###### Abstract  
Drug-induced sleep endoscopy (DISE) has been progressively used to determine the individual patient responsiveness to therapy with a mandibular advancement device (MAD) for obstructive sleep apnea (OSA). This retrospective cohort study compared the general and polygraphic characteristics, as well as the sites, degrees, and patterns of upper airway collapse, in patients who responded to advancement with a titralable mandibular advancement (TMA) simulator during DISE--referred to as responders--to those in non-responders. The sample included 335 OSA patients (307 males) with a mean age of 49.98 (SD = 9.88) years, and a mean AHI of 34.14 (SD = 18.61). Once the TMA simulator customized to the patient's dental arches was inserted and the examination was performed at 0%, 25%, 50%, and 75% of the patient's range of antero-posterior mandibular excursion, the simulator was removed and the upper airway behavior was studied in the baseline situation. Without TMA simulator non-responders had a higher percentage of oropharyngeal complete latency-lateral and complete concentric velopharyngeal collapse. With TMA simulators, there was a significant difference between responders and non-responders in individual obstructive sites at velopharyngeal, oropharyngeal, and epiglottis levels, while at the tongue level, responders and non-responders showed the same response tendency. If confirmed in future prospective studies, these results suggest that the presence of complete latero-lateral obstruction at the oropharynx level and complete circular obstruction at the velopharyngealx level could be adverse phenotypes for MAD treatment outcomes in OSA patients and MAD treatment should not be considered in these patients (at least as a single therapy). obstructive sleep apnea; mandibular advancement device; sleep dentistry +
Footnote †: journal:individual well-being. It is estimated that roughly one billion people between the ages of 30 and 69 years are affected all over the world [3]. Data from a large population-based sample of patients suggest a prevalence of moderate to severe OSA (\(\text{AHI}\geq 15\)) in the general population aged \(\geq\)40 years of 23.4% in women and 49.7% in men [4]. Despite being acknowledged as a potentially life-threatening chronic condition with a high economic and social burden, OSA is still underdiagnosed and undertreated [5]. A recent epidemiological investigation focused on determining the societal and economic impacts of OSA within Italy concluded that approximately 56% of the adult population, ranging from 15 to 74 years of age, may suffer from OSA. However, the investigation revealed that merely 4% of these individuals have been officially diagnosed, and only 2% have received treatment [6]. OSA is recognized as a multifactorial disease, and an array of therapeutic interventions has been explored. Currently, continuous positive airway pressure (CPAP) constitutes the \"gold standard\" therapy for OSA [7]. It involves wearing a mask during sleep that is connected to a pump that delivers constant pressure to keep the airway open. Treatment with CPAP is characterized by high clinical efficacy, but therapeutic effectiveness is often limited by poor patient compliance [8]. Upper airway surgery, mandibular advancement device (MAD), and positional therapy are well-recognized non-CPAP treatment options for OSA. A proper patient selection is crucial given the endotypic variability associated with OSA [7]. However, the analysis of the four endotypic traits (i.e., pharyngeal airway collapsibility, upper airway neuromuscular compensation, loop gain, and arousal threshold) using detailed, physiology-based techniques is not commonly accessible in clinical practice and necessitates specialized equipment or methodologies that are technically challenging [7]. MAD is increasingly used for the treatment of patients with mild to moderate OSA or primary snoring and often represents an accepted therapy for patients with severe OSA who are unable or unwilling to tolerate CPAP [9; 10].