Computed Tomographic-Based Assessment of Airway Remodeling in COPD

描述(申请人提供)：慢性阻塞性肺疾病(COPD)是一种异质性的肺部疾病，以进行性肺功能丧失为特征，随后呼吸困难加剧，生活质量恶化。这种情况是由于肺气肿和呼吸道重塑的混合体造成的。这种不可预测的组织病理混合物，用常规的肺功能肺活量测量是无法辨别的。计算机断层扫描(CT)越来越多地被用来描述COPD患者的肺气肿和呼吸道疾病。然而，传统的呼吸道CT测量方法在评估气道重塑方面是有限的。申请者开发了新的呼吸道CT测量方法，可以深入了解呼吸道的机械特性及其在晚期肺气肿中的消失。在这份职业发展建议书中，申请人假设CT呼吸道特征可以独立预测COPD的临床表现和疾病进展。该应用程序的目标1包括对两种新的呼吸道CT指标进行组织学验证。目标2的目标是分析COP基因研究的胸部CT扫描，并将气道扩张性(衡量从呼气末呼吸到完全吸气时的气道内径变化的指标)和总气道计数(衡量近端气道脱落的指标)与肺活量参数、疾病的临床表现和运动能力联系起来。在目标3中，申请者将在ECLIPSE研究的CT扫描中测量总气道计数，然后确定总气道计数预测肺功能下降、COPD恶化和死亡率的能力。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。通过国际知名的慢性阻塞性肺疾病临床研究员Bartolome Celli医学博士和定量CT成像领域的著名内科研究员George ashko医学博士的积极合作，这项研究计划的目标是可能的。(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)