Sleep in restrictive and neuromuscular respiratory disorders

Thoracic restrictive disorders (i.e., chest wall deformities or neuromuscular diseases), may predispose to sleep-disordered breathing, poor sleep quality, and nocturnal hypoventilation. These disorders intensify the effects of reductions in both respiratory center output and central chemosensitivity and increases in upper airway resistance that occur with the onset of sleep. Normally, rapid eye movement (REM) sleep suppresses the activity of nondiaphragmatic breathing muscles, further reducing ventilation. Diaphragmatic or upper airway muscle weakness and reduced chest wall compliance in patients with thoracic restrictive disorders enhance the severity of sleep-disordered breathing during REM sleep, worsening gas exchange abnormalities and sleep fragmentation and impairing daytime functioning. Although daytime respiratory function and nocturnal oxygen saturation are not well correlated, some markers may be useful for identifying patients with thoracic restriction at risk for sleep-disordered breathing. Although some patients may respond to continuous positive airway pressure (CPAP) alone, noninvasive positive pressure ventilation (NPPV) is a more important part of disease management for patients with restrictive thoracic disorders. This technique improves nocturnal ventilation and sleep quality but may also contribute to sleep fragmentation in some patients. If the patient is an unsuitable candidate for or fails NPPV, tracheostomy mechanical ventilation should be considered.     

Comparison of upper airway collapse during general anaesthesia and sleep

Measurement of the collapsibility of the upper airway while a patient is awake is not a good guide to such collapsibility during sleep, presumably because of differences in respiratory drive, muscle tone, and sensitivity of reflexes. To assess whether a relation existed between general anaesthesia and sleep, we measured collapsibility of the upper airway during general anaesthesia and severity of sleep-disordered breathing in 25 people who were having minor surgery on their limbs. Anaesthetised patients who needed positive pressure to maintain airway patency had more severe sleep-disordered breathing than did those whose airways remained patent at or below atmospheric pressure. Such an association was strongest during rapid-eye-movement (REM) sleep. Our findings suggest that sleep-disordered breathing should be considered in all patients with a pronounced tendency for upper airway obstruction during anaesthesia or during recovery from it.     

Computerized tomography in obstructive sleep apnea. Correlation of airway size with physiology during sleep and wakefulness

Pathophysiologic changes during sleep in patients with obstructive apnea are often associated with alterations in upper airway function during awake periods. To determine whether these functional changes are related to abnormal airway structure, we performed computerized tomography (CT) in 20 awake patients with obstructive apnea and in 10 control subjects. The CT scan measurements of cross-sectional areas of the nasopharynx, oropharynx, and hypopharynx in apneic patients were significantly reduced (p less than 0.05) compared with those in the control subjects. Sites of obstruction varied, and apparent airway occlusion occurred in 6 patients. Reduced pharyngeal size correlated with increased sleep-disordered breathing rates (p less than 0.05), more severe nocturnal oxygen desaturation (p less than 0.05), and the presence of a saw-tooth pattern of flow-volume curves obtained during awake periods (p less than 0.05). Structural upper airway narrowing is detectable with CT in awake patients with obstructive sleep apnea.     

Upper airway function and non-intubated, assisted ventilation

The influence of upper airway patency on ventilation assisted by chest negative pressure ventilation (CNPV) or nasal intermittent positive pressure ventilation (nIPPV) was studied as follows. 1) In seven patients with chronic respiratory failure (PaCO2 more than 50 Torr), the increase in tidal volume (VT) induced by CNPV was larger during mouth breathing than during nose breathing in the awake state. On CNPV transcutaneous PCO2 (PtcCO2) decreased during awake state, but increased during NREM sleep. 2) In four patients with chronic respiratory failure (PaCO2 more than 60 Torr), nIPPV induced the leakage of air from mouth in more than 20 cmH2O of nasal mask pressure during sleep. PtcCO2 increased during sleep, especially during REM sleep in spite of nIPPV. The change in PtcCO2 during REM sleep on nIPPV comparing awake state was 16.1 +/- 1.4 torr and comparing REM sleep in usual sleep was -6.0 +/- 1.4 Torr. 3) Upper airway resistance (UAR) was measured in two patients with tracheostomy. An increase in UAR was associated with a linear decrease in VT during nIPPV, although associated with a curvilinear decrease in VT during CNPV. These results indicate that the efficiency of CNPV and nIPPV depends on the patency of upper airway.     

