Hypoglossal nerve stimulation (HNS) is a surgical treatment for obstructive sleep apnea that activates in a phasic manner. The most widely available HNS device has respiratory entrainment programming settings that are not widely utilized. We present an algorithm for office-based respiratory sensing adjustments to optimize HNS respiratory entrainment. Laryngoscope, 135:1532-1536, 2025.

Abstract Introduction Surgical management of Obstructive Sleep Apnea (OSA) is utilized in patients unable to tolerate positive airway pressure (PAP). The American Academy of Sleep Medicine (AASM) recently published guidelines for referral for surgical consultation. The aim of this study was to characterize surgical referrals from an academic sleep medicine practice. Methods A retrospective chart review was conducted of 249 patients referred for sleep surgery from a sleep medicine practice from 01/01/2016 to 01/01/2023. All patients were initially evaluated by a sleep medicine provider at National Jewish Hospital. All patients considering sleep surgery were referred to the University of Colorado. A total of 142 patients (57.0%) completed at least one visit for surgical consultation. Demographics, polysomnographic parameters, details from evaluation in sleep surgery clinic and eventual surgical treatment were assessed. Pearson chi-square test, fisher exact test were utilized for ordinal variables. Analysis of variance and student t tests were utilized for continuous variables to determine statistically significant relationships with P< 0.05. Results Those completing a surgical visit were older at time of referral with mean (SD) age 59.0 (14.0) compared to 54.4 (14.5). Of patients referred for surgery, 24 (8.4%) had BMI>40, 43 (19.7%) had AHI< 15 and 27 (10.8%) had AHI>65. The majority, 107 of 142 (75.4%), of patients completing surgical evaluation did not undergo eventual surgery. Of the non-surgical cohort, 49 (45.8%) underwent a repeat trial of PAP, 22 (20.6%) had repeat sleep testing and 10 (9.3%) underwent trial of oral appliance therapy. Conclusion Sleep surgery is a viable alternative to management of OSA. In this study, a large proportion of patients originally referred for surgical evaluation did not complete follow up. Furthermore, the majority of patients seen in surgical clinic did not necessarily undergo surgery for OSA. Non-surgical modalities remained an option for patients with sleep surgery referral and likely enhanced decision-making by informing patients of risks and benefits of both surgical and non-surgical management. Further efforts should be made to understand reasons for incomplete follow-up or pursuit of non-surgical options to optimize surgical referrals for OSA. Support (if any)

Background: Obstructive sleep-disordered breathing (oSDB) is a heterogeneous phenotype that is increasing in prevalence worldwide and has many potential comorbidities that could severely affect quality of life. There is a need to identify biomarkers for oSDB and its comorbidities to improve clinical management, particularly in children. Methods: We performed bulk mRNA-sequencing, differential expression analysis, and qPCR replication of selected differentially expressed genes (DEGs) using RNA samples extracted from tonsils of children with oSDB. Two variables were used as classifier, namely, detection of Epstein-Barr virus (EBV) in tonsils and need for continuous positive airway pressure (CPAP) treatment. Standard statistical tests were used to determine associations across clinical, EBV, and DEG variables. Results: Nineteen genes were dysregulated in tonsils that are EBV+ or from children needing CPAP. Of these genes, APOBR was downregulated in both EBV+ and CPAP+ tonsils, and this downregulation was replicated by qPCR in an independent set of pediatric samples. In the tonsils of adult patients with oSDB, APOBR was positively correlated with age, and potentially with diastolic blood pressure. Conclusions: Taken together, APOBR and DEGs in tonsillar tissues may be useful as potential biomarkers of oSDB severity and comorbidity across the lifespan, with APOBR levels being dependent on latent EBV infection.

BackgroundEvaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). MethodsUsing previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. ResultsThe ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. ConclusionThis review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.

