Neuromechanical interaction in human snoring and upper airway obstruction.

The fact that snoring and obstructive apnea only occur during sleep means that effective neuromuscular functioning of the upper airway during sleep is vital for the maintenance of unimpeded breathing. Recent clinical studies in humans have obtained evidence demonstrating that upper airway neural receptors sense the negative pressure generated by inspiration and "trigger," with a certain delay, reflex muscle activation to sustain the airway that might otherwise collapse. These findings have enabled us to propose a model in which the mechanics is coupled to the neuromuscular physiology through the generation of reflex wall stiffening proportional to the retarded fluid pressure. Preliminary results on this model exhibit three kinds of behavior typical of unimpeded breathing, snoring, and obstructive sleep apnea, respectively. We suggest that the increased latency of the reflex muscle activation in sleep, together with the reduced strength of the reflex, have important clinical consequences.     

Sleep-related obstructive disordered breathing in cleft palate patients after palatoplasty

Sleep-disordered breathing is frequently associated with children presenting congenital midface defects. Because of structural and functional anomalies in the upper airway, children with cleft palate, especially after surgery, may carry a higher risk of developing sleep-disordered breathing. However, the presence of such sleep-disordered breathing in older cleft palate children has not been emphasized. The aim of this comparative overnight cardiorespiratory sleep study was to evaluate cleft palate patients according to sleep-disordered breathing. A group of 43 cleft palate children (17 girls and 26 boys; mean age, 12.1 +/- 3.8 years) was compared with a control group of 20 randomly selected, noncleft children matched for age, sex, and body mass index. None of the patients suffered from manifest sleep-disordered breathing. Cleft palate patients had a statistically significantly higher respiratory disturbance index and snoring index, but no increased apnea index. The data suggest that cleft palate patients having undergone primary closure of the palate demonstrate microsymptoms of nocturnal upper airway obstruction.     

A model of a snorer's upper airway

In snorers, the physiologic decrease of postural muscle tone during sleep results in increased collapsibility of the upper airway. Measurement of nasal pressure changes with prongs is increasingly used to monitor flow kinetics through a collapsing upper airway. This report presents a mathematical model to predict nasal flow profile from three critical components that control upper airway patency during sleep. The model includes the respiratory pump drive, the stiffness of the pharyngeal soft tissues, and the dynamic support of the muscles surrounding the upper airway. Depending on these three components, the proposed model is able to reproduce the characteristic changes in flow profile that are clinically observed in snorers and non-snorers during sleep.     

Assessment of pharyngeal airway stability in normal and micrognathic infants

A current hypothesis for obstructive sleep apnea states that 1) negative airway pressure during inspiration can collapse the pharyngeal airway, and 2) neural control of pharyngeal airway-dilating muscles is important in preventing this collapse. To test this hypothesis we performed nasal mask occlusions to increase negative pharyngeal airway pressures during inspiration in eight normal and five micrognathic infants. Both groups developed midinspiratory pharyngeal obstruction, but obstruction was more frequent in micrognathic infants and varied in some infants with sleep state. The airway usually reopened with the subsequent expiration. The occasional failure to reopen was presumably due to pharyngeal wall adhesion. If airway obstruction occurred in sequential breaths during multiple-breath nasal mask occlusions in normal infants, there was a breath-by-breath change in the airway pressure associated with airway closure (airway closing pressure); the airway closing pressure became progressively more negative. Micrognathic infants showed less ability to improve the airway closing pressure, but this ability increased with age. These findings suggest that nasal mask occlusion can test the competence of the neuromuscular mechanisms that maintain pharyngeal airway patency in infants. Micrognathic infants had spontaneous midinspiratory pharyngeal airway obstructions during snoring. Their episodes of obstructive apnea began with midinspiratory pharyngeal obstruction similar to that seen during snoring and nasal mask occlusions. These findings imply a similar pathophysiology for snoring, spontaneous airway obstruction, and obstruction during snoring.     

