Effect of Upper Airway Stimulation in Patients with Obstructive Sleep Apnea (EFFECT): A Randomized Controlled Crossover Trial

Background: Several single-arm prospective studies have demonstrated the safety and effectiveness of upper airway stimulation (UAS) for obstructive sleep apnea. There is limited evidence from randomized, controlled trials of the therapy benefit in terms of OSA burden and its symptoms. Methods: We conducted a multicenter, double-blinded, randomized, sham-controlled, crossover trial to examine the effect of therapeutic stimulation (Stim) versus sham stimulation (Sham) on the apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS). We also examined the Functional Outcomes of Sleep Questionnaire (FOSQ) on sleep architecture. We analyzed crossover outcome measures after two weeks using repeated measures models controlling for treatment order. Results: The study randomized 89 participants 1:1 to Stim (45) versus Sham (44). After one week, the AHI response rate was 76.7% with Stim and 29.5% with Sham, a difference of 47.2% (95% CI: 24.4 to 64.9, p < 0.001) between the two groups. Similarly, ESS was 7.5 ± 4.9 with Stim and 12.0 ± 4.3 with Sham, with a significant difference of 4.6 (95% CI: 3.1 to 6.1) between the two groups. The crossover phase showed no carryover effect. Among 86 participants who completed both phases, the treatment difference between Stim vs. Sham for AHI was −15.5 (95% CI −18.3 to −12.8), for ESS it was −3.3 (95% CI −4.4 to −2.2), and for FOSQ it was 2.1 (95% CI 1.4 to 2.8). UAS effectively treated both REM and NREM sleep disordered breathing. Conclusions: In comparison with sham stimulation, therapeutic UAS reduced OSA severity, sleepiness symptoms, and improved quality of life among participants with moderate-to-severe OSA.

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Aerodynamics Analysis of the Impact of Nasal Surgery on Patients with Obstructive Sleep Apnea and Nasal Obstruction

ORL ◽

10.1159/000516243 ◽

2021 ◽

pp. 1-8

Author(s):

Lifeng Li ◽

Demin Han ◽

Hongrui Zang ◽

Nyall R. London

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Nasal Obstruction ◽

Upper Airway ◽

Apnea Hypopnea Index ◽

Nasal Surgery ◽

Subjective Sleep Quality ◽

Obstructive Sleep ◽

Significant Difference ◽

The Impact

Objective: The purpose of this study was to evaluate the effects of nasal surgery on airflow characteristics in patients with obstructive sleep apnea (OSA) by comparing the alterations of airflow characteristics within the nasal and palatopharyngeal cavities. Methods: Thirty patients with OSA and nasal obstruction who underwent nasal surgery were enrolled. A pre- and postoperative 3-dimensional model was constructed, and alterations of airflow characteristics were assessed using the method of computational fluid dynamics. The other subjective and objective clinical indices were also assessed. Results: By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (p < 0.05), while the Apnea-Hypopnea Index (AHI) changed little (p = 0.492); the postoperative airflow velocity and pressure in both nasal and palatopharyngeal cavities, nasal and palatopharyngeal pressure differences, and total upper airway resistance statistically decreased (all p < 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (p < 0.05), except with the AHI (p > 0.05). Conclusion: Nasal surgery can decrease the total resistance of the upper airway and increase the nasal airflow volume and subjective sleep quality in patients with OSA and nasal obstruction. The altered airflow characteristics might contribute to the postoperative reduction of pharyngeal collapse in a subset of OSA patients.

