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

项目摘要 这个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 作为一名独立的医生-科学家和呼吸流行病学的领导者， 预防和阻断间质性肺病（ILD）。候选人和她的导师设计了一个 具体的培训计划，建立在她的背景，在内科，肺医学和临床 她的目标是开始她作为一名独立调查员的职业生涯。该计划包括 在获奖期间，通过（1）旨在扩大知识面的课程学习， 和临床研究技术培训，（2）与多学科申办者团队的互动， 合作者，包括那些在肺，先进的成像和流行病学，和（3）监督 国家资助的研究项目。 本项目的总体科学目标是确定亚临床ILD和受损ILD的标志物， 通过两个主要的具体目标来确定具有间质表型的呼吸健康：（1）确定什么样的血液 生物标志物与中年（CARDIA 25岁）CT肺损伤相关，以及（2）确定CT是否 CARDIA第25年的肺损伤和蛋白质生物标志物与视觉发育相关。 在第35年的CARDIA中发现了间质性肺异常。这将是第一个研究，以获得定量的 肺损伤的测量以及间质性肺异常的定性、目视评估， 年轻人冠状动脉疾病风险（CARDIA）队列。CARDIA队列具有多种优势， 包括最初登记的18-30岁的年轻人，51%的参与者认为自己是黑人或 非裔美国人，有35年的随访数据。在《国家法律文书》讲习班关于 慢性肺疾病的一级预防：间质性肺疾病，列为第一优先研究领域 正在改进疾病早期检测的策略。作者认为有必要制定方法 客观地测量CT扫描特征，以筛查未来发展的风险人群， 肺纤维化我们的提案通过验证一种新的成像方法来推进所述目标， 客观地检测肺损伤的最早表现并确定相关的血浆生物标志物 CT肺损伤和未来ILA可能允许精细ILD风险评估。 这个项目，沿着拟议的课程和导师计划，将使刘博士成为 精通临床研究方法，重点是纵向队列研究，数据分析和 管理，先进的成像分析和科学写作。作为该项目一部分开发的技能将 作为未来研究亚临床ILD的血液和成像生物标志物的指南， 旨在在最早期阻断间质性肺病。

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.