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

美国政府宣布该国出现阿片类药物危机，联邦卫生机构正在 采取紧急措施，消除与处方阿片类药物使用有关的高死亡率。那里 睡眠呼吸紊乱(SDB)、睡眠相关的呼吸不足和呼吸不规律的风险增加 长期服用处方阿片类药物的个人。几乎30%的资深睡眠诊所人口有 阿片类药物相关性中枢性睡眠呼吸暂停(CSA)。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显著危险因素以及CsA合并慢性 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治疗方法。 治疗这种睡眠障碍。 然而，阿片类药物在成人体内产生SDB的确切机制仍不清楚，以及 已经提出了各种不同和相互冲突的通风控制机制。因此，我们将系统地 探讨导致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。我们将调查长期使用阿片类药物对呼吸机的影响 二氧化碳的化学反应性和脑血管反应性，并确定 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。这个 从拟议的实验中获得的信息将推动新的个性化治疗的开发 减少退伍军人与慢性阿片类药物相关的SDB，最终将对他们的长期健康产生积极影响 健康和幸福。

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.