Defining the role of early pulmonary vascular disease in COPD

定义早期肺血管疾病在慢性阻塞性肺病中的作用

• 批准号: 8861973
• 负责人: ERIC Alfred HOFFMAN
• 金额: $ 79.07万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8861973
• 关键词: 3-Dimensional; Acute; Adopted; Anatomy; Biological; Biological Markers; Blood Vessels; Blood Volume; Blood flow; Chest; Chronic Obstructive Airway Disease; Clinical; Cohort Studies; Complex; Development; Disease; Disease Progression; Etiology; Evaluation; Frequencies; Funding; Geometry; Goals; Heterogeneity; Hypoxia; Image; Image Analysis; Individual; Inflammation; Intervention; Laboratories; Lesion; Longitudinal Studies; Lung; Measures; Methodology; Methods; Outcome Measure; Parents; Pathology; Patients; Perfusion; Peripheral; Phenotype; Physiological; Population; Predisposition; Protocols documentation; Pulmonary Emphysema; Pulmonary Hypertension; Resolution; Respiratory physiology; Risk; Role; Scanning; Smoker; Smoking; Staging; Structural defect; Structure; Study Subject; Target Populations; Techniques; Testing; Time; Tissues; Tobacco smoke; Trees; United States National Institutes of Health; Vascular Diseases; X-Ray Computed Tomography; alveolar destruction; animal data; base; cohort; contrast enhanced; detector; follow-up; imaging modality; improved; indexing; innovation; novel; novel therapeutics; pressure; public health relevance; pulmonary function; repaired; response; tool; vascular abnormality; vascular bed; vasoconstriction

 DESCRIPTION (provided by applicant): Our goal is to understand how thoracic multi detector-row computed tomography (MDCT) combined with innovative image analysis techniques can be used to identify COPD patients at greatest risk. The overall objective of this proposal is to focus on the pulmonary vasculature. We hypothesize that novel quantitative MDCT-based metrics that characterize heterogeneity of pulmonary parenchymal perfusion and pulmonary vascular anatomy in early stage COPD subjects will allow us to identify subjects at greater risk for rapid disease progression. Numerous observations from our own laboratories and others point to an abnormal pulmonary vascular response to smoking induced parenchymal inflammation that leads to the development of emphysema. We have established imaging methods for the quantitative assessment of the pulmonary vascular tree and regional pulmonary parenchymal perfusion status. The former measure takes advantage of volumetric MDCT and the later makes use of dual energy MDCT (DE-MDCT) to provide clinically implementable tools for the interrogation of lung structure and function. Our Specific Aims are as follows: (1) determine whether objective, quantitative measures of increased PBV heterogeneity derived from DE-MDCT, as an index of emphysema susceptibility, will serve as a very early indicator of rapid emphysema progression (assessed by MDCT) and lung function decline; (2) determine whether anatomic changes in pulmonary vascular geometry will identify subjects at risk for more rapid emphysema progression and lung function decline, possibly in more urgent need of intervention; and (3) determine whether early anatomic and functional markers of vascular disease will combine to identify subjects at increased risk for development of frequent exacerbations who require more intense therapy before significant lung function decline has occurred. In this time-sensitive proposal, we will leverage the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). SPIROMICS offers a unique opportunity to study at risk smokers and individuals with COPD in a longitudinal study that are well-characterized in terms of repeated clinical, physiological and biological evaluations. We propose to insert a baseline DE-MDCT scan to evaluate an index of pulmonary perfusion heterogeneity (Perfused Blood Volume: PBV) in 200 GOLD 0/I subjects at baseline and to insert a 3rd year MDCT exam into the SPIROMICS protocol for these same individuals. We also propose a year 3 MDCT exam in an additional 125 GOLD II-III SPIROMICS subjects. Our over-riding goal is to evaluate early functional and anatomic indices of vascular dysfunction to determine the association between these metrics and rate of emphysema progression, lung function decline and risk of AECOPD.

 描述（由申请人提供）：我们的目标是了解如何使用胸部多排计算机断层扫描 (MDCT) 与创新图像分析技术相结合来识别风险最大的 COPD 患者。该提案的总体目标是关注肺血管系统。我们假设，基于 MDCT 的新型定量指标能够表征早期 COPD 受试者肺实质灌注和肺血管解剖的异质性，这将使我们能够识别疾病快速进展风险更大的受试者。我们自己的实验室和其他实验室的大量观察结果表明，肺血管对吸烟引起的实质炎症反应异常，从而导致肺气肿的发展。我们建立了定量评估肺血管树和局部肺实质灌注状态的成像方法。前者利用体积MDCT，后者利用双能MDCT（DE-MDCT）为检查肺结构和功能提供临床上可实施的工具。我们的具体目标如下：（1）确定 DE-MDCT 得出的 PBV 异质性增加的客观、定量测量（作为肺气肿易感性指标）是否将作为肺气肿快速进展（通过 MDCT 评估）和肺功能下降的早期指标； (2) 确定肺血管几何形状的解剖学变化是否将识别处于肺气肿更快进展和肺功能下降风险的受试者，可能更迫切需要干预； (3)确定血管疾病的早期解剖和功能标志物是否会结合起来，以识别经常恶化的风险增加的受试者，这些受试者在肺功能发生显着下降之前需要更强烈的治疗。在这个时间敏感的提案中，我们将利用 COPD 研究中的亚人群和中间结果测量 (SPIROMICS)。 SPIROMICS 提供了一个独特的机会，可以通过纵向研究来研究高危吸烟者和慢性阻塞性肺病患者，这些研究在重复的临床、生理和生物学评估方面具有良好的特征。我们建议插入基线 DE-MDCT 扫描，以评估基线时 200 名 GOLD 0/I 受试者的肺灌注异质性指数（灌注血量：PBV），并将第三年 MDCT 检查插入到这些相同个体的 SPIROMICS 方案中。我们还建议在第 3 年额外进行 125 个 GOLD II-III SPIROMICS 科目的 MDCT 考试。我们的首要目标是评估血管功能障碍的早期功能和解剖指标，以确定这些指标与肺气肿进展率、肺功能下降和 AECOPD 风险之间的关联。