Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders

2008 ◽  
Vol 105 (5) ◽  
pp. 1389-1405 ◽  
Author(s):  
Magdy Younes
Keyword(s):  
Sleep Disorders ◽  
Present Report ◽  
Sleep Onset ◽  
Respiratory Control ◽  
Upper Airway ◽  
Maximum Flow ◽  
Control Mechanisms ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
High Level

Obstructive sleep disorders develop when the normal reduction in pharyngeal dilator activity at sleep onset occurs in an individual whose pharynx requires a relatively high level of dilator activity to remain sufficiently open. They range from steady snoring, to slowly evolving hypopneas, to fast-recurring obstructive hypopneas and apneas. A fundamental observation is that the polysomnographic picture differs substantially among subjects with the same pharyngeal collapsibility, and even in the same subject at different times, indicating that the type and severity of the disorder is determined to a large extent by the individual's response to the obstruction. The present report reviews the various mechanisms involved in the response to sleep-induced obstructive events. When the obstructive event takes the form of mild-moderate flow limitation, compensation can take place through an increase in the fraction of time spent in inspiration (Ti/Ttot) without any increase in maximum flow (V̇MAX). With more severe obstructions, V̇MAX must increase. Recent data indicate that the obstructed upper airway can reopen reflexly, without arousal, if chemical drive is allowed to reach a threshold (TER) but that this is often preempted by a low arousal threshold. The relation between TER and arousal threshold, as well as the lung-to-carotid circulation time and the rate of rise of chemical drive during the obstructive event, determine the magnitude of ventilatory overshoot at the end of an event and, by extension, whether initial obstructive events will be followed by stable breathing, slow evolving hypopneas with occasional arousals, or repetitive events.

scholarly journals P019 Obstructive sleep apnoea endotypes in people with multiple sclerosis

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A27-A28
Author(s):  
S Carter ◽  
H Hensen ◽  
A Krishnan ◽  
A Chiang ◽  
J Carberry ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Obstructive Sleep Apnoea ◽  
Group Analysis ◽  
Respiratory Control ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Loop Gain ◽  
Male Predominance ◽  
Arousal Threshold ◽  
Obstructive Sleep

Abstract Purpose Obstructive sleep apnoea (OSA) is common in people with multiple sclerosis (MS) despite a lack of typical risk factors for OSA in people with MS such as obesity and male predominance. Therefore, underlying factors other than sex and obesity may be particularly important in the pathogenesis of OSA in people with MS. Thus, the primary aim of this study was to determine the relative contributions of OSA endotypes in people with MS and compare this to matched controls with OSA only. Methods Eleven people with MS and OSA (MS-OSA group) (apnoea-hypopnoea index [AHI]>5events/h) and eleven controls matched for OSA severity, age and sex without MS (OSA group) were studied. Participants underwent a detailed overnight polysomnography with an epiglottic pressure catheter and genioglossus intramuscular electrodes to allow for quantification of pathophysiological contributors to OSA. This included the respiratory arousal threshold, genioglossus muscle responsiveness, respiratory loop gain and upper airway collapsibility. Results Measures of the four primary OSA endotypes were not different between the MS-OSA and OSA groups (e.g. NREM respiratory arousal threshold -27±15 vs. -23±8 cmH2O respectively, p=0.24). Within group analysis indicated higher loop gain in non-obese MS-OSA participants compared to obese MS-OSA participants (0.53±0.11 vs. 0.37±0.11, p=0.04). Conclusions Overall, OSA endotypes are similar between MS-OSA participants and matched OSA controls. However, within the MS-OSA group, non-obese participants have higher loop gain (unstable respiratory control) compared to obese participants. Thus, unstable respiratory control may play an important role in OSA pathogenesis in many people with MS.

