Influence of cardiac function and failure on sleep-disordered breathing: evidence for a causative role.

Heart failure is an increasingly common public health problem that is strongly linked to both central and obstructive sleep apnea, collectively referred to as sleep-disordered breathing. Much attention has been given to the deleterious effects of sleep-disordered breathing on the failing heart and potential mechanisms by which treatment of sleep-disordered breathing may result in improved cardiac performance and long-term outcomes. However, there is compelling evidence that cardiac dysfunction may contribute to sleep-disordered breathing. Although there is recognized overlap between pathophysiological mechanisms in central sleep apnea and obstructive sleep apnea, data supporting the role of cardiac function are certain forms of central sleep apnea are well established, whereas investigation into the relationship with obstructive sleep apnea is less mature but continues to evolve. This review will examine experimental and observational data that explore possible pathophysiological mechanisms and potential targets for therapy in heart failure and sleep-disordered breathing.     

Compensatory responses to upper airway obstruction in obese apneic men and women

Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age (n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow (P = 0.003) and inspiratory duty cycle (P = 0.017) in response to prolonged periods of UAO and an ～20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) (P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep.     

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.     

Positive outcome of average volume-assured pressure support mode of a Respironics V60 Ventilator in acute exacerbation of chronic obstructive pulmonary disease: a case report

ABSTRACT: INTRODUCTION: We were able to treat a patient with acute exacerbation of chronic obstructive pulmonary disease who also suffered from sleep-disordered breathing by using the average volume-assured pressure support mode of a Respironics V60 Ventilator (Philips Respironics: United States). This allows a target tidal volume to be set based on automatic changes in inspiratory positive airway pressure. This removed the need to change the noninvasive positive pressure ventilation settings during the day and during sleep. The Respironics V60 Ventilator, in the average volume-assured pressure support mode, was attached to our patient and improved and stabilized his sleep-related hypoventilation by automatically adjusting force to within an acceptable range. CASE PRESENTATION: Our patient was a 74-year-old Japanese man who was hospitalized for treatment due to worsening of dyspnea and hypoxemia. He was diagnosed with acute exacerbation of chronic obstructive pulmonary disease and full-time biphasic positive airway pressure support ventilation was initiated. Our patient was temporarily provided with portable noninvasive positive pressure ventilation at night-time following an improvement in his condition, but his chronic obstructive pulmonary disease again worsened due to the recurrence of a respiratory infection. During the initial exacerbation, his tidal volume was significantly lower during sleep (378.9 +/- 72.9mL) than while awake (446.5 +/- 63.3mL). A ventilator that allows ventilation to be maintained by automatically adjusting the inspiratory force to within an acceptable range was attached in average volume-assured pressure support mode, improving his sleep-related hypoventilation, which is often associated with the use of the Respironics V60 Ventilator. Polysomnography performed while our patient was on noninvasive positive pressure ventilation revealed obstructive sleep apnea syndrome (apnea-hypopnea index = 14), suggesting that his chronic obstructive pulmonary disease was complicated by obstructive sleep apnea syndrome. CONCLUSION: In cases such as this, in which patients with severe acute respiratory failure requiring full-time noninvasive positive pressure ventilation therapy also show sleep-disordered breathing, different ventilator settings must be used for waking and sleeping. On such occasions, the Respironics V60 Ventilator, which is equipped with an average volume-assured pressure support mode, may be useful in improving gas exchange and may achieve good patient compliance, because that mode allows ventilation to be maintained by automatically adjusting the inspiratory force to within an acceptable range whenever ventilation falls below target levels.     

Lung volume and collapsibility of the passive pharynx in patients with sleep-disordered breathing.

Lung volume dependence of pharyngeal airway patency suggests involvement of lung volume in pathogenesis of obstructive sleep apnea. We examined the structural interaction between passive pharyngeal airway and lung volume independent of neuromuscular factors. Static mechanical properties of the passive pharynx were compared before and during lung inflation in eight anesthetized and paralyzed patients with sleep-disordered breathing. The respiratory system volume was increased by applying negative extrathoracic pressure, thereby leaving the transpharyngeal pressure unchanged. Application of -50-cmH(2)O negative extrathoracic pressure produced an increase in lung volume of 0.72 (0.63-0.91) liter [median (25-75 percentile)], resulting in a significant reduction of velopharyngeal closing pressure of 1.22 (0.14-2.03) cmH(2)O without significantly changing collapsibility of the oropharyngeal airway. Improvement of the velopharyngeal closing pressure was directly associated with body mass index. We conclude that increase in lung volume structurally improves velopharyngeal collapsibility particularly in obese patients with sleep-disordered breathing.     

