Using Computed Tomographic Imaging as a biomarker for Clinical COPD Research

描述(由申请人提供)：COPD是一种异质性的肺部疾病，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，但这种情况是由肺气肿和呼吸道疾病混合造成的。通过常规的肺功能肺活量测量，这种不可预测的组织病理混合是无法辨别的。这导致了大量受试者被招募到临床研究中，以包括各种疾病亚型。最近，NHLBI提出了一项共识声明，明确了需要新的技术来对COPD的肺成分进行表型，包括基于图像的分析。我们的总体假设是，COPD患者的呼吸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。此应用程序的目标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参数相关联。目标2涉及对我们在目标1中定义的新的呼吸道疾病CT衍生指标的组织学验证。在目标3中，我们的新的呼吸道疾病CT指标将应用于从COPD遗传流行病学调查(1 RO1 HL089897和1 RO1 HL089856-01A1)中收集的前瞻性队列受试者。在当地注册的受试者中，我将使用布里格姆妇女医院首创的技术对呼吸道吸气阻力、顺应性和电导进行生理学测量。验证这些呼吸道疾病指标，并与CT评估肺气肿负担的相关性，可为慢性阻塞性肺疾病的临床研究提供一种无创性的生物标志物。这项研究计划的目标是通过以下各方的积极合作实现的：公认的慢性阻塞性肺病临床研究员约翰·J·赖利医学博士、慢性阻塞性肺病研究遗传流行病学的国家联合首席调查员埃德温·西尔弗曼博士、公认的慢性阻塞性肺病临床/遗传学研究专家、以及定量图像分析和解释专家罗恩·基基尼斯博士。(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)