A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: A randomized, blinded, trial

Amal M. Osman, Barbara Toson, Ganesh R. Naik, Sutapa Mukherjee, Martina Delbeck, Michael Hahn, Gerrit Weimann, Danny J. Eckert

Research output: Contribution to journalArticlepeer-review

Abstract

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K þ 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) ¼ 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 lg), or BAY2586116 nasal spray (160 lg) 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 cmH 2O) 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, P ¼ 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 ¼ 28 ± 11 vs. 36 ± 12 events/h, P ¼ 0.03 and ODI3 ¼ 18 ± 10 vs. 28 ± 12 events/h, P ¼ 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure ¼ 137 ± 24 vs. 147 ± 21 mmHg, P < 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. NEW & NOTEWORTHY 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.

Original languageEnglish
Pages (from-to)H715-H723
Number of pages9
JournalAmerican Journal of Physiology-Heart and Circulatory Physiology
Volume326
Issue number3
Early online date22 Feb 2024
DOIs
Publication statusPublished - 1 Mar 2024

Keywords

  • endotyping
  • pharmacotherapy
  • sleep apnea
  • sleep disordered breathing
  • upper airway physiology.
  • sleep-disordered breathing
  • upper airway physiology

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