Individualized Nutrition to Help Asthmatics Improve Lung Function and Energetics (INHALE)

个性化营养帮助哮喘患者改善肺功能和能量（INHALE）

• 批准号: 10724851
• 负责人: Jacob T Mey
• 金额: $ 14.17万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10724851
• 关键词: Address; Adult; Affect; American; Asthma; Award; Bioenergetics; Biological; Biology; Biomedical Research; Biometry; Breathing; Caring; Cell physiology; Cells; Chronic; Clinic; Clinical; Clinical Management; Clinical Research; Clinical Trials Design; Conduct Clinical Trials; Crossover Design; Data; Defect; Development; Diet; Dietitian; Disease; Disease Management; Electron Transport; Evolution; Fatty acid glycerol esters; Functional disorder; Future; Goals; Grant; Growth; Heart Diseases; In Vitro; Individual; Intake; Ketones; Kidney Diseases; Knowledge; Link; Literature; Lung; Lung diseases; Machine Learning; Medical; Medical Nutrition Therapy; Medium chain triglycerides; Mentored Research Scientist Development Award; Mentors; Mentorship; Metabolic; Metabolic Diseases; Metabolism; Methods; Mission; Mitochondria; Modeling; National Heart, Lung, and Blood Institute; Nutrient; Nutritional; Nutritional Study; Nutritional Support; Pathology; Patient Care; Patient-Focused Outcomes; Patients; Permeability; Physicians; Plasma; Play; Prevalence; Productivity; Protons; Quality of life; Randomized; Recommendation; Recording of previous events; Research; Research Personnel; Respiration; Respiratory Failure; Role; Scientist; Services; Smooth Muscle Myocytes; Symptoms; Testing; Training; Translational Research; Translations; Writing; asthmatic; career; career development; clinical application; clinical care; clinical translation; cost; dietary approach; dietary guidelines; educational atmosphere; feeding; improved; individual response; innovation; insight; inter-individual variation; interest; ketogenic diet; metabolomics; mitochondrial metabolism; novel; nutrient metabolism; nutrition; nutritional approach; precision nutrition; professor; programs; pulmonary function; respiratory smooth muscle; response; tool; trial design; vasoconstriction

PROJECT SUMMARY/ABSTRACT Dr. Mey is a productive young scientist applying for this mentored K01 award to transition to an independent research career. He has a strong nutrition (registered dietitian) and metabolism (translational research) background, focusing on metabolic disease. He has a history of growth and productivity throughout the evolution of his research career into his current role as an assistant professor. His recent findings have directed his interest towards a major literature gap: the impact of nutrition on asthma control and lung function – relevant to the mission of NHLBI. An emerging concept in asthma pathophysiology is altered nutrient metabolism and mitochondrial bioenergetics. Nutritional intake has a direct impact on whole-body and cellular nutrient metabolism, and several nutritional approaches show promise to improve lung function. However, well-controlled feeding trials are lacking, leaving a major knowledge gap in our understanding of nutrition in asthma. Further, nutrition research has come under intense scrutiny for major barriers, including inter-individual variability, slow development and poor translation to clinical application. To address this important knowledge gap and overcome critical barriers in nutrition research, the proposed aims will utilize an innovative multi-diet crossover clinical feeding trial design in combination with an n-of-1 qualitative pilot. The feeding trial will test three distinct, fully-provided, isocaloric diets to identify nutritional and metabolic factors that impact asthma control and lung function. This will be followed by a qualitative pilot of an n-of-1 approach, which incorporates patient- informed decisions into the nutrition treatment model and is critical to the progression of individualized nutrition care. Additionally, untargeted plasma metabolomic profiling will be used in combination with machine-learning biostatistics to generate preliminary precision nutrition models for future clinical research. Finally, an in vitro approach will define the mitochondrial defects in airway smooth muscle cells from an asthmatic donor and determine whether chronic ketone exposure can normalize altered mitochondrial bioenergetics. Together, the clinical findings, qualitative pilot and elucidation of a biological mechanism defining the diet-asthma relationship will support Dr. Mey’s transition to independence. To enable Dr. Mey to carry out these aims and transition his nutrition and metabolism expertise into the pulmonary field, Dr. Mey has enlisted the mentorship of 5 established researchers and clinicians for the fulfillment of the training detailed within this project, including: 1) academic and professional development in asthma and mitochondrial biology, 2) clinical management of asthma, 3) support to implement a multi-diet crossover feeding trial, and 4) career development and grant writing guidance. In addition, Dr. Mey assembled a team of 4 collaborators and advisors for technical and scientific insight. Pennington Biomedical Research Center will provide an ideal learning environment, with exceptional core services to conduct clinical trials, supplemented by training with physician-mentors both locally (Tulane) and abroad (Cleveland Clinic). Together, this coordinated clinical-translational training will provide Dr. Mey with the tools to complete the proposed aims, expand his expertise of nutrition and metabolism into the pulmonary field, and establish independence in the pursuit of his long-term goal: to identify precision nutrition approaches for the treatment and management of asthma.

