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

BACKGROUND: Differences in the pharyngeal site of collapse influence efficacy of non-continuous positive airway pressure therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the level of 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 with non-CCCp. The odds ratio for CCCp in predicted positive versus negative subgroups was 5.0 (95% CI 1.9-13.1). The same characteristics provided significant cross-validated prediction of lateral wall (OR 6.3, 95% CI 2.4-16.5), tongue base (OR 3.2, 95% CI 1.4-7.3) and epiglottis (OR 4.4, 95% CI 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.

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.

The effect of CPAP on the upper airway and ventilatory flow in patients with obstructive sleep apnea.

BACKGROUND: Continuous positive airway pressure (CPAP) is the mainstay of treatment for obstructive sleep apnea (OSA). However, data about its effect on the upper airway, especially the epiglottis, are scarce. The aim of this study was to investigate the changes in upper airway dimensions and inspiratory flow in response to incremental pressure levels. METHODS: This is a secondary analysis of a prospective clinical trial in which patients with moderate to severe OSA underwent drug-induced sleep endoscopy with simultaneous recordings of flow and mask pressure. CPAP was titrated in small increments. For each pressure level a representative 3-breath segment was selected to determine specific flow features. The corresponding endoscopic footage was reviewed to assess the degree of upper airway collapse in a semi-quantitative manner. RESULTS: A total of 214 breath segments were obtained from 13 participants (median [Q1-Q3]; apnea-hypopnea index, 24.9 [20.1-43.9] events/h; body mass index 28.1 [25.1-31.7] kg/m²). CPAP significantly increased cross-sectional dimensions of the soft palate, lateral walls and tongue base, but not of the epiglottis, and induced epiglottis collapse in one subject. Increased pressure improved peak inspiratory flow and median ventilation in all patients, even in the presence of persistent epiglottis collapse. CONCLUSION: CPAP does not effectively address epiglottis collapse in patients with OSA. However, it normalizes inspiratory flow regardless of its effect on the epiglottis. This clinical trial was registered on January 18th, 2020 on ClinicalTrials.gov with identifier NCT04232410.

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.

Clinical polysomnographic methods for estimating pharyngeal collapsibility in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea has major health consequences but is challenging to treat. For many therapies, efficacy is determined by the severity of underlying pharyngeal collapsibility, yet there is no accepted clinical means to measure it. Here, we provide insight into which polysomnographic surrogate measures of collapsibility are valid, applicable across the population, and predictive of therapeutic outcomes. METHODS: Seven promising polysomnography-derived surrogate collapsibility candidates were evaluated: Vpassive (flow at eupneic ventilatory drive), Vmin (ventilation at nadir drive), event depth (depth of the average respiratory event), oxygen desaturation slope and mean oxygen desaturation (events-related averages), Fhypopneas (fraction of events scored as hypopneas), and apnea index. Evaluation included (1) validation by comparison to physiological gold-standard collapsibility values (critical closing pressure, Pcrit), (2) capacity to detect increased collapsibility with older age, male sex, and obesity in a large community-based cohort (Multi-Ethnic Study of Atherosclerosis, MESA), and (3) prediction of treatment efficacy (oral appliances and pharmacological pharyngeal muscle stimulation using atomoxetine-plus-oxybutynin). RESULTS: Pcrit was significantly correlated with Vmin (r = -0.54), event depth (r = 0.49), Vpassive (r = -0.38), Fhypopneas (r = -0.46), and apnea index (r = -0.46; all p < .01) but not others. All measures detected greater collapsibility with male sex, age, and obesity, except Fhypopneas and apnea index which were not associated with obesity. Fhypopneas and apnea index were associated with oral appliance and atomoxetine-plus-oxybutynin efficacy (both p < .05). CONCLUSIONS: Among several candidates, event depth, Fhypopneas, and apnea index were identified as preferred pharyngeal collapsibility surrogates for use in the clinical arena.

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.

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.

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.

Comparison of Drug-Induced Sleep Endoscopy and Natural Sleep Endoscopy in the Assessment of Upper Airway Pathophysiology During Sleep: Protocol and Study Design.

