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，其特征是肺功能进行性丧失，随后呼吸困难增加，生活质量恶化。这种情况是由于肺气肿和气道重塑的混合。这种不可预测的混合组织病理是无法与传统肺功能的肺活量测量方法。计算机断层扫描（CT）越来越多地被用于表征COPD患者的肺气肿和气道疾病。然而，气道的经典CT测量在评估气道重塑方面是有限的。申请人开发了气道的新型CT指标，该指标可以深入了解气道的机械特性及其在晚期肺气肿中的消失。在本职业发展建议中，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。本应用的目的1涉及气道两种新型CT指标的组织学验证。Aim 2的目的是分析来自COP基因研究的胸部CT扫描，并将气道扩张率（从末潮汐呼吸到完全吸气时气道内径变化的测量值）和气道总计数（近端气道退出的测量值）与肺活量测定参数、疾病临床表现和运动能力相关联。在Aim 3中，申请人将测量ECLIPSE研究中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加重和死亡率的能力。这些基于ct的气道指标有可能被用作COPD临床研究的非侵入性生物标志物。通过国际知名COPD临床研究者Bartolome Celli博士和George Washko博士的积极合作，这项研究计划的目标得以实现。他是定量CT成像领域的杰出医师研究者。（摘要结束）

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)