Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers

吸烟者纤维化和肺气肿的独特和重叠途径

基本信息

批准号：
9113651
负责人：
Augustine M Choi
金额：
$ 241.09万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-06 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9113651
关键词：
Address Autophagocytosis Basic Science Bronchoscopy Chest Chronic Obstructive Airway Disease Chronic lung disease Cigarette Smoker Clinical Clinical/Radiologic Communities DNA Methylation Data Development Disease Epidemiology Epigenetic Process Experimental Models Fibrosis Future Gene Expression Genetic Goals Hamman-Rich syndrome Health Individual Lung Lung diseases Molecular Analysis Molecular Target Outcome Pathogenesis Pathway interactions Patients Pattern Phenotype Predisposition Pulmonary Emphysema Pulmonary Fibrosis Reporting Research Personnel Risk Risk Factors Role Science of genetics Smoker Smoking Statistical Data Interpretation TGFB1 gene Tissue Sample Total Lung Capacity Visual Work X-Ray Computed Tomography biobank cigarette smoking cigarette smoking cohort interest molecular phenotype mouse model programs respiratory

项目摘要

DESCRIPTION (provided by applicant): Cigarette smoking is the greatest known single risk factor for the development of lung disease, being a dominant risk for the development of both emphysema and idiopathic pulmonary fibrosis. While pulmonary fibrosis and emphysema can co-exist in the same individual, our recent report indicates that subclinical idiopathic pulmonary fibrosis (IPF) is inversely associated with total lung capacity and emphysema in smokers. Along with the fact that most former smokers with IPF do not have radiographic evidence of emphysema, suggests that these patterns of disease are likely to be due to distinct consequences of smoking reflecting unique individual susceptibilities, and its associated differential pathogenetic pathway(s). We have assembled a team of investigators who have worked efficiently and synergistically to better understand the mechanism(s) by which cigarette smoke can induce either fibrotic or emphysematous, or both phenotype. We have integrated the expertise of investigators from COPD and IPF community, both basic and translational, to come together to tackle this important challenge. The impact of reaching this major goal will be significant in the pulmonary community as we hope to unravel new molecular targets and/or treatment(s) for COPD and IPF. We will attempt to reach our goals by the addressing the following projects and cores: Projects: 1) Homeostatic Role of Autophagy in Lung Emphysema and Fibrosis 2) Genetic Modifiers of TGF-Beta1 and Cigarette Smoke in Fibrosis and Emphysema 3) Genetics and Epigenetics of COPD and IPF 4) Clinical Outcomes and Molecular Phenotypes in Smokers with Parenchymal Lung Disease Cores: 1) Administrative Core 2) Respiratory Computational Discovery Core 3) Clinical Biorepository Core 4) Murine Models and Molecular Analysis Core

描述（由申请人提供）：吸烟是肺部疾病发展的最大的单一危险因素，是肺气肿和特发性肺纤维化发展的主要风险。虽然肺纤维化和肺气肿可以在同一个人中共存，但我们最近的报告表明亚临床特发性肺纤维化（IPF）与吸烟者中的总肺活量和肺气肿成反比。除了大多数患有IPF的前吸烟者没有肺气肿的放射学证据的事实，这些疾病模式可能是由于吸烟反映了独特的个体敏感性的明显后果，其相关的不同病原途径（S）。我们已经组建了一个研究人员团队，他们在有效，协同工作中的工作，以更好地理解香烟烟雾可以诱导纤维化或过滤或两者兼有表型的机制。我们已经整合了COPD和IPF社区的调查人员的专业知识，包括基本和翻译，以解决这一重要挑战。达到这一主要目标的影响在肺部社区将是重要的，因为我们希望揭开COPD和IPF的新分子靶标和/或治疗。 We will attempt to reach our goals by the addressing the following projects and cores: Projects: 1) Homeostatic Role of Autophagy in Lung Emphysema and Fibrosis 2) Genetic Modifiers of TGF-Beta1 and Cigarette Smoke in Fibrosis and Emphysema 3) Genetics and Epigenetics of COPD and IPF 4) Clinical Outcomes and Molecular Phenotypes in Smokers with Parenchymal Lung Disease Cores: 1)行政核心2）呼吸计算发现核心3）临床生物座核4）鼠模型和分子分析核心