Phrenic nerve stimulation enhances upper airway patency during drug-induced sleep endoscopy in OSA

RATIONALE: Obstructive sleep apnea (OSA) is characterized by recurrent upper airway (UA) collapse during sleep. Continuous positive airway pressure (CPAP) is an effective but often poorly tolerated treatment. Neurostimulation targeting UA dilators has emerged as an alternative therapy, though coordinating stimulation of multiple effector muscles may be challenging. Phrenic nerve stimulation (PNS) offers a potential alternative that may engage both efferent and afferent respiratory mechanisms to enhance airway patency. OBJECTIVE: To examine how PNS timing affects UA patency in OSA patients undergoing drug-induced sleep endoscopy (DISE). METHODS: OSA patients underwent drug-induced sleep endoscopy. Subtherapeutic CPAP was applied to maintain stable flow-limited breathing for PNS experiments. Transcutaneous PNS was delivered via a cervical electrode at different phases of respiration: end-expiration to inspiration (E→I), inspiration only (I→I), and mid-inspiration to expiration (I→E). Sequential stimulations were also performed at E→I to observe sustained effects. Effect of stimulation on inspiratory flow (VI), tidal volume (TV), and minute ventilation (MV) were quantified using mixed-effects models. MEASUREMENTS AND MAIN RESULTS: Nineteen patients participated: 13 completed both isolated and sequential protocols, and 6 completed only the sequential protocol. Isolated PNS timed to E→I increased VI (64%) and TV (71%) compared with baseline. Sequential PNS at E→I produced sustained improvements with further increases in VI (171%), TV (173%), and MV (169%). CONCLUSIONS: PNS delivered at end-expiration significantly improved UA patency and ventilation, with sequential stimulation further potentiating these effects. Phase-locked PNS responses implicate underlying neural afferent mechanisms and suggest novel PNS strategies for treating OSA.