In-home mandibular repositioning during sleep using MATRx plus predicts outcome and efficacious positioning for oral appliance treatment of obstructive sleep apnea.

STUDY OBJECTIVES: Oral appliance therapy is not commonly used to treat obstructive sleep apnea due to inconsistent efficacy and lack of established configuration procedures. Both problems may be overcome by information gathered while repositioning the mandible during sleep. The purpose of this investigation was to determine if an unattended sleep study with a mandibular positioner can predict therapeutic success and efficacious mandibular position, assess the contribution of artificial intelligence analytics to such a system, and evaluate symptom resolution using an objective titration approach. METHODS: Fifty-eight individuals with obstructive sleep apnea underwent an unattended sleep study with an auto-adjusting mandibular positioner followed by fitting of a custom oral appliance. Therapeutic outcome was assessed by the 4% oxygen desaturation index with therapeutic success defined as oxygen desaturation index < 10 h-1. Outcome was prospectively predicted by an artificial intelligence system and a heuristic, rule-based method. An efficacious mandibular position was also prospectively predicted by the test. Data on obstructive sleep apnea symptom resolution were collected 6 months following initiation of oral appliance therapy. RESULTS: The artificial intelligence method had significantly higher predictive accuracy (sensitivity: 0.91, specificity: 1.00) than the heuristic method (P = .016). The predicted efficacious mandibular position was associated with therapeutic success in 83% of responders. Appliances titrated based on oxygen desaturation index effectively resolved obstructive sleep apnea symptoms. CONCLUSIONS: The MATRx plus device provides an accurate means for predicting outcome to oral appliance therapy in the home environment and offers a replacement to blind titration of oral appliances. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Predictive Accuracy of MATRx plus in Identifying Favorable Candidates for Oral Appliance Therapy; Identifier: NCT03217383; URL: https://clinicaltrials.gov/ct2/show/NCT03217383. CITATION: Mosca EV, Bruehlmann S, Zouboules SM, et al. In-home mandibular repositioning during sleep using MATRx plus predicts outcome and efficacious positioning for oral appliance treatment of obstructive sleep apnea. J Clin Sleep Med. 2022;18(3):911-919.

Validation of a new unattended sleep apnea monitor using two methods for the identification of hypopneas.

STUDY OBJECTIVES: The objective of the present study was to evaluate the accuracy of a home sleep apnea test (HSAT), MATRx plus (Zephyr Sleep Technologies, Calgary, Alberta, Canada), in identifying apneas and hypopneas and estimating indices of obstructive sleep apnea (OSA). METHODS: Individuals with suspected OSA underwent a one-night study wearing both HSAT and polysomnogram (PSG) sensors. The results provided by the overnight HSAT were compared with those from the simultaneously recorded PSG. The PSG data were scored manually, and the HSAT data were analyzed automatically using both preceding peak (PP) and moving average window (MW) methods for determining the reference oxyhemoglobin saturation (O2 Sat). Accuracy of the HSAT in detecting individual apneic and hypopneic events was evaluated on an epoch-by-epoch basis. The apnea-hypopnea indices from the two recording systems were compared. RESULTS: Agreement analysis for the individual apneic and hypopneic events yielded median values for sensitivity and specificity of 0.89 and 0.98 and positive and negative likelihood ratios of 37.35 and 0.11, respectively. Comparison of OSA indices between the two systems yielded correlation coefficients in the range of 0.95-0.96 and intraclass correlation coefficients ranging from 0.92-0.96. Bland-Altman analyses showed 0-2 cases lying outside the ± 2 standard deviation (SD) band and biases ranging from 2.1 to 5.3 events/h. The biases were larger for MW than PP. CONCLUSIONS: The MATRx plus HSAT identifies apneic and hypopneic events and estimates OSA indices with accuracy suitable for clinical purposes but not in children, patients with underlying lung disease, and habitual mouth-breathers. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: PSG Validation of MATRx plus AHI; Identifier: NCT03627169.

A Feedback-Controlled Mandibular Positioner Identifies Individuals With Sleep Apnea Who Will Respond to Oral Appliance Therapy.

