Comparative analysis of two custom-made mandibular advancement devices with varied designs for treating moderate to severe obstructive sleep apnea.

INTRODUCTION: Custom-made titratable mandibular advancement device (MAD) treatment can nowadays be considered a promising first-line treatment in patients with mild to severe obstructive sleep apnea (OSA). Specific manufacturing designs and titration mechanisms of MAD are on the market, characterized by their titration approach, vertical opening, and materials selection. The wing-designed MAD (SomnoDent® Flex™, SomnoMed Ltd, Sydney, Australia) has a lateral screw mechanism to advance the lower jaw in incremental steps of 0.1 up to 6.0 mm. The newer uniquely designed custom-made MAD with passive mouth closing (SomnoDent® Avant™ SomnoMed Ltd, Sydney, Australia) has a frontal exchangeable advancement strap of fixed lengths as a specific titration mechanism, all supporting freedom of lateral movement. We aimed to assess the associations between the type of MAD prescribed and OSA treatment outcome. METHODS: Data from 209 patients (165 male, mean age 53.9 (±10.9) years, median baseline BMI and AHI 27.02 [24.8; 29.7] kg/m2 and 22.8 [17.7; 31.6]/hour sleep, respectively) were collected. Of this cohort, 91 patients with the traditional, wing-based SomnoDent® Flex™ and 118 patients with SomnoDent® Avant™. All patients were diagnosed with a type 1 polysomnography demonstrating moderate to severe OSA (15 ≤ AHI ≤65 per hour sleep). The selected MAD was fitted in the so-called maximal comfortable protrusion. After 3 months of subjective titration until resolution of subjective symptoms and/or achieving physical limits, a checkup with validated home sleep monitoring was conducted. Treatment success was defined as "AHI reduction ≥50% with MAD compared to baseline AHI and AHI with MAD <10 events per hour". RESULTS: These real-world data set showed that 67% of patients achieved treatment success, with a statistically significant reduction in AHI from 22.8 [17.7; 31.6] to 7.45 [3.4; 15.0]/h sleep. The SomnoDent® Avant™ achieved 75% treatment success versus 56% for the traditional, wing-based SomnoDent® Flex™ (P < 0.05). Overall, AHI reduction was 70% for SomnoDent® Avant™ (P < 0.05) vs. 63% for SomnoDent® Flex™ (P < 0.05). CONCLUSIONS: This study shows that choice of MAD design can impact the treatment outcome and could become an important consideration in selecting the type of MAD for personalized treatment for OSA patients. While the results of the traditional wing-based MAD design were comparable to the therapeutic outcome with other titratable, custom-made MADs, the MAD with the passive mouth closing feature showed significantly greater reduction in total AHI potentially due to encouraged nasal breathing, reduced mouth breathing and lesser vertical opening thereby decreasing the probability of tongue base collapse.

Polysomnographic airflow shapes and site of collapse during drug-induced sleep endoscopy.

RATIONALE: Differences in the pharyngeal site-of-collapse influences efficacy of non-CPAP therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the palate (CCCp) during drug-induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE-based site-of-collapse using overnight polysomnography. METHODS: 182 OSA patients provided DISE and polysomnography data. Six polysomnographic flow-shape characteristics (mean during hypopnoeas) were identified as candidate predictors of CCCp (primary outcome variable, N=44/182), including inspiratory skewness and inspiratory scoopiness. Multivariable logistic regression combined the six characteristics to predict clear presence (N=22) versus absence (N=128) of CCCp (partial collapse and concurrent tongue-base collapse excluded). Odds ratios for actual CCCp between predicted subgroups were quantified after cross-validation. Secondary analyses examined complete lateral wall, tongue-base, or epiglottis collapse. External validation was performed on a separate dataset (Ntotal=466). RESULTS: CCCp was characterised by greater scoopiness (ß=1.5±0.6 per 2SD, multivariable estimate±se) and skewness (ß=11.4±2.4) compared to non-CCCp. Odds ratio [95%CI] for CCCp in predicted positive versus negative subgroups was 5.0[1.9-13.1]. The same characteristics provided significant cross-validated prediction of lateral wall (OR=6.3[2.4-16.5]), tongue-base (3.2[1.4-7.3]), and epiglottis (4.4[1.5-12.4]) collapse. CCCp and lateral wall collapse shared similar characteristics (skewed, scoopy), diametrically opposed to tongue-base and epiglottis collapse characteristics. External validation confirmed model prediction. CONCLUSIONS: The current study provides a means to recognise patients with likely CCCp or other DISE-based site-of-collapse categories using routine polysomnography. Since site-of-collapse influences therapeutic responses, polysomnographic airflow shape analysis could facilitate precision site-specific OSA interventions.

