Role of polyunsaturated fatty acids in pulmonary fibrosis

多不饱和脂肪酸在肺纤维化中的作用

基本信息

批准号：
10356093
负责人：
John S Kim
金额：
$ 17.16万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-02-20 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10356093
关键词：
Address Adult Anti-Inflammatory Agents Attenuated Biological Biological Markers Biology Biometry Bronchoalveolar Lavage Fluid CD59 Antigen Carbon Monoxide Cessation of life Chronic Clinical Clinical Trials Communities Data Development Plans Diffuse Disease Progression Docosahexaenoic Acids Eicosanoid Production Elderly Enrollment Epidemiology Extracellular Matrix Fatty Acids Fibrosis Foundations Future Gene Expression Goals Hospitalization Individual Inflammatory Intake Interstitial Lung Diseases K-Series Research Career Programs Lead Ligands Light Lung Lung Transplantation Matrilysin Measures Mediating Medical Mentors Mentorship Multi-Institutional Clinical Trial Mus Omega-3 Fatty Acids Omega-6 Fatty Acids Oxidative Stress PPAR gamma Participant Pathogenesis Pathway interactions Patients Phenotype Phospholipids Pilot Projects Plasma Polyunsaturated Fatty Acids Positioning Attribute Pre-Clinical Model Production Prognosis Property Prospective cohort Pulmonary Fibrosis Pulmonary Inflammation Pulmonary Surfactant-Associated Protein D Research Research Personnel Respiratory Failure Risk Risk Factors Role Sample Size Sampling Serum Severity of illness Therapeutic Therapy Clinical Trials Time Training Translational Research Vital capacity Walking alveolar epithelium antifibrotic treatment base beta-Chemokines biobank career development cell injury clinical diagnosis cohort design exercise capacity fibrotic interstitial lung disease fibrotic lung hospitalization rates idiopathic pulmonary fibrosis lipid mediator lung injury modifiable risk mortality mouse model novel novel marker patient oriented research personalized medicine population based pulmonary function respiratory secondary outcome symptomatic improvement therapy design transcriptome sequencing transcriptomics translational scientist

项目摘要

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.

项目概要/摘要我的目标是成为间质性肺疾病 (ILD) 的独立临床和转化研究员我在这份 5 年 K23 职业发展奖申请中概述了这一点。我的提案的中心目标是建立 omega-3 脂肪酸摄入量（以血浆磷脂测量）作为特发性肺病的新危险因素纤维化（IPF）。 IPF 是老年人的一种慢性间质性肺疾病，几乎没有可用的药物治疗预后较差，中位生存期为 3 至 4 年。该提案基于我的初步数据显示较高的血浆 omega-3 脂肪酸磷脂水平与较少的亚临床 ILD 相关 CT 以及降低社区居住成年人 ILD 相关住院和死亡率的风险。之中对于临床诊断为 ILD 的成年人，我的数据显示 omega-3 脂肪酸血浆磷脂水平与较高的用力肺活量和运动能力相关。我的数据与小鼠研究一致表明服用 omega-3 脂肪酸可以减轻肺损伤和纤维化，这可能是由产生 omega-3 衍生的促分解脂质介质 (SPM)。在伊姆雷·诺特博士的指导下，我提议检查血浆磷脂 omega-3 脂肪酸水平及其代谢物的关联 (SPM) 与 IPF 成人疾病严重程度和进展有关。我将关联 omega-3 的循环水平衍生出肺部的 SPM，并通过不同的 SPM 水平识别不同的基因表达谱和途径。我制定了严格的 5 年职业发展计划，其中包括呼吸道流行病学培训（合作）导师：Barr博士）脂肪酸生物学（共同导师：Leitinger博士）、生物统计学（共同导师：马博士）和临床- 转化研究和 ILD（主要导师：Noth 博士）将使我成为一名临床和以患者为导向的研究中的转化独立研究者。通过实现 K23 提案的目标，我将建立多不饱和脂肪酸作为 IPF 的新型调节因子，使我能够确定特定的将从 omega-3 治疗中获益最多的表型，并设计和实施未来的临床试验。