scholarly journals O001 Reboxetine reduces obstructive sleep apnea severity: a randomized trial

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A1-A1
Author(s):  
T Altree ◽  
A Aishah ◽  
K Loffler ◽  
R Grunstein ◽  
D Eckert
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Respiratory Control ◽  
Upper Airway ◽  
Apnea Hypopnea Index ◽  
Loop Gain ◽  
Double Blind ◽  
Obstructive Sleep ◽  
High Loop ◽  
Control Stability

Abstract Introduction Noradrenergic and muscarinic processes are crucial for pharyngeal muscle control during sleep. Selective norepinephrine reuptake inhibitors (SNRIs) such as reboxetine combined with an antimuscarinic reduce obstructive sleep apnea (OSA) severity. The effects of reboxetine alone on OSA severity are unknown. Methods Double-blind, placebo-controlled, three-way crossover trial in 16 people with OSA. Each participant completed three overnight polysomnograms (~1-week washout). Single doses of reboxetine 4mg, placebo, or reboxetine+oxybutynin 5mg were administered before sleep (randomized order). The primary outcome was apnea-hypopnea index (AHI). Secondary outcomes included other polysomnography parameters, next day sleepiness and alertness. Endotyping analysis was performed to determine the medications’ effects on OSA pathophysiological mechanisms. Results Reboxetine reduced the AHI by 5.4 [95% CI -10.4 to -0.3] events/h, P=0.03 (men: -24±27%; women: -0.7±32%). The addition of oxybutynin did not further reduce AHI. Reboxetine alone and reboxetine+oxybutynin reduced overnight hypoxemia versus placebo (e.g. 4% oxygen desaturation index 10.4±12.8 vs. 10.6±12.8 vs. 15.7±14.7 events/h, P=0.02). Mechanistically, reboxetine and reboxetine+oxybutynin improved pharyngeal collapsibility and respiratory control stability. Men had higher baseline loop gain. Larger reductions in AHI with reboxetine occurred in those with high loop gain. Neither drug intervention changed next day sleepiness or alertness. Discussion A single 4mg dose of reboxetine modestly reduces OSA severity without further improvement with the addition of an antimuscarinic. Reboxetine increases breathing stability via improvements in pharyngeal collapsibility and respiratory control. These findings provide new insight into the role of SNRIs on upper airway stability during sleep and have important implications for pharmacotherapy development for OSA.

scholarly journals O013 The pathogenesis of obstructive sleep apnea in individuals with comorbid insomnia and obstructive sleep apnoea (COMISA)

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A6-A7
Author(s):  
E Brooker ◽  
L Thomson ◽  
S Landry ◽  
B Edwards ◽  
S Drummond
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Severity Index ◽  
Loop Gain ◽  
Comorbid Insomnia ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
High Loop ◽  
Insomnia Severity

Abstract Obstructive sleep apnea (OSA) and Insomnia are prevalent sleep disorders which are highly comorbid. This frequent co-occurrence suggests a shared etiology may exist. OSA is caused by the interaction of four pathophysiological traits: a highly collapsible upper airway, elevated loop gain, a low arousal threshold, and poor muscle compensation. No study has ascertained whether these traits are influenced by insomnia. We aimed to quantify the four traits which contribute to OSA in individuals diagnosed with comorbid insomnia and OSA (COMISA). We non-invasively determined these traits in 52 COMISA patients (Age: 56±14 years) with mild-to-severe OSA (AHI=21.2±10.63 events/h) using polysomnography. Our results indicated that 83% of COMISA patients had a low arousal threshold and only 2% of patients exhibited a highly collapsible airway using previously defined thresholds. Multiple linear regression revealed the arousal threshold (b=0.24, 95%CI[0.11, 0.37], β=0.47, p<0.001) and loop gain (b=23.6, 95%CI[7.02, 40.18], β=0.33, p<0.01) were the strongest predictors of OSA severity in our sample. There was no significant relationship between the arousal threshold and insomnia severity measured by the insomnia severity index (ISI). Further work is being performed to compare these findings with a matched sample of OSA only participants. Our preliminary findings demonstrate OSA in COMISA is characterized by a mildly collapsible airway/low arousal threshold phenotype and is largely driven by non-anatomical factors including a low arousal threshold and high loop gain. OSA treatments which are effective in patients with mild anatomical compromise and raise the arousal threshold may provide therapeutic benefit in COMISA patients.

