Using Vessel Caliber to Assess Cardiac Impairment in COPD

使用血管口径评估慢性阻塞性肺病患者的心脏损伤

• 批准号: 8581541
• 负责人: Carolyn E Come
• 金额: $ 16.34万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581541
• 关键词: Affect; Aorta; Area; Biometry; Blood; Blood Pressure; Blood Vessels; Blood Volume; Caliber; Cardiac; Cardiac Catheterization Procedures; Cardiac Output; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Chest; Chronic Obstructive Airway Disease; Clinical; Clinical Research; Clinical Trials; Collaborations; Comorbidity; Country; Critical Care; Data; Databases; Diagnostic; Disease; Echocardiography; Educational Curriculum; Enrollment; Esophageal; Exercise; Exercise stress test; Framingham Heart Study; Functional disorder; Future; Goals; Grant; Health; Heart; Heart Rate; Heterogeneity; Hospitals; Hypoxia; Image; Image Analysis; Impairment; Impedance Cardiography; Inferior; Inferior vena cava structure; Inflammation Mediators; Institution; Left; Lung; Lung Volume Reductions; Lung volume reduction surgery; Magnetic Resonance; Malignant neoplasm of lung; Measurable; Measurement; Measures; Mechanics; Medical; Medicine; Mentors; Metric; Modality; Molecular; Morbidity - disease rate; Nature; Operative Surgical Procedures; Outcome; Oxygen; Pathogenesis; Patients; Performance; Physicians; Physiologic pulse; Positioning Attribute; Principal Investigator; Publishing; Pulmonary Emphysema; Pulmonary Heart Disease; Pulmonary veins; Pulmonary vessels; Randomized; Relative (related person); Research; Research Personnel; Respiratory physiology; Rest; Right pulmonary artery; Risk; Risk Factors; Role; Scanning; Scientist; Severity of illness; Smoker; Smoking; Stroke Volume; Teaching Hospitals; Techniques; Testing; Time; Training; Training Programs; United States; United States National Institutes of Health; Ventricular; Woman; Work; X-Ray Computed Tomography; base; cardiovascular imaging; career; career development; cohort; cone-beam computed tomography; design; disease phenotype; experience; follow-up; improved; insight; lung volume; medical schools; meetings; mortality; novel; patient oriented research; population based; pressure; respiratory; risk sharing; skills; tool; translational study; treatment trial; vascular inflammation; vasoconstriction

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is very common, affecting up to 24 million people in the United States, and is associated with considerable and increasing morbidity and mortality. Cardiac comorbidities are prevalent in patients with COPD and contribute significantly to worse health outcomes. In fact, studies have shown that, in patients with COPD, cardiac causes of death are even more common than COPD-related causes. While COPD and cardiovascular disease share a common risk factor, smoking, it is clear that their association is multifactorial, going beyond this shared risk. One o the factors influencing the relationship is the shared position of the heart and lungs in a closed thoracic cage. It has been shown that many patients with COPD have increased lung volumes and that this hyperinflation impairs cardiac performance. In this career development proposal, the applicant hypothesizes that the abnormal cardiac performance in hyperinflated COPD patients is at least in part related to changes in the distribution of intrathoracic blood volume (.e. alterations in ventricular preload and afterload) that can be corrected with deflation. She proposes to use a novel noninvasive technique to develop a more detailed understanding of the relationship between hyperinflation and cardiac performance. Specifically, she will utilize computed tomographic vascular measurements to non-invasively estimate the distribution of blood within the thorax and assess how that distribution varies with changes in lung volumes and further, relates to cardiac chamber size and function at rest and during exercise in normals and in patients with different levels of COPD severity. In her first aim, she will explore the relationships between lung volumes, CT measurements of intrathoracic vessel caliber, and cardiac chamber size and function in a population based cohort (The Framingham Heart Study). This cohort will allow her to develop normative values for the size and relationships of extraparenchymal intrathoracic vessels and small pulmonary vessels. In her second aim, using data from the National Emphysema Treatment Trial, she will assess the effect of lung deflation (via lung volume reduction surgery) and transpulmonary pressure on intrathoracic vessel caliber. Use of this cohort will also allow her to correlate her CT vascular measurements with invasive measures of cardiac filling pressures and function. Finally, in her third aim, she will determine whether CT vascular measurements can predict cardiac performance during exercise. The results of this research may yield new insights into disease pathogenesis and suggest which patients would experience greatest benefit from pharmacologic or surgical deflation. This work will be performed in the Division of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital, a core teaching hospital of Harvard Medical School. The division has an outstanding record of training physician scientists, one of the largest NIH grant portfolios of any pulmonary division in the country, and collaborations with multiple local and national institutions. There is abundant opportunity for intellectual stimulation with regular research meetings and seminars. Within the division, the candidate will work specifically in the Applied Chest Imaging Lab, where she will have access to all of the data bases and image analysis tools necessary to complete the proposed project. With the guidance of her mentors, Drs. George Washko, a leader in pulmonary research using quantitative chest imaging and director of ACIL, and Bartolome Celli, a world-renowned COPD clinical researcher, the principal investigator has formulated a comprehensive five-year training program to develop the skills necessary to become an independent physician-scientist conducting patient-oriented research on the association between COPD and cardiovascular disease. This curriculum includes advanced training in cardiac and respiratory pathophysiology, biostatistics, and clinical trial work, as well as in thoracic and cardiovascular imaging. In addition to her mentors, the candidate will have regular interactions with a committee of advisors with expertise relevant to the proposal. The candidate is dedicated to academic medicine and clinical research and hopes to build a career based on better understanding the heterogeneity and systemic manifestations of COPD. Her current proposal probes the mechanical nature of the heart-lung interaction; in future work, she would like to incorporate additional contributors including the important role of molecular and inflammatory mediators, more broadly considering COPD phenotypes through imaging- and biomolecular-based approaches. Ultimately, she would like to design and perform clinical and translational studies to assess therapies for patients with cardiopulmonary disease and in particular, understand how treatment of one condition (either through medical or surgical approaches) impacts the outcomes of another, and how therapies may be better targeted through improved diagnostic tools

