Understanding the interstitial phenotype of impaired respiratory health through CT imaging and blood biomarkers

项目总结 NRSA个人博士后奖学金的目标是促进加布里埃尔·刘博士的发展 作为一名独立的内科科学家和呼吸道流行病学的领导者，专注于初级 间质性肺病(ILD)的预防和拦截。这位候选人和她的导师设计了一个 根据她在内科、肺部内科和临床方面的背景制定的具体培训计划 调查，她的目标是开始作为一名独立调查员的职业生涯。该计划包括 在授课期间，通过(1)旨在扩展她的知识的课程来发展额外的技能 和临床研究技术培训，(2)与赞助商和 合作者，包括肺部、高级成像和流行病学方面的人员，以及(3)受监督的 国家资助的研究项目。 该项目的总体科学目标是确定亚临床ILD和受损的标志物。 呼吸健康与间质表型通过两个主要的特定目标：(1)确定什么是血液 生物标记物与中年CT肺损伤相关(CARDIA第25年)和(2)决定CT是否 CARDIA第25年的肺损伤和蛋白质生物标记物与视力的发展相关 在CARDIA第35年发现间质性肺异常。这将是第一次获得这两个定量数据的研究 肺损伤的测量以及对间质性肺异常的定性和目测评估 青年冠心病风险(CARDIA)队列。CARDIA的队列有多种优势， 包括18-30岁的年轻人的原始入学人数，51%的参与者认为是黑人或 非裔美国人，并有35年的跟踪数据。在NHLBI研讨会关于 慢性肺病的一级预防：间质性肺病，列为优先研究领域 正在改进及早发现疾病的战略。作者认为有必要开发方法 客观地测量CT扫描特征，以便筛查大量面临未来发展风险的人群 肺纤维化。我们的提案通过验证一种新的成像方法来推进这一既定目标 客观检测肺损伤早期表现及相关血浆生物标志物 CT肺损伤和未来的ILA可能允许进行精细化的ILD风险评估。 这个项目，连同拟议的课程作业和导师计划，将使刘博士成为 精通临床研究方法，注重纵向队列研究、数据分析和 管理、高级图像分析和科学写作。作为该项目的一部分开发的技能将 为今后对亚临床ILD的血液和影像生物标志物的研究提供指导 目标是在间质性肺病的最早阶段拦截它。

PROJECT SUMMARY The goal of this NRSA individual postdoctoral fellowship is to facilitate Dr. Gabrielle Liu’s development as an independent physician-scientist and a leader in respiratory epidemiology, with a focus on the primary prevention and interception of interstitial lung disease (ILD). The candidate and her mentors have designed a specific training plan that builds upon her background in internal medicine, pulmonary medicine, and clinical investigation and aims toward launching her career as an independent investigator. This plan includes developing additional skills during the award period through (1) coursework designed to expand her knowledge and training in clinical research techniques, (2) interaction with a multidisciplinary team of sponsors and collaborators, including those in pulmonary, advanced imaging and epidemiology, and (3) a supervised research project with national funding. The overall scientific objective of this project is to identify markers of subclinical ILD and impaired respiratory health with an interstitial phenotype through two primary specific aims: (1) determine what blood biomarkers are associated with CT lung injury in middle age (CARDIA year 25) and (2) determine whether CT lung injury and protein biomarkers at CARDIA year 25 are associated with the development of visually identified interstitial lung abnormalities in CARDIA year 35. This will be the first study to obtain both quantitative measures of lung injury as well as qualitative, visual assessments of interstitial lung abnormalities in the Coronary Artery Disease Risk in Young Adults (CARDIA) cohort. The CARDIA cohort has multiple strengths, including the original enrollment of young adults aged 18-30, 51% of participants identifying as Black or African-American, and having 35 years of follow-up data. In the report from the NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases: Interstitial Lung Disease, the first priority research area listed was improving strategies for early detection of disease. The authors argue for the need to develop methods that objectively measure CT scan features in order to screen large populations at risk for future development of pulmonary fibrosis. Our proposal advances that stated goal by validating a novel imaging method for objectively detecting the earliest manifestations of lung injury and determining plasma biomarkers associated with CT lung injury and future ILA that may allow for refined ILD risk assessment. This project, along with the proposed coursework and mentorship plan, will allow Dr. Liu to become proficient in clinical research methodology with an emphasis on longitudinal cohort studies, data analysis and management, advanced imaging analysis, and scientific writing. The skills developed as part of this project will serve as a guide for future investigation into both blood and imaging biomarkers of subclinical ILD that can be targeted to intercept interstitial lung disease at its earliest stages.