The effect of CPAP therapy on excessive daytime sleepiness and quality of life in subjects with obstructive sleep apnoea: an AB design study

Sleep and Breathing - Obstructive sleep apnoea (OSA) is a disorder characterized by apnoeas and hypopnoeas due to repetitive upper airway collapse during sleep. So far, there are no published data...     

Pathogenesis of central and complex sleep apnoea

Central sleep apnoea (CSA) – the temporary absence or diminution of ventilatory effort during sleep – is seen in a variety of forms including periodic breathing in infancy and healthy adults at altitude and Cheyne–Stokes respiration in heart failure. In most circumstances, the cyclic absence of effort is paradoxically a consequence of hypersensitive ventilatory chemoreflex responses to oppose changes in airflow, that is elevated loop gain, leading to overshoot/undershoot ventilatory oscillations. Considerable evidence illustrates overlap between CSA and obstructive sleep apnoea (OSA), including elevated loop gain in patients with OSA and the presence of pharyngeal narrowing during central apnoeas. Indeed, treatment of OSA, whether via continuous positive airway pressure (CPAP), tracheostomy or oral appliances, can reveal CSA, an occurrence referred to as complex sleep apnoea. Factors influencing loop gain include increased chemosensitivity (increased controller gain), reduced damping of blood gas levels (increased plant gain) and increased lung to chemoreceptor circulatory delay. Sleep–wake transitions and pharyngeal dilator muscle responses effectively raise the controller gain and therefore also contribute to total loop gain and overall instability. In some circumstances, for example apnoea of infancy and central congenital hypoventilation syndrome, central apnoeas are the consequence of ventilatory depression and defective ventilatory responses, that is low loop gain. The efficacy of available treatments for CSA can be explained in terms of their effects on loop gain, for example CPAP improves lung volume (plant gain), stimulants reduce the alveolar‐inspired PCO₂ difference and supplemental oxygen lowers chemosensitivity. Understanding the magnitude of loop gain and the mechanisms contributing to instability may facilitate personalized interventions for CSA.     

Occurrence of breathing disorders during CPAP administration in obstructive sleep apnoea syndrome

The spectrum of breathing events during sleep in patients with obstructive sleep apnoea syndrome (OSAS) after the abolition of obstructive apnoeas has been extensively studied in tracheostomized patients, but has received much less attention in patients submitted to continuous positive airway pressure (CPAP). We analysed the breathing pattern during sleep in forty patients while CPAP was administered. A regular breathing pattern throughout the sleep study was observed in 15 patients. In the remaining 25 subjects, one or more of the following events was observed: central apnoeas, hypopnoeas, periodic breathing, prolonged oxyhaemoglobin desaturations. Central apnoeas during non-rapid eye movement (NREM) sleep appeared almost exclusively after arousals or wakefulness periods; their prevalence did not significantly differ between subjects who showed and who did not show similar events before CPAP. Central apnoeas in rapid eye movement (REM) sleep had a random occurrence. Hypopnoeas were found only in REM sleep, and, like central apnoeas, occurred randomly; in one patient they had a prolonged duration (up to 110 s). Periodic breathing was observed in only two subjects, one of whom had congestive heart failure: it was limited to NREM sleep and was not associated with arousals or shifts in sleep stage. Prolonged oxyhaemoglobin desaturations were found mainly in REM sleep; most subjects with such abnormalities had daytime blood gas alterations. In conclusion, abnormalities of the breathing pattern of patients with OSAS can be observed during CPAP and after tracheostomy, but periodic breathing is less common than is reported after tracheostomy, and is probably caused by different mechanisms.     

Cheyne-Stokes respiration and supine dependency.

The influence of position during sleep on central apnoeas during Cheyne-Stokes respiration has not previously been studied systematically. The current authors aimed to study the effect of body position and sleep stages on central sleep apnoeas during Cheyne-Stokes respiration. A total of 20 consecutive patients with cardiovascular diseases and central sleep apnoea during Cheyne-Stokes respiration were investigated using nocturnal polysomnography, including a body position sensor mounted on the patient's sternum. The mean central apnoea-hypopnoea index was significantly higher in the supine position than in nonsupine positions (41+/-13 versus 26+/-12). The central apnoea-hypopnoea index was highest in sleep stages 1 and 2, and lowest in slow-wave sleep and rapid eye movement sleep. In every sleep stage, central apnoeas and hypopnoeas were more prevalent in the supine position compared with nonsupine positions. In conclusion, sleep in the supine body position increases the frequency of apnoeas and hypopnoeas in patients with Cheyne-Stokes respiration.     