Rationale: Prior work suggests that Black patients have more severe obstructive sleep apnea (OSA) upon clinical presentation. However, the extent to which this may reflect differences in symptoms or other standard measures of OSA risk is unclear. Objectives: We assessed for racial disparities in OSA characteristics at time of initial clinical diagnosis. Methods: Data from 890 newly diagnosed patients with OSA at an urban academic sleep center were included in this analysis. All patients completed a standardized questionnaire on demographics and sleep-related symptoms and underwent laboratory polysomnography. Symptom severity at the time of evaluation was compared across race and sex. Results: Black men were underrepresented in the sleep lab, making up only 15.8% of the cohort and 31.3% of Black participants (P < 0.001). Despite this, Black men had the most severe OSA with a mean apnea hypopnea index of 52.4 +/- 39.4 events/hour, compared with 39.0 +/- 28.9 in White men, 33.4 +/- 32.3 in Black women, and 26.2 +/- 23.8 in White women (P < 0.001 for test of homogeneity). Black men also had the greatest burden of OSA symptoms with the highest mean Epworth Sleepiness Scale score (12.2 +/- 5.9 versus 9.4 +/- 5.2 in White men, 11.2 +/- 5.9, in Black women, and 9.8 +/- 5.6 in White women; P < 0.001). Compared with White men, Black men were 1.61 (95% CI [1.04-2.51]) times more likely to have witnessed apneas and 1.56 (95% CI [1.00-2.46]) times more likely to have drowsy driving at the time of OSA diagnosis. Conclusions: At the time of clinical diagnosis, Black men have greater disease severity, suggesting delay in diagnosis. Further, the greater burden of classic OSA symptoms suggests the delayed diagnosis of OSA in Black men is not due to atypical presentation. Further research is needed to identify why screening methods for OSA are not equitably implemented in the care of Black men.

Neurostimulation is an electrical therapy for obstructive sleep apnea and is now an approved therapy option for patients whom positive airway pressure (PAP) therapy is not tolerated. This review describes its implementation, efficacy and safety, the available multi-year clinical outcomes for stimulation devices, and future prospects. The clinical literature on upper airway neurostimulation was surveyed from July 2014 to December 2021, with a focus on the origins of new therapies, the components of devices, evidences for clinical utility, and adverse events. The basic science literature began as demonstrations of muscle actions leading to neurostimulator prototypes that brought industry interest to clinical therapy. Currently, Inspire® and Nyxoah Genio® are the only two neurostimulators available in the USA. Inspire®, FDA-approved in 2014 as first-in-class therapy, is a hypoglossal nerve (cranial nerve XII) stimulator that is time-coordinated with breathing to prevent upper airway collapse, and its use has the longest experience in the clinic. Given the general narrow inclusion criteria (BMI < 35, ideally < 32), AHI 15–65/h, and a favorable anterior–posterior velopharyngeal collapse pattern on drug-induced sleep endoscopy (DISE), 65

Objective: An increasing number of facilities offer Upper Airway Stimulation (UAS) with varying levels of experience. The goal was to quantify whether a surgical learning curve exists in operative or sleep outcomes in UAS. Methods: International multi-center retrospective review of the ADHERE registry, a prospective international multi-center study collecting UAS outcomes. ADHERE registry centers with at least 20 implants and outcomes data through at least 6-month follow-up were reviewed. Cases were divided into two groups based on implant order (the first 10 or second 10 consecutive implants at a given site). Group differences were assessed using Mann-Whitney U-tests, Chi-squared tests, or Fisher's Exact tests, as appropriate. A Mann-Kendall trend test was used to detect if there was a monotonic trend in operative time. Sleep outcome equivalence between experience groups was assessed using the two one-sided tests approach. Results: Thirteen facilities met inclusion criteria, contributing 260 patients. Complication rates did not significantly differ between groups (P = .808). Operative time exhibited a significant downward trend (P < .001), with the median operative time dropping from 150 minutes for the first 10 implants to 134 minutes for the subsequent 10 implants. The decrease in AHI from baseline to 12-month follow-up was equivalent between the first and second ten (22.8 vs 21.2 events/hour, respectively,P < .001). Similarly, the first and second ten groups had equivalent ESS decreases at 6 months (2.0 vs 2.0, respectively,P < .001). ESS outcomes remained equivalent for those with data through 12-months. Conclusions: Across the centers' first 20 implants, an approximately 11% reduction operative time was identified, however, no learning curve effect was seen for 6-month or 12-month AHI or ESS over the first twenty implants. Ongoing monitoring through the ADHERE registry will help measure the impact of evolving provider and patient specific characteristics as the number of implant centers increases.

Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states, and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment’s molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea-hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g. interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.

None Despite excellent positive airway pressure (PAP) adherence, a subset of obstructive sleep apnea (OSA) patients experience residual elevation of the apnea-hypopnea index (AHI). Drug-induced sleep endoscopy (DISE) during PAP application provides an opportunity to examine the anatomic effect of PAP therapy on the upper airway and to troubleshoot refractory residual AHI elevation. We present a patient who demonstrated persistent moderate-severe AHI elevation during titration polysomnogram and subsequent data download reports despite numerous mask refits, chin strap, positional modifications, and multiple pressure and mode adjustments in both the clinic and sleep laboratory settings. DISE was performed with the flexible endoscope passed through the PAP circuit into the upper airway. Jaw laxity and associated mandibular retrusion at sleep onset was found to result in a complete fixed tongue base obstruction that PAP therapy, delivered via the patient's oronasal interface, was unable to overcome. Various strategies to overcome these obstacles are discussed.

Upper Airway Stimulation (UAS) therapy is a treatment option for CPAP intolerant obstructive sleep apnea. An increasing number of facilities offer UAS with varying levels of experience. Referring physicians may want to know whether the first set of patients have different outcomes from subsequent patients. We sought to quantify whether the surgical learning curve affects patient AHI and ESS outcomes. The ADHERE international multi-center registry is tracking UAS outcomes, including Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS) score, and surgical procedure time. Data were retrospectively reviewed from centers with at least 20 implants. The outcomes from each center’s first ten implants were compared against the subsequent ten implants. Data are presented as mean (± standard deviation). A total of 8 facilities had at least 20 implants for analysis, yielding 80 in the first ten implants group and 80 subjects in the subsequent ten implants group. Baseline age, gender, BMI, and pre-operative AHI and ESS were similar in both groups. UAS implantation time decreased significantly from 160 (±37) minutes (range: 72-287) for the first 10 implants to 145 (± 42) minutes (range: 77-329) for the subsequent 10 implants. (p<0.05) A learning curve effect is present in implantation time, yet similar improvements in post-titration AHI and ESS occurred over the first twenty implants. This finding may address referring physician concerns about initial patient outcomes when starting an UAS program. ADHERE registry was sponsored by Inspire Medical Systems

Objectives/Hypothesis Upper airway stimulation has demonstrated marked improvements in apnea-hypopnea index, oxygen desaturation index, and quality-of-life measures in patients with moderate to severe obstructive sleep apnea (OSA) who cannot tolerate continuous positive airway pressure. Cardiac arrhythmias are common in patients with OSA and can require electrical cardioversion. We describe the first four reported cases of hypoglossal nerve stimulator (HGNS) dysfunction after electrical cardioversion and illustrate our operative approach to device troubleshooting and repair. Study Design Retrospective case series. Methods A retrospective review of 201 HGNS implantations performed at two academic institutions revealed four cases of HGNS device dysfunction after electrical cardioversion requiring surgical revision. Preoperative and postoperative device performance metrics and electrical cardioversion specifications were retrospectively assessed and compiled for this case series. The senior authors (R.J.S., M.S.B.) detail operative planning and approach for HGNS implantable pulse generator (IPG) replacement. Results At least two patients with HGNS device dysfunction had received cardioversion via anterolateral electrode pad placement. Three patients had received multiple shocks. All four patients experienced a change in device functionality or complete cessation of functionality after electrocardioversion. Operatively, each patient required replacement of the IPG, with subsequent intraoperative interrogation revealing proper device functionality. Conclusion Counseling for patients with HGNS undergoing external electrical cardioversion should include possible device damage and need for operative replacement. Anteroposterior electrode pad placement should be considered for patients with HGNS who require electrocardioversion. Operative replacement of an HGNS system damaged by electrocardioversion begins with IPG replacement and intraoperative device interrogation. Level of Evidence 4 Laryngoscope, 129:1949-1953, 2019