The prevalence of treatment-emergent central sleep apnea with mandibular advancement device therapy.

STUDY OBJECTIVES: Treatment-emergent central sleep apnea (TECSA) describes the appearance or persistence of central sleep apnea while undergoing treatment for obstructive sleep apnea. TECSA is well studied in continuous positive airway pressure therapy with an estimated prevalence of 8%. Based on a few case reports, mandibular advancement devices (MAD) may also provoke TECSA. This study aims to gain insight into the prevalence of TECSA with MAD therapy. METHODS: This retrospective study includes a total of 129 patients with moderate to severe obstructive sleep apnea who were treated with a custom-made titratable MAD. Baseline and follow-up sleep studies were compared to identify patients with TECSA. Since different diagnostic criteria to define TECSA are used in literature, prevalence was calculated according to three definitions (TECSA-1, -2, and -3). Demographics, MAD treatment variables, and findings of the diagnostic polysomnography were compared between TECSA and non-TECSA patients to identify possible predictors. RESULTS: Depending on the definition used, TECSA was found in 3.1%-7.8% of patients undergoing MAD therapy. TECSA patients had a higher apnea index (9.2 vs 2.0 events/h, P = .042), central apnea-hypopnea index (4.1 vs 0.2 events/h, P = .045) and oxygen desaturation index (23.9 vs 16.3 events/h, P = .018) at baseline compared to non-TECSA patients. No differences were found in demographics and treatment variables. CONCLUSIONS: These findings demonstrate that TECSA also occurs in patients starting MAD treatment. Patients with TECSA had a higher apnea index, central apnea-hypopnea index, and oxygen desaturation index at baseline compared to non-TECSA patients. CITATION: Hellemans S, Van de Perck E, Braem MJ, Verbraecken J, Dieltjens M, Vanderveken OM. The prevalence of treatment-emergent central sleep apnea with mandibular advancement device therapy. J Clin Sleep Med. 2023;19(12):2035-2041.

Quantitative Measurement of Pharyngeal Dimensions During Drug-induced Sleep Endoscopy for Oral Appliance Outcome.

OBJECTIVE: To quantitatively investigate the effect of mandibular advancement devices (MADs) on pharyngeal airway dimensions in a transverse plane as measured during drug-induced sleep endoscopy (DISE). METHODS: Data from 56 patients, treated with MAD at 75% maximal protrusion and with baseline Apnea-Hypopnea Index ≥10 events/h, were analyzed. For each patient, three snapshots were selected from DISE video footage at baseline, with MAD presence, and during chin lift, resulting in 498 images (168/168/162, baseline/MAD/chin lift). Cross-sectional areas, anteroposterior (AP) and laterolateral (LL) dimensions on both retroglossal and retro-epiglottic levels were measured. To define the effect of MAD and chin lift on pharyngeal dimensions, linear mixed-effect models were built. Associations between MAD treatment response and pharyngeal expansion (MAD/chin lift) were determined. RESULTS: Significant differences were found between retroglossal cross-sectional areas, AP, and LL dimensions at baseline and with MAD presence. At a retro-epiglottic level, only LL dimensions differed significantly with MAD presence compared to baseline, with significant relation of LL expansion ratio to treatment response (p = 0.0176). After adjusting the response definition for the sleeping position, greater retroglossal expansion ratios were seen in responders (1.32 ± 0.48) compared to non-responders (1.11 ± 0.32) (p = 0.0441). No significant association was found between response and pharyngeal expansion by chin lift. CONCLUSION: Our observations highlight the additional value of quantitative pharyngeal airway measurements during DISE with MAD presence in evaluating MAD treatment outcome. These findings demonstrate an increase in retroglossal airway dimensions during DISE, with MAD presence, and more pronounced increase in retroglossal expansion ratios in MAD treatment responders compared to non-responders after sleeping position correction. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3619-3627, 2023.

