Ventilatory dynamics during transient arousal from NREM sleep: implications for respiratory control stability

The polysomnographic and ventilatory patterns of nine normal adults were measured during non-rapid-eye-movement (NREM) stage 2 sleep before and after repeated administrations of a tone (40-72 dB) lasting 5 s. The ventilatory response to arousal (VRA) was determined in data sections showing electrocortical arousal following the start of the tone. Mean inspiratory flow and tidal volume increased significantly above control levels in the first seven breaths after the start of arousal, with peak increases (64.2% > control) occurring on the second breath. Breath-to-breath occlusion pressure 100 ms after the start of inspiration showed significant increases only on the second and third postarousal breaths, whereas upper airway resistance declined immediately and remained below control for > or = 7 consecutive breaths. These results suggest that the first breath and latter portion of the VRA are determined more by upper airway dynamics than by changes in the neural drive to breathe. Computer model simulations comparing different VRA time courses show that sustained periodic apnea is more likely to occur when the fall in the postarousal increase in ventilation is more abrupt.     

Daniel's story: congenital central hypoventilation syndrome

Central hypoventilation syndrome (CHS) is a disorder characterized by little or no ventilatory or arousal sensitivity to hypercapnia and variable reactivity to hypoxemia, with little or no hypoxic arousal responsiveness. CHS may be congenital or acquired and can be idiopathic or secondary to a known central nervous system abnormality. Infants often present with life-threatening apnea during quiet sleep and develop severe respiratory acidosis because of the inadequate response to hypercapnia and hypoxia. Long-term treatment usually involves use of mechanical ventilation during sleep.     

Kyphosis secondary to tuberculosis osteomyelitis as a cause of ventilatory failure. Clinical features, mechanisms, and management

STUDY OBJECTIVES: To investigate the relationship of thoracic kyphosis following tuberculosis to the development of ventilatory failure and to assess the efficacy on nocturnal noninvasive ventilatory support. DESIGN: Retrospective consecutive case series with crossover from a phase without noninvasive ventilatory support to a phase with this treatment. SETTING: The Respiratory Support and Sleep Centre, Papworth, Hospital, Cambridge, England. PATIENTS: Seven patients with thoracic kyphosis following tuberculous osteomyelitis which had been contracted by the age of 4 years were studied. Their mean age was 53 (SD 7.1) years and the mean angle of kyphosis was 113.60. All patients were in ventilatory failure. INTERVENTIONS: The patients were treated with nocturnal noninvasive ventilation with either an individually constructed cuirass shell and a negative pressure pump or nasal intermittent positive pressure ventilation using a volume preset ventilator. MEASUREMENT AND RESULTS: Each patient underwent an initial clinical assessment along with radiologic studies of the spine, pulmonary function tests, daytime arterial blood gas tensions, and overnight recordings of arterial saturation, and transcutaneous carbon dioxide tension. They were reassessed in detail at a mean of 5 years after starting ventilatory support. Symptoms, vital capacity, daytime carbon dioxide tension, and overnight oximetry had all improved following treatment. Temporary withdrawal of ventilatory support led to severe sleep fragmentation in four patients and the appearance of central apneas and hypopneas in the other three. Six of the 7 patients were alive at a mean of 5.7 years after starting nocturnal ventilation. CONCLUSION: These results show that ventilatory failure may develop, after an interval of many years, in patients with a severe thoracic kyphosis due to tuberculosis in childhood. Noninvasive nocturnal ventilatory support can control the symptoms of ventilatory failure, improve the physiologic abnormalities, and is associated with prolonged survival.     

Factors influencing successful discontinuance of mechanical ventilation after open heart surgery: a clinical study of 41 patients

Circulatory, respiratory, and metabolic variables were measured with a mobile clinical bedside unit in 41 patients during the first 48 hours after open heart surgery. Calculations were carried out off-line by a computer program. The variables were measured during controlled mechanical ventilation and compared with those obtained during spontaneous breathing and after resumption of mechanical ventilation; attempts at spontaneous breathing were categorized as successful or unsuccessful. The variables were compared before, during, and after the successful and the unsuccessful attempts at spontaneous breathing. In the series as a whole, the onset of spontaneous breathing was characterized by increases in cardiac output, radial arterial and pulmonary arterial pressures, and mixed venous oxygen tension (PVO2) and content (CVO2), as well as diminished arterial and mixed venous oxygen content differences (avDO2); no significant changes in oxygen consumption (VO2) were seen. Unsuccessful attempts disturbed the patient's physiological equilibrium by reducing oxygen delivery and not increasing VO2, while increasing ventilatory work. In general, resumption of controlled ventilation restored the physiological variables to their control conditions. Successful attempts at spontaneous breathing did not greatly affect the physiological variables. The indication for resumption of controlled ventilation after periods of spontaneous breathing is the combination of increased ventilatory work with diminished circulatory and respiratory functions.     