Snoring and breathing pauses during sleep: telephone interview survey of a United Kingdom population sample.

OBJECTIVES: To determine the prevalence of snoring, breathing pauses during sleep, and obstructive sleep apnoea syndrome and determine the relation between these events and sociodemographic variables, other health problems, driving accidents, and consumption of healthcare resources. DESIGN: Telephone interview survey directed by a previously validated computerised system (Sleep-Eval). SETTING: United Kingdom. SUBJECTS: 2894 women and 2078 men aged 15-100 years who formed a representative sample of the non-institutionalised population. MAIN OUTCOME MEASURES: Interview responses. RESULTS: Forty per cent of the population reported snoring regularly and 3.8% reported breathing pauses during sleep. Regular snoring was significantly associated with male sex, age 25 or more, obesity, daytime sleepiness or naps, night time awakenings, consuming large amounts of caffeine, and smoking. Breathing pauses during sleep were significantly associated with obstructive airways or thyroid disease, male sex, age 35-44 years, consumption of anxiety reducing drugs, complaints of non-restorative sleep, and consultation with a doctor in the past year. The two breathing symptoms were also significantly associated with drowsiness while driving. Based on minimal criteria of the International classification of Sleep Disorders (1990), 1.9% of the sample had obstructive sleep apnoea syndrome. In the 35-64 year age group 1.5% of women (95% confidence interval 0.8% to 2.2%) and 3.5% of men (2.4% to 4.6%) had obstructive sleep apnoea syndrome. CONCLUSIONS: Disordered breathing during sleep is widely underdiagnosed in the United Kingdom. The condition is linked to increased use of medical resources and a greater risk of daytime sleepiness, which augments the risk of accidents. Doctors should ask patients and bed partners regularly about snoring and breathing pauses during sleep.     

Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse

Sleep is associated with marked alterations in ventilatory control that lead to perturbations in respiratory timing, breathing pattern, ventilation, pharyngeal collapsibility, and sleep-related breathing disorders (SRBD). Mouse models offer powerful insight into the pathogenesis of SRBD; however, methods for obtaining the full complement of continuous, high-fidelity respiratory, electroencephalographic (EEG), and electromyographic (EMG) signals in unrestrained mice during sleep and wake have not been developed. We adapted whole body plethysmography to record EEG, EMG, and respiratory signals continuously in unrestrained, unanesthetized mice. Whole body plethysmography tidal volume and airflow signals and a novel noninvasive surrogate for respiratory effort (respiratory movement signal) were validated against simultaneously measured gold standard signals. Compared with the gold standard, we validated 1) tidal volume (correlation, R(2) = 0.87, P < 0.001; and agreement within 1%, P < 0.001); 2) inspiratory airflow (correlation, R(2) = 0.92, P < 0.001; agreement within 4%, P < 0.001); 3) expiratory airflow (correlation, R(2) = 0.83, P < 0.001); and 4) respiratory movement signal (correlation, R(2) = 0.79-0.84, P < 0.001). The expiratory airflow signal, however, demonstrated a decrease in amplitude compared with the gold standard. Integrating respiratory and EEG/EMG signals, we fully characterized sleep and breathing patterns in conscious, unrestrained mice and demonstrated inspiratory flow limitation in a New Zealand Obese mouse. Our approach will facilitate studies of SRBD mechanisms in inbred mouse strains and offer a powerful platform to investigate the effects of environmental and pharmacological exposures on breathing disturbances during sleep and wakefulness.     

