The Impact of Sleep Disordered Breathing in People who use Opioids

项目摘要/摘要 这份提案详细说明了杰里米·E·奥尔医学博士的五年研究和职业发展计划，他是一名 肺病学和重症监护医学，加州大学旧金山分校医学助理教授 迭戈。他的研究得到了国家研究服务奖奖学金的支持，目前是 美国胸科学会基金会奖。他的研究的总体重点是理解 使用慢性阿片类药物的患者睡眠期间呼吸问题的评估，并确定治疗策略 对于这些复杂的呼吸问题，这将改善健康。这项K23奖项将为 奥尔博士在面向患者的临床研究、睡眠呼吸障碍的应用生理学方面获得专业知识， 和临床试验。奥尔博士组建了一支全面的导师团队来支持他的研究和职业生涯 发展。他的主要导师阿图尔·马尔霍特拉博士是睡眠呼吸障碍(SDB)和睡眠障碍(SDB)的世界专家 应用呼吸生理学，在指导和促进初级教员成为 独立调查人员。罗伯特·欧文斯博士是美国国立卫生研究院资助的内科科学家，具有先进的 测量SDB生理学的技术，并将作为“动手”的共同导师。委员会的其他成员 小组成员是Sonia Jain博士(统计和试验)、Mark Wallace博士(阿片类药物和疼痛)、Shamim Nemati博士(Signal 分析)和弗兰克·鲍威尔博士(呼吸控制)。使用慢性阿片类药物的慢性疼痛患者 健康不良的风险增加，包括持续疼痛、睡眠不佳、生活质量下降和风险增加 死亡的威胁。众所周知，阿片类药物对呼吸有影响，可能会导致SDB，这是一个被低估的因素 可能会导致这些患者的不良后果。SDB会导致睡眠中断和 氧水平受损，但在使用阿片类药物的高危患者中研究很少。在一个 使用慢性阿片类药物的慢性疼痛受试者的广泛群体，这项研究将确定治疗 持续气道正压(CPAP)的SDB导致睡眠质量改善，以及调查 其他症状，包括这些患者的疼痛(目标1)。CPAP治疗对某些患者可能无效 由于呼吸不稳定(由于阿片类药物)，因此将研究识别这些人的技术， 包括呼吸不稳定的新指标。对CPAP后仍有持续性SDB的患者，治疗 选择是有限的。这项研究将评估一种药物(乙酰唑胺)是否有助于减少 呼吸不稳定将有助于解决SDB(目标2)。这项研究将为奥尔博士提供坚实的基础 成为研究SDB的影响、发病机制和治疗的独立调查者 慢性阿片类药物。

Project Summary/Abstract This proposal details a five-year research and career development plan for Jeremy E. Orr, M.D., a specialist in pulmonology and critical care medicine, and Assistant Professor of Medicine at the University of California, San Diego. His research has been supported by a National Research Service Award fellowship and currently an American Thoracic Society Foundation award. The overall focus of his research is understanding the importance of breathing issues during sleep in patients using chronic opioid medications, and identifying treatment strategies for these complex breathing issues that will improve health. This K23 award will provide necessary support for Dr. Orr to gain expertise in patient-oriented clinical research, applied physiology of sleep disordered breathing, and clinical trials. Dr. Orr has assembled a comprehensive team of mentors to support his research and career development. His primary mentor, Dr. Atul Malhotra, is a world expert in sleep disordered breathing (SDB) and applied respiratory physiology, with a strong track record of mentoring and promoting junior faculty to become independent investigators. Dr. Robert Owens is a NIH-funded physician-scientist with expertise in advanced techniques to measure SDB physiology, and will serve as a “hands-on” co-mentor. Additional members of the team are Dr. Sonia Jain (statistics and trials), Dr. Mark Wallace (opioids and pain), Dr. Shamim Nemati (signal analysis), and Dr. Frank Powell (control of breathing). Patients with chronic pain who use chronic opioids are at increased risk for poor health including ongoing pain, poor sleep, decreased quality of life, and an increased risk of mortality. Opioids are known to have effects on breathing which may lead to SDB, an under-recognized factor potentially contributing to adverse outcomes in these patients. SDB contributes to sleep disruption and impairments in oxygen levels, but has been little studied in this high-risk group of patients using opioids. In a broad group of subjects with chronic pain who use chronic opioids, this research will determine whether treatment of SDB with continuous positive airway pressure (CPAP) leads to improved sleep quality, as well as investigating other symptoms including pain in these patients (Aim 1). CPAP treatment may not be effective in some patients due to unstable breathing (due to opioids), so techniques to identify such individuals will be investigated, including new measures of breathing instability. For patients with persistent SDB despite CPAP, treatment options are limited. The research will evaluate whether a medication (acetazolamide) that helps to reduce the instability of breathing will help to resolve SDB (Aim 2). This research will provide Dr. Orr with a strong foundation to become an independent investigator studying the impact, pathogenesis and treatment of SDB in those using chronic opioids.