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

• 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
• 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

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）：吸烟是发展肺部疾病的最已知的单一危险因素，是发展肺气肿和特发性肺纤维化的主要风险。虽然肺纤维化和肺气肿可以在同一个体中共存，但我们最近的报告表明，亚临床特发性肺纤维化（IPF）与吸烟者的总肺活量和肺气肿呈负相关。大多数患有 IPF 的前吸烟者没有肺气肿的放射学证据，这表明这些疾病模式可能是由于吸烟的独特后果造成的，反映了独特的个体易感性及其相关的差异致病途径。我们组建了一个研究小组，他们高效、协同地工作，以更好地了解香烟烟雾诱发纤维化或肺气肿或两种表型的机制。我们整合了 COPD 和 IPF 界研究人员的基础专业知识和转化专业知识，共同应对这一重要挑战。实现这一主要目标将对肺部界产生重大影响，因为我们希望找到 COPD 和 IPF 的新分子靶点和/或治疗方法。我们将尝试通过解决以下项目和核心来实现我们的目标： 项目：1) 自噬在肺气肿和纤维化中的稳态作用 2) 纤维化和肺气肿中 TGF-Beta1 和香烟烟雾的基因修饰剂 3) COPD 和 IPF 的遗传学和表观遗传学 4) 患有实质肺病的吸烟者的临床结果和分子表型 核心：1) 管理核心 2) 呼吸计算发现核心 3) 临床生物样本库核心 4) 小鼠模型和分子分析核心