Electroencephalographic spectral analysis: detection of cortical activity changes in sleep apnoea patients.

There are no visible electroencephalographic (EEG) changes at the termination of some apnoeas and hypopnoeas. This study tests the hypothesis that cortical activity fluctuates at apnoea/hypopnoea termination, despite the lack of visible changes. To detect these changes, EEG spectral analysis was performed and centred around the end of apnoeas/hypopnoeas in 15 sleepy patients. Ten second windows were applied and comparisons were conducted between the normalised power of the same frequency bands before and after termination of each apnoea/hypopnoea. Comparisons were performed within patients between apnoeas/hypopnoeas and periods of undisturbed sleep as well as between patients and healthy subjects during sleep. Normalised theta power (4-8 Hz) decreased significantly at apnoea/hypopnoea termination. No significant changes were found between consecutive periods of undisturbed sleep across the 15 patients. During nonrapid eye movement sleep, changes were detected irrespective of arousal visibility. During rapid eye movement sleep, nonarousal apnoeas/hypopnoeas were not accompanied by any significant spectral power changes. Theta power was significantly lower across patients compared to healthy subjects (p=0.03) and was correlated to the apnoea/hypopnoea index (rho=0.6, p=0.008). The authors conclude that electroencephalographic spectral analysis improves detection of changes at apnoea/hypopnoea termination. Further validation is needed to determine whether it improves correlation between nocturnal measures and daytime symptoms.     

Some factors affecting cerebral tissue saturation during obstructive sleep apnoea.

Measurement of cerebral tissue saturation during obstructive sleep apnoea (OSA) may provide additional information to conventional peripheral oxygen saturation. Thirteen subjects with OSA (mean apnoea/hypopnoea index 65.7+/-27.9) were monitored using full polysomnography and monitoring of near-infrared cerebral tissue oxygenation index (TOI). One-thousand and thirty-six apnoeas and hypopnoeas were analysed, in terms of duration, sleep stage, arterial oxygen saturation (Sa,O2) dip, minimum Sa,O2, TOI dip and minimum TOI. Cerebral TOI is a measure of cerebral tissue saturation of haemoglobin with oxygen, calculated using near-infrared spatially resolved spectroscopy, which has been shown to have a high specificity for intracranial changes. Decreases in cerebral oxygenation were observed during apnoeas and hypopnoeas. Baseline TOI ranged from 50.1-73.0% and mean apnoea/hypopnoea related TOI dips ranged from 1.43-6.85%. Mean Sa,O2 dips varied from 3.8-21.7%. In regression analysis, factors significantly predicting the magnitude of the TOI dip were Sa,O2 dip, minimum Sa,O2, apnoea duration and rapid eye movement sleep stage. The effect of apnoea duration and sleep stage remained significant after Sa,O2 was included in the regression equation. Near-infrared spectroscopy provides a noninvasive technique for monitoring cerebral tissue saturation during obstructive sleep apnoea.     

Arousability in sleep apnoea/hypopnoea syndrome patients.

Sleep disruption and daytime sleepiness in obstructive sleep apnoea/hypopnoea syndrome (OSAHS) patients result from recurrent apnoeas/hypopnoeas and arousals from sleep. Around 30% of apnoeas/hypopnoeas are not terminated by visible cortical arousals. The current authors tested the hypotheses that arousal induction is linked to sleep stage, oxygen desaturation, event type, event duration and time of occurrence during the night. Fifteen patients with OSAHS of varying severity were studied and all their apnoeas/hypopnoeas were evaluated. Eight of 15 patients had apnoeas/hypopnoeas in all sleep stages, and all their 610 apnoeas/hypopnoeas were analysed in the between stages comparison; data from all 15 patients were included in other comparisons. Thirty-four per cent of apnoeas/hypopnoeas during slow wave sleep (SWS) were associated with arousal, significantly less than the 77% during nonrapid eye movement (NREM) 1 and 2 and 62% during rapid eye movement (REM) sleep. Arousal induction was not affected by oxygen desaturation, event type, duration or time of the night. The apnoeal/hypopnoea index was 39 x h(-1) in REM 1 and 2, significantly higher compared to 17 x h(-1) in REM or to 11 x h(-1) in SWS sleep. In conclusion, apnoeas/hypopnoeas in slow wave sleep are associated with fewer cortically apparent, visually detected arousals.     

