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

项目总结/摘要 博士梅伊是一个富有成效的年轻科学家申请这个指导K 01奖过渡到独立的研究 事业他有很强的营养学（注册营养师）和代谢（转化研究）背景，专注于 代谢性疾病他有一个成长和生产力的历史，在他的研究生涯的演变， 目前担任助理教授。他最近的发现将他的兴趣引向了一个主要的文献空白： 营养对哮喘控制和肺功能的影响--与NHLBI的使命相关。 哮喘病理生理学中的一个新兴概念是改变的营养代谢和线粒体生物能量学。营养 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 改善肺功能然而，缺乏控制良好的喂养试验，在我们的研究中留下了重大的知识空白。 了解哮喘的营养。此外，营养研究受到严格审查的主要障碍， 包括个体间的差异性、缓慢的发展和临床应用的转化差。 为了解决这一重要的知识差距，克服营养研究中的关键障碍，拟议的目标将利用 创新的多种饮食交叉临床喂养试验设计结合n-of-1定性试验。进料 一项试验将测试三种不同的、完全提供的、等热量的饮食，以确定影响哮喘的营养和代谢因素 控制和肺功能。随后将进行一个定性试点的n-of-1方法，其中包括患者- 在营养治疗模式中纳入知情决策，对个性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， 为未来的临床研究建立初步的精确营养模型。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，并确定慢性酮 暴露可以使改变的线粒体生物能量学正常化。总之，临床发现，定性试点和阐明 确定饮食与哮喘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， 博士梅伊已经招募了5名成熟的研究人员和临床医生的指导，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）职业发展和补助金 写作指导。此外，Mey博士组建了一个由4名合作者和顾问组成的团队，以获得技术和科学见解。 彭宁顿生物医学研究中心将提供理想的学习环境，并提供卓越的核心服务， 进行临床试验，辅以当地（杜兰）和国外（克利夫兰）的医生导师培训 诊所）。总之，这种协调的临床翻译培训将为Mey博士提供完成 提出的目标，扩大他的营养和代谢的专业知识到肺部领域，并建立独立的， 追求他的长期目标：确定治疗和管理哮喘的精确营养方法。

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.