Defining the role of early pulmonary vascular disease in COPD

 描述(由申请人提供)：我们的目标是了解如何结合创新的图像分析技术使用胸部多排计算机断层扫描(MDCT)来识别风险最高的COPD患者。该提案的总体目标是将重点放在肺血管上。我们假设，基于多层螺旋CT的新的定量指标表征了早期COPD患者肺实质灌注和肺血管解剖的异质性，将使我们能够识别出疾病快速进展的更大风险的受试者。来自我们自己的实验室和其他实验室的大量观察表明，吸烟引起的实质炎症导致肺血管异常反应，导致肺气肿的发展。我们已经建立了定量评估肺血管树和区域肺实质灌注状态的成像方法。前者利用容积多层螺旋CT的优势，后者利用双能量多层螺旋CT(DE-MDCT)为肺结构和功能的检查提供了临床可操作的工具。我们的具体目标如下：(1)确定来自DE-MDCT的PBV异质性增加的客观、定量指标，作为肺气肿易感性的指标，是否将作为快速肺气肿进展(MDCT评估)和肺功能下降的非常早期的指标；(2)确定肺血管几何结构的变化是否将确定有可能出现更快的肺气肿进展和肺功能下降的风险，可能更迫切地需要干预；以及(3)确定血管疾病的早期解剖和功能标志物是否将结合使用血管疾病的早期解剖和功能标志物来确定在肺功能显著下降之前需要更密集治疗的频繁加重的风险增加的患者。在这个时间敏感的提案中，我们将利用COPD研究中的亚群和中间结果指标(SPIROMICS)。SPIROMICS提供了一个独特的机会来研究有风险的吸烟者和COPD患者，这项纵向研究在重复的临床、生理和生物学评估方面具有很好的特点。我们建议插入基线DE-MDCT扫描，以评估在基线时200名GOLD 0/I受试者的肺灌注异质性指数(血流灌注量：PBV)，并在SPIROMICS方案中加入针对这些相同个体的3年MDCT检查。我们还建议在另外125门GOLD II-III SPIROMICS科目中进行3年级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。

 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.