Dental sleep-related conditions and the role of oral healthcare providers: A scoping review.

Dental sleep medicine as a discipline was first described about a quarter of a century ago. Snoring, obstructive sleep apnea, sleep bruxism, xerostomia, hypersalivation, gastroesophageal reflux disease, and orofacial pain were identified as dental sleep-related conditions. This scoping review aimed to: i) identify previously unidentified dental sleep-related conditions; and ii) identify the role of oral healthcare providers in the prevention, assessment, and management of dental sleep-related conditions in adults. A systematic literature search was conducted in PubMed, Embase.com, Web of Science, and Cochrane. Studies that reported an actual or likely role of oral healthcare providers in the prevention, assessment, and/or management of sleep-related conditions were included. Of the 273 included studies, 260 were on previously listed dental sleep-related conditions; the other 13 were on burning mouth syndrome. Burning mouth syndrome was therefore added to the list of dental sleep-related conditions for the first aim and categorized into sleep-related orofacial pain. For the second aim, the role of oral healthcare providers was found to be significant in the prevention, assessment, and management of obstructive sleep apnea and sleep bruxism; in the assessment and management of snoring, sleep-related orofacial pain, and oral dryness; and in the assessment of sleep-related gastroesophageal reflux condition.

Non-CPAP therapy for obstructive sleep apnoea.

Treatment of obstructive sleep apnoea in adults is evolving, from a "one treatment fits all" to a more individualised approach. The spectrum of treatment options is broad and heterogeneous, including conservative, technological and pharmaceutical modalities. This raises the questions of which patients these modalities might be useful for, and if there are specific criteria for single or combined treatment. The most commonly used non-CPAP treatment is a mandibular advancement device. Furthermore, it appears from the available evidence that upper airway surgery, bariatric surgery, and maxillomandibular advancement can be effective in particular patient groups and should be indicated more readily in clinical practice. Technically, a tracheotomy is the most effective surgical treatment, but is not socially acceptable and is associated with major side-effects. Other treatment options are emerging, like positional therapy, hypoglossal nerve stimulation, and myofunctional exercises. Drug therapy is also promising when pathophysiological traits are considered. The range of currently available treatment options will be discussed in this review, with emphasis on the selection of appropriate patients, therapeutic efficacy and compliance, and reference to recent guidelines. In the selection process, routine application of drug-induced sleep endoscopy to assess the site(s) of collapse during sleep can increase the success rate of both surgical interventions and oral appliance therapy. Educational aims: To outline recommendations concerning the proper management of obstructive sleep apnoea (OSA) patients that cannot be treated adequately with continuous positive airway pressure (CPAP) due to intolerance, poor adherence or compliance, or CPAP refusal.To provide information about the selection of appropriate patients for alternative non-CPAP treatment options.To better understand the different aspects of OSA treatment with noninvasive approaches, such as oral appliances, positional therapy, drug treatment and myofunctional therapy, including indications, contraindications, and expected short- and long-term results.To discuss the different surgical options for the treatment of OSA and to provide information on the important issue of proper patient selection for surgery, as most OSA surgical outcomes are associated with the pre-operative assessment of the level(s) of upper airway collapse.

Multimodal phenotypic labelling using drug-induced sleep endoscopy, awake nasendoscopy and computational fluid dynamics for the prediction of mandibular advancement device treatment outcome: a prospective study.

