Pulmonary Vascular Disease as a Contributor to Respiratory Morbidity in Chronic Obstructive Pulmonary Disease

肺血管疾病是慢性阻塞性肺疾病呼吸系统疾病发病的一个原因

• 批准号: 10621941
• 负责人: Aparna Balasubramanian
• 金额: $ 19.82万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621941
• 关键词: Address; Adult; Affect; Alveolar capillary destruction; Alveolus; American; Award; Biometry; Blood Vessels; Blood flow; Cardiac Catheterization Procedures; Cardiology; Caring; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Trials; Cohort Studies; Development; Diagnostic tests; Diffusion; Disease; Disease Management; Echocardiography; Environment; Epidemiology; Evaluation; Foundations; Funding; Future; Gases; Guidelines; Impairment; Individual; Institution; International; Intervention; Knowledge; Longitudinal Studies; Longitudinal cohort; Lung; Lung Capacity; Magnetic Resonance Imaging; Measurement; Measures; Mentorship; Methodology; Modality; Morbidity - disease rate; Multicenter Studies; Outcome; Participant; Patients; Physiological; Population; Procedures; Prospective cohort; Pulmonary Hypertension; Pulmonary Vascular Resistance; Radiology Specialty; Recommendation; Recording of previous events; Research; Research Design; Research Personnel; Research Priority; Resources; Right ventricular strain; Severities; Severity of illness; Site; Specificity; Symptoms; Techniques; Testing; Therapeutic; Therapeutic Trials; Time; Training; United States; United States National Institutes of Health; Validation; Vascular remodeling; cardiac magnetic resonance imaging; career development; clinically relevant; cohort; comorbidity; diagnosis standard; diagnostic accuracy; functional status; health related quality of life; hemodynamics; improved outcome; insight; mortality; multidisciplinary; multimodality; novel; novel marker; prevent; prognostic; prospective; pulmonary arterial pressure; pulmonary vascular disorder; respiratory morbidity; right ventricular failure; skills; study population; vascular bed

Project Summary/Abstract Chronic obstructive pulmonary disease (COPD) occurs in over 15 million adults in the US. As many as 35% of those patients develop pulmonary vascular disease (PVD), but the recommendations for assessment and management of PVD in COPD have been limited by key knowledge gaps. Firstly, assessment of the pulmonary vasculature has relied upon invasive right heart catheterization as the gold standard, limiting studies to select populations with severe PVD. Noninvasive techniques, though widely available, have also been primarily validated in populations with severe PVD applying markers that are likely to reflect end-stage PVD, such as right ventricular failure. As a result, another key knowledge gap is the unknown contribution of PVD to COPD morbidity across its observed spectrum of severity. While the concomitant presence of severe PVD is observed to portend increased morbidity and mortality compared to those with COPD alone, the contribution of less severe PVD, at potentially more intervenable points in the disease course is less well-understood. This proposal seeks to address these knowledge gaps in three aims by (SA1) testing the diagnostic accuracy of three noninvasive markers that are selected for plausible sensitivity to early PVD, (SA2) and applying these noninvasive markers to understand the contribution of PVD to respiratory morbidity in cross-sectional and (SA3) longitudinal study designs. This application will add noninvasive markers to a general COPD cohort unselected for PVD and will further assemble a prospective longitudinal cohort of COPD patients enriched for PVD with the same noninvasive testing. The results of this proposal will identify novel noninvasive approaches for assessing PVD, define their clinical relevance across the spectrum of PVD, and establish opportunities to study the use of noninvasive markers as candidate outcomes in clinical trials targeting the pulmonary vasculature to manage COPD. Dr. Balasubramanian’s proposal is a strong training vehicle for her career development, offering her skills in hands-on cohort study design and execution, advanced biostatistical and epidemiologic methodology, and noninvasive and invasive assessment of PVD in COPD through numerous modalities including right heart catheterization, magnetic resonance imaging, speckle-tracking echocardiography, and physiologic measurements of diffusing capacity of the lung. Dr. Balasubramanian will be supported by a strong multi- disciplinary mentorship team with expertise in COPD, pulmonary hypertension, cardiology, radiology, and biostatistics. She further will leverage an exceptional institutional environment with its collaborative and supportive culture, extensive intellectual and physical resources, and strong history of supporting junior investigators. This award will establish Dr. Balasubramanian as an independent investigator with a unique research niche, distinct from her mentorship team, and establish a foundation for future studies evaluating and managing PVD in COPD.

项目总结/摘要 慢性阻塞性肺疾病（COPD）发生在美国超过1500万成年人中。多达 这些患者中有35%发生肺血管疾病（PVD），但评估建议 COPD中PVD的治疗和管理受到关键知识缺口的限制。首先，评估 肺血管依赖于有创右心导管插入术作为金标准，限制了研究 选择患有严重PVD的人群。非侵入性技术，虽然广泛使用，也已被 主要在重度PVD人群中验证，应用可能反映终末期PVD的标记物， 例如右心室衰竭。因此，另一个关键的知识差距是PVD对 观察到的严重程度范围内的COPD发病率。虽然严重PVD的伴随存在是 与单纯COPD患者相比， 不太严重的PVD，在疾病过程中潜在的更多的干预点是不太好理解的。这 该提案旨在通过（SA 1）测试以下三个目标的诊断准确性来解决这些知识差距： 选择三种非侵入性标志物，用于对早期PVD的合理敏感性（SA 2），并应用这些标志物 非侵入性标志物，以了解PVD对呼吸系统发病率的影响， (SA3)纵向研究设计。本申请将为一般COPD队列添加无创性标志物 并将进一步收集COPD患者的前瞻性纵向队列， PVD采用相同的非侵入性测试。这项建议的结果将确定新的非侵入性方法 评估PVD，定义其在PVD范围内的临床相关性，并建立机会， 研究非侵入性标志物作为靶向肺动脉高压的临床试验中的候选结局的使用 治疗COPD。 Balasubramanian博士的建议是她职业发展的一个强大的培训工具，为她提供 动手队列研究设计和执行的技能，先进的生物统计学和流行病学方法， 通过多种方式（包括右心）对COPD患者的PVD进行无创和有创评估 导管插入术、磁共振成像、斑点追踪超声心动图和生理 肺弥散量的测量。Balasubramanian博士将得到一个强大的多- 学科导师团队，拥有COPD、肺动脉高压、心脏病学、放射学和 生物统计学她还将利用一个特殊的机构环境， 支持文化，广泛的智力和物质资源，以及支持青少年的强大历史 investigators.该奖项将建立博士Balasubramanian作为一个独立的研究人员与独特的 研究利基，从她的导师团队不同，并建立了未来的研究评估和基础， 在COPD中管理PVD。