Different antimuscarinics when combined with atomoxetine have differential effects on obstructive sleep apnea severity

2021 ◽  
Author(s):  
Atqiya Aishah ◽  
Richard Lim ◽  
Scott A. Sands ◽  
Luigi Taranto-Montemurro ◽  
Andrew Wellman ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Loop Gain ◽  
Double Blind ◽  
Receptor Selectivity ◽  
Arousal Threshold ◽  
Solifenacin Succinate ◽  
Obstructive Sleep ◽  
Airway Physiology

The combination of the noradrenergic agent atomoxetine plus the anti-muscarinic oxybutynin has recently been shown to improve upper airway physiology and reduce obstructive sleep apnea (OSA) severity. However, the effects of different anti-muscarinics when combined with atomoxetine is limited. This study aimed to determine the effects of atomoxetine combined with two different anti-muscarinics with varying M-subtype receptor selectivity on OSA severity and upper airway physiology.10 people with predominantly severe OSA completed a double-blind, randomised, placebo-controlled, cross-over trial. Participants completed 3 overnight in-laboratory sleep studies after either 80mg atomoxetine+5mg solifenacin succinate (ato-sol) or 80mg atomoxetine+2mg biperiden hydrochloride (ato-bip) or placebo. OSA severity, ventilatory stability (loop gain), respiratory-arousal threshold (via epiglottic manometry), next day subjective sleepiness (Karolinska Sleepiness Scale:KSS) and alertness were compared between conditions. Neither drug combination altered the apnea/hypopnoea index versus placebo (p=0.63). Ato-sol caused a shift towards milder respiratory events with reduced frequency of obstructive apneas (13±14vs. 22±17events/h; mean±SD, p=0.04) and increased hypopneas during NREM (38±21vs. 24±18events/h, p=0.006) with improved nadir oxygenation versus placebo (83±4vs. 80±8%, p=0.03). Both combinations reduced loop gain by ~10% versus placebo; sleep efficiency and arousal threshold were unaltered. Ato-bip reduced next-day sleepiness versus placebo (KSS=4.3±2.2vs. 5.6±1.6, p=0.03).Atomoxetine+biperiden hydrochloride reduces perceived sleepiness and atomoxetine+solifenacin modestly improves upper airway function in people with OSA but to a lesser extent versus recently published atomoxetine+oxybutynin (broad M-subtype receptor selectivity) findings. These results provide novel mechanistic insight into the role of noradrenergic and anti-muscarinic agents on sleep and breathing and are important for pharmacotherapy development for OSA.

scholarly journals The Role of Animal Models in Developing Pharmacotherapy for Obstructive Sleep Apnea

2019 ◽  
Vol 8 (12) ◽  
pp. 2049
Author(s):  
Lenise Jihe Kim ◽  
Carla Freire ◽  
Thomaz Fleury Curado ◽  
Jonathan C. Jun ◽  
Vsevolod Y. Polotsky
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Animal Models ◽  
Respiratory Control ◽  
Upper Airway ◽  
Pharmacological Agents ◽  
Obstructive Sleep ◽  
High Loop ◽  
Prevalent Disease ◽  
Key Factor

Obstructive sleep apnea (OSA) is a highly prevalent disease characterized by recurrent closure of the upper airway during sleep. It has a complex pathophysiology involving four main phenotypes. An abnormal upper airway anatomy is the key factor that predisposes to sleep-related collapse of the pharynx, but it may not be sufficient for OSA development. Non-anatomical traits, including (1) a compromised neuromuscular response of the upper airway to obstruction, (2) an unstable respiratory control (high loop gain), and (3) a low arousal threshold, predict the development of OSA in association with anatomical abnormalities. Current therapies for OSA, such as continuous positive airway pressure (CPAP) and oral appliances, have poor adherence or variable efficacy among patients. The search for novel therapeutic approaches for OSA, including pharmacological agents, has been pursued over the past years. New insights into OSA pharmacotherapy have been provided by preclinical studies, which highlight the importance of appropriate use of animal models of OSA, their applicability, and limitations. In the present review, we discuss potential pharmacological targets for OSA discovered using animal models.

