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.

美国政府宣布该国出现阿片类药物危机，联邦卫生机构也宣布了这一消息