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

基本信息

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
项目类别：
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

项目摘要

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.

美国政府宣布该国发生阿片类药物危机，联邦卫生机构是采取紧急措施来消除与处方阿片类药物使用相关的高死亡率。那里是呼吸失调（SDB），与睡眠相关的不足和呼吸不规则的风险增加在慢性处方阿片类药物的个人中。几乎30％的退伍军人睡眠诊所人口阿片类药物相关的中央睡眠呼吸暂停（CSA）。严重的是，在国家退伍军人样本中，睡眠呼吸暂停是一个阿片类药物相关的毒性和过量的危险因素以及CSA的存在与慢性处方阿片类药物的使用加剧了死亡率风险。只有有限且有效的疗法对于这种睡眠障碍。然而，阿片类药物在成年人中产生SDB的确切机制尚不清楚，并且已经提出了变化和冲突的通风控制机制。因此，我们将系统地研究有助于SDB倾向增加的化学感受器控制机制使用慢性处方阿片类药物使用。我们将研究慢性阿片类药物对通风的影响化学回应性和对二氧化碳的脑血管反应性，并确定是否是否用高氧或乙酰唑胺修饰这些机制将减轻与阿片类药物相关的SDB/CSA。这从拟议的实验中获得的信息将推动新型个性化疗法的开发到减少与退伍军人慢性阿片类药物相关的SDB，最终将对他们的长期产生积极影响健康与福祉。