scholarly journals 0710 Hypoglossal Neurostimulation In Rem- Vs. Nrem-predominant Obstructive Sleep Apnea

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A270-A270
Author(s):  
C I Cabrera ◽  
B Szelestey ◽  
K Strohl ◽  
A Schell
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Univariate Analysis ◽  
Disease Process ◽  
Loop Gain ◽  
Upper Airway Stimulation ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
Baseline Characteristics ◽  
Star Trial

Abstract Introduction Obstructive sleep apnea (OSA) is a chronic condition that requires appropriate treatment strategies to optimize outcomes while minimizing risk. In addition to anatomy, physiologic factors such as arousal threshold and loop gain (i.e. “endotypes”) play a known role in the disease process. Because loop gain tends to be higher and arousal threshold lower in NREM sleep, we hypothesize that patients with NREM-predominance may achieve less success with anatomical therapy such as upper airway stimulation (UAS). Our study aims to evaluate baseline characteristics and objective results related to NREM-predominance in patients treated with UAS. Methods Using data from the STAR trial, we identified patients (n=103) with at least 20 minutes of REM on baseline testing and complete demographic and disease data at baseline and month 18. Baseline NREM-predominant disease (percent NREM events > 50) was defined as a binary variable. We created two cohorts: 1) patients with REM-predominant disease and 2) those with NREM-predominant disease. ODI and AHI were evaluated at month 18. Results Overall 62% (n=64) of patients had NREM-predominant disease at baseline. Other baseline characteristics were similar between both groups. In univariate analysis, age was significantly associated with lower AHI in the NREM-predominant population (p<0.05) but not in the REM-predominant group (p>0.05). Results were similar for ODI. For both groups, increasing age was correlated negatively with increasing AHI; this correlation was stronger in the NREM-predominant group Conclusion A majority of patients in the STAR trial had NREM-predominant OSA at baseline. There appears to be an interaction between NREM-predominance and age as predictors of UAS outcomes. Support  

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.

scholarly journals Variations in loop gain and arousal threshold during NREM sleep are affected by time of day over a 24-hour period in participants with obstructive sleep apnea

2020 ◽  
Vol 129 (4) ◽  
pp. 800-809
Author(s):  
Shipra Puri ◽  
Mohamad El-Chami ◽  
David Shaheen ◽  
Blake Ivers ◽  
Gino S. Panza ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Nrem Sleep ◽  
Time Of Day ◽  
Loop Gain ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
Critical Closing Pressure ◽  
Chemoreflex Sensitivity ◽  
Closing Pressure

Loop gain and the arousal threshold during non-rapid eye movement (NREM) sleep are greater in the morning compared with the afternoon and evening. Loop gain measures are correlated to chemoreflex sensitivity and the critical closing pressure measured during NREM sleep in the evening, morning, and afternoon. Breathing (in)stability and efficaciousness of treatments for obstructive sleep apnea may be modulated by a circadian rhythmicity in loop gain and the arousal threshold.

scholarly journals Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature

2019 ◽  
Vol 8 (11) ◽  
pp. 1846 ◽  
Author(s):  
Taranto-Montemurro ◽  
Messineo ◽  
Wellman
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Muscle Activity ◽  
Upper Airway ◽  
Loop Gain ◽  
Arousal Threshold ◽  
The Past ◽  
Obstructive Sleep ◽  
Near Future ◽  
Made In

Obstructive sleep apnea (OSA) is a highly prevalent condition with few therapeutic options. To date there is no approved pharmacotherapy for this disorder, but several attempts have been made in the past and are currently ongoing to find one. The recent identification of multiple endotypes underlying this disorder has oriented the pharmacological research towards tailored therapies targeting specific pathophysiological traits that contribute differently to cause OSA in each patient. In this review we retrospectively analyze the literature on OSA pharmacotherapy dividing the medications tested on the basis of the four main endotypes: anatomy, upper airway muscle activity, arousal threshold and ventilatory instability (loop gain). We show how recently introduced drugs for weight loss that modify upper airway anatomy may play an important role in the management of OSA in the near future, and promising results have been obtained with drugs that increase upper airway muscle activity during sleep and reduce loop gain. The lack of a medication that can effectively increase the arousal threshold makes this strategy less encouraging, although recent studies have shown that the use of certain sedatives do not worsen OSA severity and could actually improve patients’ sleep quality.

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 Long-Term Cost-Effectiveness of Upper Airway Stimulation for the Treatment of Obstructive Sleep Apnea: A Model-Based Projection Based on the STAR Trial

SLEEP ◽  
2015 ◽  
Vol 38 (5) ◽  
pp. 735-744 ◽  
Author(s):  
Jan B. Pietzsch ◽  
Shan Liu ◽  
Abigail M. Garner ◽  
Eric J. Kezirian ◽  
Patrick J. Strollo
Keyword(s):  
Obstructive Sleep Apnea ◽  
Cost Effectiveness ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Upper Airway Stimulation ◽  
Model Based ◽  
Obstructive Sleep ◽  
Star Trial

The physiological phenotype of obstructive sleep apnea differs between Caucasian and Chinese patients

SLEEP ◽  
2019 ◽  
Vol 42 (11) ◽  
Author(s):  
Denise M O’Driscoll ◽  
Shane A Landry ◽  
Jonathan Pham ◽  
Alan Young ◽  
Scott A Sands ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Chinese Patients ◽  
Future Research ◽  
Phenotypic Traits ◽  
Loop Gain ◽  
Significant Group ◽  
Arousal Threshold ◽  
Relative Contribution ◽  
Obstructive Sleep

