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: 9268442
• 负责人: Carolyn E Come
• 金额: $ 19.98万
• 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 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268442
• 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 Abnormalities; Heart Rate; Heterogeneity; Hospitals; Hypoxia; Image; Image Analysis; Impairment; Impedance Cardiography; Inferior; Inferior vena cava structure; Inflammation; Inflammation Mediators; Institution; Left; Lung; Lung Volume Reductions; Lung volume reduction surgery; Magnetic Resonance; Measurable; Measurement; Measures; Mechanics; Medical; Medicine; Mentors; Modality; Molecular; Morbidity - disease rate; Nature; Operative Surgical Procedures; Outcome; Oxygen; Pathogenesis; Patients; Performance; Pharmacology; Physicians; Physiologic pulse; Positioning Attribute; Principal Investigator; Publishing; Pulmonary Emphysema; Pulmonary Heart Disease; Pulmonary artery structure; Pulmonary veins; Pulmonary vessels; Radiology Specialty; Randomized; Research; Research Personnel; Respiratory physiology; Rest; 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; Vascular remodeling; 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 cancer screening; lung volume; medical schools; meetings; mortality; novel; patient oriented research; patient subsets; population based; pressure; respiratory; risk sharing; skills; tool; translational study; treatment trial; 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）：慢性阻塞性肺病 (COPD) 非常常见，在美国影响着多达 2400 万人，并且与相当大且不断增加的发病率和死亡率相关。心脏合并症在慢性阻塞性肺病患者中很常见，并且会导致健康状况恶化。事实上，研究表明，在慢性阻塞性肺病患者中，心脏原因死亡甚至比慢性阻塞性肺病相关原因更常见。虽然慢性阻塞性肺病和心血管疾病有一个共同的危险因素——吸烟，但很明显，它们之间的关联是多因素的，超出了这种共同的风险。影响这种关系的因素之一是心脏和肺在封闭的胸廓中的共享位置。研究表明，许多慢性阻塞性肺病患者的肺容量增加，这种过度膨胀会损害心脏功能。在此职业发展提案中，申请人假设过度充气的 COPD 患者的异常心脏功能至少部分与胸腔内血容量分布的变化（即心室前负荷和后负荷的变化）有关，而胸腔内血容量的分布变化可以通过通气来纠正。她建议使用一种新颖的无创技术来更详细地了解恶性通货膨胀与心脏功能之间的关系。具体来说，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的血液分布，并评估该分布如何随肺容量的变化而变化，以及与正常人和运动时的心室大小和功能的关系。不同程度 COPD 严重程度的患者。 在她的第一个目标中，她将在基于人群的队列中探索肺容量、胸腔内血管口径的 CT 测量以及心室大小和功能之间的关系（弗雷明汉心脏研究）。该队列将使她能够制定胸腔内实质外血管和小肺血管的大小和关系的标准值。她的第二个目标是利用国家肺气肿治疗试验的数据，评估肺通缩（通过肺减容手术）和跨肺压对胸内血管口径的影响。该队列的使用还将使她能够将 CT 血管测量值与心脏充盈压和功能的侵入性测量值关联起来。最后，她的第三个目标是确定 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发病机制产生新的见解，并表明哪些患者将从药物或手术通气中获得最大的益处。 这项工作将在哈佛医学院核心教学医院布莱根妇女医院的肺科和重症监护医学科进行。该部门在培训医师科学家方面拥有出色的记录，是美国国立卫生研究院肺科部门中获得最多资助的项目之一，并与多个地方和国家机构合作。定期的研究会议和研讨会有丰富的激发智力的机会。在该部门内，候选人将专门在应用胸部成像实验室工作，在那里她将可以访问完成拟议项目所需的所有数据库和图像分析工具。在导师的指导下，博士。使用定量胸部成像进行肺部研究的领导者、ACIL 主任 George Washko 和首席研究员 Bartolome Celli 是世界著名的 COPD 临床研究员，他们制定了一个全面的五年培训计划，以培养成为独立治疗师所需的技能。医生科学家对慢性阻塞性肺病和心血管疾病之间的关联进行以患者为导向的研究。该课程包括心脏和呼吸病理生理学、生物统计学、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，候选人还将与具有与提案相关的专业知识的顾问委员会定期互动。 该候选人致力于学术医学和临床研究，希望在更好地了解慢性阻塞性肺病的异质性和系统表现的基础上建立自己的职业生涯。她目前的提议探讨了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，通过基于成像和生物分子的方法更广泛地考虑 COPD 表型。最终，她希望设计并进行临床和转化研究，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，以及治疗方法如何通过改进的诊断工具更好地定位

项目成果

A randomised trial of lung sealant versus medical therapy for advanced emphysema.

• DOI: 10.1183/09031936.00205614
• 发表时间: 2015-09
• 期刊: The European respiratory journal
• 作者: Come CE;Kramer MR;Dransfield MT;Abu-Hijleh M;Berkowitz D;Bezzi M;Bhatt SP;Boyd MB;Cases E;Chen AC;Cooper CB;Flandes J;Gildea T;Gotfried M;Hogarth DK;Kolandaivelu K;Leeds W;Liesching T;Marchetti N;Marquette C;Mularski RA;Pinto-Plata VM;Pritchett MA;Rafeq S;Rubio ER;Slebos DJ;Stratakos G;Sy A;Tsai LW;Wahidi M;Walsh J;Wells JM;Whitten PE;Yusen R;Zulueta JJ;Criner GJ;Washko GR
• 通讯作者: Washko GR