Upper airway muscles: influence on obstructive sleep apnoea pathophysiology and pharmacological and technical treatment options

Purpose of review Obstructive sleep apnoea (OSA) is highly prevalent with numerous deleterious effects on neurocognitive and cardiovascular health. It is characterized by collapse of the upper airway during sleep, due to the decrease in both basal and compensatory UA muscle activities. However, the leading treatment, continuous positive airway pressure, is often poorly tolerated. This review presents latest works focusing on novel interventions targeting upper airway muscles to alleviate OSA severity. Recent findings In the last years, researchers have focused on the development of alternative treatment strategies targeting UA muscle activation, including pharmacological and nonpharmacological interventions. Among the nonpharmacological treatments, hypoglossal nerve stimulation aims to increase upper airway muscle phasic activity during sleep through electrical stimulation, while myofunctional therapy improves the activity and coordination of upper airway dilator muscles. Regarding OSA pharmacotherapy, recent findings strongly suggest that selective norepinephrine reuptake inhibitors such as atomoxetine and reboxetine, when administered with antimuscarinics such as oxybutynin, can alleviate OSA in most patients increasing pharyngeal dilator muscles activity during sleep. New combinations of norepinephrine reuptake inhibitors and antimuscarinics have further been explored with variable success and animal models showed that leptin, thyrothropin releasing hormone analogues and gene therapy hold potential for the future of OSA pharmacotherapy.