Pathophysiology of obstructive sleep apnea

The pharyngeal muscles are essential for effective lung ventilation because they help maintain an open upper airspace for the unhindered passage of air into the lungs. Sleep, especially rapid-eye-movement sleep, however, causes fundamental modifications of pharyngeal muscle tone and reflex responses that in normal individuals lead to airway narrowing and hypoventilation. In individuals with already anatomically narrow upper airways, these effects of sleep predispose them to inspiratory flow limitation (hypopneas), airway closure, and obstructive sleep apnea. Obstructive sleep apnea is a common disorder affecting at least 2% to 4% of North American adults and is associated with serious clinical, social, and economic consequences. This review addresses the physiology and pathophysiology of obstructive sleep apnea, hypopneas, and snoring, that is, the full spectrum of the most common sleep-related breathing events involving the upper airway. Specifically, the anatomical features of the upper airway that are important to its mechanical properties and degree of collapsibility are reviewed. The sites of airway narrowing and closure and the implications for common treatments strategies are also discussed. This article also focuses on the neuromuscular control mechanisms operating in wakefulness and sleep that influence pharyngeal muscle tone and upper airway collapsibility. The effects of sleep on the reflex mechanisms that normally operate to protect the upper airspace from suction collapse during breathing are also addressed. Throughout this review, these mechanisms are discussed with an emphasis on understanding the physiology and pathophysiology of sleep-disordered breathing and obstructive sleep apnea.     

Bedeutung des Schlafs bei Patienten mit Lungenerkrankungen

Sleep is characterized by a profound change of load and capacity of the respiratory system. Load increases due to a rise in upper and lower airway resistance. Capacity decreases due to reduced chemosensitivity, a decrease in muscle activity and minute ventilation. Whereas these changes do not lead to relevant blood gas changes and do not disturb sleep in healthy subjects, patients with respiratory diseases frequently show the first symptoms of their disease during sleep. Pulmonary diseases in which sleep plays an important role are asthma, COPD, hypercapnic respiratory failure, sleep disordered breathing, the overlap-syndrome and cystic fibrosis.Medical history should include sleep and complaints during the night. In asthmatics peak-flow measurements during the night may provide valuable information. In all other disorders mentioned, nocturnal ambulatory recording of respiration and arterial oxygen saturation often allow the detection of relevant disorders of breathing during sleep. If ambulatory monitoring reveals relevant pathology, then further evaluation and treatment in the sleep laboratory are warranted.     

Influence of airway pressure on genioglossus activity during sleep in normal children

RATIONALE: Most children with obstructive sleep apnea are able to sustain stable breathing during portions of sleep, despite an anatomic predisposition toward airway collapse. This suggests that additional determinants of airway patency are active, such as neuromuscular compensation. OBJECTIVES/METHODS: Using a custom intraoral surface electrode to record pharyngeal dilator muscle activity (the genioglossus [EMGgg]), we evaluated the muscle, ventilatory, and arousal responses to negative-pressure challenges during sleep in 19 healthy control children. MEASUREMENTS AND MAIN RESULTS: In response to these challenges, we observed (1) marked variability in individual EMGgg responsiveness (peak EMGgg [mean+/-SD], 214+/-101% baseline), which was consistent within subjects; (2) a relationship between EMGgg activity and inspiratory flow and airway collapsibility; (3) reflex increases in flow (peak flow increase from challenge breaths 1-5 [mean+/-SD], 49+/-41% baseline) and respiratory rate often sufficient to sustain minute ventilation near baseline levels, without arousal; and (4) arousal threshold to be highest in stage 4, intermediate in stage 2, and lowest in REM sleep. CONCLUSIONS: Healthy children have wide variation in upper airway neuromuscular compensatory responses and arousal thresholds that could represent intermediate phenotypes affecting the expression of sleep apnea. Children with robust upper airway neuromuscular responsiveness, or a very high arousal threshold, may be able to sustain minute ventilation when challenged with negative airway pressure.     

