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，其特征是肺功能进行性丧失，导致呼吸困难增加和生活质量下降。虽然美国肺损伤的主要机制是吸烟，但这种情况是由于肺气肿和气道疾病的混合。这种不可预测的混合组织病理是无法分辨的常规肺功能的肺活量测量。这导致招募非常大量的受试者进入临床研究，包括各种亚群的疾病。最近，NHLBI提出了一项共识声明，明确需要新技术来“表型”COPD的肺成分，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和肺功能临床指标的独立预测因子。本应用程序的目的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活量测定参数相关联。目的2涉及我们在目的1中定义的气道疾病的新CT衍生指标的组织学验证。在Aim 3中，我们的新型气道疾病CT测量方法将应用于COPD遗传流行病学调查（1 RO1 HL089897和1 RO1 HL089856-01A1）前瞻性收集的受试者队列。在当地招募的受试者中，我将使用布里格姆妇女医院首创的技术对气道吸气阻力、顺应性和传导进行生理测量。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，可能为慢性阻塞性肺疾病的临床研究提供一种非侵入性的生物标志物。这项研究计划的目标是通过John J. Reilly博士（公认的慢性阻塞性肺病临床研究者）、Edwin Silverman博士（COPD研究遗传流行病学国家联合首席研究员，公认的慢性阻塞性肺病临床/遗传学研究专家）和Ron Kikinis博士（定量图像分析和解释专家）的积极合作实现的。（摘要结束）

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)