Mandibular advancement device (MAD) treatment outcome for obstructive sleep apnea (OSA) is variable and patient dependent. A global, clinically applicable predictive model is lacking. Our aim was to combine characteristics obtained during drug-induced sleep endoscopy (DISE), awake nasendoscopy, and computed tomography scan-based computational fluid dynamic (CFD) measurements in one multifactorial model, to explain MAD treatment outcome. A total of 100 patients with OSA were prospectively recruited and treated with a MAD at fixed 75% protrusion. In all, 72 underwent CFD analysis, DISE, and awake nasendoscopy at baseline in a blinded fashion and completed a 3-month follow-up polysomnography with a MAD. Treatment response was defined as a reduction in the apnea-hypopnea index (AHI) of ≥50% and deterioration as an increase of ≥10% during MAD treatment. To cope with missing data, multiple imputation with predictive mean matching was used. Multivariate logistic regression, adjusting for body mass index and baseline AHI, was used to combine all potential predictor variables. The strongest impact concerning odds ratios (ORs) was present for complete concentric palatal collapse (CCCp) during DISE on deterioration (OR 28.88, 95% confidence interval [CI] 1.18-704.35; p = 0.0391), followed by a C-shape versus an oval shape of the soft palate during wakefulness (OR 8.54, 95% CI 1.09-67.23; p = 0.0416) and tongue base collapse during DISE on response (OR 3.29, 95% CI 1.02-10.64; p = 0.0464). Both logistic regression models exhibited excellent and fair predictive accuracy. Our findings suggest DISE to be the most robust examination associated with MAD treatment outcome, with tongue base collapse as a predictor for successful MAD treatment and CCCp as an adverse DISE phenotype.

Critical to Know Pcrit: A Review on Pharyngeal Critical Closing Pressure in Obstructive Sleep Apnea.

It is crucial to understand the underlying pathophysiology of obstructive sleep apnea (OSA). Upper airway collapsibility is an important pathophysiological factor that affects the upper airway in OSA. The aim of the current study was to review the existing body of knowledge on the pharyngeal collapsibility in OSA. After a thorough search through Medline, PubMed, Scopus, and Web of science, the relevant articles were found and used in this study. Critical closing pressure (Pcrit) is the gold standard measure for the degree of collapsibility of the pharyngeal airway. Various physiological factors and treatments affect upper airway collapsibility. Recently, it has been shown that the baseline value of Pcrit is helpful in the upfront selection of therapy options. The standard techniques to measure Pcrit are labor-intensive and time-consuming. Therefore, despite the importance of Pcrit, it is not routinely measured in clinical practice. New emerging surrogates, such as finite element (FE) modeling or the use of peak inspiratory flow measurements during a routine overnight polysomnography, may enable clinicians to have an estimate of the pharyngeal collapsibility. However, validation of these techniques is needed.

Critical closing pressure of the pharyngeal airway during routine drug-induced sleep endoscopy: feasibility and protocol.

In obstructive sleep apnea (OSA), there are various pathophysiological factors affecting the upper airway during sleep. Two prominent factors contributing to OSA are site and pattern of upper airway collapse and degree of pharyngeal collapsibility. In a clinical setting, drug-induced sleep endoscopy (DISE) is used to visualize the structures of the upper airway. Critical closing pressure (Pcrit) is the gold standard measure of pharyngeal collapsibility. This prospective clinical study aimed to investigate the feasibility and protocol of Pcrit measurements during DISE. Thirteen patients with OSA were included. Pcrit was calculated using peak inspiratory airflow and inspiratory ventilation. The proposed protocol was successful in Pcrit measurement during DISE in all subjects [median[Q1;Q3] Pcrit for "peak inspiratory method" (n = 12): -0.84[-2.07;0.69] cmH2O, "ventilation method" (n = 13): -1.32[2.32;0.47] cmH2O], highlighting the feasibility of the approach. There was no significant difference (P = 0.67) between calculated Pcrit with either of the calculation methods, indicating high reliability. Correlation analysis showed Pcrit as an independent parameter of any of the anthropometric or polysomnographic parameters. The ventilation method proved to be more successful in assessment of Pcrit in subjects with epiglottic collapse (e.g., with high negative effort dependence). Subjects with palatal complete concentric collapse during DISE had a wide Pcrit range ([-2.86;2.51]cmH2O), suggesting no close correlation between Pcrit and this DISE pattern (P = 0.38). Incorporation of Pcrit measurements into DISE assessments is feasible and may yield valuable additional information for OSA management. Combining Pcrit and DISE provides information on both the site and degree of upper airway collapse and the degree of pharyngeal collapsibility.NEW & NOTEWORTHY The protocol of this study was successful in concomitant measurement of Pcrit during routine clinical endoscopy. Comparison of two calculation methods for Pcrit showed that the inspiratory ventilation method was more successful in assessment of Pcrit in subjects with epiglottic collapse who have high negative effort dependence. Subjects with palatal complete concentric collapse during DISE had a wide Pcrit range and did not have a greater Pcrit than patients in other site of collapse categories.