Study Objectives: Obstructive sleep apnea (OSA) is increasingly recognized as a complex and heterogenous disorder. As a result, a "one-size-fits-all" management approach should be avoided. Therefore, evaluation of pathophysiological endotyping in OSA patients is emphasized, with upper airway collapse during sleep as one of the main features. To assess the site(s) and pattern(s) of upper airway collapse, natural sleep endoscopy (NSE) is defined as the gold standard. As NSE is labor-intensive and time-consuming, it is not feasible in routine practice. Instead, drug-induced sleep endoscopy (DISE) is the most frequently used technique and can be considered as the clinical standard. Flow shape and snoring analysis are non-invasive measurement techniques, yet are still evolving. Although DISE is used as the clinical alternative to assess upper airway collapse, associations between DISE and NSE observations, and associated flow and snoring signals, have not been quantified satisfactorily. In the current project we aim to compare upper airway collapse identified in patients with OSA using endoscopic techniques as well as flow shape analysis and analysis of tracheal snoring sounds between natural and drug-induced sleep. Methods: This study is a blinded prospective comparative multicenter cohort study. The study population will consist of adult patients with a recent diagnosis of OSA. Eligible patients will undergo a polysomnography (PSG) with NSE overnight and a DISE within 3 months. During DISE the upper airway is assessed under sedation by an experienced ear, nose, throat (ENT) surgeon using a flexible fiberoptic endoscope in the operating theater. In contrast to DISE, NSE is performed during natural sleep using a pediatric bronchoscope. During research DISE and NSE, the standard set-up is expanded with additional PSG measurements, including gold standard flow and analysis of tracheal snoring sounds. Conclusions: This project will be one of the first studies to formally compare collapse patterns during natural and drug-induced sleep. Moreover, this will be, to the authors' best knowledge, the first comparative research in airflow shape and tracheal snoring sounds analysis between DISE and NSE. These novel and non-invasive diagnostic methods studying upper airway mechanics during sleep will be simultaneously validated against DISE and NSE. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04729478.

Natural sleep endoscopy in obstructive sleep apnea: A systematic review.

This study's objective is to systematically review the literature on natural sleep endoscopy (NSE), including the set-up, different scoring systems, visualized collapse patterns during natural sleep, additional measurements, and comparison of upper airway collapse between NSE and drug-induced sleep endoscopy (DISE). A computerized search on Medline, Web of Science and the Cochrane library was conducted, obtaining 39 hits. Ten prospective studies were included in which NSE was performed in adults with obstructive sleep apnea (OSA). This study's findings suggest the soft palate to be the most frequent site of obstruction (58.8 %), followed by the tongue base (43.2 %), lateral walls (29.9 %), and epiglottis (22.4 %), which is in line with previous findings during DISE. Based on this literature review, the authors conclude that at this stage high quality, comparative research between DISE and NSE is missing. To adequately compare findings between OSA patients, endoscopic classification of upper airway collapse should be standardized. Non-invasive predictive tools to determine pharyngeal collapse are currently under investigation and may obviate the need for invasive endoscopy. This review highlights the contribution of NSE in validating such novel diagnostic methods and in studying upper airway mechanics in a research setting, yet larger and adequately powered studies are needed.

Physiological Traits and Adherence to Sleep Apnea Therapy in Individuals with Coronary Artery Disease.

Rationale: Untreated obstructive sleep apnea (OSA) is associated with adverse outcomes in patients with coronary artery disease (CAD). Continuous positive airway pressure (CPAP) is the most common treatment, but despite interventions addressing established adherence determinants, CPAP use remains poor. Objectives: To determine whether physiological traits that cause OSA are associated with long-term CPAP adherence in patients with CAD. Methods: Participants in the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) trial with objective CPAP adherence (h/night) over 2 years and analyzable raw polysomnography data were included (N = 249). The physiological traits-loop gain, arousal threshold (ArTH), pharyngeal collapsibility (Vpassive), and pharyngeal muscle compensation (Vcomp)-were measured by using polysomnography. Linear mixed models were used to assess the relationship between the traits and adherence. We also compared actual CPAP adherence between those with physiologically predicted "poor" adherence (lowest quartile of predicted adherence) and those with physiologically predicted "good" adherence (all others). Measurements and Main Results: The median (interquartile range) CPAP use declined from 3.2 (1.0-5.8) h/night to 3.0 (0.0-5.6) h/night over 24 months (P < 0.001). In analyses adjusted for demographics, anthropometrics, OSA characteristics, and clinical comorbidities, a lower ArTH was associated with worse CPAP adherence (0.7 h/SD of the ArTH; P = 0.021). Both high and low Vcomp were associated with lower adherence (P = 0.008). Those with predicted poor adherence exhibited markedly lower CPAP use than those with predicted good adherence for up to 2 years of follow-up (group differences of 2.0-3.2 h/night; P < 0.003 for all). Conclusions: A low ArTH, as well as a very low and high Vcomp, are associated with worse long-term CPAP adherence in patients with CAD and OSA. Physiological traits-alongside established determinants-may help predict and improve CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).

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).

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.

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).

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.

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.

Predicting sleep apnea responses to oral appliance therapy using polysomnographic airflow.

STUDY OBJECTIVES: Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. METHODS: Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea-hypopnea index [AHI] from baseline plus a treatment AHI <10 events/h). Model performance was quantified using (1) accuracy and (2) the difference in oral appliance treatment efficacy (percent reduction in AHI) and treatment AHI between predicted responders and nonresponders. RESULTS: In addition to age and body mass index (BMI), event depth and expiratory "pinching" (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, "pinched" expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). CONCLUSIONS: A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management.