Hierarchy of micro-arousals and the microstructure of sleep

This review is aimed at providing an overview concerning the hierarchy of different kinds of micro-arousals (without awakening) during slow wave sleep (SWS), and to summarize available data on the dynamic interplay of phasic events constituting the microstructural web of sleep EEG. K-complexes are considered elementary forms of arousal during SWS. They carry characteristics of evoked potentials, which provide subattentive information processing and have at the same time level-setting sleep maintenance functions. Micro-arousals are more complex arousal-dependent phasic events in the hierarchy. One class of recurring micro-arousals are preceded by K-complexes, while others, such as phases of spontaneous transitory activation--type micro-arousals-- represent higher levels of arousal, and are associated with EEG desyncronization, increased muscle activity and signs of autonomous arousal. All types of micro-arousals function in a complex interrelationship with another phasic event--sleep spindles--interpreted as microstates inhibiting sensory inflow through the thalamic relay system. Lastly the CAP (cyclic alternating pattern) phenomenon offers a global framework for characterizing and measuring arousal instability. Appearance of CAP sequences reflects arousal instability in a higher duration range than individual micro-arousals. They represent an arousal control mechanism reflecting that all arousing influences set into motion an oscillatory level setting system around the referential state providing a flexible adaptation for the system to defend it against perturbations. The whole arousal (without awakening) hierarchy thus seems to play an essential role in sleep regulation, serving both cyclicity and maintenance of sleep and providing at the same time flexible contact between sleeper and environment--preserving the possibility to wake up in case of any biological danger, and tailoring sleep program according to actual environmental or inner demands. Although at present there are no accepted rules for microstructural evaluation of sleep, microstructural aspects provide a more dynamic picture both about the preprogrammed and reactive changes in sleep. This approach gives us some clues to better understand sleep disorders as well. Several studies concerning microstructural analysis of certain sleep disorders are also reviewed.     

Chronic alveolar hypoventilation: a review for the clinician

Chronic alveolar hypoventilation may present in an insidious fashion with nonspecific manifestations. The clinician should be aware of the potential for developing this condition in patients with certain thoracic and systemic diseases. Once chronic alveolar hypoventilation is confirmed with arterial blood gas analysis, a systematic evaluation can often point to the underlying etiology. As sleep in affected individuals is often associated with marked worsening of gas exchange and may also contribute to worsening daytime cardiopulmonary dysfunction, polysomnography is often indicated to determine the severity of nocturnal aberrations and to look for coexistent obstructive sleep apnea. Therapy of chronic alveolar hypoventilation often focuses on elimination of the nocturnal deterioration in gas exchange, and recent applications of noninvasive positive pressure ventilation during sleep have proven useful in the management of individuals with obesity-hypoventilation syndrome, restrictive thoracic disorders, neuromuscular diseases and central causes for hypoventilation. It is unclear whether wide-spread application of nocturnal ventilatory support to patients with chronic ventilatory failure due to chronic obstructive pulmonary disease is of long-term benefit.     

Respiratory arousal from sleep: mechanisms and significance

The mechanisms by which respiratory stimuli induce arousal from sleep and the clinical significance of these arousals have been explored by numerous studies in the last two decades. Evidence to date suggests that the arousal stimulus in nonrapid eye movement sleep (NREM) is related to the level of inspiratory effort rather than the individual stimuli that contribute to ventilatory drive. A component of the arousal stimulus proportional to the level of inspiratory effort may originate in mechanoreceptors either in the upper airway or respiratory pump. Medullary centers responsible for ventilatory drive may also send a signal proportionate to the level of drive to higher centers in the brain which are responsible for arousal. Thus, the arousal stimulus may consist of multiple components, each increasing as inspiratory effort increases. The level of effort triggering arousal is an index of the arousability of the brain (arousal threshold). A deeper stage of sleep, central nervous system depressants, prior sleep fragmentation, and the presence of obstructive sleep apnea (OSA) have been observed to increase the arousal threshold to airway occlusion. Less information is available concerning the mechanisms of arousal from rapid eye movement (REM) sleep. While REM sleep is associated with the longest obstructive apneas in patients with OSA, normal human subjects appear to have a similar or lower arousal threshold to respiratory stimuli in REM compared to NREM sleep. Recent studies have challenged the assumption that the termination of all obstructive apnea is dependent on arousal from sleep. Improvements in methods to detect and quantitate changes in the cortical electroencephalogram (EEG) may better define the relationship between arousal and apnea termination. This may result in improved criteria for identifying EEG changes of clinical significance. While little is known concerning the mechanisms of arousal in central sleep apnea, arousal may play an important role in inducing this type of apnea in some patients.     

