Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities

7.项目总结 这项建议的主要目标是描述遗传和基因组图谱的特征。 那些从早期肺纤维化(PF)发展和进展的人。 特发性肺纤维化(IPF)是最常见和最严重的肺间质纤维化，具有 死亡率与许多终末期恶性肿瘤相当。尽管取得了进展，但 对于IPF的药物治疗，越来越多的人认识到，进一步尝试 改善IPF患者的预后将需要另外关注预防 从早期但可检测的PF阶段进展到PF的末期，这有助于 定义IPF。最近的证据表明，研究参与者特别是 胸部CT异常(称为间质性肺异常[ILA])可具有 症状与IPF患者相似。从这项工作中获得的见解包括 尽管据报道，尽管ILA在50岁的成年人中比IPF更普遍(7-9%) BE(占人口的0.002-0.04%)，患有ILA的研究参与者可以有基因 IPF患者注意到的预测因素，限制性生理和运动障碍， 放射学进展，肺功能加速下降，并增加 死亡。基于这些发现，我们假设ILA在某些情况下代表和 IPF的早期/轻度阶段将导致大量的遗传和 这两种情况之间的基因组预测因子。此外，我们假设 早期/轻度PF的全面遗传和基因组图谱不仅将 提高了我们对早期疾病发病机制的认识，但也可以转化为 进行临床测试，这将有助于确定哪些人有最大的患病风险， 和进步，来自PF。为了解决这些假设，我们提出了以下具体建议 目标：目标1)基因图谱是否可以在那些从 PF的早期阶段？目的2)能否确定肺和外周血的基因组图谱 在那些从PF的早期发展和进步的人中？和目标3)是否可以 临床数据以及遗传和基因组数据的整合提高了我们对 早期的疾病发病机制，并使疾病的早期发现，PF？结果是 这些研究将提高我们对PF早期疾病发病机制的理解，因为 并为针对早期机构小说和现有医学的试验奠定了基础 对有IPF风险的人进行治疗。

7. Project Summary The primary objective of this proposal is to characterize the genetic and genomic profiles of those who develop, and progress from, early stages of pulmonary fibrosis (PF). Idiopathic pulmonary fibrosis (IPF), the most common and severe form of PF, has a mortality rate comparable to that of many end-stage malignancies. Despite advances in medical therapy for IPF, it is becoming increasing recognized that further attempts to improve outcomes for patients with IPF will need to additionally focus on preventing very early, but detectable, stages of PF from progressing to the end-stages of PF that help to define IPF. Recent evidence has demonstrated that research participants with particular patterns chest CT abnormalities (termed interstitial lung abnormalities [ILA]) can have a syndrome similar to that observed in IPF patients. Insights from this work include the fact that although ILA are more prevalent (7-9% in adults > age 50) than IPF is reported to be (0.002-0.04% of the population), research participants with ILA can have genetic predictors noted in IPF patients, restrictive physiologic and exercise impairments, radiologic progression, accelerated lung function decline, and an increased risk for death. Based on these findings, we hypothesize that ILA, in some cases, represent and early/mild stage of IPF which will result in a substantial overlap in the genetic and genomic predictors between these two conditions. Furthermore, we hypothesize that comprehensive genetic and genomic profiles of early/mild stages of PF, will not only improve our understanding of early disease pathogenesis, but can also be translated into clinical tests that will help to determine those who are at the greatest risk to develop, and progress, from PF. To address these hypotheses we propose the following specific aims: Aim 1) Can genetic profiles be identified in those who develop, and progress from, early stages of PF? Aim 2) Can lung and peripheral blood genomic profiles be identified in those who develop, and progress from, early stages of PF? And Aim 3) Can the integration of clinical, as well as genetic and genomic data improve our understanding of early disease pathogenesis, and enable early disease detection for, PF? The results of these studies will improve our understanding of early disease pathogenesis in PF, as well as setting the stage for trials aimed at the early institution novel and existing medical therapies in those at risk for IPF.