Disordered Control of Breathing in Infants and Children

1993 ◽  
Vol 14 (2) ◽  
pp. 51-65
Author(s):  
John L. Carroll ◽  
Carole L. Marcus ◽  
Gerald M. Loughlin
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Respiratory Control ◽  
Upper Airway ◽  
Control Of Breathing ◽  
Control Mechanisms ◽  
Airway Patency ◽  
Breathing Control ◽  
Airway Control ◽  
Obstructive Sleep

Introduction Breathing must be tightly regulated so that the amount of oxygen inhaled and carbon dioxide exhaled matches precisely the metabolic needs of the body. Acute malfunction of breathing control mechanisms, even for a few seconds, may lead rapidly to serious physiologic derangements, with death as the final outcome if the system fails to recover. Chronic malfunction of breathing control mechanisms may lead to chronically abnormal blood gases (eg, hypoxemia), with such consequent complications as developmental delay or cor pulmonale. Because the upper airway is shared for breathing, eating, drinking, and talking, control of breathing also encompasses coordination of these actions in such a way that all are carried out effectively. The upper airway also must be actively held open during sleep or it will collapse during the inspiratory phase of breathing. Tone and activity of the muscles that maintain upper airway patency are controlled, in part, by the respiratory control systems. Malfunction of upper airway control mechanisms may play a role in obstructive sleep apnea. Thus, respiratory control not only refers to the control of gas exchange, but encompasses breathing pattern, apnea, respiratory protective reflexes, and upper airway control—specifically, maintenance of upper airway patency. This review will cover infant apnea and home cardiorespiratory monitoring, apparent life-threatening events (ALTEs) and home monitoring, obstructive sleep apnea syndrome (OSAS) in children, central hypoventilation syndromes, and hyperventilation syndromes.

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.

Improvement of obstructive sleep apneas caused by hydrocephalus associated with Chiari malformation Type II following surgery

2010 ◽  
Vol 6 (4) ◽  
pp. 336-339 ◽  
Author(s):  
Marco Luigetti ◽  
Anna Losurdo ◽  
Serena Dittoni ◽  
Elisa Testani ◽  
Salvatore Colicchio ◽  
...  
Keyword(s):  
Chiari Malformation ◽  
Third Ventricle ◽  
Sleep Apnea Syndrome ◽  
Respiratory Control ◽  
Upper Airway ◽  
Respiratory Pattern ◽  
Ventricular Catheter ◽  
Type Ii ◽  
Obstructive Sleep ◽  
Severe Airway Obstruction

Chiari malformation (CM) is the downward herniation of the caudal part of the cerebellum and/or medulla oblongata into the spinal canal. It can alter several neurological functions, including respiratory control and upper airway motility, and can be the cause of sleep-disordered breathing (SDB). The authors describe a 6-year-old boy affected by CM Type II associated with myelomeningocele who showed symptoms indicative of severe airway obstruction during sleep. Polysomnography revealed severe obstructive sleep apnea syndrome (OSAS). Magnetic resonance imaging demonstrated herniation of the cerebellar tonsils and diffuse ventricular dilation with a large pseudocystic formation in the third ventricle. Surgical marsupialization of the cystic wall was performed, associated with ventriculocystostomy and endoscopic replacement of the ventricular catheter. Polysomnography repeated 2 months after surgery revealed a striking improvement in the sleep-related respiratory pattern. The pathogenesis of OSAS was probably referable to a combination of CM and elevated intracranial pressure. However, the striking improvement of symptoms after ventriculoatrial shunt placement suggested that hydrocephalus plays a major role in this condition. Assessment and effective treatment of SDB is crucial in the care of patients with CM.

scholarly journals Differences of Sleep Disorders Between Vestibular Migraine and Benign Paroxysmal Positional Vertigo

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Xue ◽  
Baojun Wang ◽  
Tianyu Meng ◽  
Shijun Zhao ◽  
Qingyin Wang ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Sleep Disorders ◽  
Incidence Rate ◽  
Benign Paroxysmal Positional Vertigo ◽  
Sleep Onset ◽  
Vestibular Migraine ◽  
Positional Vertigo ◽  
Obstructive Sleep ◽  
Paroxysmal Positional Vertigo