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Comparison of Traditional Upper Airway Surgery and Upper Airway Stimulation for Obstructive Sleep Apnea

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489420953178 ◽

2020 ◽

pp. 000348942095317

Author(s):

Colin Huntley ◽

Maurits Boon ◽

Samuel Tschopp ◽

Kurt Tschopp ◽

Carolyn M Jenks ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Upper Airway ◽

Apnea Hypopnea Index ◽

Upper Airway Stimulation ◽

Sleep Surgery ◽

Medical Centers ◽

Academic Medical ◽

Obstructive Sleep ◽

Quality Life

Objective: To compare patients with moderate-severe obstructive sleep apnea (OSA) undergoing traditional single and multilevel sleep surgery to those undergoing upper airway stimulation (UAS). Study Design: Case control study comparing retrospective cohort of patients undergoing traditional sleep surgery to patients undergoing UAS enrolled in the ADHERE registry. Setting: 8 multinational academic medical centers. Subjects and Methods: 233 patients undergoing prior single or multilevel traditional sleep surgery and meeting study inclusion criteria were compared to 465 patients from the ADHERE registry who underwent UAS. We compared preoperative and postoperative demographic, quality of life, and polysomnographic data. We also evaluated treatment response rates. Results: The pre and postoperative apnea hypopnea index (AHI) was 33.5 and 15 in the traditional sleep surgery group and 32 and 10 in the UAS group. The postoperative AHI in the UAS group was significantly lower. The pre and postoperative Epworth sleepiness scores (ESS) were 12 and 6 in both the traditional sleep surgery and UAS groups. Subgroup analysis evaluated those patients undergoing single level palate and multilevel palate and tongue base traditional sleep surgeries. The UAS group had a significantly lower postoperive AHI than both traditional sleep surgery subgroups. The UAS group had a higher percentage of patients reaching surgical success, defined as a postoperative AHI <20 with a 50% reduction from preoperative severity. Conclusion: UAS offers significantly better control of AHI severity than traditional sleep surgery. Quality life improvements were similar between groups.

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Randomized Controlled Withdrawal Study of Upper Airway Stimulation on OSA

Otolaryngology ◽

10.1177/0194599814544445 ◽

2014 ◽

Vol 151 (5) ◽

pp. 880-887 ◽

Cited By ~ 74

Author(s):

B. Tucker Woodson ◽

M. Boyd Gillespie ◽

Ryan J. Soose ◽

Joachim T. Maurer ◽

Nico de Vries ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Outcome Measures ◽

Hypoglossal Nerve ◽

Upper Airway ◽

Oxygen Desaturation ◽

Upper Airway Stimulation ◽

Randomized Controlled ◽

Obstructive Sleep ◽

Therapy Withdrawal

Objective To assess the efficacy and durability of upper airway stimulation via the hypoglossal nerve on obstructive sleep apnea (OSA) severity including objective and subjective clinical outcome measures. Study Design A randomized controlled therapy withdrawal study. Setting Industry-supported multicenter academic and clinical setting. Subjects A consecutive cohort of 46 responders at 12 months from a prospective phase III trial of 126 implanted participants. Methods Participants were randomized to either therapy maintenance (“ON”) group or therapy withdrawal (“OFF”) group for a minimum of 1 week. Short-term withdrawal effect as well as durability at 18 months of primary (apnea hypopnea index and oxygen desaturation index) and secondary outcomes (arousal index, oxygen desaturation metrics, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, snoring, and blood pressure) were assessed. Results Both therapy withdrawal group and maintenance group demonstrated significant improvements in outcomes at 12 months compared to study baseline. In the randomized assessment, therapy withdrawal group returned to baseline, and therapy maintenance group demonstrated no change. At 18 months with therapy on in both groups, all objective respiratory and subjective outcome measures showed sustained improvement similar to those observed at 12 months. Conclusion Withdrawal of therapeutic upper airway stimulation results in worsening of both objective and subjective measures of sleep and breathing, which when resumed results in sustained effect at 18 months. Reduction of obstructive sleep apnea severity and improvement of quality of life were attributed directly to the effects of the electrical stimulation of the hypoglossal nerve.