Waking and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs

We studied waking and genioglossus electromyographic (EMGgg) responses to oscillating pressure waves applied to the upper airways of three sleeping dogs. The dogs were previously prepared with a permanent side-hole tracheal stoma and were trained to sleep with a tight-fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria, and EMGgg activity was measured using fine bipolar electrodes inserted directly into the muscle. Oscillatory pressure waves of 30 Hz and +/- 3 cmH2O (tested at atmospheric and subatmospheric upper airway pressures) were applied at the dog's nostrils or larynx, either constantly for a period of 1 min or in 0.5-s bursts. We found that the pressure stimulus had two major effects. First, it was a potentially powerful arousal-promoting stimulus. Arousal occurred in 78% of tests in slow-wave sleep (SWS) and 55% of tests in rapid-eye-movement (REM) sleep, with swallowing and sighing accompanying many of the arousals. Second, it produced an immediate and sustained augmentation of EMGgg, in wakefulness, SWS, and REM sleep. We conclude that oscillatory pressure waves in the upper airway, as found in snoring, produce reflex responses that help maintain upper airway patency during sleep. Loss of this type of reflex might contribute to the onset of obstructive sleep apnea in chronic snorers.     

Diagnosis of obstructive sleep apnea syndrome]

Symptoms and signs in 12 patients with severe obstructive sleep apnea (OSA) syndrome have been presented. The most common symptoms were snoring , increased motor activity during sleep and excessive daytime somnolence. The factors predisposing to OSA syndrome were obesity and anatomic abnormalities of the upper airway structure. In some cases the signs of OSA syndrome included hypertension, right heart failure, chronic alveolar hypoventilation and polycythemia. Polysomnography showed sleep fragmentation and the prevalence of light sleep stages. Obstructive sleep apneas repeated 73 +/- 23 times per hour of sleep. The mean apnea duration was 19 +/- 8 s. The mean arterial oxygen saturation during apnea was 72 +/- 14%.     

Obstructive Sleep Apnea Syndrome: From Phenotype to Genetic Basis

Obstructive sleep apnea syndrome (OSAS) is a complex chronic clinical syndrome, characterized by snoring, periodic apnea, hypoxemia during sleep, and daytime hypersomnolence. It affects 4-5% of the general population. Racial studies and chromosomal mapping, familial studies and twin studies have provided evidence for the possible link between the OSAS and genetic factors and also most of the risk factors involved in the pathogenesis of OSAS are largely genetically determined. A percentage of 35-40% of its variance can be attributed to genetic factors. It is likely that genetic factors associated with craniofacial structure, body fat distribution and neural control of the upper airway muscles interact to produce the OSAS phenotype. Although the role of specific genes that influence the development of OSAS has not yet been identified, current researches, especially in animal model, suggest that several genetic systems may be important. In this chapter, we will first define the OSAS phenotype, the pathogenesis and the risk factors involved in the OSAS that may be inherited, then, we will review the current progress in the genetics of OSAS and suggest a few future perspectives in the development of therapeutic agents for this complex disease entity.Key Words: Obstructive sleep apnea, genetic, hypopnea, AHI, snoring, risk factors, phenotype, multifactorial disease.     

Early detection of upper airway obstructions by analysis of acoustical respiratory input impedance

Repetitive occurrence of partial or total upper airway obstruction characterizes several respiratory dysfunctions such as the obstructive sleep apnea syndrome (OSAS). In OSAS patients, pharyngeal collapses are linked to a decrease in upper airway muscle activity during sleep which causes decreased upper airway wall stiffness. Continuous positive airway pressure (CPAP) is recommended as the treatment of choice. Advancements in CPAP therapy require early detection of respiratory events in real time to adapt the level of the applied pressure to airway collapsibility. The forced oscillation technique (FOT) is a noninvasive method which reflects patients' airway patency by measuring respiratory impedance. The aim of this study was to evaluate by a mathematical model of the respiratory system if FOT can provide an early detection index of total or partial upper airway obstruction. Furthermore, the simulation should suggest which characteristic features are relevant for early apnea detection in measured clinical data. The respiratory system has been treated as a series of cylindrical segments. The oropharynx analog of the model allows simulation of upper airway collapse, mimicking the situation in patients with OSAS. We calculated the input impedance for different degrees of upper airway obstruction ranging from unobstructed airways to total occlusion. Furthermore, we simulated different upper airway wall compliances. We compared the simulation with real data. The results of the study suggest that FOT is a valuable tool for assessing the degree of upper airway obstruction in patients with OSAS. Especially, the phase angle of the impedance seems to be a potentially useful tool for early apnea detection by assessing the upper airway wall collapsibility. Received: 23 July 1998 / Accepted in revised form: 26 January 1999     