Influence of testosterone on breathing during sleep

Apneas and hypopneas during sleep occur more frequently in men than women. Disordered breathing is also reported to increase in hypogonadal men following testosterone administration. This suggests a hormonal influence on sleeping respiratory pattern. We therefore studied respiratory rhythm during sleep in 11 hypogonadal males both on and off testosterone-replacement therapy. In four subjects the anatomy (computerized tomography) and airflow resistance of the upper airway were also determined on both occasions. Sleep stage distribution and duration were unchanged following androgen administration. However, both apneas and hypopneas increased significantly during testosterone replacement so that the total number of disordered breathing events (apneas + hypopneas) per hour of sleep rose from 6.4 +/- 2.1 to 15.4 +/- 7.0 (P less than 0.05). This was a highly variable event with some subjects demonstrating large increases in apneas and hypopneas when androgen was replaced, whereas others had little change in respiration during sleep. Upper airway dimensions, on the other hand, were unaffected by testosterone. These results suggest that testosterone contributes to sleep-disordered breathing through mechanisms independent of anatomic changes in the upper airway.     

Modulation of upper airway collapsibility during sleep: influence of respiratory phase and flow regimen.

We hypothesized that upper airway collapsibility is modulated dynamically throughout the respiratory cycle in sleeping humans by alterations in respiratory phase and/or airflow regimen. To test this hypothesis, critical pressures were derived from upper airway pressure-flow relationships in six tracheostomized patients with obstructive sleep apnea. Pressure-flow relationships were generated by varying the pressure at the trachea and nose during tracheostomy (inspiration and expiration) (comparison A) and nasal (inspiration only) breathing (comparison B), respectively. When a constant airflow regimen was maintained throughout the respiratory cycle (tracheostomy breathing), a small yet significant decrease in critical pressure was found at the inspiratory vs. end- and peak-expiratory time point [7.1 +/- 1.6 (SE) to 6.6 +/- 1.9 to 6.1 +/- 1.9 cmH(2)O, respectively; P < 0.05], indicating that phasic factors exerted only a modest influence on upper airway collapsibility. In contrast, we found that the inspiratory critical pressure fell markedly during nasal vs. tracheostomy breathing [1.1 +/- 1.5 (SE) vs. 6.1 +/- 1.9 cmH(2)O; P < 0.01], indicating that upper airway collapsibility is markedly influenced by differences in airflow regimen. Tracheostomy breathing was also associated with a reduction in both phasic and tonic genioglossal muscle activity during sleep. Our findings indicate that both phasic factors and airflow regimen modulate upper airway collapsibility dynamically and suggest that neuromuscular responses to alterations in airflow regimen can markedly lower upper airway collapsibility during inspiration.     

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.     

Pattern of simulated snoring is different through mouth and nose

Cineradiography of the pharynx during simulated snoring was done in 6 healthy volunteers, and supraglottic pressure and flow rate were recorded in 12 others. We observed, immediately before snoring, a decrease in the sagittal diameter of the oropharynx followed, during snoring, by high-frequency oscillations of soft palate and pharyngeal walls. The pattern of soft palate oscillations was different while snoring through the nose or mouth. During inspiratory snoring through the nose, the soft palate remained in close contact with the back of the tongue and only the uvula presented high-frequency oscillations. Snoring through the mouth resulted in ample high-frequency oscillations of the whole soft palate. Frequency of airflow and supraglottic pressure oscillations was less (P less than 0.05) during mouth (28.2 +/- 7.5 Hz) than during nasal snoring (77.8 +/- 36.7 Hz). This difference may be related to the smaller oscillating mass (i.e., uvula) during nasal snoring. At variance with our previous data, which showed that snoring during sleep, in both heavy (nonapneic) snorers and obstructive sleep apnea patients, was systematically preceded by flow limitation, this was not true during simulated snoring.     

Sleep apnea in obese miniature pigs

Lonergan, Robert P., III, J. Catsby Ware, Richard L. Atkinson, W. Christopher Winter, and Paul M. Suratt. Sleep apnea in obese miniature pigs. J. Appl.Physiol. 84(2): 531-536, 1998.We postulated thatthree extremely obese Yucatan miniature pigs would have more sleepapnea than three nonobese Yucatan miniature pigs. Pigs were studiedwith the use of electroencephalograms, inductance plethysmography,oximetry, expired nasal CO₂, orthermistors. All of the obese pigs, but none of the nonobese pigs, hadboth sleep apnea (8.5, 10.3, and 97.0 in obese pigs vs. 0 apnea + hypopnea/h in all nonobese pigs; P < 0.05) and oxyhemoglobin desaturation episodes during sleep [9.4 ± 3.0 vs. 0 + 0.53 (SD) mean desaturation episodes/h in obese pigsvs. nonobese pigs, respectively; P < 0.05]. Two of the extremely obese pigs had obstructive sleepapnea, whereas the third obese pig had central sleep apnea. We conclude that sleep apnea occurs in extremely obese Yucatan minipigs and suggestthat this animal can be used as a model for sleep apnea in obesity.

