Ludovico Messineo

Predicting epiglottic collapse in patients with obstructive sleep apnoea

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. Epiglottic collapse can be identified from airflow characteristics during sleep http://ow.ly/IafB30dbD60

Cardiac Sympathetic Hyperactivity in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea

ABSTRACT Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in 0.5–1% of the general population. Both OSA and COPD are associated with increased sympathetic nervous activity, and patients affected by both disorders have higher risk for increased morbidity and mortality as compared with patients with COPD or OSA alone. We tested the hypothesis that patients with COPD and OSA (Overlap syndrome) have higher sympathetic and lower parasympathetic modulation of heart rate variability (HRV) in comparison with patients suffering from COPD or OSA alone. HRV indices in the frequency domain were evaluated from daytime electrocardiographic recordings in 14 patients with both severe OSA (apnea–hypopnea index ≥ 30) and mild-to-moderate COPD and compared with those with OSA (n = 24) or COPD (n = 16) alone. We found that, in the Overlap syndrome group, high-frequency (HF, 0.4–0.15 Hz) power was significantly lower (0.18 nu vs 0.34 nu in OSA and 0.44 nu in COPD patients, p < 0.01) and low-frequency (LF, 0.15–0.05 Hz) power was significantly greater (0.82 nu vs 0.66 nu in OSA and 0.57 nu in COPD patients, p < 0.01) compared with COPD and OSA groups. Patients with both OSA and COPD had higher LF/HF ratio as compared with patients in OSA and COPD groups (4.5 [5.9] vs 1.9 [2.6] and 1.3 [1.3], respectively, p < 0.01). For the Overlap syndrome group, there was a significant direct relationship between LF/HF ratio and residual volume (r2 = 0.62, p = 0.007). These findings show that patients with both OSA and COPD have higher sympathetic modulation of heart rate compared with those with OSA or COPD alone. Furthermore, the findings provide a potential mechanism for the increased morbidity and mortality reported in patients suffering from both disorders, suggesting new therapeutic perspectives in Overlap syndrome.

Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults

Rationale: The reduction in upper airway muscle activity from wakefulness to sleep plays a key role in the development of obstructive sleep apnea. Potassium (K+) channels have been recently identified as the downstream mechanisms through which hypoglossal motoneuron membrane excitability is reduced both in non‐rapid eye movement (NREM) sleep and REM sleep. In animal models, the administration of 4‐aminopyridine (4‐AP), a voltage‐gated K+ channel blocker, increased genioglossus activity during wakefulness and across all sleep stages. Objectives: We tested the hypothesis that administration of a single dose of 4‐AP 10 mg extended release would increase genioglossus activity (electromyography of the genioglossus muscle [EMGGG]) during wakefulness and sleep, and thereby decrease pharyngeal collapsibility. Methods: We performed a randomized controlled crossover proof‐of‐concept trial in 10 healthy participants. Participants received active treatment or placebo in randomized order 3 hours before bedtime in the physiology laboratory. Results: EMGGG during wakefulness and NREM sleep and upper airway collapsibility measured during NREM sleep were unchanged between placebo and 4‐AP nights. Tonic but not phasic EMGGG during REM sleep was higher on the 4‐AP night when measured as a percentage of maximal voluntary activation (median [interquartile range] 0.3 [0.5] on placebo vs. 0.8 [1.9] %max on 4 AP; P = 0.04), but not when measured in &mgr;V or as a percentage of wakefulness value. Conclusions: A single dose of 4‐AP 10 mg extended release showed only a small increase in tonic EMGGG during REM sleep in this group of healthy subjects. We speculate that a higher dose of 4‐AP may further increase EMGGG. However, given the potentially severe, dose‐related adverse effects of this drug, including seizures, the administration of 4‐AP does not appear to be an effective strategy to increase genioglossus activity during sleep in humans. Clinical Trial registered with clinicaltrials.gov (NCT02656160).

Neural memory of the genioglossus muscle during sleep is stage‐dependent in healthy subjects and obstructive sleep apnoea patients

In most patients with obstructive sleep apnoea (OSA), there is a spontaneous resolution of the breathing disorders during slow wave sleep (SWS) for yet unknown reasons related to non‐anatomical factors. Some recently identified forms of neural memory specific of upper airway muscles may play a role in this phenomenon. In the present study, we show for the first time that a form of memory of the genioglossus (tongue) muscle is greatly enhanced during SWS compared to non‐rapid eye movement stage 2 sleep. The present study represents a step forward in understanding the mechanisms responsible for the spontaneous development of stable breathing during SWS in OSA patients and may help the discovery of novel therapeutic strategies for this disease.