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Comparison of Predictor of Desaturation Disorders and Daytime Sleepiness Based On Epworth Sleepiness Scale and STOP-BANG Questionnaires in Mild to Moderate Obstructive Sleep Apnea Patients

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.258 ◽

2018 ◽

Vol 6 (9) ◽

pp. 1617-1621 ◽

Cited By ~ 1

Author(s):

Zohreh Kahramfar ◽

Besharat Rahimi

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Epworth Sleepiness Scale ◽

Upper Airway ◽

Apnea Hypopnea Index ◽

Predictive Values ◽

Desaturation Index ◽

Obstructive Sleep ◽

Significant Difference ◽

Severity Of The Disease

BACKGROUND: Obstructive sleep apnea (OSA) is characterised by recurrence in upper airway obstruction during sleep. AIM: This study aimed to compare the predictive values of the Epworth Sleepiness Scale (ESS) and STOP-BANG in the desaturation of patients with mild to moderate obstructive apnea based on the apnea-hypopnea index (AHI) scale. METHODS: A group of 79 patients (43 male and 36 female) were selected. The suspected patients were introduced to the sleep clinic, and the ESS and STOP-BANG questionnaires were filled up, then subjected to polysomnography test, and the scores of the disease were also determined based on an apnoea-hypopnoea index (AHI). Finally, the desaturation rate (SO2 < 3% based on the baseline) and desaturation index were determined in patients. Consequently, the finding was compared with the results of the questionnaires. RESULTS: Patients with STOP-BANG score above 3 had significantly higher weight, oxygen desaturation index (ODI) index and average desatu, while peripheral capillary oxygen saturation (SpO2) base and average SpO2 were lower than those with scores below 3 (P < 0.05). However, there was no significant difference between the patients with the ESS questionnaire score above 10 and below 10 (P > 0.05). CONCLUSION: The results of these two questionnaires reflect the unsaturated oxygen index in the blood, and can be considered for the evaluation of the severity of the disease.

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0691 Comparison Of Odds Ratio Product And Other Polysomnographic Metrics Among Responders And Non-responders To Upper Airway Stimulation Treatment Of Obstructive Sleep Apnea

SLEEP ◽

10.1093/sleep/zsaa056.687 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A263-A264

Author(s):

J L Yu ◽

B T Keenan ◽

S T Kuna ◽

M Younes

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Odds Ratio ◽

Statistical Significance ◽

Upper Airway ◽

Research Society ◽

Apnea Hypopnea Index ◽

Upper Airway Stimulation ◽

Sleep Depth ◽

Obstructive Sleep

Abstract Introduction Upper airway stimulation (UAS) is a surgical method of treating obstructive sleep apnea (OSA). UAS involves an implantable neuro-stimulator that stimulates the hypoglossal nerve to protrude the tongue during sleep. OSA fails to improve in 22% of patients who receive UAS as defined by a > 50% reduction in Apnea-Hypopnea Index (AHI) and an AHI <20 events/hour. Light sleep may predict UAS failure in that it may limit the stimulus strength that can be applied. The odds ratio product (ORP) is a novel polysomnographic (PSG) metric of sleep depth. We hypothesized that ORP values prior to surgery will be higher (lighter sleep) in non-responders. Having markers that predict surgical success can help reduce unnecessary surgeries. Methods This is a retrospective cohort study of 126 patients (83 responders vs. 43 non-responders) who received UAS implantation for the treatment of OSA. PSG data was obtained from the Stimulation for Apnea Reduction (STAR) trial. Raw baseline PSG data were analyzed and ORP values calculated using Michele Sleep Scoring Software (Cerebra Medical, Winnipeg, CA). In addition, 13 PSG metrics that were considered possibly relevant to surgical outcome were calculated as an exploratory analysis. The measurements included: spindle density, spindle power, spindle frequency, alpha intrusion, Right/Left sleep depth correlation coefficient, respiratory duty cycle, respiratory flow limitation, and arousal intensity. Statistical Analysis: Comparisons between responders and non-responders used parametric t-tests for continuous data and chi-squared or Fisher’s exact tests for categorical data. Statistical significance was based on a Bonferroni-corrected p<0.00357. Results Differences in ORP values and other PSG metrics between responders and non-responders were not statistically significant. Of all PSG metrics only differences in spindle density approached statistical significance (Responders = 2.33 spindles/minute vs Non-Responders = 1.39 spindles/minute, p=0.00360). Conclusion The findings suggest that differences in sleep depth and several other sleep characteristics do not play a significant role in determining response to UAS therapy. Support This project was supported by a Sleep Research Society Career Development Award #023-JP-19