     

Sleep-induced periodic breathing and apnea: a theoretical study

To elucidate the mechanisms that lead to sleep-disordered breathing, we have developed a mathematical model that allows for dynamic interactions among the chemical control of respiration, changes in sleep-waking state, and changes in upper airway patency. The increase in steady-state arterial PCO2 accompanying sleep is shown to be inversely related to the ventilatory response to CO2. Chemical control of respiration becomes less stable during the light stage of sleep, despite a reduction in chemoresponsiveness, due to a concomitant increase in "plant gain" (i.e., responsiveness of blood gases to ventilatory changes). The withdrawal of the "wakefulness drive" during sleep onset represents a strong perturbation to respiratory control: higher magnitudes and rates of withdrawal of this drive favor instability. These results may account for the higher incidence of periodic breathing observed during light sleep and sleep onset. Periodic ventilation can also result from repetitive alternations between sleep onset and arousal. The potential for instability is further compounded if the possibility of upper airway occlusion is also included. In systems with high controller gains, instability is mediated primarily through chemoreflex overcompensation. However, in systems with depressed chemoresponsiveness, rapid sleep onset and large blood gas fluctuations trigger repetitive episodes of arousal and hyperpnea alternating with apneas that may or may not be obstructive. Between these extremes, more complex patterns can arise from the interaction between chemoreflex-mediated oscillations of shorter-cycle-duration (approximately 36 s) and longer-wavelength (approximately 60-80 s) state-driven oscillations.     

Osteopathy may decrease obstructive apnea in infants: a pilot study

Background

Obstructive apnea is a sleep disorder characterized by pauses in breathing during sleep: breathing is interrupted by a physical block to airflow despite effort. The purpose of this study was to test if osteopathy could influence the incidence of obstructive apnea during sleep in infants.

Methods

Thirty-four healthy infants (age: 1.5–4.0 months) were recruited and randomized in two groups; six infants dropped out. The osteopathy treatment group (n = 15 infants) received 2 osteopathic treatments in a period of 2 weeks and a control group (n = 13 infants) received 2 non-specific treatments in the same period of time. The main outcome measure was the change in the number of obstructive apneas measured during an 8-hour polysomnographic recording before and after the two treatment sessions.

Results

The results of the second polysomnographic recordings showed a significant decrease in the number of obstructive apneas in the osteopathy group (p = 0.01, Wilcoxon test), in comparison to the control group showing only a trend suggesting a gradual physiologic decrease of obstructive apneas. However, the difference in the decline of obstructive apneas between the groups after treatment was not significant (p = 0.43).

Conclusion

Osteopathy may have a positive influence on the incidence of obstructive apneas during sleep in infants with a previous history of obstructive apneas as measured by polysomnography. Additional research in this area appears warranted.     

Is pulse transit time useful in differentiating respiratory events for patients with a sleep breathing disorder? A pilot study

Variation of inspiratory effort in sleep disordered breathing induces the oscillation in blood pressure, which corresponds inversely to pulse transit time (PTT). This study evaluated the feasibility of PTT as a visual parameter for differentiating respiratory events in patients with a sleep breathing disorder. Sixteen patients who complained of snoring and sleep apnea were booked into the study. Polysomnographic data of Zopiclone induced daytime sleep were analyzed, PTT and intraesophageal pressure (Peso) were assessed for each respiratory event. With respect to Peso, the total accuracy of PTT was 51.8% for 1266 events. The relatively high coincidence rate could be observed in obstructive events (57.1%), with crescendo Peso pattern (71.5%), in lateral position (82.2%). Pulse transit time oscillation could only partly reflect respiratory rhythm to some degree (56.5%). Absolute PTT value presented a poor relationship with respiratory effort. Pulse transit time coincided well with crescendo Peso in lateral position for obstructive events. Swings in PTT could only partly fit respiratory wave data. Absolute PTT value and its change could not reflect respiratory effort. Although PTT is a non-invasive and convenient way for assessing inspiratory effort, its variable sensitivity to different events, respiratory patterns, positions, different patients and other situations, limit its feasibility. Further work is required.

