Using Computed Tomographic Imaging as a biomarker for Clinical COPD Research

描述（由申请人提供）：COPD是一种异质性肺部疾病，其特征为肺功能进行性丧失，导致呼吸困难加重和生活质量下降。虽然在美国肺损伤的主要机制是香烟烟雾暴露，但这种情况是由于肺气肿和气道疾病的混合物。这种不可预测的组织病理学混合是无法通过肺功能的常规肺量计测量来辨别的。这导致临床研究招募了大量受试者，以纳入各种疾病亚组。最近，NHLBI提出了一项共识声明，规定需要新的技术来“表型”COPD的肺部成分，包括基于图像的分析。我们的总体假设是COPD患者的气道特征是疾病病理生理学和肺功能临床指标的独立预测因子。本申请的目的1是分析来自3个独立队列的胸部CT扫描，并将结构特征与临床和肺功能参数相关联。目标2涉及我们的新的CT衍生指标的气道疾病定义在目标1的组织学验证。在目标3中，我们的新型气道疾病CT指标将应用于从COPD遗传流行病学研究中前瞻性收集的受试者队列（1个RO 1 HL 089897和1个RO 1 HL 089856 - 01 A1）。在当地招募的受试者中，我将使用布莱根妇女医院开创的技术进行气道吸气阻力、顺应性和传导性的生理测量。验证这些气道疾病的测量方法，并研究它们与CT评估的肺气肿负担的相互依赖性，可以提供一种非侵入性工具，用作慢性阻塞性肺疾病临床研究的生物标志物。本研究提案的目的是通过以下人员的积极合作实现的：John J. Reilly博士（医学博士，COPD的公认临床研究者）、Edwin Silverman博士（医学博士，哲学博士，COPD遗传流行病学调查的国家共同主要研究者，COPD临床/遗传学研究的公认专家）和罗恩Kikinis博士（医学博士，定量图像分析和解释专家）。 (End摘要）

DESCRIPTION (provided by applicant): COPD is a heterogeneous lung condition characterized by progressive loss of lung function causing increasing breathlessness and loss of quality of life. While the predominant mechanism of lung injury in the US is cigarette smoke exposure, the condition is due to an admixture of emphysema and airways disease. This unpredictable mix of tissue pathology is indiscernible by conventional spirometric measures of lung function. This has lead to the recruitment of very large numbers of subjects into clinical studies to include the various subsets of disease. Recently, the NHLBI put forth a consensus statement specifying the need for new techniques to "phenotype" the pulmonary component of COPD, including image-based analysis. Our overall hypothesis is that airway characteristics in subjects with COPD are independent predictors of disease pathophysiology and clinical indices of lung function. Aim 1 of this application is to analyze chest CT scans from 3 independent cohorts and correlate the structural characteristics with clinical and spirometric parameters. Aim 2 involves the histologic validation of our novel CT derived metrics of airways disease defined in Aim 1. In Aim 3, our novel CT measures of airway disease will be applied to a prospectively collected cohort of subjects from the Genetic Epidemiology of COPD Investigation (1 RO1 HL089897 and 1 RO1 HL089856-01A1). In subjects enrolled locally, I will perform physiologic measures of airway inspiratory resistance, compliance and conductance using techniques pioneered at Brigham and Women's Hospital. Validation of these measures of airway disease and investigation of their interdependence with the CT assessed burden of emphysema may provide a non-invasive tool to be used as a biomarker for clinical investigation in chronic obstructive pulmonary disease. The aims of this research proposal are possible through the active collaboration of Dr. John J. Reilly, MD, a well recognized clinical investigator in COPD, Dr. Edwin Silverman MD, PhD, the national co-primary investigator of the Genetic Epidemiology of COPD Investigation and a well recognized specialist in clincial/genetics research of COPD, and Dr. Ron Kikinis, MD, an expert in quantitative image analysis and interpretation. (End of Abstract)