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.

项目摘要/摘要 Mey博士是一位富有成效的年轻科学家，申请了这一重要的K01奖，以过渡到独立研究 职业。他有强大的营养（注册营养师）和代谢（翻译研究）背景，重点是 代谢疾病。在整个研究生涯的演变中，他都有增长和生产力的历史 目前担任助理教授。他最近的发现将他的兴趣引向了主要文献差距：影响 哮喘控制和肺功能的营养 - 与NHLBI的任务有关。 哮喘病理生理学中的一个新兴概念是营养代谢和线粒体生物能学的改变。营养 摄入量直接影响全身和细胞营养代谢，几种营养方法显示出希望 改善肺功能。但是，缺乏控制良好的喂养试验，在我们的 了解哮喘中的营养。此外，营养研究对主要障碍的严格审查， 包括个体间的变异性，缓慢的发展和临床应用的不良翻译。 为了解决这个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 创新的多型跨界临床喂养试验设计与N-OF-1定性飞行员结合使用。进食 试验将测试三种不同的，完全提供的等量平衡饮食，以鉴定影响哮喘的营养和代谢因素 控制和肺功能。接下来是N-1-1方法的定性飞行员，该试验纳入患者 - 对营养治疗模型的明智决定，对个性化营养护理的发展至关重要。 此外，未靶向的血浆代谢组分析将与机器学习生物统计学结合使用 为未来的临床研究生成初步的精确营养模型。最后，一种体外方法将定义 哮喘供体的气道平滑肌细胞中的线粒体缺陷，并确定是否慢性酮 暴露会使线粒体生物能学的改变归一化。一起，临床发现，定性飞行员和阐明 定义饮食 - 染色关系的生物学机制将支持Mey博士向独立的过渡。 为了使Mey博士实现这些目标并将其营养和新陈代谢专业知识转变为肺部领域， 迈伊博士招募了5位成熟的研究人员和临床医生的心态，以详细培训 在该项目中，包括：1）哮喘和线粒体生物学的学术和专业发展，2）临床 哮喘的管理，3）支持实施多迪特跨界喂养试验，以及4）职业发展和授予 写作指导。此外，Mey博士组建了一个由4个合作者和技术和科学见解的顾问组成的团队。 Pennington生物医学研究中心将提供理想的学习环境，并提供出色的核心服务 进行临床试验，并通过本地（图兰）和国外（克利夫兰）进行物理训练补充 诊所）。这项协调的临床译本培训一起将为Mey博士提供完成工具以完成 拟议的目标，将他的营养和代谢专业知识扩展到肺部领域，并在 追求他的长期目标：确定哮喘治疗和管理的精确营养方法。