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）：慢性阻塞性肺疾病（COPD）非常普遍，影响了美国多达2400万人，并且与大量和增加的发病率和死亡率有关。 COPD患者的心脏合并症普遍存在，并显着促进健康结果。实际上，研究表明，在患有COPD的患者中，心脏原因比与COPD相关的原因更为普遍。尽管COPD和心血管疾病具有共同的危险因素，但很明显，他们的关联是多因素，超出了这种共同的风险。一个o影响关系的因素是心脏和肺在封闭的胸腔笼中的共同位置。已经表明，许多COPD患者的肺量增加，并且这种过度充气会损害心脏表现。在这项职业发展建议中，申请人假设，高浮力COPD患者的心脏异常性能至少与胸腔血容量的分布变化有关（.e。可以通过屈曲来校正的室性血容量变化）。她建议使用一种新型的非侵入性技术来对过度通货膨胀和心脏性能之间的关系有更详细的了解。具体而言，她将利用计算机断层图血管测量，非侵入性地估计胸部内的血液分布，并评估该分布如何随肺体积的变化而变化，并且进一步涉及与心脏腔室的大小和功能有关，在正常性和运动过程中的静止性和功能不同。 在她的第一个目标中，她将探索基于人群的队列中的肺体积，胸腔腔口径的CT测量以及心脏腔室的大小和功能（Framingham Heart研究）。该队列将使她能够为脑外鞘腹血管和小肺部血管的大小和关系发展规范值。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，她将评估肺部通气的影响（通过肺部体积减少手术）和转肺压力对胸腔内血管口径的影响。该队列的使用还将使她能够将其CT血管测量与心脏填充压力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过程中的心脏表现。这项研究的结果可能会产生对疾病发病机理的新见解，并表明哪些患者将在药理学或手术放气中获得最大的好处。 这项工作将在哈佛医学院核心教学医院Brigham and妇女医院的肺和重症监护医学部门进行。该部门拥有培训医师科学家的出色记录，该部门是该国任何肺部部门最大的NIH赠款投资组合之一，并与多家地方和国家机构合作。定期的研究会议和研讨会有很多智力刺激的机会。在该部门内，候选人将在应用的胸部成像实验室中专门工作，在那里她将可以访问所有数据库和图像分析工具，以完成拟议的项目。在她的导师的指导下，博士。首席研究员乔治·沃沃科（George Washko）是使用定量胸部成像和ACIL主管的领导者，也是世界知名的COPD临床研究人员Bartolome Celli，他已经制定了一项全面的五年培训计划，以开发一项必要的技能，以成为一项独立的医生 - 科学家与科普德和Cardiovascult Cardiovascult Caspascustalsival病之间的独立医师 - 科学家指导性研究。该课程包括心脏和呼吸病理生理学，生物统计学和临床​​试验工作以及胸腔和心血管成像中的高级培训。除了她的导师外，候选人还将与顾问委员会定期进行与该提案有关的专业知识的互动。 候选人致力于学术医学和临床研究，并希望基于更好地了解COPD的异质性和系统性表现而建立职业。她目前的建议探究了心肺相互作用的机械性质。在将来的工作中，她想结合其他贡献者，包括分子和炎症介质的重要作用，更广泛地考虑通过基于成像和基于生物分子的方法来考虑COPD表型。最终，她想设计和执行临床和翻译研究，以评估心肺疾病患者的疗法，尤其是了解一种疾病的治疗（通过医疗或手术方法）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来更好地靶向治疗

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