Aerodynamics Analysis of the Impact of Nasal Surgery on Patients with Obstructive Sleep Apnea and Nasal Obstruction

ORL ◽  
2021 ◽  
pp. 1-8
Author(s):  
Lifeng Li ◽  
Demin Han ◽  
Hongrui Zang ◽  
Nyall R. London
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Nasal Obstruction ◽  
Upper Airway ◽  
Apnea Hypopnea Index ◽  
Nasal Surgery ◽  
Subjective Sleep Quality ◽  
Obstructive Sleep ◽  
Significant Difference ◽  
The Impact

<b><i>Objective:</i></b> The purpose of this study was to evaluate the effects of nasal surgery on airflow characteristics in patients with obstructive sleep apnea (OSA) by comparing the alterations of airflow characteristics within the nasal and palatopharyngeal cavities. <b><i>Methods:</i></b> Thirty patients with OSA and nasal obstruction who underwent nasal surgery were enrolled. A pre- and postoperative 3-dimensional model was constructed, and alterations of airflow characteristics were assessed using the method of computational fluid dynamics. The other subjective and objective clinical indices were also assessed. <b><i>Results:</i></b> By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (<i>p</i> &#x3c; 0.05), while the Apnea-Hypopnea Index (AHI) changed little (<i>p</i> = 0.492); the postoperative airflow velocity and pressure in both nasal and palatopharyngeal cavities, nasal and palatopharyngeal pressure differences, and total upper airway resistance statistically decreased (all <i>p</i> &#x3c; 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (<i>p</i> &#x3c; 0.05), except with the AHI (<i>p</i> &#x3e; 0.05). <b><i>Conclusion:</i></b> Nasal surgery can decrease the total resistance of the upper airway and increase the nasal airflow volume and subjective sleep quality in patients with OSA and nasal obstruction. The altered airflow characteristics might contribute to the postoperative reduction of pharyngeal collapse in a subset of OSA patients.

scholarly journals Effect of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea in multiple sclerosis: A randomized, double-blind, placebo-controlled trial (SAMS-PAP study)

2021 ◽  
pp. 135245852110103
Author(s):  
Sulaiman Khadadah ◽  
R John Kimoff ◽  
Pierre Duquette ◽  
Vincent Jobin ◽  
Yves Lapierre ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Continuous Positive Airway Pressure ◽  
Airway Pressure ◽  
Primary Outcome ◽  
Positive Airway Pressure ◽  
Apnea Hypopnea Index ◽  
Double Blind ◽  
Obstructive Sleep

Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the Fatigue Severity Scale (FSS, preplanned primary outcome), another fatigue measure, sleep quality, somnolence, pain, disability, and quality of life in multiple sclerosis (MS) patients with obstructive sleep apnea-hypopnea (OSAH). Methods: In a randomized, double-blind trial (NCT01746342), MS patients with fatigue, poor subjective sleep quality, and OSAH (apnea-hypopnea index of ⩾ 15 events per hour/sleep), but without severe OSAH (apnea-hypopnea index > 30, and 4% oxygen desaturation index > 15 events/hour or severe somnolence), were randomized to fixed CPAP or sham CPAP for 6 months. Outcome assessments were performed at 3 and 6 months. Results: Of 49 randomized patients, 34 completed the protocol. Among completers, FSS did not improve with CPAP compared to sham at 6 months. FSS tended to improve ( p = 0.09), and sleepiness (Epworth Sleepiness Scale) improved significantly ( p = 0.03) at 3 months with CPAP compared to sham, but there were no other improvements with CPAP at either study evaluation. Conclusion: In non-severe OSAH patients, CPAP did not significantly improve the primary outcome of FSS change at 6 months. In secondary analyses, we found a trend to improved FSS, and a significant reduction in somnolence with CPAP at 3 months.

