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

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.

Stepwise Add-On and Endotype-informed Targeted Combination Therapy to Treat Obstructive Sleep Apnea: A Proof-of-Concept Study.

Oral appliance therapy (OAT) is an effective treatment for many people with obstructive sleep apnea (OSA). However, OSA pathogenesis is heterogeneous, and, in ∼50% of cases, OAT does not fully control OSA. This study aimed to control OSA in individuals with an incomplete response to OAT alone by using additional targeted therapies informed by OSA endotype characterization.

Topical Potassium Channel Blockage Improves Pharyngeal Collapsibility: A Translational, Placebo-Controlled Trial.

Background: Potassium (K) channel inhibition has been identified in animal models as a potential target to increase pharyngeal dilator muscle activity and to treat OSA. However, these findings have not yet been translated to humans.

Research Question: Does a novel, potent, tandem of P domains in a weak inward rectifying K channel (TWIK)-related acid-sensitive K (TASK) 1/3 channel antagonist, BAY2586116, improve pharyngeal collapsibility in pigs and humans, and secondarily, what is the optimal dose and method of topical application?

Study Design And Methods: In the preclinical study, pharyngeal muscle activity and upper-airway collapsibility via transient negative pressure application was quantified in 13 anesthetized pigs during administration of placebo, 0.

Regional genioglossus reflex responses to negative pressure pulses in people with obstructive sleep apnea.

Tongue and upper airway dilator muscle movement patterns during quiet breathing vary in people with obstructive sleep apnea (OSA). Many patients have inadequate or counterproductive responses to inspiratory negative airway pressure that likely contributes to their OSA. This may be due, at least in part, to inadequate or nonhomogeneous reflex drive to different regions of the largest upper airway dilator, genioglossus.

Impaired pharyngeal reflex responses to negative pressure: a novel cause of sleep apnea in multiple sclerosis.

Obstructive sleep apnea (OSA) is common in people with multiple sclerosis (MS). However, people with MS often do not have "typical" anatomical risk factors (i.e.

An assessment of a simple clinical technique to estimate pharyngeal collapsibility in people with obstructive sleep apnea.

Study Objectives: Quantification of upper airway collapsibility in obstructive sleep apnea (OSA) could help inform targeted therapy decisions. However, current techniques are clinically impractical. The primary aim of this study was to assess if a simple, novel technique could be implemented as part of a continuous positive airway pressure (CPAP) titration study to assess pharyngeal collapsibility.

Changes in pharyngeal collapsibility and genioglossus reflex responses to negative pressure during the respiratory cycle in obstructive sleep apnoea.

Key Points: Impaired pharyngeal anatomy and increased airway collapsibility is a major cause of obstructive sleep apnoea (OSA) and a mediator of its severity. Upper airway reflexes to changes in airway pressure provide important protection against airway closure. This study shows increased pharyngeal collapsibility and attenuated genioglossus reflex responses during expiration in people with OSA.

Upper airway collapsibility measured using a simple wakefulness test closely relates to the pharyngeal critical closing pressure during sleep in obstructive sleep apnea.

Study Objectives: A collapsible or crowded pharyngeal airway is the main cause of obstructive sleep apnea (OSA). However, quantification of airway collapsibility during sleep (Pcrit) is not clinically feasible. The primary aim of this study was to compare upper airway collapsibility using a simple wakefulness test with Pcrit during sleep.

Obstructive sleep apnea: current perspectives.

The prevalence of obstructive sleep apnea (OSA) continues to rise. So too do the health, safety, and economic consequences. On an individual level, the causes and consequences of OSA can vary substantially between patients.

Airway Inflammatory Biomarker: Could It Tailor the Right Medications for the Right Asthmatic Patient?

Asthma is a heterogeneous disease, in which asthmatic patients present with different clinical phenotypes, variable endotypes, and different response to asthma medicines. Thus, we are faced with an asthma paradox; asthma is diagnosed subjectively by clinical history and treated with biologically active drugs. To solve this paradox, we need objective airway biomarkers to tailor the proper medications to the proper patient.

Clinical asthma phenotyping: A trial for bridging gaps in asthma management.

Asthma is a common disease affecting millions of people worldwide and exerting an enormous strain on health resources in many countries. Evidence is increasing that asthma is unlikely to be a single disease but rather a series of complex, overlapping individual diseases or phenotypes, each defined by its unique interaction between genetic and environmental factors. Asthma phenotypes were initially focused on combinations of clinical characteristics, but they are now evolving to link pathophysiological mechanism to subtypes of asthma.