Pathophysiology of pediatric obstructive sleep apnea

Sleep-disordered breathing is a common and serious cause of metabolic, cardiovascular, and neurocognitive morbidity in children. The spectrum of obstructive sleep-disordered breathing ranges from habitual snoring to partial or complete airway obstruction, termed obstructive sleep apnea (OSA). Breathing patterns due to airway narrowing are highly variable, including obstructive cycling, increased respiratory effort, flow limitation, tachypnea, and/or gas exchange abnormalities. As a consequence, sleep homeostasis may be disturbed. Increased upper airway resistance is an essential component of OSA, including any combination of narrowing/retropositioning of the maxilla/mandible and/or adenotonsillar hypertrophy. However, in addition to anatomic factors, the stability of the upper airway is predicated on neuromuscular activation, ventilatory control, and arousal threshold. During sleep, most children with OSA intermittently attain a stable breathing pattern, indicating successful neuromuscular activation. At sleep onset, airway muscle activity is reduced, ventilatory variability increases, and an apneic threshold slightly below eupneic levels is observed in non-REM sleep. Airway collapse is offset by pharyngeal dilator activity in response to hypercapnia and negative lumenal pressure. Ventilatory overshoot results in sudden reduction in airway muscle activation, contributing to obstruction during non-REM sleep. Arousal from sleep exacerbates ventilatory instability and, thus, obstructive cycling. Paroxysmal reductions in pharyngeal dilator activity related to central REM sleep processes likely account for the disproportionate severity of OSA observed during REM sleep. Understanding the pathophysiology of pediatric OSA may permit more precise clinical phenotyping, and therefore improve or target therapies related to anatomy, neuromuscular compensation, ventilatory control, and/or arousal threshold.     

Pathogenesis of obstructive and central sleep apnea

Considerable progress has been made over the last several decades in our understanding of the pathophysiology of both central and obstructive sleep apnea. Central sleep apnea, in its various forms, is generally the product of an unstable ventilatory control system (high loop gain) with increased controller gain (high hypercapnic responsiveness) generally being the cause. High plant gain can contribute under certain circumstances (hypercapnic patients). On the other hand, obstructive sleep apnea can develop as the result of a variety of physiologic characteristics. The combinations of these may vary considerably between patients. Most obstructive apnea patients have an anatomically small upper airway with augmented pharyngeal dilator muscle activation maintaining airway patency awake, but not asleep. However, individual variability in several phenotypic characteristics may ultimately determine who develops apnea and how severe the apnea will be. These include: (1) upper airway anatomy, (2) the ability of upper airway dilator muscles to respond to rising intrapharyngeal negative pressure and increasing Co(2) during sleep, (3) arousal threshold in response to respiratory stimulation, and (4) loop gain (ventilatory control instability). As a result, patients may respond to different therapeutic approaches based on the predominant abnormality leading to the sleep-disordered breathing.     

Genioglossal inspiratory activation: central respiratory vs mechanoreceptive influences.

Upper airway dilator muscles are phasically activated during respiration. We assessed the interaction between central respiratory drive and local (mechanoreceptive) influences upon genioglossal (GG) activity throughout inspiration. GG(EMG) and airway mechanics were measured in 16 awake subjects during baseline spontaneous breathing, increased central respiratory drive (inspiratory resistive loading; IRL), and decreased respiratory drive (hypocapnic negative pressure ventilation), both prior to and following dense upper airway topical anesthesia. Negative epiglottic pressure (P(epi)) was significantly correlated with GG(EMG) across inspiration (i.e. within breaths). Both passive ventilation and IRL led to significant decreases in the sensitivity of the relationship between GG(EMG) and P(epi) (slope GG(EMG) vs P(epi)), but yielded no change in the relationship (correlation) between GG(EMG) and P(epi). During negative pressure ventilation, pharyngeal resistance increased modestly, but significantly. Anesthesia in all conditions led to decrements in phasic GG(EMG), increases in pharyngeal resistance, and decrease in the relationship between P(epi) and GG(EMG). We conclude that both central output to the GG and local reflex mediated activation are important in maintaining upper airway patency.     