项目概要/摘要 Mey 博士是一位多产的年轻科学家，正在申请这项 K01 指导奖以过渡到独立研究 他拥有深厚的营养学（注册营养师）和新陈代谢（转化研究）背景，专注于研究领域。 从他的研究生涯到他的职业生涯，他都有着成长和生产力的历史。 他目前担任助理教授，最近的发现使他对一个主要的文献空白产生了兴趣：影响。 营养对哮喘控制和肺功能的影响——与 NHLBI 的使命相关。 哮喘病理生理学的一个新兴概念是营养代谢和线粒体营养生物能学的改变。 摄入量对全身和细胞营养代谢有直接影响，几种营养方法显示出前景 然而，缺乏良好控制的喂养试验，这给我们留下了重大的知识空白。 此外，营养研究因主要障碍而受到严格审查， 包括个体间差异、发展缓慢以及临床应用转化不佳。 为了解决这一重要的知识差距并克服营养研究中的关键障碍，拟议的目标将利用 创新的多饮食交叉临床喂养试验设计与 n-of-1 定性试验相结合。 试验将测试三种不同的、全面提供的等热量饮食，以确定影响哮喘的营养和代谢因素 随后将进行 n-of-1 方法的定性试点，其中包括患者- 营养治疗模式中的明智决策对于个体化营养护理的进展至关重要。 此外，非靶向血浆代谢组学分析将与机器学习生物统计学结合使用，以 为未来的临床研究生成初步的精准营养模型。最后，体外方法将定义。 哮喘供体气道平滑肌细胞的线粒体缺陷，并确定是否存在慢性酮 暴露可以使改变的线粒体生物能正常化，临床发现、定性试验和阐明。 定义饮食与哮喘关系的生物机制的研究将支持梅伊博士向独立的过渡。 为了使 Mey 博士能够实现这些目标并将他的营养和代谢专业知识转移到肺部领域， Mey 博士征集了 5 名知名研究人员和反叛者的指导，以完成详细的培训 该项目包括：1）哮喘和线粒体生物学的学术和专业发展，2）临床 哮喘管理，3) 支持实施多种饮食交叉喂养试验，以及 4) 职业发展和资助 此外，Mey 博士还组建了一个由 4 名合作者和顾问组成的团队，以提供技术和科学见解。 彭宁顿生物医学研究中心将为学生提供理想的学习环境和卓越的核心服务 进行临床试验，并辅以本地（杜兰）和国外（克利夫兰）医师导师的培训 总之，这种协调的临床转化培训将为 Mey 博士提供完成该项目的工具。 提出的目标，将他的营养和代谢专业知识扩展到肺部领域，并建立独立性 他追求的长期目标是：找到治疗和管理哮喘的精准营养方法。