Mandibular advancement device therapy in patients with epiglottic collapse.

PURPOSE: Epiglottic collapse is a specific sleep-endoscopic finding that can prove challenging to treat in patients with obstructive sleep apnea (OSA). Its effect on mandibular advancement devices (MAD) remains largely unknown. Therefore, this study assessed whether or not epiglottic collapse affects treatment outcome with MAD. METHODS: Patients with diagnosed OSAD underwent drug-induced sleep endoscopy (DISE) and were treated with a titratable MAD. Two age- and gender-matched controls were selected for every subject with primary epiglottic collapse (i.e., complete closure without involvement of other upper airway structures). Treatment response was defined as a reduction in oxygen desaturation index (ODI) of ≥ 50% following MAD therapy. RESULTS: Of 101 patients who underwent DISE, twenty (20%) showed primary epiglottic collapse (mean [SD]: 17 men; age 49.8 [10.1]; body mass index 28.3 [2.9] kg/m2; apnea-hypopnea index 27.0 [16.9] events/h). There were no significant differences in baseline clinical characteristics between cases and controls. MAD therapy was equally effective in patients with and without epiglottic collapse (mean [SD]; ODI with MAD, 8.7 [7.7] events/h vs. 7.8 [7.5] events/h, P = .62; ΔODI, 53.3 [29.6]% vs. 50.6 [37.7]%, P = .82; responder status, 10/20 vs. 22/40, P = .79). Logistic regression analysis revealed no associations between epiglottic collapse and treatment outcome. CONCLUSION: The presence of epiglottic collapse during DISE does not impair the effectiveness of MAD. Therefore, MAD therapy should be considered in patients with predominant epiglottic collapse.

A pilot study on comparison of subjective titration versus remotely controlled mandibular positioning during polysomnography and drug-induced sleep endoscopy, to determine the effective protrusive position for mandibular advancement device therapy.

STUDY OBJECTIVES: The aim of this pilot study was to evaluate the clinical effectiveness of subjective titration versus objectively guided titration during polysomnography (PSG) and drug-induced sleep endoscopy (DISE) in mandibular advancement device (MAD) therapy for patients with obstructive sleep apnea (OSA). METHODS: In this pilot cross-over study, patients underwent three titration procedures in randomized order: (1) subjective titration, (2) PSG-guided titration using a remotely controlled mandibular positioner (RCMP) and (3) DISE-assisted titration using RCMP. After each titration procedure, patients used the MAD for 1 month at the targeted protrusion obtained according to the preceding titration procedure. For each procedure, a follow-up PSG was performed after 1 month of MAD use in order to evaluate the efficacy of the MAD. RESULTS: Ten patients were included in the study. Overall, no significant differences in targeted optimal protrusion compared to maximal comfortable protrusion among the three titration methods were observed. There was no significant difference in reduction in AHI. In this study, PSG titration correctly classified 50% of patients as 'responder'. A higher predictive accuracy was found for DISE titration with a sensitivity of 83.3% and a specificity of 100%. CONCLUSIONS: This pilot randomized cross-over trial showed no differences in optimal mandibular positioning and corresponding efficacy of MAD between subjective titration, DISE titration or PSG titration.