Objective sleep measures and subjective sleep satisfaction: How do older adults with insomnia define a good night's sleep?

The relationship between objective sleep measures and subjective sleep satisfaction was explored in a sample of 47 older adults (59 years and older; 35 women, 12 men) with primary insomnia. Participants submitted to all-night sleep evaluations (polysomnography) for 2 nights. After each night, participants provided subjective sleep-satisfaction ratings. Depth of sleep (decreased Stage 1 sleep and increased Stages 3 and 4 sleep) and sleep latency were the best predictors of subjective sleep satisfaction. For other sleep variables such as sleep efficiency and wake time after sleep onset, no value predicted satisfaction on a particular night. However, for these sleep variables, relative improvement from Night 1 to Night 2 predicted greater subjective satisfaction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep-assisted instruction.

The question of learning from materials presented during sleep has been answered positively by Soviet studies and negatively by Western studies. However, procedural differences among studies have been confounded with the absence of an established criterion for sleep. The present paper reviews 11 studies in sleep learning for the potential practical value of sleep-assisted instruction (SAI). A strategy of optimizing compatibility between learning and sleep variables to support SAI is proposed within the context of both wake and sleep research on attention, perception, and memory. Age, sex, health, wake learning capacity, and suggestibility are important moderating variables in SAI. The individual's motivation and set, meaningful-relevant learning material, activation of low-voltage EEG sleep patterns and coordinated wake learning with extended training are tentatively deduced as necessary conditions in applied SAI. (111/2 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A behavioural basis for distinguishing wakefulness from sleep in insomniac and good sleepers.

Distinguished between the sleep of normal Ss and insomniacs, using the behaviorally-based sleep/wake monitor. 18 Ss with insomnia (aged 26–65 yrs) and 11 controls (aged 30–44 yrs) underwent a hearing test, and completed the Brock Sleep and Insomnia Questionnaire (K. A. Cote and R. D. Ogilvie, 1993). They used the behavioral response sleep/wake monitors for 3 consecutive nights, to assess behavioral sleep data. Results indicate group differences for wakefulness, sleep onset latency, total percent sleep, and percent wakefulness prior to sleep onset. Significant night effects were present in a number of measures. Group by Night interactions were found for total percent sleep, and after sleep onset, total percent wakefulness and after sleep onset. These findings support differences between normal and insomniac sleep. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A negative association of schizophrenia with an allele of the HLA DQB1 gene among African-Americans

The present study investigated the relationship between the time of nocturnal onset of urinary 6-sulfatoxymelatonin (aMT6s) secretion, and the timing of the steepest increase in nocturnal sleepiness ("sleep gate"), as determined by an ultrashort sleep-wake cycle test (7 min sleep, 13 min wake). Twenty-nine men (mean age 23.8 +/- 2.7 years) participated. The ultrashort sleep-wake paradigm started at 0700 hr after a night of sleep deprivation and continued for 24 hr until 0700 hr the next day. Electrophysiological recordings were carried out during the 7-min sleep trials, which were then scored conventionally for sleep stages. Urinary aMT6s was measured every 2 hr. The results showed that the timing of the sleep gate was significantly correlated with the onset of aMT6s secretion. These results are discussed in light of the possible role of melatonin in sleep-wake regulation.     

The effects of sleep loss on task performance and the electroencephalogram in young and elderly subjects

The effects of 28-h sleep loss on performance, reaction time (RT) distribution functions, and spectral composition of the EEG were evaluated in three choice-RT tasks for young (N = 12, aged 18-24 years) and old (N = 12, aged 62-73 years) subjects. Manipulations of stimulus degradation, stimulus-response compatibility, and interstimulus interval variability were to affect encoding, response selection, and motor adjustment stages, respectively. In order to discriminate between independent variables that were presumed to be computational or energetical in nature, effects on EEG spectra and RT-distributions were studied. Spectra of the EEG indicated higher cortical arousal levels for the elderly than for the young. The most dramatic effect of sleep loss on performance was a marked increase in the number of omitted responses. This effect was smaller for the elderly than for the young. The results suggest that the detrimental effects of sleep loss are smaller in the elderly, which is consistent with an inverted-U relationship between arousal and performance. The age effects on the processing stages were mainly limited to response selection.     