Introduction: Sleep disorders can affect the overall health and quality of life of patients. This study was conducted to compare the differences of sleep disorders in vestibular migraine (VM) patients and benign paroxysmal positional vertigo (BPPV) patients.Methods: VM patients, BPPV patients, and healthy controls (HCs) were recruited. Pittsburgh sleep quality index and polysomnography monitoring were used as subjective and objective, respectively, evaluation methods to evaluate the sleep quality of participants in the latest month.Results: Fifty-seven BPPV patients, 48 VM patients, and 42 HCs were included in this study. There were 79.16% VM patients, 54.39% BPPV patients, and 14.28% HCs with sleep disorders. The difference in the incidence rate of sleep disorders was significant between VM patients and BPPV patients (p = 0.008) and significantly higher in both the VM group (p < 0.00001) and BPPV group (p = 0.00004) than in the HC groups (14.28%). Compared with BPPV patients, the VM patients had the significantly lower sleep efficiency (p < 0.001) and N3 (p < 0.001) and the significantly higher time of wake-up after sleep onset (p < 0.001), N1 (p < 0.001), and N2 (p < 0.001). Meanwhile, the VM patients had significantly higher incidence rates of severe obstructive sleep apnea hypoventilation syndrome (p = 0.001) and periodic leg movement in sleep (p = 0.016).Conclusion: The incidence rate of sleep disorders was significantly higher in both VM and BPPV patients than in the HC groups. To improve the curative effects, clinicians should pay more attention to the comorbidity of sleep disorders in treating VM and BPPV.

Arousal and ventilatory responses during sleep in children with obstructive sleep apnea

1998 ◽  
Vol 84 (6) ◽  
pp. 1926-1936 ◽  
Author(s):  
Carole L. Marcus ◽  
Janita Lutz ◽  
John L. Carroll ◽  
Owen Bamford
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sleep Apnea Syndrome ◽  
Upper Airway ◽  
Respiratory Drive ◽  
Ventilatory Control ◽  
Arousal Threshold ◽  
Ventilatory Responses ◽  
Obstructive Sleep ◽  
Upper Airway Muscles

Abnormal central regulation of upper airway muscles may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). We hypothesized that this was secondary to global abnormalities of ventilatory control during sleep. We therefore compared the response to chemical stimuli during sleep between prepubertal children with OSAS and controls. Patients with OSAS aroused at a higher[Formula: see text] (58 ± 2 vs. 60 ± 5 Torr, P < 0.05); those with the highest apnea index had the highest arousal threshold ( r = 0.52, P < 0.05). The hypercapnic arousal threshold decreased after treatment. For all subjects, hypoxia was a poor stimulus to arousal, whereas hypercapnia and, particularly, hypoxic hypercapnia were potent stimuli to arousal. Hypercapnia resulted in decreased airway obstruction in OSAS. Ventilatory responses were similar between patients with OSAS and controls; however, the sample size was small. We conclude that children with OSAS have slightly blunted arousal responses to hypercapnia. However, the overall ventilatory and arousal responses are normal in children with OSAS, indicating that a global deficit in respiratory drive is not a major factor in the etiology of childhood OSAS. Nevertheless, subtle abnormalities in ventilatory control may exist.

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.

scholarly journals Role of common hypnotics on the phenotypic causes of obstructive sleep apnoea: paradoxical effects of zolpidem

2017 ◽  
Vol 50 (6) ◽  
pp. 1701344 ◽  
Author(s):  
Jayne C. Carberry ◽  
Lauren P. Fisher ◽  
Ronald R. Grunstein ◽  
Simon C. Gandevia ◽  
David K. McKenzie ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Muscle Activity ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Double Blind ◽  
Genioglossus Muscle ◽  
Airway Narrowing ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
Airway Collapsibility