Despite excellent positive airway pressure (PAP) adherence, a subset of obstructive sleep apnea (OSA) patients experience residual elevation of the apnea-hypopnea index (AHI). Drug-induced sedation endoscopy (DISE) during PAP application provides an opportunity to examine the anatomic effect of PAP therapy on the upper airway and to troubleshoot refractory residual AHI elevation. We present a patient who demonstrated persistent moderate-severe AHI elevation on both in-lab titration studies and data download reports despite excellent objective adherence, mask refits, chinstraps, positional modifications, and multiple pressure and mode adjustments. DISE was performed with the flexible endoscope passed through the PAP circuit into the upper airway. Jaw laxity and associated mandibular retrusion during the procedure was associated with baseline tongue base collapse. Application of PAP therapy with an oronasal interface appeared to exacerbate the tongue base obstruction by further displacing the mandible posteriorly and opening the mouth. Mandibular repositioning relieved the obstruction and allowed more successful delivery of positive pressure. Treatment considerations based on these findings included a customized mask that provides more effective mandibular stabilization or an oral appliance and PAP combination therapy approach. DISE-PAP allows for a dynamic evaluation of PAP therapy effects on the upper airway anatomy under a sedated exam that mimics the obstructive sleep-disordered breathing state. For patients with residual AHI elevation despite standard troubleshooting approaches, DISE-PAP offers anatomic insight into factors associated with PAP failure and opportunities for improved outcomes.

Objectives Obstructive sleep apnea (OSA) presents several challenges in skull base surgery, including increased intracranial pressure, worsened OSA with nasal packing, and avoidance of positive airway pressure (PAP) therapy postoperatively. The objective of this study was to examine the risk of postoperative complications in a skull base population with OSA in which PAP therapy is withheld. Study Design Retrospective cohort study. Setting Tertiary care hospital. Subjects and Methods Medical records of 414 adult patients undergoing anterior skull base procedures between January 1, 2014, and January 7, 2017, were retrospectively reviewed. Revision surgeries, skull base infections, sinus surgery, and orbital cases were excluded. Results Fifty-four (13.0%) patients with a diagnosis of OSA were identified. While the known patients with OSA were more likely to require postoperative supplemental oxygen (odds ratio [OR], 4.29; 95% confidence interval [CI], 2.38-7.75; P < .001), there was no increased risk of serious respiratory events or cerebrospinal fluid leak (CSF). To address the likely underdiagnosis of OSA in this cohort, subgroup analyses were performed of patients at high risk for OSA (body mass index >30 kg/m2 and hypertension) and demonstrated an increased risk of serious respiratory events (OR, 4.41; 95% CI, 1.24-15.7; P = .034) and CSF leak (13.6% vs 4.7%; P = .018). Conclusions Skull base patients with known OSA can be successfully managed with diligent care in the perioperative period when PAP therapy is withheld. However, OSA is likely underdiagnosed in the skull base population, and patients at high risk for undiagnosed OSA may be at the greatest risk for respiratory complications and CSF leak. Increased presurgical awareness and implementation of a perioperative management algorithm is needed.

Objectives/Hypothesis: Despite reports of lower positive pressure adherence rates with oronasal masks, patients with sinonasal problems are often prescribed this interface over a nasal interface. The aim of this study was to characterize the relationship between mask type and therapy adherence in the setting of sinonasal symptoms. Study Design: Retrospective case series with chart review. Methods: We reviewed 328 patients who underwent positive pressure titration between January 2012 and May 2015. Follow- up adherence data were available for 218 patients (66.5%). Multivariate analysis examined whether patients with sinonasal symptoms have improved adherence with oronasal masks compared to nasal or nasal pillow interfaces. Results: At a median follow- up of 95 days, positive pressure adherence in patients with sinonasal symptoms was highest with the nasal pillow interface. When compared with oronasal interfaces, the odds of adequate therapy adherence were >5 times greater with nasal pillow interfaces (odds ratio [OR] = 5.20, 95% confidence interval [CI] = 1.61-16.80, P = .006) and >3 times greater with nasal interfaces (OR = 3.67, 95% CI = 1.20-11.26, P = .02) in these symptomatic patients. Conclusions: The presence of nasal problems does not predict the need for an oronasal mask. Positive pressure adherence rates are higher with nasal and nasal pillow interfaces compared to oronasal masks, even in patients with sinonasal complaints.