A nasal cannula can be used to treat obstructive sleep apnea

RATIONALE: Obstructive sleep apnea syndrome is due to upper airway obstruction and is associated with increased morbidity. Although continuous positive airway pressure efficaciously treats obstructive apneas and hypopneas, treatment is impeded by low adherence rates. OBJECTIVES: To assess the efficacy on obstructive sleep apnea of a minimally intrusive method for delivering warm and humidified air through an open nasal cannula. METHODS: Eleven subjects (age, 49.7+/-5.0 yr; body mass index, 30.5+/-4.3 kg/m2), with obstructive apnea-hypopnea syndrome ranging from mild to severe (5 to 60 events/h), were administered warm and humidified air at 20 L/minute through an open nasal cannula. MEASUREMENTS AND MAIN RESULTS: Measurements were based on standard sleep-disordered breathing and arousal indices. In a subset of patients pharyngeal pressure and ventilation were assessed to determine the mechanism of action of treatment with nasal insufflation. Treatment with nasal insufflation reduced the mean apnea-hypopnea index from 28+/-5 to 10+/-3 events per hour (p<0.01), and reduced the respiratory arousal index from 18+/-2 to 8+/-2 events per hour (p<0.01). Treatment with nasal insufflation reduced the apnea-hypopnea index to fewer than 10 events per hour in 8 of 11 subjects, and to fewer than 5 events per hour in 4 subjects. The mechanism of action appears to be through an increase in end-expiratory pharyngeal pressure, which alleviated upper airway obstruction and improved ventilation. CONCLUSIONS: Our findings demonstrate clinical proof of concept that a nasal cannula for insufflating high airflows can be used to treat a diverse group of patients with obstructive sleep apnea.     

Effect of obesity and erect/supine posture on lateral cephalometry: relationship to sleep-disordered breathing.

Craniofacial and upper airway anatomy, obesity and posture may all play a role in compromising upper airway patency in patients with the sleep apnoea/hypopnoea syndrome. The aim of this study was to investigate the relationship between obesity, facial structure and severity of sleep-disordered breathing using lateral cephalometric measurements and to assess the effect of body posture on cephalometric measurements of upper airway calibre variables in obese and non-obese subjects. Lateral cephalometry was carried out in erect and supine postures in 73 awake male subjects randomly selected from patients referred for polysomnography who had a wide range of apnoea/hypopnoea frequencies (1-131 events x h sleep(-1)). Subjects were divided into non-obese (body mass index (BMI) < 30 kg x m(-2); n=42) and obese (BMI > or = 30 kg x m(-2); n=31) groups. Significant but weak correlations were found between apnoea/hypopnoea index (AHI) and measurements reflecting upper airway dimensions: uvular protrusion-posterior pharyngeal wall (r=-0.26, p<0.05) and hyoid-posterior pharyngeal wall (r=0.26, p<0.05). Multiple regression using both upper airway dimensions improved the correlation to AHI (r=0.34, p=0.01). Obese subjects had greater hyoid-posterior pharyngeal wall distances than non-obese subjects, both erect (42+/-5 versus 39+/-4 mm, respectively (mean+/-SD) p<0.01) and supine (43+/-5 versus 40+/-4 mm, p<0.05). Skeletal craniofacial structure was similar in obese and non-obese subjects. In conclusion, measurements reflecting upper airway size were correlated with the severity of sleep-disordered breathing. Differences in upper airway size measurements between obese and non-obese subjects were independent of bony craniofacial structure.     

Gender differences in the expression of sleep-disordered breathing : role of upper airway dimensions.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a common disorder that is characterized by repetitive episodes of upper airway narrowing and collapse. Obesity is a major risk factor for OSA. Compared with men, women have greater total body fat and are more obese, and yet the prevalence of OSA is much higher in men. The airway size and compliance and pharyngeal muscle tone are important determinants of upper airway patency during sleep. The discrepancy between greater frequency of obesity and lower prevalence of OSA in women has not been explained and suggests a different pathogenetic mechanism underlying this condition. Most clinical studies in OSA have either combined the sexes or have described results from men only. The object of this study was twofold: (1) to examine the effect of obesity on pharyngeal size in both men and women, and (2) to determine the role of upper airway dimensions in the expression of sleep-disordered breathing (SDB) and its relationship to gender. DESIGN: Prospective study of subjects referred for evaluation of SDB. SETTING: University-based sleep center. SUBJECTS: Seventy-eight male patients (mean +/- SE age, 49.2 +/- 1.5 years) and 52 female patients (mean age, 47.4 +/- 1.5 years). MEASUREMENTS AND RESULTS: All subjects underwent in-laboratory polysomnography with measurement of upper airway size using the acoustic reflectance method. Although the two groups were similar in age, the female patients were slightly heavier than the male patients (body mass index [BMI], 36.0 +/- 1.7 kg/m(2) vs 33.3 +/- 0.8 kg/m(2), respectively; p < 0.0001). Despite similar clinical presentation of snoring and excessive daytime sleepiness, women had mild OSA (respiratory disturbance index [RDI], 9.2 +/- 2.7 events per hour) or increased upper airway resistance syndrome compared with men with more severe OSA (RDI, 28.0 +/- 3.5 events per hour; p < 0.0001). In contrast, women had a significantly smaller oropharyngeal junction and pharynx than men (p < 0.02). Upper airway size correlated significantly with the severity of sleep apnea in men only. There was no correlation between BMI and pharyngeal size in either gender. CONCLUSIONS: This study demonstrates that the static properties of upper airway in awake men but not women correlate with the severity of sleep apnea. This suggests inherent structural and functional differences in upper airway during sleep between men and women with more favorable airway mechanics in women.     

