Interstitial Lung Abnormalities: Defining the Phenotype, Causes, and Consequences

间质性肺异常：定义表型、原因和后果

• 批准号: 9295054
• 负责人: GARY MATTHEW HUNNINGHAKE
• 金额: $ 63.32万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9295054
• 关键词: Animal Model; Awareness; Belief; Biology; Case Study; Cicatrix; Clinical; Clinical/Radiologic; Cohort Studies; Data; Detection; Diagnosis; Disease; Epidemiology; Epigenetic Process; Experimental Models; Family member; Framingham Heart Study; Genes; Genetic; Genotype; Hamman-Rich syndrome; Histopathology; Hospitals; Human; Inflammasome; Institutes; Institutional Review Boards; Interstitial Lung Diseases; Interstitial Pneumonia; Lead; Left; Link; Lung; Lung diseases; MUC5B gene; Malignant Neoplasms; Medical; Methylation; Modification; Molecular; Molecular Profiling; Pathologic; Patient Care; Patients; Pattern; Pharmacotherapy; Phenotype; Physiological; Pulmonary Emphysema; Pulmonary Fibrosis; Radiology Specialty; Research; Resolution; Respiratory Signs and Symptoms; Rheumatoid Arthritis; Risk; Risk Factors; Smoke; Smoker; Smoking; Specimen; Structure of parenchyma of lung; Testing; Tobacco smoke; Total Lung Capacity; Variant; Woman; X-Ray Computed Tomography; chest computed tomography; clinical predictors; cohort; density; exercise capacity; genetic epidemiology; genetic variant; high risk; improved; insight; interstitial; lung volume; mortality; outcome forecast; public health relevance

DESCRIPTION (provided by applicant): Idiopathic pulmonary fibrosis (IPF), the most common and severe interstitial lung disease (ILD), is minimally responsive to current medical therapies, and has a mortality rate comparable to that of many end-stage malignancies. There is increasing awareness that IPF may transition through an asymptomatic stage where the primary detectable abnormalities are radiologic. It is our belief that risk factor modification and medical therapies, when instituted at an early stage, will lead to improved care for patients at risk to develop IPF. However, for this field to progress it will be imperative to develop comprehensive clinical, radiologic, physiologic, and molecular profiles to determine which subjects are at greatest risk to develop pulmonary fibrosis. Recently we demonstrated that smokers with interstitial lung abnormalities (ILA) on chest computed tomography (CT), who had not been previously diagnosed with ILD, had reduced total lung capacity, exercise capacity, and emphysema compared to smokers without ILA. We hypothesize that some of these subjects with ILA are at increased risk to develop IPF. To pursue our hypothesis we will capitalize on existing chest CTs, histopathologic, and genotypic data from large well-phenotyped cohorts. This proposal has the following Specific Aims: Aim 1) We will identify the clinical predictors of ILA and ILA progression utilizing both the COPDGene and Framingham Heart Study cohorts; Aim 2) Using a Brigham and Women's Hospital cohort of subjects with both preoperative chest CTs and lung tissue specimens we will determine the correlation between ILA and histopathologic evidence of interstitial pneumonitis/pulmonary fibrosis and; Aim 3) we will evaluate the genetics and epigenetic correlations between ILA and IPF utilizing the above cohorts.

描述（由申请人提供）：特发性肺纤维化（IPF）是最常见和最严重的间质性肺疾病（ILD），对当前的药物治疗反应最小，死亡率与许多终末期恶性肿瘤相当。人们越来越认识到，特发性肺纤维化可能会经历无症状阶段，其中主要可检测到的异常是放射学的。我们相信风险因素的改变和医疗 如果在早期阶段开始治疗，将改善对有患 IPF 风险的患者的护理。然而，为了使这一领域取得进展，必须开发全面的临床、放射学、生理和分子特征，以确定哪些受试者发生肺纤维化的风险最大。最近，我们证明，胸部计算机断层扫描 (CT) 上显示间质性肺异常 (ILA) 的吸烟者（之前未诊断出 ILD）与没有 ILA 的吸烟者相比，其肺总量、运动能力和肺气肿均有所降低。我们假设其中一些患有 ILA 的受试者患 IPF 的风险增加。为了实现我们的假设，我们将利用来自大型良好表型队列的现有胸部 CT、组织病理学和基因型数据。该提案有以下具体目标： 目标 1) 我们将利用 COPDGene 和弗雷明汉心脏研究队列确定 ILA 和 ILA 进展的临床预测因子；目标 2) 使用布莱根妇女医院的受试者队列以及术前胸部 CT 和肺组织标本，我们将确定 ILA 与间质性肺炎/肺纤维化的组织病理学证据之间的相关性；目标 3）我们将利用上述队列评估 ILA 和 IPF 之间的遗传学和表观遗传相关性。