Effect of baseline oxygenation on the ventilatory response to inhaled 100% oxygen in preterm infants

We tested the hypothesis that the immediate (< 1 min) ventilatory response to 100% O2 in preterm infants, a test of peripheral chemoreceptor activity characterized by a decrease in ventilation due to apnea, is more pronounced at lower baseline O2 concentrations. We studied 12 healthy preterm infants [birth weight 1,425 +/- 103 (SE) g; study weight 1,670 +/- 93 g; gestational age 30 +/- 1 wk; postnatal age 27 +/- 7 days] during quiet sleep. The infants inhaled 15, 21, 25, 30, 35, 40, and 45% O2 for 5 min in a randomized manner (control period), followed by 100% O2 for 2 min, and then the same initial O2 concentration again for 2 min (recovery period). A nose piece and a flow-through system were used to measure ventilation. The immediate decrease in ventilation with 100% O2 was 46% on 15% O2, 24% on 21% O2, 11% on 25% O2, 8% on 30% O2, 12% on 35% O2, and 8% on 40% O2; there was no decrease on 45% O2 (P < 0.01). The corresponding mean duration of apnea was 29 s during 15% O2, 18 s during 21% O2, 8 s during 25% O2, 9 s during 30 and 35% O2, and 3 s during 40% O2; only one infant developed a 5-s apnea during 45% O2 (P < 0.001). The findings suggest that 1) the ventilatory decrease in response to 100% O2 is dependent on the baseline oxygenation, being more pronounced the lower the baseline O2 concentration; and 2) this ventilatory decrease is entirely related to more prolonged apneas observed with lower baseline O2 concentrations. We speculate that the peripheral chemoreceptors, being so active in the small preterm infant with relatively low arterial PO2, are highly susceptible to changes in PO2, and this makes them prone to irregular or periodic breathing, especially during sleep.     

Clinical applications of cardiopulmonary interactions

The hemodynamic consequences of both spontaneous and positive-pressure ventilation may be profound and may have opposite effects on cardiovascular stability in differing patient populations. Thus, no firm rules apply as to the specific response that will be seen in all patients and under all conditions. Some generalities, however, are probably reasonable. In patients with markedly increased work of breathing, hypervolemia, or impaired LV pump function, the institution of mechanical ventilatory support can be lifesaving because of its ability to support the cardiovascular system, independent of any beneficial effects that mechanical ventilation may have on gas exchange. In patients with decreased pulmonary elastic recoil, increased pulmonary vascular resistance, hypovolemia, or airflow obstruction, the institution of mechanical ventilatory support may induce cardiovascular instability, which, if not corrected, can lead to total cardiovascular collapse. Similarly, withdrawal of ventilatory support invariably increases intrathoracic blood volume and LV afterload and can be thought of as a type of cardiovascular stress test. Patients who pass this test easily can usually be successfully weaned from mechanical ventilatory support, whereas those who fail often are not ready to be weaned. Some patients who fail weaning trials do so because of the cardiovascular effects of spontaneous ventilation, not because the work of breathing is too great. Identification of such patients early on may improve their treatment by directing supportive therapies toward cardiovascular rather than ventilatory endpoints. However, in many situations, it will be difficult to single out a primary process determining cardiovascular instability, because multiple factors are compounded to create the observed situation and the patient's response to initiation of ventilatory support or weaning. Thus, the clinician is left with a series of therapeutic options, which if depending on the patient's response, suggest specific origins of the ventilatory and cardiovascular dysfunction. In that regard, the initiation and withdrawal of ventilatory support can be seen as a ventilatory probe into the determinants of cardiovascular homeostasis in the ventilatory-dependent patient.     

