Respiration-triggered olfactory stimulation reduces obstructive sleep apnea severity – a prospective pilot study

Study Objectives: Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing condition characterized by repetitive reduction in breathing during sleep. Current standard of care for OSA management is continuous positive air pressure (CPAP) devices, which often suffer from low tolerance due to limited adherence. Capitalizing on the unique neurocircuitry of the olfactory system and its retained function during sleep, we set out to test whether presenting transient, respiration-based olfactory stimulation can be used as a treatment for OSA markers. Methods: Thirty-two OSA patients (Apnea-Hypopnea Index (AHI) > 15 events/hour) were recruited and underwent two polysomnography sessions, Odor and Control, counterbalanced for order. In Odor nights, patients were presented with transient respiratory-based olfactory stimulation delivered via a computer-controlled olfactometer. The olfactometer, equipped with a wireless monitoring unit, analyzed respiratory patterns and presented odor stimulation upon detection of respiratory events. No odors were presented in Control nights. Following exclusions, 17 patients entered the analyses (n = 17, 49.2 ± 10.2 years, range: 30 - 66). Results: Olfactory stimulation during sleep reduced AHI (AHI Odor: 22.16 ± 16.2, AHI Control: 31.65 ± 17.4, z = 3.34, p = 0.000846, BF10 = 57.9), reflecting an average decrease of 31.3% in the number of events. Relatedly, stimulation reduced the oxygen desaturation index (ODI) by 26.9 % (ODI Odor: 20.63 ± 18.9, ODI Control: 28.81 ± 22.2, z = 3.3373, p = 0.0008458, BF10 = 9.522). Post hoc planned comparisons revealed reductions in both Hypopnea Index (HI Odor: 12.85 ± 8.33, HI Control: 17.64 ± 6.56, z = 2.1065, p = 0.03515, BF10 = 1.24), and Apnea Index (AI Odor: 9.31 ± 10.1, AI Control: 14.01 ± 17.6, z = 2.5329, p = 0.01131, BF10 = 1.586). This effect was not linked to baseline OSA markers severity (rho = -0.042, p = 0.87). Notably, olfactory stimulation did not arouse from sleep or affect sleep structure (F(1,16) = 0.088, p = 0.77). Conclusions: Olfactory stimulation during sleep was effective in reducing OSA markers severity without inducing arousals and may provide a novel treatment modality for OSA, therefore prompting continued research on this front. ### Competing Interest Statement OP is a paid consultant at AppScent Medical. AA is a non-paid consultant at AppScent Medical. Both OP and AA received the PSG clinical data for analysis only once data collection was terminated and were not involved in data collection for the experiment.