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).

Study Objectives:Mandibular advancement device (MAD) outcome varies between patients. We hypothesized that upper airway collapse sites, patterns, and degrees assessed during baseline drug-induced s...

Obstructive sleep apnoea (OSA) is characterised by pharyngeal obstruction occurring at different sites. Endoscopic studies reveal that epiglottic collapse renders patients at higher risk of failed oral appliance therapy or accentuated collapse on continuous positive airway pressure. Diagnosing epiglottic collapse currently requires invasive studies (imaging and endoscopy). As an alternative, we propose that epiglottic collapse can be detected from the distinct airflow patterns it produces during sleep.23 OSA patients underwent natural sleep endoscopy. 1232 breaths were scored as epiglottic/nonepiglottic collapse. Several flow characteristics were determined from the flow signal (recorded simultaneously with endoscopy) and used to build a predictive model to distinguish epiglottic from nonepiglottic collapse. Additionally, 10 OSA patients were studied to validate the pneumotachograph flow features using nasal pressure signals.Epiglottic collapse was characterised by a rapid fall(s) in the inspiratory flow, more variable inspiratory and expiratory flow and reduced tidal volume. The cross-validated accuracy was 84%. Predictive features obtained from pneumotachograph flow and nasal pressure were strongly correlated.This study demonstrates that epiglottic collapse can be identified from the airflow signal measured during a sleep study. This method may enable clinicians to use clinically collected data to characterise underlying physiology and improve treatment decisions.

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.

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 (NCT 01532050)

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 (NCT 00519597).