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NIH已将睡眠障碍鉴定为具有巨大科学生长潜力的地区，但研究与睡眠相关问题的患者研究人员很少。宾夕法尼亚大学很幸运拥有国际认可的教职员工和强大的基础设施，以支持高质量的面向患者的研究和培训。该基础设施包括：睡眠和呼吸神经生物学中心，临床流行病学与生物统计学中心，一般临床研究中心，3个睡眠培训补助物和肺成像组。 Schwab博士是每个程序中每个程序中不可或缺的一部分，并且高度致力于以患者为导向的睡眠研究，建议研究阻塞性睡眠呼吸暂停的遗传学和生物力学基础。 Schwab博士对睡眠呼吸暂停患者的上呼吸道变化进行了开创性观察，他成功指导了几名肺部研究员和初级教师。 Schwab博士通过这项K24的资金可以进一步发展成为学术领导者，并培训睡眠场地迫切需要的其他调查员。具体而言，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方面开发进一步的专业知识；进一步，他在遗传流行病学和生物信息学方面的专业知识；为指导年轻科学家和与科学家建立新的合作领域的时间增加时间。 Schwab博士开发了一项最新的上呼吸道成像计划，重点是了解阻塞性睡眠呼吸暂停的发病机理和治疗。最近，施瓦布（Schwab）博士已开始将其上呼吸道成像专业知识应用于研究睡眠呼吸暂停的表型危险因素。他是第一个采用先进的定量MR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。该赠款的科学部分将利用上呼吸道成像研究睡眠呼吸暂停的发病机理和遗传学。我的具体目的是：1）在清醒和睡眠期间评估和比较apneics和正常重量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，使用三维磁共振成像，以确定与阻塞性睡眠呼吸暂停相关的中间性状，利用正常和呼吸暂停中的案例控制设计与阻塞性睡眠呼吸暂停相关的中间性状； 3）为了确定表现出家庭聚集的睡眠呼吸暂停的上呼吸道结构危险因素，并且最有可能通过比较邻里控制的概率，邻里控制和兄弟姐妹的概率，兄弟姐妹来具有遗传成分。为了解决这些特定目标，我们计划了一系列逻辑研究，这些研究将为阻塞性睡眠呼吸暂停的发病机理和这种情况的解剖风险因素提供见解。