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.

Abstract-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.

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.

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 Keywords: home sleep test, obstructive sleep apnea, oral appliance therapy, predictive accuracy, sleep-disordered breathing Citation: Remmers JE, Topor Z, Grosse J, Vranjes N, Mosca EV, Brant R, Bruehlmann S, Charkhandeh S, Jahromi SA. A feedback-controlled mandibular positioner identifies individuals with sleep apnea who will respond to oral appliance therapy. J Clin Sleep Med. 2017;13(7):871-880. I NTRO DUCTI O NObstructive sleep apnea (OSA) is a chronic disease caused by repeated narrowing or closure of the pharynx during sleep. The disease compromises quality of life, 1,2 increases risk of accidents, [3][4][5] and is associated with an increased risk of cardiovascular events 6 and reduced survival rate. 7,8 Continuous positive airway pressure (CPAP), the standard therapy for this disease, is efficacious and benign. However, long-term compliance with CPAP is low, 9,10 and this may contribute to its ineffectiveness in preventing adverse...