Periodic leg movements during sleep and sleep disturbances in elders

BACKGROUND: Periodic limb movements in sleep (PLMS) are an increasingly pervasive disturbance for aging adults. The aims of this experiment were: (a) to describe the index of periodic limb movements in sleep (myoclonus index [MI] in elderly subjects with complaints of poor sleep or depression (N = 22; 68 +/- 5.5 SD years); and (b) to correlate MI with sleep history, depression scores, and objective and subjective indices of sleep. METHOD: Sleep and leg movements were assessed for 5 consecutive nights. Between-subjects, nonparametric correlations were examined between mean MI and sleep history, depression scores, and objective and subjective sleep characteristics. Associations among within-subject night-to-night variabilities of MI, objective, and subjective variables were examined with repeated measures ANCOVA, entering MI as a covariate. RESULTS: A remarkably high level of MI was found (median 25.8 events per hour; 86% of subjects > 5). Nevertheless, no associations were found between MI and sleep disturbance measures. CONCLUSION: These results extend previous reports that PLMS are remarkably persuasive in elderly volunteers and support other reports questioning whether there is a distinct PLMS syndrome.     

Chronic headaches and sleep disorders

BACKGROUND: Headaches and sleep problems are common complaints in the daily practice of the general practitioner. Since the relationship between headaches and sleep complaints is complex, clear models of interaction are needed for adequate diagnosis and treatment. METHODS: All subjects, successively seen in a headache clinic during a defined period, were subdivided based on the time of onset of cephalalgia. Subjects who reported onset of headache on a long-term basis, during the nocturnal or early morning (before final awakening) period, were systematically studied by a headache clinic and a sleep disorders center. This subgroup represented 17% of the total headache group. RESULTS: Although the results of the headache clinic study did not differentiate this subgroup from the other patients, the sleep disorders center's interviews and questionnaires demonstrated a significant impact of the sleep disorders on headache and daytime function. Nocturnal monitoring during sleep identified specific sleep disorders in 55% of the subjects with onset of headache during the nocturnal sleep period. Follow-up after treatment of the sleep disorder showed that all subjects with an identifiable sleep disorder reported either an improvement or absence of their headache. The subjects identified with periodic limb movement syndrome were mostly those who reported only an improvement in their sleep and still needed treatment for their headaches. The question of the interaction and association of sleep-related headache and periodic limb movement syndrome is unresolved. CONCLUSION: Headaches occurring during the night or early morning are often related to a sleep disturbance.     

The determinants of respiratory rate during mechanical ventilation

The independent and interactive effect of feedback related to volume, CO2, inspiratory flow, and arousal state on the regulation of respiratory rate in mechanically ventilated humans is not well characterized. We examined the rate response of eight normal volunteers during both quiet wakefulness and non-rapid-eye-movement (NREM) sleep, while mechanically ventilated through a nasal mask in an assist/control mode with a machine back-up rate of 2 breaths/min. Tidal volume (VT) was set slightly above spontaneous VT and then increased by 0.2 L every 3 min up to 1.8 L or 25 ml/kg. Either an inspiratory flow of 40 L/min or an inspiratory time of 2 s (iso-T(I)) was set, with CO2 added (F(I)CO2 > 0) or F(I)CO2 = 0. Measurements were made during both quiet wakefulness and NREM sleep. We found that as VT increased, the respiratory rate decreased; the rate decline was observed during wakefulness and sleep, and under isocapnic as well as hypocapnic conditions. Increasing inspiratory flow raised the respiratory rate during wakefulness and NREM sleep. During NREM sleep, hypocapnia resulted in wasted ventilator trigger efforts. In summary, both VT and inspiratory flow settings affect the respiratory rate, and depending on state, can affect CO2 homeostasis. Ventilator settings appropriate for wakefulness may cause ventilatory instability during sleep.     

