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

描述（由申请方提供）：特发性肺纤维化（IPF）是最常见和最严重的间质性肺病（ILD），对当前药物治疗的反应最小，死亡率与许多终末期恶性肿瘤相当。越来越多的人意识到IPF可能会过渡到无症状阶段，其中主要可检测到的异常是放射学异常。我们相信，风险因素的修改和医疗 在早期阶段开始治疗，将改善对有发生IPF风险的患者的护理。然而，对于这一领域的进展，必须开发全面的临床，放射学，生理学和分子特征，以确定哪些受试者发生肺纤维化的风险最大。最近，我们证明了在胸部计算机断层扫描（CT）上有间质性肺异常（ILA）的吸烟者，与没有ILA的吸烟者相比，先前未被诊断为ILD的吸烟者的总肺容量、运动能力和肺气肿降低。我们假设其中一些ILA受试者发生IPF的风险增加。为了实现我们的假设，我们将利用现有的胸部CT，组织病理学和基因型数据，从大型良好的表型队列。该提议具有以下具体目的：目的1）我们将利用COPDGene和Frachial Heart研究队列来鉴定ILA和ILA进展的临床预测因子;目的2）使用具有术前胸部CT和肺组织标本的受试者的Brigham and Women's Hospital队列，我们将确定ILA和间质性肺炎/肺纤维化的组织病理学证据之间的相关性;目的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学相关性。

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.