Mandibular advancement device treatment and reverse left ventricular hypertrophic remodeling in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with cardiovascular comorbidities such as left ventricular (LV) hypertrophy. Whether OSA is an independent etiological factor for this hypertrophic remodeling is yet unknown. Continuous positive airway pressure partially reverses this hypertrophy, but data regarding the effect of mandibular advancement devices on LV remodeling are scarce. The aim of this prospective trial is to evaluate the effect of mandibular advancement device therapy on LV geometry and function in patients with OSA. METHODS: At baseline and 6-month follow-up, participants underwent a home sleep apnea test, 24-hour ambulatory blood pressure monitoring and a 2-dimensional Doppler and tissue Doppler echocardiography. RESULTS: Sixty-three patients (age: 49 ± 11 years; body mass index: 27.0 ± 3.4 kg/m2; baseline apnea-hypopnea index home sleep apnea test: 11.7 [8.2; 24.9] events/h) completed the 6-month follow-up visit. Overall, blood pressure values and parameters of LV function were within normal ranges at baseline and did not change under mandibular advancement device therapy. In contrast, the interventricular septum thickness was at the upper limits of normal at baseline and showed a significant decrease at 6-month follow-up (11.1 ± 2.1 mm vs 10.6 ± 2.0 mm, P = .03). This significant improvement is only found in responders but not in nonresponders. There was no correlation between the decrease of interventricular septum thickness and the change in blood pressure. CONCLUSIONS: In mildly obese, normotensive patients with OSA we observed significant reverse hypertrophic remodeling after 6 months of successful mandibular advancement device therapy, with maintained normotensive systemic blood pressure. This suggests that OSA is an independent factor in the pathophysiology of LV hypertrophy in these patients. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Evaluation of the Cardiovascular Effects of the MAS in the Treatment of Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02320877; Identifier: NCT02320877. CITATION: Dieltjens M, Vanderveken OM, Shivalkar B, et al. Mandibular advancement device treatment and reverse left ventricular hypertrophic remodeling in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(3):903-909.

Functional imaging improves patient selection for mandibular advancement device treatment outcome in sleep-disordered breathing: a prospective study.

STUDY OBJECTIVES: Mandibular advancement devices (MADs) are a noninvasive treatment option for patients with obstructive sleep apnea (OSA) and act by increasing the upper airway volume. However, the exact therapeutic mechanism of action remains unclear. The aim of this study was to assess MAD mechanisms using functional imaging that combines imaging techniques and computational fluid dynamics and assess associations with treatment outcome. METHODS: One hundred patients with OSA were prospectively included and treated with a custom-made MAD at a fixed 75% protrusion. A low-dose computed tomography scan was made with and without MADs for computational fluid dynamics analysis. Patients underwent a baseline and 3-month follow-up polysomnography to evaluate treatment efficacy. A reduction in apnea-hypopnea index ≥ 50% defined treatment response. RESULTS: Overall, 71 patients completed both 3-month follow-up polysomnography and low-dose computed tomography scan with computational fluid dynamics analysis. MAD treatment significantly reduced the apnea-hypopnea index (16.5 [10.4-23.6] events/h to 9.1 [3.9-16.4] events/h; P < .001, median [quartile 1-quartile 3]) and significantly increased the total upper airway volume (8.6 [5.4-12.8] cm3 vs 10.7 [6.4-15.4] cm3; P = .003), especially the velopharyngeal volume (2.1 [0.5-4.1] cm3 vs 3.3 [1.8-6.0] cm3; P < .001). However, subanalyses in responders and nonresponders only showed a significant increase in the total upper airway volume in responders, not in nonresponders. CONCLUSIONS: MAD acts by increasing the total upper airway volume, predominantly due to an increase in the velopharyngeal volume. Responders showed a significant increase in the total upper airway volume with MAD treatment, while there was no significant increase in nonresponders. Findings add evidence to implement functional imaging using computational fluid dynamics in routine MAD outcome prediction. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Predicting Therapeutic Outcome of Mandibular Advancement Device Treatment in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT01532050; Identifier: NCT01532050. CITATION: Van Gaver H, Op de Beeck S, Dieltjens M, et al. Functional imaging improves patient selection for mandibular advancement device treatment outcome in sleep-disordered breathing: a prospective study. J Clin Sleep Med. 2022;18(3):739-750.