Predicting critical closing pressure in children with obstructive sleep apnea using fluid structure interaction simulations

2021 ◽  
Author(s):  
Goutham Mylavarapu ◽  
Ephraim Gutmark ◽  
Sally Shott ◽  
Robert J. Fleck ◽  
Mohamed Mahmoud ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Dynamic Mri ◽  
Patient Specific ◽  
Apnea Hypopnea Index ◽  
Structure Interaction ◽  
Obstructive Sleep ◽  
Mri Scans ◽  
Closing Pressure

Surgical treatment of obstructive sleep apnea (OSA) in children requires knowledge of upper airway dynamics, including the closing pressure (Pcrit), a measure of airway collapsibility. We applied a Flow-Structure Interaction (FSI) computational model to estimate Pcrit in patient-specific upper airway models obtained from magnetic resonance imaging (MRI) scans. We sought to examine the agreement between measured and estimated Pcrit from FSI models in children with Down syndrome. We hypothesized that the estimated Pcrit would accurately reflect measured Pcrit during sleep and therefore reflect the severity of OSA as measured by the obstructive apnea hypopnea index (AHI). All participants (n=41) underwent polysomnography and sedated sleep MRI scans. We used Bland Altman Plots to examine the agreement between measured and estimated Pcrit. We determined associations between estimated Pcrit and OSA severity, as measured by AHI, using regression models. The agreement between passive and estimated Pcrit showed a fixed bias of -1.31 (CI=-2.78, 0.15) and a non-significant proportional bias. A weaker agreement with active Pcrit was observed. A model including AHI, gender, an interaction term for AHI and gender and neck circumference explained the largest variation (R2 = 0.61) in the relationship between AHI and estimated Pcrit. (P <0.0001). Overlap between the areas of the airway with lowest stiffness, and areas of collapse on dynamic MRI, was 77.4%±30% for the nasopharyngeal region and 78.6%±33% for the retroglossal region. The agreement between measured and estimated Pcrit and the significant association with AHI supports the validity of Pcrit estimates from the FSI model.

scholarly journals An assessment of a simple clinical technique to estimate pharyngeal collapsibility in people with obstructive sleep apnea

SLEEP ◽  
2020 ◽  
Vol 43 (10) ◽  
Author(s):  
Amal M Osman ◽  
Benjamin K Tong ◽  
Shane A Landry ◽  
Bradley A Edwards ◽  
Simon A Joosten ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Characteristic Curve ◽  
Upper Airway ◽  
Clinical Intervention ◽  
Apnea Hypopnea Index ◽  
Cpap Titration ◽  
Obstructive Sleep ◽  
Airway Collapsibility ◽  
Upper Airway Collapsibility

Abstract Study Objectives Quantification of upper airway collapsibility in obstructive sleep apnea (OSA) could help inform targeted therapy decisions. However, current techniques are clinically impractical. The primary aim of this study was to assess if a simple, novel technique could be implemented as part of a continuous positive airway pressure (CPAP) titration study to assess pharyngeal collapsibility. Methods A total of 35 participants (15 female) with OSA (mean ± SD apnea–hypopnea index = 35 ± 19 events/h) were studied. Participants first completed a simple clinical intervention during a routine CPAP titration, where CPAP was transiently turned off from the therapeutic pressure for ≤5 breaths/efforts on ≥5 occasions during stable non-rapid eye movement (non-REM) sleep for quantitative assessment of airflow responses (%peak inspiratory flow [PIF] from preceding 5 breaths). Participants then underwent an overnight physiology study to determine the pharyngeal critical closing pressure (Pcrit) and repeat transient drops to zero CPAP to assess airflow response reproducibility. Results Mean PIF of breaths 3–5 during zero CPAP on the simple clinical intervention versus the physiology night were similar (34 ± 29% vs. 28 ± 30% on therapeutic CPAP, p = 0.2; range 0%–90% vs. 0%–95%). Pcrit was −1.0 ± 2.5 cmH2O (range −6 to 5 cmH2O). Mean PIF during zero CPAP on the simple clinical intervention and the physiology night correlated with Pcrit (r = −0.7 and −0.9, respectively, p &lt; 0.0001). Receiver operating characteristic curve analysis indicated significant diagnostic utility for the simple intervention to predict Pcrit &lt; −2 and &lt; 0 cmH2O (AUC = 0.81 and 0.92), respectively. Conclusions A simple CPAP intervention can successfully discriminate between patients with and without mild to moderately collapsible pharyngeal airways. This scalable approach may help select individuals most likely to respond to non-CPAP therapies.