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Comparison of transoral robotic surgery with other surgeries for obstructive sleep apnea

Scientific Reports ◽

10.1038/s41598-020-75215-1 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Yung-An Tsou ◽

Wen-Dien Chang

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Robotic Surgery ◽

Operation Time ◽

Transoral Robotic Surgery ◽

Apnea Hypopnea Index ◽

Clinical Effects ◽

Upper Airway Stimulation ◽

Obstructive Sleep ◽

Significant Difference

Abstract This study compared the characteristic surgical parameters and clinical effects of transoral robotic surgery (TORS) and other available methods used to alleviate obstructive sleep apnea. Articles on TORS and other surgeries for obstructive sleep apnea were identified in the PubMed and EMBASE databases. Two investigators independently reviewed the articles and classified the data for meta-analysis. The pooled effect sizes of TORS (standardized mean difference; SMD = − 2.38), coblation tongue base resection (CTBR; SMD = − 2.00) and upper airway stimulation (UAS; SMD = − 0.94) revealed significant improvement in the apnea–hypopnea index (AHI; p < 0.05). The lowest O2 saturation reported was significantly increased following TORS (SMD = 1.43), CTBR (SMD = 0.86) and UAS (SMD = 1.24, p < 0.05). Furthermore, TORS (SMD = − 2.91) and CTBR (SMD = − 1.51, p < 0.05) significantly reduced the Epworth Sleepiness Scale (ESS) score. No significant difference in operation time, success rate, or instances of complication were observed between TORS and the other compared interventions. The use of TORS in obstructive sleep apnea has the same rate of success and failure as other methods of surgical intervention for obstructive sleep apnea with no statistical difference in operation times. The reported clinical effects on the AHI, lowest O2 saturation, and ESS scores of TORS were similar to those of other surgeries.

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0676 Long-term Effects Of Upper Airway Stimulation For Treatment Of Obstructive Sleep Apnea On Measurements Of Central And Mixed Apneas

SLEEP ◽

10.1093/sleep/zsaa056.672 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A258-A258

Author(s):

S A Myers ◽

K M Sundar ◽

P J Strollo

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Upper Airway ◽

Phase Iii ◽

Apnea Hypopnea Index ◽

Medical Systems ◽

Long Term Effects ◽

Upper Airway Stimulation ◽

Obstructive Sleep

Abstract Introduction Upper airway stimulation (UAS) of the hypoglossal nerve for obstructive sleep apnea (OSA) is well-tolerated and results in sustained reduction in the apnea-hypopnea index (AHI). Treatment-emergent CSA is reported to occur in 3.5-19.8% of OSA patients treated with CPAP. We aimed to examine the occurrence or emergence of central and mixed apneas in a cohort of participants that received UAS and were followed for 5 years post implantation. Methods The Stimulation Trial for Apnea Reduction (STAR) was a Phase III trial evaluating the safety and efficacy of UAS for CPAP-intolerant OSA. Major inclusion criteria were CPAP intolerance, AHI between 20-50, less than 25% central and mixed apneas and BMI <= 32. Polysomnography was performed at baseline, 12, 18, 36 and 60-month follow-up. Data were scored by a core lab and was then retrospectively analyzed via the STAR PSG database to measure the evolution of central and mixed apneas on UAS therapy. Results Baseline age was 54.5 ± 10.2 years, BMI was 28.4 ± 2.6 kg/m2 and 83% male (n=126). AHI data were non-normally distributed. Median AHI was 29.3/hr at baseline, that was reduced to 9/hr at 12-months and 6/hr at 60-months. Median central apnea index (CAI) was 0.8/hr at baseline, 0.4/hr at 12-months, and 0.2/hr at 60-months. Median mixed apnea index (MAI) was 0.2/hr at baseline, 0.7/hr at 12-months and 0.4/hr at 60-months. The 12- and 60-month CAI was significantly lower than baseline (p<0.05), but MAI was not. The percentage of central and mixed events remained stable throughout follow-up, approximately at 5% of the total AHI. Conclusion UAS reduced the overall AHI and results in a small but significant decrease in CAI. Given that OSA and CSA frequently co-exist, the role of UAS on reducing CSA in patients with combined OSA and CSA deserves further investigation. Support STAR study was sponsored by Inspire Medical Systems