Endotypic Mechanisms of Successful Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

Rationale: Approximately one-third of patients with obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation (HGNS) therapy are incomplete responders, despite careful patient selection based on baseline characteristics and drug-induced sleep endoscopy.Objectives: Here we use polysomnographic endotyping to assess the pathophysiological mechanisms underlying favorable versus incomplete responses to HGNS therapy.Methods: Baseline polysomnography data of the STAR (Stimulation Therapy for Apnea Reduction) trial were included. Raw baseline polysomnographic data from 91/126 patients were available for analysis. Traits-loop gain, arousal threshold, collapsibility, and muscle compensation-were calculated from the baseline polysomnography data according to Sands and colleagues (AJRCCM 2018, SLEEP 2018). Logistic regression assessed apnea-hypopnea index (AHI)-adjusted associations between HGNS response (>50% reduction in AHI to <10/h at 1 yr) and OSA traits.Measurements and Main Results: Overall, HGNS treatment reduced AHI from 30.7 (24.9-39.9) to 8.5 (4.0-19.5) events/h (P < 0.0001; median [quartiles 1-3]); N = 53/91 were responders. In adjusted analysis, a favorable response to therapy was independently associated with higher arousal threshold (odds ratio [95% confidence interval]: 6.76 [2.44-23.3], P = 0.001), greater compensation (odds ratio: 4.22 [1.70-12.55] per SD, P = 0.004), and lower loop gain (in milder collapsibility, per significant interaction, P = 0.003). The higher arousal threshold was evident in responders before adjusted analysis. Predicted responders had an approximately fourfold lower treatment AHI versus predicted nonresponders (4.9 [2.7-8.5] vs. 20.7 [10.9-29.7], P < 0.0001; median [quartiles 1-3]); differences remained significant after cross-validation.Conclusions: Favorable responses to HGNS therapy are associated with the pathophysiological traits causing OSA, particularly a higher arousal threshold. Along with established criteria, individuals with favorable traits could potentially be prioritized for precision HGNS therapy.This analysis was a secondary analysis of the STAR trial registered with clinicaltrials.gov (NCT01161420).

Awake endoscopic assessment of the upper airway during tidal breathing: Definition of anatomical features and comparison with drug-induced sleep endoscopy.

OBJECTIVES: Awake nasopharyngoscopy is routinely performed in the assessment of patients who require treatment for sleep-disordered breathing (SDB). However, the applicability and accuracy of Müller's manoeuvre, the main evaluation method for this purpose, are disputable. The current study aimed to introduce an alternative method for awake nasopharyngoscopy in patients with SDB. DESIGN: We defined qualitative anatomical features during tidal breathing at the levels of the soft palate, oropharynx, tongue base, epiglottis and hypopharynx, and compared these awake features to the sites and patterns of collapse as observed during drug-induced sleep endoscopy (DISE). SETTING: Tertiary care academic centre. PARTICIPANTS: Seventy-three patients diagnosed with SDB. MAIN OUTCOME MEASURES: The primary outcome measure was the Kendall's tau correlation coefficient (τ) between observations during awake nasopharyngoscopy and DISE. Kappa-statistics (κ) were calculated to assess the agreement on awake endoscopic features with a second observer. RESULTS: In contrast to epiglottis shape, the modified Cormack-Lehane scale was significantly associated with epiglottis collapse during DISE (P < .0001; τ = .45). Other upper airway features that were correlated with DISE collapse were the position of the soft palate (P = .007; τ = .29), crowding of the oropharynx (P = .026; τ = .32) and a posteriorly located tongue base (P = .046; τ = .32). Interobserver agreement of endoscopic features during tidal breathing was moderate (0.60 ≤ κ < 0.80). CONCLUSION: The current study introduces a comprehensive and reliable assessment method for awake nasopharyngoscopy based on anatomical features that are compatible with DISE collapse patterns.

Mandibular Advancement Device Treatment Efficacy Is Associated with Polysomnographic Endotypes.