scholarly journals Speech Signal and Facial Image Processing for Obstructive Sleep Apnea Assessment

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Fernando Espinoza-Cuadros ◽  
Rubén Fernández-Pozo ◽  
Doroteo T. Toledano ◽  
José D. Alcázar-Ramírez ◽  
Eduardo López-Gonzalo ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Speech Processing ◽  
Upper Airway ◽  
Support Vector ◽  
Apnea Hypopnea Index ◽  
Active Appearance Models ◽  
Obstructive Sleep ◽  
Craniofacial Features ◽  
Low Dimensional

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by recurring breathing pauses during sleep caused by a blockage of the upper airway (UA). OSA is generally diagnosed through a costly procedure requiring an overnight stay of the patient at the hospital. This has led to proposing less costly procedures based on the analysis of patients’ facial images and voice recordings to help in OSA detection and severity assessment. In this paper we investigate the use of both image and speech processing to estimate the apnea-hypopnea index, AHI (which describes the severity of the condition), over a population of 285 male Spanish subjects suspected to suffer from OSA and referred to a Sleep Disorders Unit. Photographs and voice recordings were collected in a supervised but not highly controlled way trying to test a scenario close to an OSA assessment application running on a mobile device (i.e., smartphones or tablets). Spectral information in speech utterances is modeled by a state-of-the-art low-dimensional acoustic representation, called i-vector. A set of local craniofacial features related to OSA are extracted from images after detecting facial landmarks using Active Appearance Models (AAMs). Support vector regression (SVR) is applied on facial features and i-vectors to estimate the AHI.

scholarly journals Lateral-Expansion Pharyngoplasty: Combined Technique for the Treatment of Obstructive Sleep Apnea Syndrome

2019 ◽  
Vol 24 (01) ◽  
pp. e107-e111 ◽  
Author(s):  
José Antonio Pinto ◽  
Luciana Balester Mello de Godoy ◽  
Heloisa dos Santos Sobreira Nunes ◽  
Kelly Elia Abdo ◽  
Gabriella Spinola Jahic ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Obstructive Sleep Apnea Syndrome ◽  
Sleep Apnea Syndrome ◽  
Surgical Techniques ◽  
Upper Airway ◽  
Apnea Hypopnea Index ◽  
Lateral Expansion ◽  
Obstructive Sleep ◽  
Apnea Syndrome

Abstract Introduction Obstructive sleep apnea syndrome (OSAS) is a multifactorial disease characterized by episodes of partial or complete collapse during sleep of different regions of the upper airway. Surgery for OSAS evolved with the introduction of different techniques, considering new surgical concept of reconstruction of the upper airway. Objective To retrospectively evaluate the effectiveness of a new approach aimed at reducing pharyngeal collapse by combining two surgical techniques: lateral and expansion pharyngoplasty. Methods We reviewed the medical records of 38 patients with OSAS undergoing lateral/expansion pharyngoplasty from January 2012 to December 2016. The following data were collected: patient age, gender, and pre- and postoperative body mass index (BMI), Epworth sleepiness scale (ESS) scores, snoring visual analogue scale (VAS) scores, and polysomnography (PSG) results. Results The PSG results showed a significant reduction in the apnea/hypopnea index (AHI) from 22.4 ± 27.3 events/h preoperatively to 13.6 ± 17.9 events/h postoperatively (p = 0.009), with postoperative AHI reduction greater than 50% in 63.2% of the patients. There was also a significant reduction in the microarousal index (19.5 ± 22.6 vs 11.0 ± 13.4 events/h; p = 0.001) and in the minimum oxygen saturation (82.6 ± 10.3 vs 86.9 ± 11.1; p = 0.007). Conclusions Lateral-expansion pharyngoplasty represents a new surgical strategy for the treatment of OSAS in patients with palatal collapse by combining two different techniques: lateral and expansion pharyngoplasty. The two techniques, performed as a one-stage procedure, led to improvements in excessive daytime sleepiness, snoring, and PSG respiratory parameters by acting on lateral and retropalatal collapse, producing favorable results with good applicability in otolaryngology clinical practice.

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