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将胸部多探测器行计算机断层扫描（MDCT）与创新的图像分析技术相结合，以识别最高风险的COPD患者。本提案的总体目标是关注肺血管。我们假设，描述早期COPD受试者肺实质灌注和肺血管解剖结构异质性的基于定量MDCT的新指标将使我们能够识别疾病快速进展风险更高的受试者。我们自己的实验室和其他实验室的大量观察表明，吸烟引起的肺实质炎症会导致肺气肿的发生，从而导致肺血管异常反应。我们已经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。前者利用容积MDCT的优势，后者利用双能量MDCT（DE-MDCT）提供临床可实施的工具，用于询问肺的结构和功能。我们的具体目标如下：（1）确定是否客观，定量测量来自DE-MDCT的PBV异质性增加，作为肺气肿易感性的指标，将作为肺气肿快速进展的早期指标（通过MDCT评估）和肺功能下降;（二）确定肺血管几何结构的解剖学变化是否能识别出有更快肺气肿进展和肺功能风险的受试者下降，可能更迫切地需要干预;和（3）确定血管疾病的早期解剖学和功能标志物是否将结合联合收割机以识别在显著肺功能下降发生之前需要更强烈治疗的处于发生频繁恶化的增加的风险的受试者。在这个时间敏感的提案中，我们将利用COPD研究（SPIROMICS）中的亚群和中间结局指标。SPIROMICS提供了一个独特的机会，可以在一项纵向研究中研究高危吸烟者和COPD患者，该研究在重复的临床、生理和生物学评价方面具有良好的特征。我们建议在200例GOLD 0/I受试者中插入基线DE-MDCT扫描，以评价基线时肺灌注异质性指数（灌注血量：PBV），并在这些受试者的SPIROMICS方案中插入第3年MDCT检查。我们还建议在另外125名GOLD II-III SPIROMICS受试者中进行第3年MDCT检查。我们的首要目标是评价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风险之间的相关性。

 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.