Abstract Study Objectives The mechanisms responsible for the development of obstructive sleep apnea (phenotypic “traits”) are known to differ between individuals and may differ across ethnicities. We aimed to examine whether loop gain, arousal threshold, pharyngeal collapsibility and muscle compensation differ between Chinese and Caucasian individuals with OSA. Methods We noninvasively determined the relative contribution of loop gain, arousal threshold, pharyngeal collapsibility, and muscle compensation from the ventilatory flow pattern recorded during a standard clinical polysomnography in a cohort of age and AHI matched Caucasian and Chinese patients with moderate-severe OSA (n = 90). Results Chinese participants had significantly more collapsible pharyngeal airways as indicated by a lower Vpassive (68.9 [51.5–75.2] vs. 74.0 [65.1–80.4] %Veupnea, U = 703, p = 0.012), but less ventilatory control instability as indicated by a lower loop gain (0.60 [0.50–0.67] vs. 0.63 [0.57–0.81], U = 762, p = 0.043) compared with Caucasian participants. Further, multiple logistic regression analyses demonstrated that the combined pharyngeal collapsibility (Vpassive) and loop gain traits help to better explain the differences between the groups beyond upper-airway collapsibility alone. No statistically significant group differences were found in muscle compensation or arousal threshold traits between groups. Conclusion Individuals of Chinese descent appear to have OSA that is driven much more by the relative contribution of their anatomical predisposition and to a lesser extent nonanatomical causes compared with Caucasians. Future research should focus on determining if Chinese versus Caucasian ethnicity is an important contributing factor to clinical outcomes and therapeutic responses in OSA.

scholarly journals Sex differences in obstructive sleep apnea phenotypes, the multi-ethnic study of atherosclerosis

SLEEP ◽  
2019 ◽  
Vol 43 (5) ◽  
Author(s):  
Christine H J Won ◽  
Michelle Reid ◽  
Tamar Sofer ◽  
Ali Azarbarzin ◽  
Shaun Purcell ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sex Differences ◽  
Sleep Apnea ◽  
Loop Gain ◽  
Sample Mean ◽  
Men And Women ◽  
Ethnic Study ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
Airway Collapsibility

Abstract Study Objectives The bases for sex disparities in obstructive sleep apnea (OSA), is poorly understood. We quantified the influences of event definitions, sleep-state, and body position on apnea–hypopnea indices (AHIs) in men and women, and evaluated sex differences in pathophysiological endotypes. Methods Polysomnography (PSG) data were analyzed from 2057 participants from the multi-ethnic study of atherosclerosis. Alternative AHIs were compared using various desaturation and arousal criteria. Endotypes (loop gain, airway collapsibility, arousal threshold) were derived using breath-by-breath analysis of PSG signals. Regression models estimated the extent to which endotypes explained sex differences in AHI. Results The sample (mean 68.5 ± 9.2 years) included 54% women. OSA (AHI4P ≥15/h, defined by events with ≥4% desaturations) was found in 41.1% men and 21.8% women. Compared to AHI4P, male/female AHI ratios decreased by 5%–10% when using 3%-desaturation and/or arousal criteria; p < 0.05. REM-OSA (REM-AHI ≥15/h) was similar in men and women regardless of event desaturation criteria. REM-AHI4P ≥15/h was observed in 57% of men and women each. In NREM, AHI4P in men was 2.49 (CI95: 2.25, 2.76) of that in women. Women demonstrated lower loop gain, less airway collapsibility, and lower arousal threshold in NREM (ps < 0.0005). Endotypes explained 30% of the relative sex differences in NREM-AHI4P. Conclusions There are significant sex differences in NREM-AHI levels and in physiological endotypes. Physiological endotypes explained a significant portion of the relative sex differences in NREM-AHI. Definitions that use 4%-desaturation criteria under-estimate AHI in women. Combining NREM and REM events obscures OSA prevalence in REM in women.

scholarly journals Pathophysiology of Obstructive Sleep Apnea in Aging Women

2021 ◽  
Author(s):  
Qingchao Qiu ◽  
Jason H. Mateika
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Loop Gain ◽  
Younger Women ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
Aging Women ◽  
Long Term Facilitation

AbstractThe following review is designed to explore the pathophysiology of sleep apnea in aging women. The review initially introduces four endotypes (i.e., a more collapsible airway, upper airway muscle responsiveness, arousal threshold, and loop gain) that may have a role in the initiation of obstructive sleep apnea. Thereafter, sex differences in the prevalence of sleep apnea are considered along with differences in the prevalence that exist between younger and older women. Following this discussion, we consider how each endotype might contribute to the increase in prevalence of sleep apnea in aging women. Lastly, we address how modifications in one form of respiratory plasticity, long-term facilitation, that might serve to mitigate apneic events in younger women may be modified in aging women with obstructive sleep apnea. Overall, the published literature indicates that the prevalence of sleep apnea is increased in aging women. This increase is linked primarily to a more collapsible airway and possibly to reduced responsiveness of upper airway muscle activity. In contrast, modifications in loop gain or the arousal threshold do not appear to have a role in the increased prevalence of sleep apnea in aging women. Moreover, we suggest that mitigation of long-term facilitation could contribute to the increased prevalence of sleep apnea in aging women.

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