Hypnotics are contraindicated in obstructive sleep apnoea (OSA) because of concerns of pharyngeal muscle relaxation and delayed arousal worsening hypoxaemia. However, human data are lacking. This study aimed to determine the effects of three common hypnotics on the respiratory arousal threshold, genioglossus muscle responsiveness and upper airway collapsibility during sleep.21 individuals with and without OSA (18–65 years) completed 84 detailed sleep studies after receiving temazepam (10 mg), zolpidem (10 mg), zopiclone (7.5 mg) and placebo on four occasions in a randomised, double-blind, placebo-controlled, crossover trial (ACTRN12612001004853).The arousal threshold increased with zolpidem and zopicloneversusplacebo (mean±sd−18.3±10 and −19.1±9versus−14.6±7 cmH2O; p=0.02 and p<0.001) but not with temazepam (−16.8±9 cmH2O; p=0.17). Genioglossus muscle activity during stable non-REM sleep and responsiveness during airway narrowing was not different with temazepam and zopicloneversusplacebo but, paradoxically, zolpidem increased median muscle responsiveness three-fold during airway narrowing (median −0.15 (interquartile range −1.01 to −0.04)versus−0.05 (−0.29 to −0.03)% maximum EMG per cmH2O epiglottic pressure; p=0.03). The upper airway critical closing pressure did not change with any of the hypnotics.These doses of common hypnotics have differential effects on the respiratory arousal threshold but do not reduce upper airway muscle activity or alter airway collapsibility during sleep. Rather, muscle activity increases during airway narrowing with zolpidem.

scholarly journals Insomnia – A Heterogenic Disorder Often Comorbid With Psychological and Somatic Disorders and Diseases: A Narrative Review With Focus on Diagnostic and Treatment Challenges

2021 ◽  
Vol 12 ◽  
Author(s):  
Bjørn Bjorvatn ◽  
Susanna Jernelöv ◽  
Ståle Pallesen
Keyword(s):  
Sleep Apnea ◽  
Sleep Disorders ◽  
Sleep Disorder ◽  
Sleep Onset ◽  
Chronic Insomnia ◽  
Diagnostic Challenge ◽  
Insomnia Disorder ◽  
Obstructive Sleep ◽  
Somatic Disorders ◽  
Insomnia Symptoms

Patients with insomnia complain of problems with sleep onset or sleep maintenance or early morning awakenings, or a combination of these, despite adequate opportunity and circumstances for sleep. In addition, to fulfill the diagnostic criteria for insomnia the complaints need to be associated with negative daytime consequences. For chronic insomnia, the symptoms are required to be present at least 3 days per week for a duration of at least 3 months. Lastly, for insomnia to be defined as a disorder, the sleep complaints and daytime symptoms should not be better explained by another sleep disorder. This criterion represents a diagnostic challenge, since patients suffering from other sleep disorders often complain of insomnia symptoms. For instance, insomnia symptoms are common in e.g., obstructive sleep apnea and circadian rhythm sleep-wake disorders. It may sometimes be difficult to disentangle whether the patient suffers from insomnia disorder or whether the insomnia symptoms are purely due to another sleep disorder. Furthermore, insomnia disorder may be comorbid with other sleep disorders in some patients, e.g., comorbid insomnia and sleep apnea (COMISA). In addition, insomnia disorder is often comorbid with psychological or somatic disorders and diseases. Thus, a thorough assessment is necessary for correct diagnostics. For chronic insomnia disorder, treatment-of-choice is cognitive behavioral therapy, and such treatment is also effective when the insomnia disorder appears comorbid with other diagnoses. Furthermore, studies suggest that insomnia is a heterogenic disorder with many different phenotypes or subtypes. Different insomnia subtypes may respond differently to treatment, but more research on this issue is warranted. Also, the role of comorbidity on treatment outcome is understudied. This review is part of a Research Topic on insomnia launched by Frontiers and focuses on diagnostic and treatment challenges of the disorder. The review aims to stimulate to more research into the bidirectional associations and interactions between insomnia disorder and other sleep, psychological, and somatic disorders/diseases.

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.

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