The Physiologic Assessment of Exercise Capacity in Pediatric Sickle Cell Anemia

描述（由申请人提供）：本申请描述了一套建议的研究和结构化的职业发展计划，精心设计，以帮助首席研究员获得成为镰状细胞性贫血（SCA）和运动生理学领域独立临床研究者所需的技能和经验。在一组有成就的导师和科学顾问的指导下，首席研究员将获得额外的以患者为导向的研究方法，生物统计学，心肺疾病和应用运动生理学的正式培训。建议的实践和课堂培训将在西北大学范伯格医学院和伊利诺伊大学芝加哥分校进行，这两所大学都是备受推崇的机构，在培养年轻的内科科学家方面有着广泛的记录。首席研究员目前是西北大学儿科助理教授，也是儿童纪念医院血液学、肿瘤学和干细胞移植部的主治医师。本研究的总体目的是利用心肺运动试验来描述在患有SCA的儿童和青少年中观察到的运动反应受损和运动能力下降的病理生理机制。尽管心肺疾病和运动后的急性炎症反应可能导致一般人群的运动限制，但它们在降低SCA儿童运动能力中的作用尚未得到系统的研究。本提案的具体目的是：1)评估通过气体交换分析获得的儿童和青少年SCA患者进行心肺运动试验时心肺反应的峰值耗氧量（VO2）和其他有氧参数；2)在接受心肺运动测试的受试者中，通过测量可溶性血管细胞粘附分子（sVCAM）活性的增加来表征运动引起的急性炎症反应；3)评估儿童和青少年SCA患者在2年期间的运动能力的纵向变化，通过心肺运动试验中的峰值VO2来测量。尽管普遍认为定期锻炼对健康且患有慢性疾病的儿童有益，但由于缺乏关于SCA儿童运动的风险和益处的数据，因此无法对这一人群提出体育锻炼的建议。如果实现，本提案中概述的具体目标将产生关键数据，这将使首席研究员能够制定以证据为基础的运动处方计划，旨在改善SCA儿童的身体功能、运动能力和整体生活质量。除了从他提出的职业发展计划中获得的指导和额外培训外，首席研究员还将处于独特的位置，将这些经验作为实现未来研究独立的基础。

DESCRIPTION (provided by applicant): This application describes a set of proposed studies and structured career development plan carefully crafted to assist the Principal Investigator acquire the skills and experience necessary for becoming an independent clinical investigator in the areas of sickle cell anemia (SCA) and exercise physiology. Under the guidance of a group of accomplished mentors and scientific advisors, the Principal Investigator will gain additional formal training in patient-oriented research methodology, biostatistics, cardiopulmonary disease and applied exercise physiology. The practical and classroom training proposed will occur at the Northwestern University Feinberg School of Medicine and the University of Illinois at Chicago, both highly regarded institutions with extensive track records for the development of young physician-scientists. The Principal Investigator is currently an Assistant Professor of Pediatrics at Northwestern and an Attending Physician in the Division of Hematology, Oncology & Stem Cell Transplant at Children's Memorial Hospital. The overall objective of this study is to use cardiopulmonary exercise testing to delineate the pathophysiologic mechanisms that contribute to the impaired exercise response and reduced exercise capacity observed in children and young adults suffering from SCA. Although cardiopulmonary disease and the acute inflammatory response to exercise may contribute to exercise limitation in the general population, their role in reducing exercise capacity in children with SCA has not been systematically addressed. The Specific Aims of this proposal are to: 1) Evaluate peak oxygen consumption (VO2) and other aerobic parameters of the cardiopulmonary response to exercise obtained from gas exchange analysis in children and young adults with SCA undergoing cardiopulmonary exercise testing; 2) Characterize the acute inflammatory response to exercise, as measured by an increase in soluble vascular cell adhesion molecule (sVCAM) activity, in subjects undergoing cardiopulmonary exercise testing; and 3) Assess the longitudinal change in exercise capacity, as measured by peak VO2 on cardiopulmonary exercise testing, over a 2-year period in children and young adults with SCA. The paucity of data regarding the risks and benefits of exercise in children with SCA has contributed to the inability to develop recommendations for physical activity in this population despite the general consensus that regular exercise is beneficial for children who are both healthy and have a chronic medical condition. If achieved, the Specific Aims outlined in this proposal will yield critical data that will allow the Principal Investigator to develop evidence-based, exercise prescription programs aimed at improving physical functioning, exercise capacity and overall quality of life in children with SCA. Along with the mentoring and additional training gained from his proposed career development plan, the Principal Investigator will also be in the unique position to build upon these experiences as the basis for achieving future research independence.