目标 1 将评估协会肺血管形态与 CT 肺气肿进展百分比之间的关系。目标2将测量 1,537 名样本中的尿液 11-脱氢血栓烷 B2，这是体内血小板活化的指标慢性阻塞性肺病研究 (SPIROMICS) 中测量的亚人群和中间结果的参与者进行测试血小板活化是否与肺气肿和肺血管形态相关截面分析，以及它是否预测肺气肿的纵向进展。目标3将招募20本小说 CT 上显示视觉肺气肿和轻度至中度慢性阻塞性肺病的参与者进行交叉研究以确定双能CT扫描双联抗血小板治疗是否改善肺微血管灌注与安慰剂相比。这些目标将肺血管系统、血小板活化和肺气肿联系起来进展，并将测试抑制血小板活化是否影响我们的微血管测量肺灌注。双联抗血小板治疗改善肺灌注表明这些疗法可能会影响肺气肿的长期进展，我建议在未来的 R01/IIb 期 RCT。在完成这些研究目标时，PI 旨在确定潜在的小说与肺气肿和慢性阻塞性肺病相关的途径，并获得建立独立研究的专业知识该计划旨在识别和测试影响肺气肿和慢性阻塞性肺病进展的疗法。