Breath‐holding as a means to estimate the loop gain contribution to obstructive sleep apnoea

A hypersensitive ventilatory control system or elevated “loop gain” during sleep is a primary phenotypic trait causing obstructive sleep apnoea (OSA). Despite the multitude of methods available to assess the anatomical contributions to OSA during wakefulness in the clinical setting (e.g. neck circumference, pharyngometry, Mallampati score), it is currently not possible to recognize elevated loop gain in patients in this context. Loop gain during sleep can now be recognized using simplified testing during wakefulness, specifically in the form of a reduced maximal breath‐hold duration, or a larger ventilatory response to voluntary 20‐second breath‐holds. We consider that easy breath‐holding manoeuvres will enable daytime recognition of a high loop gain in OSA for more personalized intervention.

Retropalatal and retroglossal airway compliance in patients with obstructive sleep apnea

OBJECTIVES We hypothesized that preferential retropalatal as compared to retroglossal collapse in patients with obstructive sleep apnea was due to a narrower retropalatal area and a higher retropalatal compliance. Patients with a greater retropalatal compliance would exhibit a recognizable increase in negative effort dependence (NED). METHODS Fourteen patients underwent upper airway endoscopy with simultaneous recordings of airflow and pharyngeal pressure during natural sleep. Airway areas were obtained by manually outlining the lumen. Compliance was calculated by the change of airway area from end-expiration to a pressure swing of -5 cm H2O. NED was quantified for each breath as [peak inspiratory flow minus flow at -5 cm H2O]/[peak flow] × 100. RESULTS Compared to the retroglossal airway, the retropalatal airway was smaller at end-expiration (p < 0.001), and had greater absolute and relative compliances (p < 0.001). NED was positively associated with retropalatal relative area change (r = 0.47; p < 0.001). CONCLUSIONS Retropalatal airway is narrower and more collapsible than retroglossal airway. Retropalatal compliance is reflected in the clinically-available NED value.

Palatal prolapse as a signature of expiratory flow limitation and inspiratory palatal collapse in patients with obstructive sleep apnoea

In some individuals with obstructive sleep apnoea (OSA), the palate prolapses into the velopharynx during expiration, limiting airflow through the nose or shunting it out of the mouth. We hypothesised that this phenomenon causes expiratory flow limitation (EFL) and is associated with inspiratory “isolated” palatal collapse. We also wanted to provide a robust noninvasive means to identify this mechanism of obstruction. Using natural sleep endoscopy, 1211 breaths from 22 OSA patients were scored as having or not having palatal prolapse. The patient-level site of collapse (tongue-related, isolated palate, pharyngeal lateral walls and epiglottis) was also characterised. EFL was quantified using expiratory resistance at maximal epiglottic pressure. A noninvasive EFL index (EFLI) was developed to detect the presence of palatal prolapse and EFL using the flow signal alone. In addition, the validity of using nasal pressure was assessed. A cut-off value of EFLI >0.8 detected the presence of palatal prolapse and EFL with an accuracy of >95% and 82%, respectively. The proportion of breaths with palatal prolapse predicted isolated inspiratory palatal collapse with 90% accuracy. This study demonstrates that expiratory palatal prolapse can be quantified noninvasively, is associated with EFL and predicts the presence of inspiratory isolated palatal collapse. Expiratory palatal prolapse can be quantified noninvasively and predicts inspiratory isolated palatal collapse http://ow.ly/vm6c30hB839

Broadband Sound Administration Improves Sleep Onset Latency in Healthy Subjects in a Model of Transient Insomnia

Background Insomnia is a major public health problem in western countries. Previous small pilot studies showed that the administration of constant white noise can improve sleep quality, increase acoustic arousal threshold, and reduce sleep onset latency. In this randomized controlled trial, we tested the effect of surrounding broadband sound administration on sleep onset latency, sleep architecture, and subjective sleep quality in healthy subjects. Methods Eighteen healthy subjects were studied with two overnight sleep studies approximately one week apart. They were exposed in random order to normal environmental noise (40.1 [1.3] dB) or to broadband sound administration uniformly distributed in the room by two speakers (46.0 [0.9] dB). To model transient insomnia, subjects went to bed (“lights out”) 90 min before usual bedtime. Results Broadband sound administration reduced sleep onset latency to stage 2 sleep (time from lights out to first epoch of non-rapid eye movement-sleep stage 2) (19 [16] vs. 13 [23] min, p = 0.011; median reduction 38% baseline). In a subgroup reporting trouble initiating sleep at home (Pittsburgh Sleep Quality Index section 2 score ≥ 1), sound administration improved subjective sleep quality (p = 0.037) and the frequency of arousals from sleep (p = 0.03). Conclusion In an experimental model of transient insomnia in young healthy individuals, broadband sound administration significantly reduced sleep onset latency by 38% compared to normal environmental noise. These findings suggest that broadband sound administration might be helpful to minimize insomnia symptoms in selected individuals.