STUDY OBJECTIVES: Mandibular protruding oral appliances represent a potentially important therapy for obstructive sleep apnea (OSA). However, their clinical utility is limited by a less-than-ideal efficacy rate and uncertainty regarding an efficacious mandibular position, pointing to the need for a tool to assist in delivery of the therapy. The current study assesses the ability to prospectively identify therapeutic responders and determine an efficacious mandibular position. METHODS: Individuals (n = 202) with OSA participated in a blinded, 2-part investigation. A system for identifying therapeutic responders was developed in part 1 (n = 149); the predictive accuracy of this system was prospectively evaluated on a new population in part 2 (n = 53). Each participant underwent a 2-night, in-home feedback-controlled mandibular positioner (FCMP) test, followed by treatment with a custom oral appliance and an outcome study with the oral appliance in place. A machine learning classification system was trained to predict therapeutic outcome on data obtained from FCMP studies on part 1 participants. The accuracy of this trained system was then evaluated on part 2 participants by examining the agreement between prospectively predicted outcome and observed outcome. A predicted efficacious mandibular position was derived from each FCMP study. RESULTS: Predictive accuracy was as follows: sensitivity 85%; specificity 93%; positive predictive value 97%; and negative predictive value 72%. Of participants correctly predicted to respond to therapy, the predicted mandibular protrusive position proved efficacious in 86% of cases. CONCLUSIONS: An unattended, in-home FCMP test prospectively identifies individuals with OSA who will respond to oral appliance therapy and provides an efficacious mandibular position. CLINICAL TRIAL REGISTRATION: The trial that this study reports on is registered on www.clinicaltrials.gov, ID NCT03011762, study name: Feasibility and Predictive Accuracy of an In-Home Computer Controlled Mandibular Positioner in Identifying Favourable Candidates for Oral Appliance Therapy.

Simulation of muscle and adipose tissue deformation in the passive human pharynx.

Quantifying the contribution of passive mechanical deformation in the human pharynx to upper airway collapse is fundamental to understanding the competing biomechanical processes that maintain airway patency. This study uses finite element analysis to examine deformation in the passive human pharynx using an intricate 3D anatomical model based on computed tomography scan images. Linear elastic properties are assigned to bone, cartilage, ligament, tendon, and membrane structures based on a survey of values reported in the literature. Velopharyngeal and oropharyngeal cross-sectional area versus airway pressure slopes are determined as functions of Young's moduli of muscle and adipose tissue. In vivo pharyngeal mechanics for small deformations near atmospheric pressure are matched by altering Young's moduli of muscle and adipose tissue. The results indicate that Young's moduli ranging from 0.33 to 14 kPa for muscle and adipose tissue matched the in vivo range of area versus pressure slopes. The developed anatomical model and determined Young's moduli range are expected to be useful as a starting point for more complex simulations of human upper airway collapse and obstructive sleep apnea therapy.

Remotely controlled mandibular protrusion during sleep predicts therapeutic success with oral appliances in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The present study addresses the need for a validated tool that prospectively identifies favorable candidates for oral appliance therapy in treatment of obstructive sleep apnea. The objective of the study was to evaluate the ability of a mandibular titration study, performed with a remotely controlled mandibular positioner (RCMP), to predict treatment outcome with a mandibular repositioning appliance (MRA) and to predict an effective target protrusive position (ETPP). DESIGN: A prospective, blinded, outcome study. SETTING: Standard clinical care with tests performed in the polysomnographic laboratory. PARTICIPANTS: Consecutive patients (n = 67) recruited from a sleep center or a dental practice using broad inclusion criteria (age 21-80 years; AHI > 10/h; BMI < 40 kg/m(2)). INTERVENTIONS: Therapeutic outcome with a mandibular protruding oral appliance was predicted following a mandibular protrusive titration study in the polysomnographic laboratory using a remotely controlled positioner and prospectively established predictive rules. An ETPP was also prospectively determined for participants predicted to be therapeutically successful with MRA therapy. All participants were blindly treated with a MRA, at either the predicted ETPP or a sham position, and therapeutic outcome was compared against prediction. MEASUREMENTS AND RESULTS: At the final protrusive position, standard predictive parameters (sensitivity, specificity, positive and negative predictive values) showed statistically significant predictive accuracy (P < 0.05) in the range of 83% to 94%. The predicted ETPP provided an efficacious protrusive position in 87% of participants predicted to be therapeutically successful with MRA therapy (P < 0.05). CONCLUSIONS: Using prospectively established rules for interpreting the polysomnographic data, the mandibular titration study predicted mandibular repositioning appliance therapeutic outcome with significant accuracy, particularly with regard to accurately predicting therapeutic success. As well, among the participants predicted to be therapeutically successful with mandibular repositioning appliance therapy, the effective target protrusive position provided efficacious mandibular protrusion in the majority.

Evaluation of respiratory muscles activity by means of cross mutual information function at different levels of ventilatory effort.