Characteristics of the upper airway pressure-flow relationship during sleep

In examining the mechanical properties of the respiratory system during sleep in healthy humans, we observed that the inspiratory pressure-flow relationship of the upper airway was often flow limited and too curvilinear to be predicted by the Rohrer equation. The purposes of this study were 1) to describe a mathematical model that would better define the inspiratory pressure-flow relationship of the upper airway during sleep and 2) to identify the segment of airway responsible for the sleep-related flow limitation. We measured nasal and total supralaryngeal pressure and flow during wakefulness and stage 2 sleep in five healthy male subjects lying supine. A right rectangular hyperbolic equation, V = (alpha P)/(beta + P), where V is flow, P is pressure, alpha is an asymptote for peak flow, and beta is pressure at a flow of alpha/2, was used in its linear form, P/V = (beta/alpha) + (P/alpha). The goodness of fit of the new equation was compared with that for the linearized Rohrer equation P/V = K1 + K2V. During wakefulness the fit of the hyperbolic equation to the actual pressure-flow data was equivalent to or significantly better than that for the Rohrer equation. During sleep the fit of the hyperbolic equation was superior to that for the Rohrer equation. For the whole supralaryngeal airway during sleep, the correlation coefficient for the hyperbolic equation was 0.90 +/- 0.50, and for the Rohrer equation it was 0.49 +/- 0.25. The flow-limiting segment was located within the pharyngeal airway, not in the nose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upper airway pressure-flow relationships in obstructive sleep apnea

We examined the pressure-flow relationships in patients with obstructive sleep apnea utilizing the concepts of a Starling resistor. In six patients with obstructive sleep apnea, we applied incremental levels of positive pressure through a nasal mask during non-rapid-eye-movement sleep. A positive critical opening pressure (Pcrit) of 3.3 +/- 3.3 (SD) cmH2O was demonstrated. As nasal pressure was raised above Pcrit, inspiratory airflow increased in proportion to the level of positive pressure applied until apneas were abolished (P less than 0.01). However, at pressures greater than Pcrit, esophageal pressures either did not correlate or correlated inversely with inspiratory airflow provided that esophageal pressure was less than Pcrit. When pressure was applied to a full face mask, inspiratory airflow did not occur and Pcrit could not be obtained at pressures well above Pcrit demonstrated with the nasal mask. These results are consistent with the view that the upper airway functions as a Starling resistor with a collapsible segment in the oropharynx. These findings offer a unifying construct for the association of sleep apnea, periodic hypopnea, and snoring.     

Sleep, respiratory physiology, and nocturnal asthma.

The nocturnal worsening of asthma is a common feature of this disease that recently has received extensive investigation. Most recent efforts have focused on the role of circadian biorhythms that could promote a nocturnal increase in airway inflammation, leading to a subsequent increase in airflow obstruction and asthma symptoms. However, definitive studies remain lacking. As discussed in this review, there is also substantial evidence that sleep itself may play a direct role in the nocturnal worsening of asthma. Potential mechanisms for such a sleep-related effect could include the supine posture, alterations in sympathetic and parasympathetic "balance," sleep-associated reductions in lung volume, intrapulmonary pooling of blood, and sleep-associated upper airway narrowing, both with and without snoring and obstructive sleep apnea (OSA). These potential contributors to this troublesome phenomenon deserve further consideration when investigating mechanisms of nocturnal asthma.     

Snoring source identification and snoring noise prediction

This paper investigates the snoring mechanism of humans by applying the concept of structural intensity to a three-dimensional (3D) finite element model of a human head, which includes: the upper part of the head, neck, soft palate, hard palate, tongue, nasal cavity and the surrounding walls of the pharynx. Results show that for 20, 40 and 60Hz pressure loads, tissue vibration is mainly in the areas of the soft palate, the tongue and the nasal cavity. For predicting the snoring noise level, a 3D boundary element cavity model of the upper airway in the nasal cavity is generated. The snoring noise level is predicted for a prescribed airflow loading, and its range agrees with published measurements. These models may be further developed to study the various snoring mechanisms for different groups of patients.     

