Project Summary Idiopathic pulmonary fibrosis (IPF), the most common and severe form of pulmonary fibrosis (PF), is increasing in prevalence, and has a median survival of 3-5 years. Recent studies have finally demonstrated that anti- fibrotic therapy can reduce the rate of decline in lung function, IPF remains a relentlessly progressive condition in part due to the advanced stages of PF at the time of presentation. There is also evidence that anti-fibrotic therapy reduces progression in patients with less severe disease; which suggests that early detection may improve outcomes. Dr. Putman’s work has shown that the early stages of PF are detectable, that radiologic progression is relatively frequent, is correlated with genetic factors seen in IPF patients (e.g. MUC5B genotype), and is associated with an accelerated rate of lung function decline and an increased risk of death. Although much work has been done to demonstrate that imaging analyses can detect patterns that help to predict adverse outcomes in IPF, it is unclear what radiologic characteristics of ILA best predict accelerated progression and mortality. Additionally, numerous studies have demonstrated that mean telomere length (MTL), and variants in multiple genes controlling MTL are associated with IPF and reduced survival, the role of these factors in determining the progression and mortality associated with ILA is not known. In the first aim, Dr. Putman will identify the radiologic factors, both qualitative and quantitative, that are most associated with the progression of PF, and relate these findings to clinical outcomes. In the second aim she will explore the relationship between reduced MTL and the progression of early stage PF. Finally, in the third aim, using whole genome sequencing data, she will explore the relationship between genetic mutations in the telomerase pathway and progression of early stage pulmonary fibrosis. This work will be performed in the Division of Pulmonary and Critical Care Medicine, at Brigham and Women’s Hospital (BWH), a core teaching hospital of Harvard Medical School. Dr. Putman will perform this work under the mentorship of Dr. Hunninghake, an expert in the field of early pulmonary fibrosis and Dr. Silverman, an expert in COPD genetics. With the guidance of her mentors and scientific advisory committee, Dr. Putman has developed a comprehensive five year training program to develop the skills needed to become an independent investigator with expertise in complex genetic analyses and their integration with image characterization. Dr. Putman is dedicated to a career in academic medicine. Her goal is to become a clinician-scientist using the skills gained during this award to better our understanding of the biologic processes that lead to PF occurrence and progression. She plans to use the knowledge gained from this award to study the downstream consequences of decreased MTL; with the ultimate goal of improving care and outcomes in patients with PF.