The Physiologic Assessment of Exercise Capacity in Pediatric Sickle Cell Anemia

描述(由申请人提供)：此申请描述了一套精心设计的拟议研究和结构化的职业发展计划，以帮助首席调查员获得成为镰状细胞性贫血(SCA)和运动生理学领域的独立临床调查员所需的技能和经验。在一批经验丰富的导师和科学顾问的指导下，首席调查员将接受以病人为导向的研究方法、生物统计学、心肺疾病和应用运动生理学的额外正式培训。拟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，这两所大学都享有很高的声誉，在培养年轻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学助理教授和儿童纪念医院血液学、肿瘤学和干细胞移植科的主治医生。这项研究的总体目标是利用心肺运动试验来描述导致SCA儿童和年轻人运动反应受损和运动能力下降的病理生理学机制。尽管心肺疾病和运动引起的急性炎症反应可能导致一般人群的运动受限，但它们在SCA儿童运动能力降低中的作用尚未得到系统的解决。这项建议的具体目的是：1)评估接受心肺运动试验的SCA儿童和青年对运动的最大耗氧量(VO2)和其他有氧参数，这些参数是通过气体交换分析获得的；2)通过接受心肺运动试验的受试者中可溶性血管细胞黏附分子(SVCAM)活性的增加来表征运动的急性炎症反应；以及3)评估SCA儿童和年轻人在两年时间里运动能力的纵向变化。缺乏关于SCA儿童锻炼的风险和好处的数据，导致无法在这一人群中制定体育锻炼的建议，尽管人们普遍认为，定期锻炼对既健康又患有慢性病的儿童有益。如果实现，本提案中概述的具体目标将产生关键数据，使首席调查员能够开发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。除了从其拟议的职业发展计划中获得指导和额外培训外，首席调查员还将处于独特的地位，能够以这些经验为基础，实现未来的研究独立。

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.