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.

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.

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.

A promising concept of combination therapy for positional obstructive sleep apnea.

PURPOSE: The objective of this randomized controlled trial was to assess the additional effect of a chest-worn sleep position trainer (SPT) in patients with residual supine-dependent obstructive sleep apnea (sdOSA) under mandibular advancement device (MAD) therapy. METHODS: Baseline and follow-up polysomnography with MAD were performed. Twenty patients with sdOSA under MAD therapy underwent two consecutive randomized polysomnographies: one with SPT and one with combination of SPT + MAD. Data are presented as median (quartile 1, quartile 3). RESULTS: The SPT reduced the time spent in supine sleeping position compared to baseline and MAD therapy. Both MAD and SPT were individually effective in reducing the overall apnea/hypopnea index (AHI) significantly when compared to baseline from 20.8 (15.1; 33.6)/h at baseline to 11.0 (6.7; 13.8)/h and to 11.1 (3.5; 17.7)/h with MAD or SPT, respectively. The combination of SPT + MAD further reduced the overall AHI to 5.7 (3.6; 7.4), which was significantly lower than with MAD alone (p < 0.001) and SPT alone (p < 0.008), respectively. CONCLUSIONS: The results of this study indicate that combination of SPT + MAD leads to a higher therapeutic efficacy in patients with sdOSA under MAD therapy when compared to one of the treatment modalities alone.

Retention of mandibular advancement devices in the treatment of obstructive sleep apnea: an in vitro pilot study.

PURPOSE: In order for a mandibular advancement device (MAD) to be efficacious, it must remain seated on the teeth during sleep. Quantitative data on the retentive characteristics of MADs are currently unavailable. The present pilot study is the first to describe an in vitro setup testing the retentive characteristics of different monobloc MADs. METHODS: A hydraulic cyclic test machine was used with MADs seated on dental casts to measure retention forces upon removal of the MADs. A custom-made monobloc (CM-mono), a thermoplastic monobloc (TP-mono), and a thermoplastic duobloc (TP-duo) configured as a monobloc were tested. Two protrusions were investigated, representing 25 and 65% of the maximal protrusion. The effects of the type of MAD, duration of the test, and amount of protrusion on removal forces were measured. RESULTS: The measured removal forces of all three MADs tested differed significantly, with the TP-duo showing the highest values (P < 0.0001). The effects of wear due to the repetitive cyclic loading became obvious by the production of wear particles in all MADs tested. However, only the TP-duo showed a significant reduction in time in removal forces for both protrusion positions (P < 0.0001; P = 0.0011). The effect of the amount of protrusion on the removal forces differed significantly between all three MADs tested (P = 0.0074). CONCLUSIONS: This in vitro pilot study reveals significant differences in retention forces for the MADs tested. The findings are consistent with clinical effects of nightly loss of MADs as reported in the literature and are within the range of reported physiological mouth-opening forces. Future research is needed to determine the key design features of MADs that explain these differences.

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.

Objective measurement of compliance during oral appliance therapy for sleep-disordered breathing.

BACKGROUND: Oral appliance (OA) therapy is increasingly prescribed as a non-continuous positive airway pressure treatment modality for sleep-disordered breathing (SDB). Although OA therapy is reported to be efficacious for the treatment of SDB, data on compliance remain limited to self-report. METHODS: In this 3-month prospective clinical trial, the main outcome was to assess the safety and feasibility of an objective measurement of compliance during OA therapy using an embedded microsensor thermometer with on-chip integrated readout electronics in 51 consecutive patients with an established diagnosis of SDB (AHI 18.0 ± 11.9/h; age 47 ± 10 y; BMI 26.6 ± 4.0 kg/m(2); men/women: 31/20). Patients were unaware of the purpose of the study. RESULTS: No microsensor-related adverse events were recorded. In addition, no problems were encountered during the readout of the compliance data. Out of 51 microsensors, one had a technical defect and was lost to follow-up. In this study, the overall objective mean rate of OA use was 6.6 ± 1.3 h per day with a regular OA users' rate of 82% at the 3-month follow-up. Statistical analysis revealed no significant differences between objective and self-reported OA compliance data in this study. Measurement of the objective OA compliance allowed us to calculate the mean disease alleviation (MDA) as the product of objective compliance and therapeutic efficacy. MDA serves as a measure of the overall therapeutic effectiveness, and turned out to be 51.1%. CONCLUSIONS: The results illustrate the safety and feasibility of objective measurement of OA compliance. The objective measurement of OA compliance allows for calculation of the MDA.

Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome.

The aim of this study was to assess the value of drug-induced sleep endoscopy (DISE) using a custom-made simulation bite in maximal comfortable protrusion (MCP) of the mandible, in the prediction of treatment outcome for obstructive sleep apnea (OSA) with a mandibular advancement device (MAD). Two hundred patients (74% male; age 46 ± 9 years; apnea-hypopnea index [AHI] 19 ± 13 h(-1) sleep; body mass index [BMI] 27 ± 4 kg m(-2) ) with sleep-disordered breathing underwent DISE with a simulation bite in MCP. One hundred and thirty-five patients with an established diagnosis of OSA commenced MAD treatment. The associations between the findings during DISE with simulation bite and treatment outcome were evaluated. Treatment response was defined as a reduction in AHI following MAD treatment of ≥ 50% compared to baseline. Overall MAD treatment response in the studied population was 69%. The results of this study demonstrated a statistically significant association between a positive effect of the simulation bite on the upper airway patency during DISE and treatment response with MAD (P < 0.01). The results of this study suggest that the use of a simulation bite in maximal comfortable protrusion (MCP) of the mandible, as used during DISE in patients with OSA, tends to be effective in predicting treatment response of MAD treatment.

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.

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.

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.

Reduction of Somatic Tinnitus Severity is Mediated by Improvement of Temporomandibular Disorders.

BACKGROUND: Successful orofacial treatment can reduce tinnitus severity in patients with somatic tinnitus (ST). However, it is still unclear to what extent the degree of reduction in temporomandibular disorders (TMD) actually contributes to the decrease in tinnitus severity after orofacial treatment. Therefore, the aim of this study was to analyze the mediating effect of reduction in TMD pain on the improvement of tinnitus severity after multidisciplinary orofacial treatment. METHODS: A total of 80 patients with moderate to severe ST attributed to the temporomandibular region, were recruited from a tertiary tinnitus clinic. At baseline, patients were randomly assigned to the orofacial treatment group or to the control group. Both groups received a minimum of information and advice regarding their tinnitus complaints. The orofacial treatment group received orofacial physical therapy complemented with occlusal splints when needed, while the control group received no other treatment. A mediation analysis was performed according to the steps described by Baron and Kenny and the proportion of the mediating effect was calculated for the potential mediator: "change in TMD pain," measured by a one-point decrease in TMD pain screener score. RESULTS: Our analysis showed that 35% of the observed decrease in tinnitus severity can be attributed to a reduction in TMD pain. A significant total effect of orofacial treatment compared with control on the change in tinnitus functional index (TFI) score was found (B = 0.253 p = 0.025 Cl for B = 1.265-18.576). Orofacial treatment was also significantly related to the change in TMD pain (Exp (B) = 2.800, p = 0.034 Cl for Exp B 1.081-7.251). Additionally, the change in TMD pain screener score was significantly related to the change in TFI score (B = -0.273 p = 0.016 Cl for B = -19.875 to -2.119). CONCLUSION: Reduction of TMD pain is a mediating factor in the decrease of tinnitus severity after multidisciplinary orofacial treatment. PRACTICAL IMPLICATIONS: Orofacial treatment can be used to decrease tinnitus severity in patients with TMD related somatic tinnitus.

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.