Anatomical and functional changes in the upper airways of sleep apnea patients due to mandibular repositioning: a large scale study

The obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep related breathing disorder. A popular treatment is the use of a mandibular repositioning appliance (MRA) which advances the mandibula during the sleep and decreases the collapsibility of the upper airway. The success rate of such a device is, however, limited and very variable within a population of patients. Previous studies using computational fluid dynamics have shown that there is a decrease in upper airway resistance in patients who improve clinically due to an MRA. In this article, correlations between patient-specific anatomical and functional parameters are studied to examine how MRA induced biomechanical changes will have an impact on the upper airway resistance. Low-dose computed tomography (CT) scans are made from 143 patients suffering from OSAHS. A baseline scan and a scan after mandibular repositioning (MR) are performed in order to study variations in parameters. It is found that MR using a simulation bite is able to induce resistance changes by changing the pharyngeal lumen. The change in minimal cross-sectional area is the best parameter to predict the change in upper airway resistance. Looking at baseline values, the ideal patients for MR induced resistance decrease seem to be women with short airways, high initial resistance and no baseline occlusion.     

Induction of periodic breathing during sleep causes upper airway obstruction in humans

To test the hypothesis that occlusive apneas result from sleep-induced periodic breathing in association with some degree of upper airway compromise, periodic breathing was induced during non-rapid-eye-movement (NREM) sleep by administering hypoxic gas mixtures with and without applied external inspiratory resistance (9 cmH2O X l-1 X s) in five normal male volunteers. In addition to standard polysomnography for sleep staging and respiratory pattern monitoring, esophageal pressure, tidal volume (VT), and airflow were measured via an esophageal catheter and pneumotachograph, respectively, with the latter attached to a tight-fitting face mask, allowing calculation of total pulmonary system resistance (Rp). During stage I/II NREM sleep minimal period breathing was evident in two of the subjects; however, in four subjects during hypoxia and/or relief from hypoxia, with and without added resistance, pronounced periodic breathing developed with waxing and waning of VT, sometimes with apneic phases. Resistive loading without hypoxia did not cause periodicity. At the nadir of periodic changes in VT, Rp was usually at its highest and there was a significant linear relationship between Rp and 1/VT, indicating the development of obstructive hypopneas. In one subject without added resistance and in the same subject and in another during resistive loading, upper airway obstruction at the nadir of the periodic fluctuations in VT was observed. We conclude that periodic breathing resulting in periodic diminution of upper airway muscle activity is associated with increased upper airway resistance that predisposes upper airways to collapse.     

Upper airway and respiratory muscle responses to continuous negative airway pressure

To determine upper airway and respiratory muscle responses to nasal continuous negative airway pressure (CNAP), we quantitated the changes in diaphragmatic and genioglossal electromyographic activity, inspiratory duration, tidal volume, minute ventilation, and end-expiratory lung volume (EEL) during CNAP in six normal subjects during wakefulness and five during sleep. During wakefulness, CNAP resulted in immediate increases in electromyographic diaphragmatic and genioglossal muscle activity, and inspiratory duration, preserved or increased tidal volume and minute ventilation, and decreased EEL. During non-rapid-eye-movement and rapid-eye-movement sleep, CNAP was associated with no immediate muscle or timing responses, incomplete or complete upper airway occlusion, and decreased EEL. Progressive diaphragmatic and genioglossal responses were observed during non-rapid-eye-movement sleep in association with arterial O2 desaturation, but airway patency was not reestablished until further increases occurred with arousal. These results indicate that normal subjects, while awake, can fully compensate for CNAP by increasing respiratory and upper airway muscle activities but are unable to do so during sleep in the absence of arousal. This sleep-induced failure of load compensation predisposes the airways to collapse under conditions which threaten airway patency during sleep. The abrupt electromyogram responses seen during wakefulness and arousal are indicative of the importance of state effects, whereas the gradual increases seen during sleep probably reflect responses to changing blood gas composition.     

Developmental changes in upper airway dynamics.

Normal children have a less collapsible upper airway in response to subatmospheric pressure administration (P(NEG)) during sleep than normal adults do, and this upper airway response appears to be modulated by the central ventilatory drive. Children have a greater ventilatory drive than adults. We, therefore, hypothesized that children have increased neuromotor activation of their pharyngeal airway during sleep compared with adults. As infants have few obstructive apneas during sleep, we hypothesized that infants would have an upper airway that was resistant to collapse. We, therefore, compared the upper airway pressure-flow (V) relationship during sleep between normal infants, prepubertal children, and adults. We evaluated the upper airway response to 1). intermittent, acute P(NEG) (infants, children, and adults), and 2). hypercapnia (children and adults). We found that adults had a more collapsible upper airway during sleep than either infants or children. The children exhibited a vigorous response to both P(NEG) and hypercapnia during sleep (P < 0.01), whereas adults had no significant change. Infants had an airway that was resistant to collapse and showed a very rapid response to P(NEG). We conclude that the upper airway is resistant to collapse during sleep in infants and children. Normal children have preservation of upper airway responses to P(NEG) and hypercapnia during sleep, whereas responses are diminished in adults. Infants appear to have a different pattern of upper airway activation than older children. We speculate that the pharyngeal airway responses present in normal children are a compensatory response for a relatively narrow upper airway.     

