Adelaide Institute for Sleep Health and FHMRI Sleep Health, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
Respiratory and Sleep Service, Southern Adelaide Local Health Network, SA Health, Adelaide, South Australia, Australia.
Am J Physiol Heart Circ Physiol. 2024 Mar 1;326(3):H715-H723. doi: 10.1152/ajpheart.00541.2023. Epub 2024 Jan 12.
Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmHO) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals. Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.
临床前和人体生理学研究表明，局部、选择性 TASK1/3 K 通道拮抗作用可增加上气道扩张肌的活性，并减少麻醉期间和睡眠期间鼻呼吸时的咽腔塌陷。本研究的主要目的是确定 BAY2586116 鼻喷雾剂对阻塞性睡眠呼吸暂停（OSA）严重程度的影响，以及个体反应是否根据生理反应和呼吸途径的差异而有所不同。10 名患有 OSA 的人（5 名女性）[呼吸暂停低通气指数（AHI）=47±26 次/小时（平均值±SD）]，他们之前完成了 BAY2586116 的睡眠生理学研究，被邀请返回进行三项多导睡眠图研究，以量化 OSA 严重程度。参与者随机接受安慰剂鼻喷雾剂（生理盐水）、BAY2586116 鼻喷雾剂（160µg）或 BAY2586116 鼻喷雾剂（160µg）限制在鼻呼吸（颏带或口带）。生理反应者是指那些在 BAY2586116 鼻喷雾剂作用下上气道塌陷性得到改善的患者（临界关闭压力≥2cmHO）（NCT04236440）。与安慰剂相比，无论是无限制还是仅鼻呼吸，BAY2586116 都没有系统地改变呼吸暂停低通气指数（AHI3）（47±26 与 43±27 与 53±33 次/小时， =0.15）。然而，与安慰剂相比，BAY2586116（无限制呼吸）在生理反应者中降低了 OSA 严重程度（例如，AHI3=28±11 与 36±12 次/小时， =0.03 和 ODI3=18±10 与 28±12 次/小时， =0.02）。与安慰剂相比，生理反应者在使用 BAY2586116 后早晨的血压也较低（例如，收缩压=137±24 与 147±21mmHg， <0.01）。总之，BAY2586116 降低了睡眠中患有上气道塌陷性生理改善的人的 OSA 严重程度。这些发现突出了这种新型药物治疗靶点在某些个体中的治疗潜力。在猪和人体的临床前研究表明，通过局部鼻腔应用阻断上气道中的钾通道可增加咽扩肌的活性并减少上气道塌陷。在这项研究中，BAY2586116 鼻喷雾剂（钾通道阻滞剂）降低了上气道塌陷性生理改善的睡眠呼吸暂停患者的严重程度。BAY2586116 降低了第二天早上的血压。这些发现突出了这种新型治疗方法在某些人群中改善睡眠呼吸暂停的潜力。
