The role of neuromuscular function in sleep apnea pathogenesis and management: A consensus of experts

Abstract

Study objectivesAlthough the importance of upper airway assessment in the consideration of obstructive sleep apnea (OSA) is recognized, there are current limitations in our approach to assessment.MethodsWe convened a group of experts in upper airway neuromuscular physiology and anatomy, sleep apnea endophenotypes, novel therapeutics and sleep epidemiology to summarize existing literature and delineate future opportunities to utilize and incorporate innovative and less invasive techniques focused on upper airway neuromuscular physiology to assess and manage OSA.ResultsIn OSA, genioglossus electromyogram (EMG) activity is reduced during sleep onset with higher levels observed during wakefulness compared to controls. Surface EMG recordings are limited due to distance from the actual muscle and while needle EMG offers more direct assessment, this approach is more invasive. Novel alternatives overcoming these limitations to assess upper airway neuromuscular physiology in OSA may therefore prove beneficial. Specifically, such an approach would facilitate identification of upstream prognostic biomarkers of OSA clinical trajectory and offer more informative mechanistic data. Novel approaches to neuromuscular assessment in OSA would enhance phenotyping to predict better tolerance to positive airway pressure therapy and set the stage to target neuromuscular function and upper airway anatomy. A quantifiable and repeatable neuromuscular physiologic metric has potential to facilitate a precision medicine strategy and personalize treatment, including measuring treatment response to neurophysiologic-focused interventions including hypoglossal nerve stimulation (HGNS), myofunctional therapy and neuromuscular electrical stimulation. A key area for future investigation is whether observed neuromuscular changes can identify patients at future risk of OSA, facilitating early intervention or prevention strategies.ConclusionsOverall, recognizing the critical contributions of abnormalities of upper airway neuromuscular function to the pathophysiology of OSA, it may be important to find accurate and reproducible neurophysiological assessments to address existing knowledge gaps in OSA assessment and management.

Development of a combination of noradrenergic and antimuscarinic drugs for the treatment of obstructive sleep apnea: Challenges and progress

“…Some of these issues related to the diagnostic paradigm of OSA are being discussed by academic experts (Mehra et al, 2023) and have been recently considered while designing larger industry-sponsored trials testing the effects of pharmacotherapies on OSA severity (Clinicaltrials.gov, 2022a,c;Hedner et al, 2022). The Mariposa trial was a large 25-center phase 2b trial recently concluded, which tested the effect of AD109 over a month of therapy in patients with a baseline AHI4 between 10 and 45 events/h.…”