Computed Tomographic-Based Assessment of Airway Remodeling in COPD

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）是一种异质性肺部疾病，其特征为肺功能进行性丧失，随后呼吸困难加重，生活质量恶化。这种情况是由于肺气肿和气道重塑的混合物。这种不可预测的组织病理学混合物是用常规肺功能肺活量测定法无法辨别的。计算机断层扫描（CT）越来越多地用于表征COPD中的肺气肿和气道疾病。然而，传统的气道CT测量方法在评估气道重塑方面存在局限性。申请人已经开发了新的气道CT度量，其提供了对气道的机械特性及其在晚期肺气肿中的消失的洞察。在本职业发展建议书中，申请人假设CT气道特征可以独立预测COPD的临床表现和疾病进展。本申请的目的1涉及气道的两种新型CT度量的组织学验证。目的2的目的是分析COP基因研究的胸部CT扫描，并将气道扩张性（从潮气末呼吸到完全吸气的气道内径变化的测量值）和总气道计数（近端气道脱落的测量值）与肺功能参数、疾病的临床表现和运动能力相关联。在目标3中，申请方将测量ECLIPSE研究CT扫描的总气道计数，然后确定总气道计数预测肺功能下降、COPD急性加重和死亡率的能力。这些基于CT的气道指标有可能用作COPD临床研究的非侵入性生物标志物。通过Bartolome Celli博士，M.D.，国际知名的COPD临床研究者和乔治沃什科医学博士，理学硕士，他是定量CT成像领域的杰出医师研究员。(End摘要）

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by progressive loss of lung function with subsequent increasing breathlessness and worsening quality of life. The condition is due to an admixture of emphysema and airways remodeling. This unpredictable mixture of tissue pathology is indiscernible with conventional spirometric measures of lung function. Computed tomography (CT) is increasingly being used to characterize emphysema and airway disease in COPD. However, classic CT measures of the airways are limited for assessing airway remodeling. The applicant has developed novel CT metrics of airways that provide insight into both the mechanical properties of airways and their disappearance in advanced emphysema. In this career development proposal, the applicant hypothesizes that CT airway characteristics can independently predict clinical manifestations and disease progression in COPD. Aim 1 of this application involves the histologic validation of two novel CT metrics of airways. The goal of Aim 2 is to analyze chest CT scans from the COP Gene Study and correlate airway distensibility (a measure of the change in airway inner diameter from end tidal breathing to full inspiration) and total airway count (a measure of proximal airway drop out) with spirometric parameters, clinical manifestations of disease, and exercise capacity. In Aim 3, the applicant will measure total airway count on CT scans from the ECLIPSE Study and then determine the ability of total airway count to predict decline in lung function, COPD exacerbations, and mortality. These CT-based airway metrics have the potential to be used as non-invasive biomarkers for clinical investigation in COPD. The aims of this research proposal are possible through the active collaboration of Dr. Bartolome Celli, M.D., an internationally renowned clinical investigator in COPD and Dr. George Washko M.D., M.M.Sc., a prominent physician investigator in quantitative CT imaging. (End of Abstract)