ICF domains covered by the Tinnitus Questionnaire and Tinnitus Functional Index.

PURPOSE: Tinnitus frequently causes disability as it affects daily living, which is objectified using several tinnitus questionnaires. To what extent they cover domains of the International Classification of Functioning, Disability and Health (ICF) is currently unknown. Therefore, this study aims to investigate which ICF domains are measured by two questionnaires and to describe the health status of somatic tinnitus patients in ICF terms. MATERIALS AND METHODS: All questions of the Tinnitus Questionnaire (TQ) and Tinnitus Functional Index (TFI) were linked to the ICF using linking rules. A count-based method was used to link all individual answers of 80 tinnitus patients, to the ICF categories. RESULTS: Most of the linked questions concerned "body functions". TFI covered more categories of "activity and participation" than TQ. Patients reported severe impairments in "mental functions", "sensory functions and pain", and "sleep functions". Additionally, severe limitations were scored in "focusing attention". CONCLUSIONS: The TFI and TQ measure distinct domains but can be used complementary or solely, depending on the research question. The TFI identifies a broad spectrum of problems, where the TQ focuses on the psychological impact of tinnitus. Somatic patients in our study reported impairments and disabilities in all covered domains, especially in "onset of sleep" and "sound detection".Implications for RehabilitationThe Tinnitus Functional Index (TFI) and the Tinnitus Questionnaire (TQ) cover different domains of the International Classification of Functioning, Disability and Health.The TFI identifies problems in "body functions" and "activity and participation".The TQ focuses on the psychological impact of tinnitus.

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.

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).

Prognostic Indicators for Positive Treatment Outcome After Multidisciplinary Orofacial Treatment in Patients With Somatosensory Tinnitus.

INTRODUCTION: Subjective tinnitus that is influenced by the somatosensory system is called somatosensory tinnitus (ST). When ST is related to the temporomandibular area, multidisciplinary orofacial treatment can reduce tinnitus severity. It is, however, unknown if we can predict this positive outcome. The aim of this study is to look for prognostic indicators that can predict a positive outcome after multidisciplinary orofacial treatment in patients with ST. METHODS: Patients were included when they were diagnosed with temporomandibular-related ST and received a maximum of 18 sessions of orofacial treatment during a 9-week program. Predictors for positive treatment outcome were identified using univariate and multiple logistic regression analyses with the Tinnitus Questionnaire (TQ) and the Tinnitus Functional Index (TFI) as dependent variables. RESULTS: The results of 101 patients were included in the analysis. Immediately after multidisciplinary orofacial treatment, a clinically relevant decrease in TQ score was significantly associated with "shorter duration of tinnitus" [odds ratio (OR) 0.99], "higher initial score on the TQ somatic subscale" (OR 1.52), and "painful palpation of the temporomandibular joint (TMJ)" (OR 2.46). After 9 weeks of follow-up, the "higher initial score on the TQ somatic subscale" remained as the sole predictor (OR 1.44). A clinically relevant decrease on TFI after 9 weeks of follow-up was predicted by "female gender" (OR 2.70), "younger age" (OR 0.96), "shorter duration of the tinnitus" (OR 0.99), "lower pressure pain thresholds (PPT) on TMJ" (OR 0.99), "lower PPT on sternocleidomastoid origin" (OR 0.99), and "better speech in noise perception" (OR 0.88). A multivariate model comprising "shorter duration of tinnitus" and "higher initial score on the somatic subscale of the TQ" correctly predicts the clinically relevant decrease in TQ score after treatment in 68.5%. A second multivariate model comprising "female gender," "younger age," and "shorter duration of the tinnitus" correctly predicts a clinically significant decrease on TFI after follow-up in 68.1%. CONCLUSION: We were able to identify various prognostic indicators. "Younger female patients" with a "shorter duration of tinnitus" and a "higher initial score on the TQ somatic subscale" appear to have the best prognosis after multimodal orofacial therapy.