Role of Sleep-Related Upper Airway Neuromuscular Dysfunction in the Pathophysiology of Obstructive Sleep Apnea

We explored the concept of obstructive sleep apnea (OSA) as a neuromuscular disorder, emphasizing the main clinical features of upper airway neuromuscular dysfunction in OSA, and providing a link between pathophysiological mechanisms and emerging pharmacotherapies. OSA is the most prevalent sleep-related breathing disease. The pathophysiology of OSA involves anatomical and non-anatomical traits with upper airway neuromuscular dysfunction being one of the most important. The underlying mechanisms of upper airway neuromuscular control are not completely known, but several neuromodulators may be involved, including noradrenaline and acetylcholine. Efforts to develop novel pharmacotherapies for OSA have accelerated in recent years, especially emerging drugs targeting the upper airway neuromuscular function. The current evidence supports OSA as a state-dependent disease in which upper airway neuromuscular dysfunction plays a key role. Emerging pharmacotherapies targeting the root cause of upper airway neuromuscular dysfunction have demonstrated clinical benefits for OSA in advanced clinical trials.