Targeting Chemoreceptor Control of Breathing during Sleep to Mitigate Opioid-Associated Sleep Disordered Breathing

针对睡眠期间呼吸的化学感受器控制，以减轻阿片类药物相关的睡眠呼吸障碍

• 批准号: 10295173
• 负责人: Susmita Chowdhuri
• 金额: --
• 依托单位: JOHN D DINGELL VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10295173
• 关键词: Accounting; Acetazolamide; Acute; Adopted; Adult; Air; Airway Resistance; Alternative Therapies; Animals; Arousal; Binding; Breathing; Carbon; Carbon Dioxide; Catheters; Central Sleep Apnea; Chemoreceptors; Chronic; Clinic; Complex; Conflict (Psychology); Continuous Positive Airway Pressure; Country; Databases; Development; Disease; Doppler Ultrasound; Emergency Situation; Epidemic; Goals; Government; Health; Human; Hypercapnia; Hyperoxia; Hypoventilation; Hypoxia; Individual; Intervention; Lead; Life; Measures; Mediating; Opioid; Opioid Analgesics; Oral; Overdose; Oxides; Oxygen; Pathway interactions; Personal Satisfaction; Pharmaceutical Preparations; Placebos; Plants; Play; Population; Reporting; Research; Risk; Risk Factors; Sampling; Sleep; Sleep Apnea Syndromes; Sleep Disorders Therapy; Toxic effect; United States; Veterans; adverse outcome; cerebrovascular; chronic pain; effective therapy; experimental study; genioglossus muscle; innovation; mortality; mortality risk; non rapid eye movement; non-opioid analgesic; novel; opioid epidemic; opioid mortality; opioid overdose; opioid use; opioid user; overdose death; personalized medicine; prescription opioid; pressure; respiratory; response; therapy development; ventilation

The U.S government has declared an opioid crisis in the country and federal health agencies are adopting emergency measures to obviate the high mortality associated with prescription opioid drug use. There is an increased risk for sleep disordered breathing (SDB), sleep-related hypoventilation and irregular breathing in individuals on chronic prescription opioid medications. Almost 30% of a veteran sleep clinic population had opioid-associated central sleep apnea (CSA). Gravely, in a national sample of Veterans, sleep apnea was a significant risk factor for opioid-related toxicity and overdose and the presence of CSA combined with chronic prescription opioid use compounded the mortality risk. There are only limited and partially effective therapies for this sleep disorder. Nevertheless, the exact mechanisms by which opioids produce SDB in adults remain unclear, and varied and conflicting ventilatory control mechanisms have been suggested. Thus, we will systematically investigate the chemoreceptor control mechanisms contributing to the increased propensity of SDB associated with chronic prescription opioid use. We will investigate the effects of chronic opioid use on ventilatory chemoresponsiveness and cerebrovascular responsiveness to carbon-dioxide and determine whether modifying these mechanisms with hyperoxia or acetazolamide will mitigate opioid-related SDB/CSA. The information garnered from the proposed experiments will drive development of novel personalized therapies to reduce SDB associated with chronic opioids in Veterans and, ultimately, will positively impact their long-term health and well-being.

美国政府已宣布该国出现阿片类药物危机，联邦卫生机构正在采取行动 采取紧急措施以避免与处方阿片类药物使用相关的高死亡率。那里 睡眠呼吸障碍 (SDB)、睡眠相关通气不足和呼吸不规则的风险增加 长期服用处方阿片类药物的个体。近 30% 的睡眠诊所资深人士曾患有 阿片类药物相关的中枢性睡眠呼吸暂停（CSA）。严重的是，在全国退伍军人样本中，睡眠呼吸暂停是一种 阿片类药物相关毒性和过量的重要危险因素以及 CSA 与慢性 处方阿片类药物的使用加剧了死亡风险。只有有限且部分有效的疗法 对于这种睡眠障碍。 然而，阿片类药物在成人中产生 SDB 的确切机制仍不清楚，并且 已经提出了各种不同且相互冲突的通气控制机制。因此，我们将系统地 研究导致 SDB 相关倾向增加的化学感受器控制机制 长期使用处方阿片类药物。我们将研究长期使用阿片类药物对通气的影响 对二氧化碳的化学反应性和脑血管反应性并确定是否 用高氧或乙酰唑胺改变这些机制将减轻阿片类药物相关的 SDB/CSA。这 从拟议的实验中收集的信息将推动新型个性化疗法的开发 减少退伍军人中与慢性阿片类药物相关的 SDB，最终将对其长期产生积极影响 健康和福祉。