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

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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.