     

Glottic and cervical tracheal narrowing in patients with obstructive sleep apnea

There are several studies showing that patients with idiopathic obstructive sleep apnea (OSA) have a narrow and collapsible pharynx that may predispose them to repeated upper airway occlusions during sleep. We hypothesized that this structural abnormality may also extend to the glottic and tracheal region. Consequently, we measured pharyngeal (Aph), glottic (Agl), cervical tracheal (Atr1), midtracheal (Atr2), and distal (Atr3) tracheal areas during tidal breathing in 66 patients with OSA (16 nonobese and 50 obese) and 8 nonapneic controls. We found that Aph, Agl, and Atr1, but not Atr2 or Atr3, were significantly smaller in the OSA group than in the control group. Obese patients with OSA had the smallest upper airway area, although the nonapneic controls had the largest areas. Multiple linear regression analysis revealed that the pharyngeal area, cervical tracheal area, and body mass index were all independent determinants of the apnea-hypopnea index, accounting for 31% of the variability in apnea-hypopnea index. Aph, Agl, and Atr showed significant correlation with the body mass index. We conclude that sleep-disordered breathing is associated with diffuse upper airway narrowing and that obesity contributes to this narrowing. Furthermore, we speculate that a common pathophysiological mechanism may be responsible for this reduction in upper airway area extending from the pharynx to the proximal trachea.     

The English bulldog: a natural model of sleep-disordered breathing

To establish a natural model of sleep-disordered breathing, we investigated respiration during wakefulness and sleep in the English bulldog. This breed is characterized by an abnormal upper airway anatomy, with enlargement of the soft palate and narrowing of the oropharynx. During sleep, the animals had disordered respiration and episodes of O2 desaturation. These were worst in rapid-eye-movement (REM) sleep, with most bulldogs having O2 saturations of less than 90% for prolonged durations. In contrast, control dogs never desaturated. In REM sleep, the bulldogs had episodes of both central and obstructive apnea, the latter being associated with paradoxical movements of the rib cage and abdomen. During wakefulness, the bulldogs were hypersomnolent as evidenced by a shortened sleep latency (mean of 12 min compared with greater than 150 min for controls). This animal model should facilitate studies of the natural history of the sleep apnea syndrome and its complications.     

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 Apnea Syndrome (SAS) Clinical Practice Guidelines 2020

Sleep and Biological Rhythms - The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously...     

Obstructive sleep apnea and chronic intermittent hypoxia: a review

Hypoxia is an important topic both physiologically and clinically. Traditionally, physiology research has been focusing on the effect of acute and chronic sustained hypoxia and human adaptive response to high altitude. In the past 20 years, genetic studies by many have expanded our understanding of hypoxia to the molecular level. However, in contrast to our extensive knowledge about acute and chronic sustained hypoxia, we know relatively little about the effect of chronic intermittent hypoxia (CIH). In recent years, CIH has attracted more research attention because of the increasing prevalence of obesity and obstructive sleep apnea (OSA) in the western countries. Clinically, CIH is commonly seen in patients with sleep-disordered breathing including OSA, Cheyne-Stokes respiration and nocturnal hypoventilation. It was estimated that for OSA of at least mild severity prevalence estimates range from 3 to 28% in the general population. OSA is characterized by recurrent upper airway collapse during sleep leading to intermittent nocturnal hypoxia and sleep fragmentation. OSA is associated with significant mortality and morbidity including neurocognitive dysfunction, hypertension, many cardiovascular disorders and metabolic disorders such as diabetes and metabolic syndrome. The intermittent hypoxia in OSA closely mimics what is seen in the ischemia-reperfusion injury. Experimentally, there is no universally accepted definition for CIH. Laboratory protocols vary greatly in duration of hypoxia exposure, numbers of hypoxia episodes per day and the total number of days of exposure. Despite the lack of a uniform definition, recent data suggest that CIH may lead to multiple long-term pathophysiologic consequences similar to what we see in patients with OSA. Recent evidences also demonstrate that there are remarkable differences in the response of the physiologic systems to sustained hypoxia and intermittent hypoxia. This review is aimed to briefly discuss the clinical significance of sleep-disordered breathing and our current understanding of CIH.