Abstract Rationale Obstructive sleep apnea (OSA) is characterized by recurrent episodes of upper airway (UA) obstruction that result from elevations in pharyngeal collapsibility during sleep. Therapeutic interventions that decrease pharyngeal collapsibility can offer alternatives for treating OSA with continuous positive airway pressure (CPAP). We have previously demonstrated that phrenic nerve stimulation (PNS) can reduce airflow obstruction in OSA patients during drug-induced sleep endoscopy (DISE) when the stimulation is timed to end-expiration. The current study aimed to quantify the effects of PNS on pharyngeal collapsibility and its effects of the severity of airflow obstruction during DISE. Methods 19 patients (age 57.7 ± 9.4 yrs; 78.9% male; BMI 30.7 ± 3.8 kg/m²; mean AHI4% 35.4 ± 17.5 events/hr) underwent drug induced sleep endoscopy (DISE). Airflow (VI) and tidal volume (TV) were measured using a pneumotachometer. Subtherapeutic positive or negative nasal pressures were applied to generate a range of inspiratory flow limitation (IFL) severity for PNS testing. PNS was delivered via a transcutaneous neck electrode in trains of 4-8 sequential stimulations. Baseline pressure-flow and pressure-tidal volume relationships were plotted to determine the nasal pressure at which non-flow-limited breathing occurred (POPEN) and the critical nasal pressure below which airflow ceased (PCRIT). Pressure-flow and pressure-TV curves from stimulated breaths were then compared to baseline to assess changes in POPEN and PCRIT. Results Leftward shifts of both pressure-flow and pressure-TV curves were observed with stimulation indicating PNS improved airflow and reduced obstruction. Compared with unstimulated baseline, PNS decreased PCRIT by 7.1cmH2O 95%CI: 4.4-9.8 and POPEN by 4.6 cmH2O 95% CI: 3.1-6.1. (Figure 1) On average, the slope of the pressure-flow relationship decreased by -0.4 with PNS, though substantial inter-subject variability was observed: some participants displayed a parallel leftward shift of the pressure-flow relationship, others showed a change in slope, and several exhibited both a shift and tilt. Conclusion Transcutaneous PNS reduced pharyngeal collapsibility and the severity of airflow obstruction during DISE, as evidenced by improvements in PCRIT, POPEN and TV. The magnitude of reduced collapsibility is comparable or exceeds effects of other therapeutic CPAP alternatives including positional therapy, mandibular advancement and hypoglossal neurostimulation. Changes in the slope of the pressure-flow relationship indicate enhanced PNS responses under conditions of increased pharyngeal neuromuscular drive, and variability in slope responses suggests that baseline neuromuscular activity may predict stimulation responsiveness. The therapeutic potential and efficacy of PNS during natural sleep warrant further investigation. This abstract is funded by: Research was supported by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) under Award Numbers UL1TR002378 and KL2TR002381. Research was also supported by Lunair Medical, Inc.
Yu et al. (Fri,) studied this question.