Sleep and long-term ventilation

The development of sleep-disordered breathing is common in patients with chronic respiratory insufficiency due to neuromuscular and restrictive disorders, as well as in those with COPD. Nocturnal hypoventilation and obstructive and central apneas result in daytime symptoms of hypersomnolence and fatigue, and contribute to abnormalities in awake gas exchange. Long-term mechanical ventilation, delivered invasively by tracheostomy or more recently by NPPV, has been shown to eliminate sleep-disordered breathing and correct abnormalities in nocturnal gas exchange, resulting in an improvement in sleep quality. Improved daytime symptoms and gas exchange, with the suggestion of a decrease in morbidity and mortality, support the use of long-term mechanical ventilation during sleep in selected patients with these disorders.     

Upper airway collapsibility, dilator muscle activation and resistance in sleep apnoea.

The calibre of the upper airway is thought to be dependant upon its passive anatomy/collapsibility and the activation of pharyngeal dilator muscles. During awake periods, the more collapsible upper airway in obstructive sleep apnoea (OSA) increases the dilator muscle activity through a negative-pressure reflex. A direct correlation between the critical closing pressure (P(crit)), as a measure of anatomy/collapsability and electromyogram (EMG) activity of genioglossus EMG (GG-EMG) and tensor palatini EMG (TP-EMG), was hypothesised. The relationship between these indices and pharyngeal resistance (R(phar)) was also examined. The study involved eight males with a mean age of 48 (interquartile range 46-52) yrs with OSA, and an apnoea/hypopnoea index of 75 (65-101).hr(-1) on two nights breathing normally and on nasal continuous positive airway pressure (nCPAP). The P(crit )was measured during nonrapid eye movement sleep on nCPAP using brief, incremental reductions in mask pressure. GG-EMG and TP-EMG were measured breath-by-breath, awake, during sleep onset and on nCPAP. R(phar) was measured using airway pressures and flow. Wakeful GG-EMG, early sleep TP-EMG and the sleep decrement in TP-EMG were directly related to P(crit). Muscle activation was negatively correlated with R(phar) for TP-EMG awake and GG-EMG early in sleep. In conclusion these results confirm that dilator muscle activation is directly related to airway narrowing and reduces resistance across patients with obstructive sleep apnoea.     

Effect of nasal or oral breathing route on upper airway resistance during sleep.

Healthy subjects with normal nasal resistance breathe almost exclusively through the nose during sleep. This study tested the hypothesis that a mechanical advantage might explain this preponderance of nasal over oral breathing during sleep. A randomised, single-blind, crossover design was used to compare upper airway resistance during sleep in the nasal and oral breathing conditions in 12 (seven male) healthy subjects with normal nasal resistance, aged 30+/-4 (mean+/-SEM) yrs, and with a body mass index of 23+/-1 kg x m2. During wakefulness, upper airway resistance was similar between the oral and nasal breathing routes. However, during sleep (supine, stage two) upper airway resistance was much higher while breathing orally (median 12.4 cmH2O x L(-1) x s(-1), range 4.5-40.2) than nasally (5.2 cmH2O x L(-1) x s(-1), 1.7-10.8). In addition, obstructive (but not central) apnoeas and hypopnoeas were profoundly more frequent when breathing orally (apnoea-hypopnoea index 43+/-6) than nasally (1.5+/-0.5). Upper airway resistance during sleep and the propensity to obstructive sleep apnoea are significantly lower while breathing nasally rather than orally. This mechanical advantage may explain the preponderance of nasal breathing during sleep in normal subjects.     

