Role of polyunsaturated fatty acids in pulmonary fibrosis

项目总结/文摘

PROJECT SUMMARY/ABSTRACT My goal is to become an independent clinical and translational researcher in interstitial lung disease (ILD) which I outline in this 5-year K23 Career Development Award application. The central goal of my proposal is to establish omega-3 fatty acid intake (as measured in plasma phospholipids), as a novel risk factor in idiopathic pulmonary fibrosis (IPF). IPF is a chronic form of interstitial lung disease in older adults with few available medical therapies and a poor prognosis with a median survival of 3 to 4 years. This proposal builds upon my preliminary data showing that higher plasma phospholipid levels of omega-3 fatty acids were associated with less subclinical ILD on CT and a lower risk of ILD-related hospitalization and mortality among community-dwelling adults. Among adults with clinically diagnosed ILD, my data shows omega-3 fatty acid plasma phospholipid levels were correlated with higher forced vital capacity and exercise capacity. My data are consistent with mouse studies that show administration of omega-3 fatty acids attenuates lung injury and fibrosis which may be driven by production of omega-3 derived pro-resolving lipid mediators (SPMs). Under the mentorship of Dr. Imre Noth, I propose to examine the associations of plasma phospholipid omega-3 fatty acid levels and their metabolites (SPMs) with disease severity and progression in adults with IPF. I will correlate circulating levels of omega-3 derived SPMs with the lung and identify distinct gene expression profiles and pathways by different SPM levels. I have crafted a rigorous 5-year career development plan that includes training in respiratory epidemiology (co- mentor: Dr. Barr) fatty acid biology (co-mentor: Dr. Leitinger), biostatistics (co-mentor: Dr. Ma), and clinical- translational research and ILD (primary mentor: Dr. Noth) that will position me to become a clinical and translational independent investigator in patient-oriented research. By achieving the aims of this K23 proposal, I will establish polyunsaturated fatty acids as a novel modifying factor in IPF leading me to identify specific phenotypes that will benefit the most from omega-3 therapy and design and implement future clinical trials.