Pathogenesis and Genetics of Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停的发病机制和遗传学

• 批准号: 6879996
• 负责人: Richard J. Schwab
• 金额: $ 13.95万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-08 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879996
• 关键词: bioimaging /biomedical imaging; biomechanics; body composition; disease /disorder proneness /risk; family genetics; human subject; magnetic resonance imaging; morphology; morphometry; pathologic process; patient oriented research; radiology; respiratory imaging /visualization; respiratory system; sleep apnea

Although sleep disorders have been identified by the NIH as an area with tremendous scientific growth potential there are a paucity of patient oriented investigators studying sleep-related questions. The University of Pennsylvania is fortunate to have internationally recognized faculty and a strong infrastructure to support high quality patient-oriented research and training m sleep disorders. This infrastructure includes: Center for Sleep and Respiratory Neurobiology, Center for Clinical Epidemiology and Biostatistics, General Clinical Research Center, 3 Sleep Training Grants and the Pulmonary Imaging Group. Dr. Schwab is an integral part of each of these programs and is highly committed to a career in patient-oriented sleep research, proposing to study the genetics and biomechanical basis for obstructive sleep apnea. Dr. Schwab has made seminal observations about changes in the upper airway in patients with sleep apnea and he has successfully mentored several pulmonary fellows and junior faculty. Dr. Schwab through funding from this K24 can further develop into an academic leader and train others investigators that the sleep field desperately needs. Specifically this award would allow Dr. Schwab to develop further expertise in new radiologic techniques in upper airway imaging and computer-based volumetric analysis; further his expertise in genetic epidemiology and bioinformatics; allow increased time for mentoring young scientists and for developing new areas of collaboration with scientists. Dr. Schwab has developed a state-of-the-art upper airway imaging program focusing on understanding the pathogenesis and treatment of obstructive sleep apnea. Recently, Dr. Schwab has begun to apply his upper airway imaging expertise to study phenotypic risk factors for sleep apnea. He is the first to apply advanced quantitative MR Imaging techniques and novel volumetric computer image analysis techniques to study the genetic basis for sleep apnea. The scientific portion of this grant will utilize upper airway imaging to study both the pathogenesis and genetics of sleep apnea. My specific aims are: 1) to evaluate and compare upper airway soft tissue structural and biomechanical properties in apneics and normal weight-matched controls during wakefulness and sleep; 2) to quantify upper airway craniofacial structure, soft tissues and regional fat deposition using three dimensional magnetic resonance imaging in order to determine the intermediate traits associated with obstructive sleep apnea utilizing a case control design in normals and apneics ; and 3) to determine the upper airway structural risk factors for sleep apnea that demonstrate family aggregation and are most likely to have a genetic component by comparing probands, siblings of probands, neighborhood controls and siblings of neighborhood controls. To address these specific aims, we have planned a logical series of studies that will provide insight in the pathogenesis of obstructive sleep apnea and the anatomic risk factors for this condition.

尽管睡眠障碍已被美国国立卫生研究院 (NIH) 认定为具有巨大科学增长潜力的领域，但研究睡眠相关问题的以患者为导向的研究人员却很少。宾夕法尼亚大学很幸运，拥有国际认可的师资队伍和强大的基础设施来支持高质量的以患者为导向的睡眠障碍研究和培训。该基础设施包括：睡眠和呼吸神经生物学中心、临床流行病学和生物统计学中心、普通临床研究中心、3 个睡眠训练补助金和肺部影像组。施瓦布博士是每个项目不可或缺的一部分，并高度致力于以患者为导向的睡眠研究事业，提议研究阻塞性睡眠呼吸暂停的遗传学和生物力学基础。施瓦布博士对睡眠呼吸暂停患者上呼吸道的变化进行了开创性的观察，并成功指导了几位肺科研究员和初级教师。 Schwab 博士通过 K24 的资助可以进一步发展成为学术带头人，并培训睡眠领域迫切需要的其他研究人员。具体来说，该奖项将使 Schwab 博士能够在上呼吸道成像和基于计算机的体积分析等新放射技术方面进一步发展专业知识；进一步提升他在遗传流行病学和生物信息学方面的专业知识；留出更多时间指导年轻科学家并与科学家开发新的合作领域。 Schwab 博士开发了最先进的上呼吸道成像程序，重点了解阻塞性睡眠呼吸暂停的发病机制和治疗。最近，施瓦布博士开始应用他的上呼吸道成像专业知识来研究睡眠呼吸暂停的表型危险因素。他是第一个应用先进的定量磁共振成像技术和新颖的体积计算机图像分析技术来研究睡眠呼吸暂停的遗传基础的人。该拨款的科学部分将利用上呼吸道成像来研究睡眠呼吸暂停的发病机制和遗传学。我的具体目标是：1）评估和比较清醒和睡眠期间呼吸暂停和正常体重匹配对照的上呼吸道软组织结构和生物力学特性； 2) 使用三维磁共振成像量化上呼吸道颅面结构、软组织和区域脂肪沉积，以便利用正常人和呼吸暂停患者的病例对照设计确定与阻塞性睡眠呼吸暂停相关的中间特征； 3) 通过比较先证者、先证者的兄弟姐妹、邻里对照和邻里对照的兄弟姐妹，确定睡眠呼吸暂停的上气道结构性危险因素，这些因素表现出家庭聚集性，并且最有可能具有遗传成分。为了实现这些具体目标，我们计划了一系列合乎逻辑的研究，这些研究将深入了解阻塞性睡眠呼吸暂停的发病机制以及这种情况的解剖学危险因素。