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 该提议的主要目的是表征遗传和基因组概况 从肺纤维化（PF）的早期阶段发展和发展的人中。 特发性肺纤维化（IPF）是PF的最常见和严重形式，具有 死亡率与许多终点恶性肿瘤相当。尽管进步 IPF的医疗疗法，人们越来越认识到进一步的尝试 IPF患者的改善结果将需要额外专注于预防 早期，但可以检测到的PF阶段从进展到PF的末端阶段，有助于 定义IPF。最近的证据表明，具有特定特定的研究参与者 模式胸部CT异常（称为间质肺异常[ILA]）可以具有 综合征类似于IPF患者中观察到的综合征。这项工作的见解包括事实 尽管ILA比IPF更普遍（成人> 50岁）比IPF更普遍（7-9％） BE（占人口的0.002-0.04％），ILA的研究参与者可以具有遗传 IPF患者指出的预测因素，限制性生理和运动障碍， 放射学进展，加速肺功能下降以及增加的风险 死亡。基于这些发现，我们假设ILA在某些情况下代表并 IPF的早期/轻度阶段将导致遗传和 这两个条件之间的基因组预测因子。此外，我们假设 PF的早期/轻度阶段的全面遗传和基因组谱，不仅将 提高我们对早期疾病发病机理的理解，但也可以翻译 进入临床测试，这些测试将有助于确定那些面临最大风险的人 和进步，来自PF。为了解决这些假设，我们提出以下特定 目的：目标1）可以在那些发展和进步的人中确定遗传特征 PF的早期阶段？目标2）可以鉴定肺和外周血基因组特征 在那些从PF的早期发展和发展的人中？目标3）可以 临床的整合以及遗传和基因组数据提高了我们对 早期疾病发病机理，并实现早期疾病检测，PF？结果 这些研究将提高我们对PF早期疾病发病机理的理解，因为 以及为针对早期机构小说和现有医学的试验奠定阶段 患有IPF风险的人的疗法。