Characterization of pharyngeal resistance during sleep in a spectrum of sleep-disordered breathing.

Aims of the study were 1) to compare Hudgel's hyperbolic with Rohrer's polynomial model in describing the pressure-flow relationship, 2) to use this pressure-flow relationship to describe these resistances and to evaluate the effects of sleep stages on pharyngeal resistances, and 3) to compare these resistances to the pressure-to-flow ratio (DeltaP/V). We studied 12 patients: three with upper airway resistance syndrome (UARS), four with obstructive sleep hypopnea syndrome (OSHS), three with obstructive sleep apnea syndrome (OSAS), and two with simple snoring (SS). Transpharyngeal pressures were calculated between choanae and epiglottis. Flow was measured by use of a pneumotachometer. The pressure-flow relationship was established by using nonlinear regression and was appreciated by the Pearson's square (r(2)). Mean resistance at peak pressure (Rmax) was calculated according to the hyperbolic model during stable respiration. In 78% of the cases, the value of r(2) was greater when the hyperbolic model was used. We demonstrated that Rmax was in excellent agreement with P/V. UARS patients exhibited higher awake mean Rmax than normal subjects and other subgroups and a larger increase from wakefulness to slow-wave sleep than subjects with OSAS, OSHS, and SS. Analysis of breath-by-breath changes in Rmax was also a sensitive method to detect episodes of high resistance during sleep.     

骨性Ⅲ类错合畸形患者正颌术后呼吸道情况随访调查

目的：通过评估骨性Ⅲ错合畸形患者正颌手术后睡眠时期的呼吸功能情况,研究该类患者正颌手术后存在呼吸道梗阻的可能性。为临床治疗提供依据。方法：分析56例接受正颌手术的骨性Ⅲ类错合畸形患者的术前及术后1周、1月、3月和术后6月的多导睡眠图报告。设计问卷调查表评估手术影响日间嗜睡度的变化。从PSG报告上获得的术前术后有代表性的2项参数睡眠呼吸暂停低通气指数与最低氧饱和度分别进行比较。结果：数据显示术前和术后AHI指数及SpO2无显著性差异（统计学上无差异）。54例病人术后均未出现睡眠呼吸障碍症状。2例病人术后出现睡眠时期打鼾,但术后随访6月后打鼾逐渐消失。结论：骨性Ⅲ类错合畸形患者正颌术后无明显呼吸道梗阻症状。但若患者同时具有超重、短颈、舌体大等其他危险因素及仅行下颌骨后退手术可能导致睡眠呼吸暂停低通气综合症的发生。     

State-dependent hypotonia in posterior cricoarytenoid muscles of the larynx caused by cholinoceptive reticular mechanisms

The neural control of the accessory respiratory muscles regulating upper airway patency is poorly understood. This is particularly true with regard to the declines in electromyographic (EMG) activity of upper airway muscles during sleep. To specify the cellular mechanisms causing decreased upper airway muscle tone during sleep, we used an established pharmacological model of rapid eye movement (REM) sleep. With this model, a REM sleep-like state was reliably produced by microinjecting the cholinergic agonist carbachol directly into the pontine reticular formation of the cat. EMG recording were taken from the posterior cricoarytenoid (PCA) muscles of the larynx during wakefulness and the carbachol-induced, REM sleep-like state. This experimental model had not been previously used to study the neuropharmacological control of the upper airway. The results revealed a dose-dependent decrease in PCA muscle tone caused by pontine microinjections of carbachol. To investigate the cholinergic specificity of these effects, the muscarinic cholinergic antagonist pirenzepine was centrally administered before carbachol. Pirenzepine pretreatment effectively blocked the carbachol-induced, REM sleep-like state and attendant changes in muscle tone. These results specify for the first time that muscarinic cholinergic mechanisms within the pontine reticular formation can causally mediate state-dependent hypotonia in accessory respiratory muscles of the upper airway.