Rationale: Mandibular advancement device (MAD) treatment efficacy varies among patients with obstructive sleep apnea.Objectives: The current study aims to explain underlying individual differences in efficacy using obstructive sleep apnea endotypic traits calculated from baseline clinical polysomnography: collapsibility (airflow at normal ventilatory drive), loop gain (drive response to reduced airflow), arousal threshold (drive preceding arousal), compensation (increase in airflow as drive increases), and the ventilatory response to arousal (increase in drive explained by arousal). On the basis of previous research, we hypothesized that responders to MAD treatment have a lower loop gain and milder collapsibility.Methods: Thirty-six patients (median apnea-hypopnea index [AHI], 23.5 [interquartile range (IQR), 19.7-29.8] events/h) underwent baseline and 3-month follow-up full polysomnography, with MAD fixed at 75% of maximal protrusion. Traits were estimated using baseline polysomnography according to Sands and colleagues. Response was defined as an AHI reduction ≥ 50%.Results: MAD treatment significantly reduced AHI (49.7%baseline [23.9-63.6], median [IQR]). Responders exhibited lower loop gain (mean [95% confidence interval], 0.53 [0.48-0.58] vs. 0.65 [0.57-0.73]; P = 0.020) at baseline than nonresponders, a difference that persisted after adjustment for baseline AHI and body mass index. Elevated loop gain remained associated with nonresponse after adjustment for collapsibility (odds ratio, 3.03 [1.16-7.88] per 1-standard deviation (SD) increase in loop gain [SD, 0.15]; P = 0.023).Conclusions: MAD nonresponders exhibit greater ventilatory instability, expressed as higher loop gain. Assessment of the baseline degree of ventilatory instability using this approach may improve upfront MAD treatment patient selection.Clinical trial registered with www.clinicaltrials.gov (NCT01532050).

Correction to: Remotely controlled mandibular positioning of oral appliance therapy during polysomnography and drug-induced sleep endoscopy compared with conventional subjective titration in patients with obstructive sleep apnea: protocol for a randomized crossover trial.

Following publication of the original article [1], the authors reported that Fig. 1 had not been corrected based on the reviewer's comments. The correct Fig. 1 is presented below.

The relationship between specific nasopharyngoscopic features and treatment deterioration with mandibular advancement devices: a prospective study.

STUDY OBJECTIVES: The variable efficacy of mandibular advancement device (MAD) treatment necessitates both accessible and accurate methods for patient selection. However, the role of awake nasopharyngoscopy for this purpose remains dubious. We introduced an assessment method based on anatomical upper airway features during tidal breathing for nasopharyngoscopy. The current study aimed to relate these features to MAD treatment outcome. METHODS: One hundred patients diagnosed with obstructive sleep apnea were prospectively recruited for MAD treatment in a fixed 75% degree of maximal protrusion. Nasopharyngoscopic observations during Müller's maneuver and tidal breathing were recorded both with and without MAD. Treatment outcome, confirmed by 3-month follow-up polysomnography with MAD, was classified as (1) apnea-hypopnea index reduction ≥ 50%, (2) treatment apnea-hypopnea index < 5 events/h, and (3) ≥ 10% increase in apnea-hypopnea index compared with baseline (treatment deterioration). RESULTS: A complete dataset was obtained in 65 patients. After adjusting for baseline apnea-hypopnea index, body mass index, and supine dependency, the position of the soft palate (odds ratio, 4.0; 95% confidence interval, 1.3-11.8; P = .013) and crowding of the oropharynx (odds ratio, 7.7; 95% confidence interval, 1.4-41.4; P = .017) were related to treatment deterioration. Addition of both features significantly (P = .031) improved the accuracy of baseline models based on clinical measurements alone. Moreover, with the MAD in situ, a posteriorly located soft palate (odds ratio, 9.8; 95% confidence interval, 1.7-56.3; P = .010) and a posteriorly located tongue base (odds ratio, 7.4; 95% confidence interval, 1.5-35.9; P = .013) were associated with treatment deterioration. CONCLUSIONS: Awake nasopharyngoscopy might be a valuable office-based examination to exclude the risk of treatment deterioration and improve patient selection for MAD treatment. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Predicting Therapeutic Outcome of Mandibular Advancement Device Treatment in Obstructive Sleep Apnea (PROMAD); URL: https://clinicaltrials.gov/ct2/show/NCT01532050; Identifier: NCT01532050.