Analysis of respiratory muscles activity is an effective technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Respiratory diseases, especially those associated with changes in the mechanical properties of the respiratory apparatus, are often associated with disruptions of the normally highly coordinated contractions of respiratory muscles. Due to the complexity of the respiratory control, the assessment of OSAS related dysfunctions by linear methods are not sufficient. Therefore, the objective of this study was the detection of diagnostically relevant nonlinear complex respiratory mechanisms. Two aims of this work were: (1) to assess coordination of respiratory muscles contractions through evaluation of interactions between respiratory signals and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF); (2) to differentiate between functioning of respiratory muscles in patients with OSAS and in normal subjects. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from three respiratory muscles: genioglossus, sternomastoid and diaphragm. Inspiratory pressure and flow were also acquired. All signals were measured in eight patients with OSAS and eight healthy subjects during an increased respiratory effort while awake. Several variables were defined and calculated from CMIF in order to describe correlation between signals. The results indicate different nonlinear couplings of respiratory muscles in both populations. This effect is progressively more evident at higher levels of respiratory effort.

Model based analysis of sleep disordered breathing in congestive heart failure.

We employed a computational model of the respiratory control system to examine which of several factors, in isolation and in combination, can contribute to or explain the development of Cheyne-Stokes breathing (CSB). Our approach uses a graphical method for stability analysis similar, in concept, to the phase plane. The results from the computer simulations indicate that a postulated three-fold increase in the chemosensitivity of the central chemoreflex (CCR) loop may, by itself, explain development of CSB. By contrast, a similar increase in the chemosensitivity of the peripheral chemoreflex (PCR) loop cannot, by itself, account for CSB. The analysis reveals that the system is more readily destabilized by increasing the gain of only one chemoreflex loop than by a combined increase in gain of both loops. Reduction in the cardiac output or cardiomegaly decreases the size of the stability region. We conclude that development of CSB is the result of a complex interaction between CCR and PCR loops which may, in turn, interact with decreased cardiac output and cardiomegaly.

A computational model of the human respiratory control system: responses to hypoxia and hypercapnia.

Although recent models offer realistic descriptions of the human respiratory system, they do not fulfill all characteristics of a stable, comprehensive model, which would allow us to evaluate a variety of hypotheses on the control of breathing. None of the models offer completely realistic descriptions of the gaseous components of blood, and their description of delays associated with the propagation of changes in partial pressures of respiratory gases between the lungs and brain and tissue compartments have shortcomings. These deficiencies are of particular significance in an analysis of periodic breathing where dynamic alterations in the circulation and in blood chemical stimuli are likely to assume considerable importance. We developed a computational model of the human respiratory control system which is an extension of the model of Grodins et al. (F. S. Grodins, J. Buell, and A. J. Bart. J. Appl. Physiol. 22(2):260-276, 1967). Our model combines an accurate description of a plant with a novel controller design that treats minute ventilation as a sum of central and peripheral components. To ensure that the developed model is stable and sufficiently robust to act as a test platform for hypotheses about control of ventilation, we simulated a series of challenging physiological conditions, specifically, the response to eucapnic hypoxia, the development of periodic breathing during hypocapnic hypoxia, and the open loop response to hypercapnic step. These steady state and transient responses of the model were compared with results from similar physiological experiments. Our simulations suggest that for a particular value of arterial Po2, the steady state difference between brain and arterial Pco2 remains approximately constant as a function of arterial Pco2. The model indicates that hypoxia-induced changes in cerebral blood flow contribute significantly to the ventilatory decline observed during eucapnic hypoxia. The model exibits hypoxic-induced periodic breathing, which can be eliminated by small increases in F(I)co2. The dynamics of the model's open loop hypercapnic ventilatory response approximates experimental data well.

Assessment of ventilatory sensitivity to carbon dioxide changes during orthostasis.

Investigators have anecdotally reported changes in respiratory pattern preceding symptoms of orthostatic intolerance for several years. Evidence from recent studies support these observations, and show that alterations in respiration often precede pre-syncope during orthostasis. These observations suggest the possibility that changes in interaction between the chemo and baro-reflex control systems may produce phasic or dynamic changes in respiratory and hemodynamic parameters such that these changes are important in orthostasis intolerance. Our objective in the present study was to develop a method to obtain a quantitative index of ventilatory sensitivity to changes in inspired during orthostasis. Based on an approach previously developed by one of the authors (EB), we used, during supine and 70 degrees head up tilt, pseudo-random binary changes in inspired CO2 to quantify ventilatory sensitivity to CO2 disturbances. A pneumotach was used to measure airflow. From these recordings, we used a prediction error based systems identification algorithm to quantify ventilatory impulse response to CO2 stimulus. Results from 7 subjects showed that the integrated ventilatory response (area under impulse response curve) to CO2 was larger during tilt than that during supine (mean [std] 5.3 [2.6] Vs 3.0 [1.6] ml/min/0.01LCO2). These results suggest that the changes in ventilation due to disturbances in CO2 are likely to be larger during orthostasis than those during supine. Such an elevated response would indicate that the role of chemo-reflex control of breathing in cardiovascular instability culminating in orthostatic intolerance is likely to be important and should be further investigated.