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）非常常见，在美国影响多达2400万人，并且与相当大且不断增加的发病率和死亡率相关。心脏合并症在COPD患者中普遍存在，并显著导致健康结局恶化。事实上，研究表明，在COPD患者中，心脏死亡原因比COPD相关原因更常见。虽然COPD和心血管疾病有一个共同的风险因素，吸烟，但很明显，它们的关联是多因素的，超越了这种共同的风险。影响这种关系的因素之一是心脏和肺在闭合胸腔中的共同位置。研究表明，许多COPD患者的肺容量增加，这种过度充气会损害心脏功能。在本职业发展建议书中，申请人假设过度充气的COPD患者的异常心脏性能至少部分与胸内血容量分布的变化有关（即，心室前负荷和后负荷的改变），可以通过放气来纠正。她建议使用一种新的非侵入性技术来更详细地了解过度充气和心脏性能之间的关系。具体而言，她将利用计算机断层扫描血管测量来非侵入性地估计胸腔内血液的分布，并评估该分布如何随肺容量的变化而变化，并进一步与正常人和不同COPD严重程度患者在静息和运动期间的心腔大小和功能相关。 在她的第一个目标中，她将探索肺容量，胸内血管口径的CT测量值，以及基于人群的队列（心脏研究）中的心腔大小和功能之间的关系。该队列将使她能够制定实质外胸内血管和肺小血管的尺寸和关系的标准值。在她的第二个目标中，使用来自国家肺气肿治疗试验的数据，她将评估肺放气（通过肺减容手术）和经肺动脉压对胸内血管口径的影响。使用该队列还将允许她将其CT血管测量与心脏充盈压和功能的侵入性测量相关联。最后，在她的第三个目标中，她将确定CT血管测量是否可以预测运动期间的心脏性能。这项研究的结果可能会对疾病的发病机制产生新的见解，并表明哪些患者将从药物或手术放气中获益最大。 这项工作将在哈佛医学院的核心教学医院布里格姆妇女医院的肺部和重症监护医学科进行。该部门在培训医生科学家方面有着出色的记录，是全国任何肺科部门中最大的NIH拨款组合之一，并与多个地方和国家机构合作。定期的研究会议和研讨会为智力刺激提供了丰富的机会。在该部门内，候选人将专门在应用胸部成像实验室工作，在那里她将有权访问完成拟议项目所需的所有数据库和图像分析工具。在她的导师乔治沃什科博士（使用定量胸部成像进行肺部研究的领导者和ACIL主任）和Bartolome Celli博士（世界知名的COPD临床研究人员）的指导下，主要研究者制定了一个全面的五年培训计划，以培养成为独立的医生-科学家所需的技能，以患者为导向开展COPD与心血管疾病之间的相关性研究。该课程包括心脏和呼吸病理生理学，生物统计学和临床试验工作以及胸部和心血管成像方面的高级培训。除了导师之外，候选人还将与具有提案相关专业知识的顾问委员会进行定期互动。 该候选人致力于学术医学和临床研究，并希望在更好地了解COPD的异质性和全身表现的基础上建立职业生涯。她目前的建议探索心肺相互作用的机械性质;在未来的工作中，她希望纳入其他贡献者，包括分子和炎症介质的重要作用，通过成像和生物分子为基础的方法更广泛地考虑COPD表型。最终，她想设计和执行临床和转化研究，以评估心肺疾病患者的治疗方法，特别是了解一种疾病的治疗（通过药物或手术方法）如何影响另一种疾病的结果，以及如何通过改进的诊断工具更好地靶向治疗。