Noninvasive monitoring of respiratory mechanics during sleep.

The sleep apnoea-hypopnoea syndrome is characterised by recurrent obstructions of the upper airway, resulting in sleep disruption and arterial oxygen desaturations. Noninvasive assessment of respiratory mechanics during sleep is helpful in facilitating the diagnosis and treatment of patients with sleep apnoea-hypopnoea syndrome. This series summarises the different tools that are currently available to noninvasively assess respiratory mechanics during sleep breathing disturbances. These techniques are classified according to the main variable monitored: ventilation, breathing effort or airway obstruction. Changes in patient ventilation are assessed by recording flow or volume signals by means of pneumotachographs, thermistors or thermocouples, nasal prongs or thoraco-abdominal bands. Common tools to noninvasively assess breathing efforts are the thoraco-abdominal bands and the pulse transit time technique. Upper airway obstruction is noninvasively characterised by its upstream resistance and its critical pressure or by means of the forced oscillation technique. Given the technical and practical limitations of each technique, combining different tools improves the reliability and robustness of patient assessment during sleep.     

Selective reduction of genioglossal muscle activity by alcohol in normal human subjects

We recorded ventilation and genioglossal electromyographic activity in 12 awake, normal subjects before and after they drank 1 ml of ethyl alcohol per kg of body weight. Measurements were made during quiet room air breathing and during hypercapnic rebreathing. Alcohol did not alter minute ventilation, the pattern of breathing, or the ventilatory response to CO2, but it significantly reduced genioglossal activity in both quiet breathing and hypercapnia. The effect was more consistent in male than in female subjects. These results indicate that the neural mechanisms underlying the respiratory activity of the genioglossus are more susceptible to depression by alcohol than those serving the muscles of the ventilatory pump. This susceptibility may be important in the exacerbation by alcohol of obstructive apnea during sleep.     

Sleep and breathing in neuromuscular disease.

Respiratory muscle weakness in neuromuscular disease causes significant morbidity and mortality. The published data on respiratory muscle activity and breathing during sleep in normal subjects, the impact of respiratory muscle weakness on sleep and breathing and the relations to daytime respiratory function in neuromuscular disease are reviewed here. In normal subjects during sleep upper airway resistance increases, chemosensitivity is reduced and the wakefulness drive to breathe is lost, resulting in a fall in ventilation. During rapid eye movement (REM) sleep, ribcage and accessory breathing muscles are suppressed, particularly during bursts of eye movements, and breathing is more irregular, rapid and shallow, with a further fall in ventilation. In subjects with respiratory muscle weakness sleep is fragmented, with shorter total sleep time, frequent arousals, an increase in stage 1 sleep and a reduction in, or complete suppression of, REM sleep. Sleep-disordered breathing and nocturnal desaturation are common and most severe during REM sleep. Correlations between daytime respiratory function and nocturnal desaturation are moderate or weak, but daytime respiratory function has greater prognostic value than nocturnal measurements. Noninvasive ventilation improves sleep quality and breathing in subjects with respiratory muscle weakness. However, the optimal criteria for initiation of ventilation and its role in rapidly progressive neuromuscular diseases are unclear.     

The persistence of a respiratory 'personality' into stage IV sleep in man

The characteristic pattern of breathing for an individual when awake at rest may be due to forebrain influences upon breathing. To examine this hypothesis we have studied the breathing pattern in 18 healthy subjects during relaxed wakefulness (W) and during Stage 4 sleep (S4), when forebrain influences upon breathing are absent or minimal. Inspiratory and expiratory times, respiratory frequency, tidal volume, and ventilation were quantified noninvasively by respiratory inductance plethysmography. The stability of respiratory variables between W and S4 sleep was tested within individuals. The results show that (i) individuals breathe differently from each other when awake and when in S4 sleep; the range between individuals during sleep being as large as it is when awake; (ii) differences in breathing pattern between two S4 periods within an individual are relatively small; (iii) the characteristic breathing pattern of an individual when awake tends to be maintained in S4 sleep. This persistence of a respiratory 'personality' into S4 sleep probably indicates that there are individual differences in respiratory rhythm generation in the absence of any forebrain influences upon breathing.