Detection: Lung Imaging and Profiling

检测：肺部成像和分析

• 批准号: 7231245
• 负责人: Richard A Pierce
• 金额: $ 42.41万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231245
• 关键词: Affect; Alveolar; Attention; B-Lymphocytes; Breathing; CD8B1 gene; Chronic; Chronic Obstructive Airway Disease; Classification Scheme; Collaborations; Detection; Disease; Elastin; Exposure to; Future; Gases; Genetic; Gold; Heterogeneity; Histology; Image; Imaging technology; Immune; Immunologics; Individual; Infiltration; Inflammatory; Inflammatory Response; Institution; Lead; Lesion; Link; Lung; Lung Transplantation; Lung diseases; Lung volume reduction surgery; Lymphoid; Magnetic Resonance Imaging; Matrix Metalloproteinases; Measures; Methods; Microarray Analysis; Mucous body substance; Nature; Obstruction; Particulate Matter; Pathogenesis; Pathology; Patients; Peripheral; Persons; Principal Investigator; Process; Pulmonary Emphysema; RNA library; Research Infrastructure; Resistance; Resolution; Resources; Sampling; Severities; Severity of illness; Site; Staging; Stimulus; Structure; Structure of parenchyma of lung; Surface; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Time; Tissues; Transplantation; airway obstruction; alveolar destruction; cell type; disease phenotype; expiration; immunopathology; in vivo; lung imaging; macrophage; novel strategies; programs; regional difference; repaired; size; small airways disease

The defining feature of chronic obstructive pulmonary disease (COPD) is irreversible airflow limitation measured during forced expiration. This results from a varying combination of increased airflow resistance in the small airways and decreased elastic recoil due to emphysematous destruction of lung tissue. We recently showed that significant obstruction of the small airways is present in the lungs of patients with advanced emphysema and that the inflammatory response in the peripheral lung tissue correlates with the severity of COPD as gauged by the GOLD classification scheme. Quantitative analysis of the inflammatory response found strong correlation with the level of lung infiltration by CD8+ T cells, B cells, and macrophages and suggested that these cell types may specially serve to drive the COPD phenotype. Using CT and 3He magnetic resonance imaging (3He MRI) to quantitatively assess regional differences in small airway obstruction and emphysematous destruction in severe COPD, our imaging group has found that regions of mild to moderate disease are found adjacent to sites of severe destruction or obstructive disease even in patients with GOLD 4-stage disease. We hypothesize that the different levels of lesion severity represent different stages in the pathogenesis of the lesions. Our active lung transplantation program, expertise in new imaging technologies and the ability to conduct quantitative analysis of the inflammatory response and tissue remodeling afford a unique opportunity to construct new criteria for assessment of COPD patients. We propose to investigate the pathogenesis of GOLD 4-stage COPD in patients awaiting lung transplant with the following Specific Aims: 1) To test the hypothesis that there is progression in both extent and severity of the inflammatory immune process in regions affected by moderate to severe degrees of emphysema and small airway disease, using morphologic analysis and quantitative immunopathology to characterize the inflammatory immune process. 2) To noninvasively quantify the regional extent and severity of disease separately in subjects with severe COPD using 3He MRI and high-resolution CT imaging. 3) To validate the in-vivo and ex-vivo imaging results in Aim II against the histology in Aim I in order to develop a new approach to quantifying both the extent and severity of emphysema and small airways disease within the lungs of individual patients with COPD.

慢性阻塞性肺疾病（COPD）的定义特征是不可逆的气流限制