Interrelations between sleep and the somatotropic axis

In the human as in other mammals, growth hormone (GH) is secreted as a series of pulses. In normal young adults, a major secretory episode occurs shortly after sleep onset, in temporal association with the first period of slow-wave (SW) sleep. In men, approximately 70% of the daily GH output occurs during early sleep throughout adulthood. In women, the contribution of sleep-dependent GH release to the daily output is lower and more variable. Studies involving shifts of the sleep-wake cycle have consistently shown that sleep-wake homeostasis is the primary determinant of the temporal organization of human GH release. Effects of circadian rhythmicity may occasionally be detected. During nocturnal sleep, the sleep-onset GH pulse is caused by a surge of hypothalamic GHRH release which coincides with a circadian-dependent period of relative somatostatin disinhibition. Extensive evidence indicates the existence of a consistent relationship between SW sleep and increased GH secretion and, conversely, between awakenings and decreased GH release. There is a linear relationship between amounts of SW sleep--whether measured by visual scoring or by delta activity--and amounts of concomitant GH secretion, although dissociations may occur, most likely because of variable levels of somatostatin inhibition. Pharmacological stimulation of SW sleep results in increased GH release, and compounds which increase SW sleep may therefore represent a novel class of GH secretagogues. During aging, SW sleep and GH secretion decrease with the same chronology, raising the possibility that the peripheral effects of the hyposomatotropism of the elderly may partially reflect age-related alterations in sleep-wake homeostasis. While the association between sleep and GH release has been well documented, there is also evidence indicating that components of the somatotropic axis are involved in regulating sleep. The studies are most consistent in indicating a role for GHRH in promoting NREM and/or SW sleep via central, rather than peripheral, mechanisms. A role for GH in sleep regulation is less well-documented but seems to involve REM, rather than NREM, sleep. It has been proposed that the stimulation of GH release and the promotion of NREM sleep by GHRH are two separate processes which involve GHRH neurons located in two distinct areas of the hypothalamus. Somatostatinergic control of GH release appears to be weaker during sleep than during wake, suggesting that somatostatinergic tone is lower in the hypothalamic area(s) involved in sleep regulation and sleep-related GH release than in the area controlling daytime GH secretion. While the concept of a dual control of daytime and sleep-related GH secretion remains to be directly demonstrated, it allows for the reconciliation of a number of experimental observations.     

Suicidal behavior in bipolar and unipolar affective disorders: a meta-analysis

Manual ventilation (MAV) or handbagging is a frequent and often life-saving procedure for neonates; however, few studies allow for an objective evaluation of techniques or possible risks. We compared parameters of ventilation and pulmonary mechanics obtained during routine pressure-limited MAV to those obtained during spontaneous breathing (SPB) in the same infant at approximately the same time. We selected 20 preterm neonates in the recovery phase of respiratory distress syndrome who received periodic MAV and were capable of optimum spontaneous minute ventilation (> 300 mL/kg/min). During MAV compared to SPB we measured higher tidal volume (8.1 +/- 0.5 SE vs. 5.4 +/- 0.4 SE mL/kg, P < 0.001), lower total pulmonary compliance (0.65 +/- 0.05 vs. 1.16 +/- 0.11 SE mL/cmH2O, P < 0.001), end-inspiratory compliance, higher pulmonary resistance (121 +/- 11 vs. 61 +/- 7 SE cmH2O/L/s, P < 0.001) and higher peak inspiratory airflow (2.8 +/- 0.2 vs. 1.6 +/- 0.1 L/s, P < 0.001). Inspiratory time (Ti) was consistently longer during MAV (0.49 +/- 0.02 vs. 0.36 +/- 0.02 SE, P < 0.001) such that during MAV the difference between actual Ti and minimal effective Ti (fivefold inspiratory time constant) was larger (0.29 +/- 0.03 vs. 0.13 +/- 0.03 s, P < 0.05). Our study suggests that operator-dependent ventilatory variables such as tidal volume, inspiratory time, frequency, and airflow need to be further evaluated in order to develop standardized guidelines for the safe administration of MAV. Until then the ventilator used for brief or augmented ventilatory support is a reasonable alternative to administering MAV by inconsistent standards.     

Starling resister and stability of sleep ventilation

The upper airway can be described as a collapsible segment (the pharynx) interposed between two rigid bony (the cavum) or cartilaginous (the trachea) segments. Due to this structure, the pharynx behaves as a collapsible tube, in which airflow does not depend on the downstream pressure, but is limited to a maximum value which depends only on the upstream pressure and on the pressure surrounding the collapsible segment; this behavior, known as a Starling resistor can be modeled by the waterfall effect. Thus, the upper airways can be in three different conditions: an occluded condition, in which no flow is possible, a patent condition, in which flow depends on the difference between upstream and downstream pressures (according to Poiseuille's law), and a situation in which flow is limited. The behavior of the upper airway is largely dependent on its anatomic structure, but functional factors play a critical role. Among these sleep state is both a determinant of the collapsibility of the pharynx, and determined by the simulation of upper airway mechanoreceptors whose activity depends on the activity of respiratory muscles. Thus the interplay of three factors: ventilatory drive, upper airway collapsibility, and arousal threshold can predict most of the situations of stable and unstable ventilatory behavior during sleep. The level of the arousal threshold governs the stability of the ventilatory pattern, as it determines whether a combination of slow, respiratory effort, and blood gases can be maintained or is interrupted by an arousal.