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

间质性肺异常发生和进展的遗传和基因组特征

• 批准号: 9982375
• 负责人: MICHAEL H. CHO
• 金额: $ 80.04万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982375
• 关键词: Address; Adult; Age; Cicatrix; Clinical; Clinical Trials; Collaborations; Data; Detection; Development; Disease; Early treatment; Exercise; Fibrosis; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genomics; Goals; Impairment; Individual; Institution; Lead; Lung; MUC5B gene; Malignant Neoplasms; Medical; Mutation; Participant; Pathogenesis; Patient-Focused Outcomes; Patients; Pattern; Pharmaceutical Preparations; Physiological; Population; Population Research; Positioning Attribute; Prevalence; Pulmonary Fibrosis; Pulmonology; Radiology Specialty; Reporting; Research; Respiratory physiology; Risk; Risk Factors; Role; Survival Rate; Syndrome; Telomerase; Testing; Translating; Treatment outcome; Variant; Work; X-Ray Computed Tomography; base; chest computed tomography; cohort; disorder risk; genetic predictors; genetic profiling; genetic risk factor; genetic variant; genome-wide; genomic data; genomic locus; genomic predictors; genomic profiles; genomic signature; idiopathic pulmonary fibrosis; improved; improved outcome; insight; interstitial; mortality; mortality risk; novel; outcome forecast; peripheral blood; predictive modeling; prevent; risk variant; screening

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.

7.项目摘要 本提案的主要目的是描述遗传和基因组概况 肺纤维化（PF）早期发展和进展的患者。 特发性肺纤维化（IPF）是PF最常见和最严重的形式， 死亡率与许多终末期恶性肿瘤相当。尽管取得了进展， 越来越多的人认识到，进一步尝试 改善IPF患者的结局需要额外关注预防非常 早期，但可检测的PF阶段，从进展到PF的终末期，这有助于 定义IPF。最近的证据表明，研究参与者特别 胸部CT异常（称为间质性肺异常[ILA]）可能具有 与IPF患者中观察到的症状相似。从这项工作中获得的见解包括 尽管据报道ILA比IPF更普遍（> 50岁的成人中为7-9%）， 如果研究参与者占总人口的0.002-0.04%，则患有ILA的研究参与者可能具有遗传性 在IPF患者中观察到的预测因素，限制性生理和运动障碍， 放射学进展，加速肺功能下降，增加风险 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，这将导致遗传和 这两种情况之间的基因预测。此外，我们假设， PF早期/轻度阶段的全面遗传和基因组图谱，不仅 提高了我们对疾病早期发病机制的认识，但也可以翻译为 临床试验，这将有助于确定谁是最大的风险发展， 为了解决这些假设，我们提出了以下具体的 目的：目的1）在那些发展和发展的人中， 早期PF？目的2）肺和外周血基因组图谱是否可以鉴定 从PF早期阶段发展并进展的患者中，目标3）可以 临床、遗传和基因组数据的整合提高了我们对 早期疾病发病，使早期疾病检测，PF？的结果 这些研究将提高我们对PF早期发病机制的理解， 以及为针对早期机构的新的和现有的医疗试验奠定基础 治疗有IPF风险的患者。