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October 3, 2025Open Access

Combined Supplemental Oxygen and Mandibular Advancement Device Therapy for Obstructive Sleep Apnea: A Randomized-Controlled Trial

Key Points

Combining supplemental oxygen with a mandibular advancement device significantly reduces AHI in OSA patients.
In a trial of 41 patients, the combination therapy led to a 68% decrease in AHI compared to 54% with MAD alone.
Multicentre randomized crossover trial design allowed comparison of four different interventions in treating OSA.
Potentially enables new pathways for OSA treatment, highlighting the benefits of targeting multiple pathophysiological factors.

Abstract

Introduction Treatment for obstructive sleep apnoea (OSA) is limited by intolerance to continuous positive airway pressure. While OSA manifests due to both increased pharyngeal collapsibility and ventilatory control instability, randomized trials targeting both components are lacking. We tested whether combining a ventilatory control intervention (supplemental oxygen) with an upper airway mechanical intervention (mandibular advancement devices, MAD) improves treatment efficacy. Methods In a multicentre randomized crossover trial, 41 patients with moderate-to-severe OSA (apnoea-hypopnoea index AHI >20 events/hr, scored without desaturation criteria) underwent polysomnography with four single-night interventions: oxygen (4 L·min −1 ), MAD, combination therapy, and sham (air). Primary analysis compared percent change in AHI from baseline between combination therapy and MAD monotherapy. Secondary outcomes included arousal index and visual analog scale for sleep quality (VASSQ). Gold-standard baseline pathophysiological traits facilitated mechanistic subgroup analysis. Results Of 41 randomized patients (14F:27 M, AHI baseline =49 29, 62 events/hr; median interquartile range), 38 completed all interventions. Compared to sham, AHI was lowered with oxygen (estimateCI: −33−46, −17%), MAD (−54−64, −41%), and the combination (−68−77, −57%); the combination provided a greater reduction than MAD monotherapy (−14−23, −4%, p=0.009). The combination also improved AHI per 3% desaturation/arousal criteria (−73−81, −62% versus sham, −17−25, −7% versus MAD). The combination improved arousal index (−36−43, −27% versus sham) and VASSQ (+0.980.39, 1.58 versus sham), albeit not significantly beyond MAD alone. Effects were greatest in those with higher loop gain and collapsibility. Conclusion Combining a ventilatory control intervention (supplemental oxygen) with an upper airway intervention (MAD) is a promising approach to markedly attenuate OSA severity beyond that offered by each intervention alone.

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