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Predicting critical closing pressure in children with obstructive sleep apnea using fluid structure interaction simulations

Journal of Applied Physiology ◽

10.1152/japplphysiol.00694.2020 ◽

2021 ◽

Author(s):

Goutham Mylavarapu ◽

Ephraim Gutmark ◽

Sally Shott ◽

Robert J. Fleck ◽

Mohamed Mahmoud ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Upper Airway ◽

Dynamic Mri ◽

Patient Specific ◽

Apnea Hypopnea Index ◽

Structure Interaction ◽

Obstructive Sleep ◽

Mri Scans ◽

Closing Pressure

Surgical treatment of obstructive sleep apnea (OSA) in children requires knowledge of upper airway dynamics, including the closing pressure (Pcrit), a measure of airway collapsibility. We applied a Flow-Structure Interaction (FSI) computational model to estimate Pcrit in patient-specific upper airway models obtained from magnetic resonance imaging (MRI) scans. We sought to examine the agreement between measured and estimated Pcrit from FSI models in children with Down syndrome. We hypothesized that the estimated Pcrit would accurately reflect measured Pcrit during sleep and therefore reflect the severity of OSA as measured by the obstructive apnea hypopnea index (AHI). All participants (n=41) underwent polysomnography and sedated sleep MRI scans. We used Bland Altman Plots to examine the agreement between measured and estimated Pcrit. We determined associations between estimated Pcrit and OSA severity, as measured by AHI, using regression models. The agreement between passive and estimated Pcrit showed a fixed bias of -1.31 (CI=-2.78, 0.15) and a non-significant proportional bias. A weaker agreement with active Pcrit was observed. A model including AHI, gender, an interaction term for AHI and gender and neck circumference explained the largest variation (R2 = 0.61) in the relationship between AHI and estimated Pcrit. (P <0.0001). Overlap between the areas of the airway with lowest stiffness, and areas of collapse on dynamic MRI, was 77.4%±30% for the nasopharyngeal region and 78.6%±33% for the retroglossal region. The agreement between measured and estimated Pcrit and the significant association with AHI supports the validity of Pcrit estimates from the FSI model.

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Upper Airway Stimulation Therapy for Obstructive Sleep Apnea

10.1093/med/9780197521625.001.0001 ◽

2021 ◽

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Upper Airway ◽

Novel Therapy ◽

Upper Airway Stimulation ◽

Current State ◽

Obstructive Sleep ◽

Long Term Follow Up ◽

Physician Extenders ◽

Primary Care Practitioners

Upper Airway Stimulation Therapy for Obstructive Sleep Apnea provides the current state of knowledge regarding this novel therapy. It reviews the pathophysiologic basis of sleep apnea and the specific mechanism by which upper airway stimulation provides airway support in this disorder. It also provides practical insights into this therapy related to patient selection, clinical outcomes, surgical technique, long-term follow-up, and adverse events and offers recommendations for those aspiring to develop an upper airway stimulation program. It provides an overview of unique populations and circumstances that may extend the utility of the procedure, and that may provide challenges in management, as well as thoughts on the future of this technology. This textbook is intended for all practitioners who have interest or care for sleep disordered breathing, including sleep medicine physicians, pulmonologists, otolaryngologists, primary care practitioners, as well as physician extenders.

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