The validity of the static charge sensitive bed in detecting obstructive sleep apnoeas

The demand for polysomnographic recordings associated with respiratory control exceeds the capacity of the few existing sleep disorder centres and therefore a simple and inexpensive method is needed for screening and diagnosing sleep-related breathing disorders. The static charge sensitive bed (SCSB) permits long-term recordings of body movements, respiratory movements and the ballistocardiogram (BCG) without electrodes or cables being attached to the subject. The aim of the present study was to test the validity of this particular method in detecting obstructive sleep apnoeas without airflow measurements. Simultaneous SCSB and spirometer recordings were compared in fourteen sleep apnoea patients and six controls. The mean sensitivity of the SCSB method to detect the obstructive apnoeas was 0.92-0.98. The specificity to detect 2 min apnoea epochs was 0.61-0.68 in the apnoea group, while in the control group it was 0.99-1.00. According to this study, the SCSB detects the obstructive events without always distinguishing between severe periodic hypopnoeas and obstructive apnoeas. The sensitivity of the SCSB makes it valuable for screening subjects suspected of having obstructive sleep apnoeas. Further studies will concentrate on a more detailed analysis of the various respiratory, BCG and body movement patterns, which may lead to additional information on the severity of the upper airway obstruction.     

Arousal in patients with gastro-oesophageal reflux and sleep apnoea.

Nocturnal gastro-oesophageal reflux has been observed in patients with obstructive sleep apnoea (OSA). Negative intrathoracic pressure during apnoeas and arousal have been suggested as the underlying mechanisms. In order to evaluate this hypothesis, the coincidence and sequence in time of arousal, apnoea and reflux events were analysed. Fifteen patients with OSA or heavy snoring were studied by means of standard polysomnograpy with parallel recording of 24-h oesophageal pH. Reflux events during the day were present in all patients, five of whom had symptoms of reflux. In three of these and in five other patients, a total of 69 nocturnal reflux events were found. In 68 events, arousal was found with the reflux event. Only one reflux without arousal was found (sleep stage 2). Seventeen events occurred during wakefulness after sleep onset. The percentage of time with a pH of <4 during wakefulness after sleep onset was significantly higher than the percentage of time with a pH of <4 during total sleep time (p<0.05). In 37 of the 52 reflux events which occurred during sleep, either an apnoea or a hypopnoea was found prior to the event. The investigation of sequence in time did not prove a causal relation between respiratory events and reflux events. The results indicate that gastro-oesophageal reflux and obstructive sleep apnoea are two separate disorders, which both have a high prevalence in obese patients.     

Effects of octreotide on sleep apnoea and tongue volume (magnetic resonance imaging) in patients with acromegaly

OBJECTIVES: Sleep apnoea has been consistently reported to occur in acromegaly. Both obstructive apnoeas, in which apnoeas are due to intermittent obstruction of the upper airways, as well as central apnoeas are known to occur. Because the relationship between disease activity and severity of sleep apnoea is currently unclear, we have performed a prospective study to address this issue. DESIGN AND METHODS: In 14 newly diagnosed patients with active acromegaly (eight females and six males; mean age 57+/-4 years; IGF-I 583+/-48 microg/l; GH 13.5+/-7.0 microg/l (means+/-s.e.m.)), tongue volume and signal intensity of the tongue were examined by magnetic resonance imaging and sleep apnoea was characterised by polysomnography before and after 6 months of treatment with octreotide acetate (Sandostatin LAR 10-30 mg every 4 weeks i.m.). RESULTS: The initial tongue volume was significantly higher in patients with acromegaly (151+/-9 ml; females 133+/-10 ml; males 172+/-10 ml) in comparison with the body mass index (BMI)- and age-matched healthy control group (97+/-5 ml, P<0.001; females 75+/-1 ml, P<0.001; males 120+/-3 ml, P<0.003). After treatment with octreotide, IGF-I was normalised within the age-adjusted normal range in 50% of the patients. In these patients, tongue volume significantly decreased (120+/-14 ml, P<0.05) in comparison with the persistent uncontrolled group of acromegalics (137+/-10 ml, P=not significant). Overall, tongue volume (128+/-8 ml, P<0.05) and the signal intensity ratio of the tongue decreased significantly after treatment with octreotide acetate (120+/-3 vs 105+/-3, P=0.003). The BMI-adjusted tongue volume correlated with IGF-I levels (r=0.60, P<0.002) and the disease duration (r=0.71, P=0.006). At baseline, 50% had obstructive sleep apnoea with a mean respiratory disturbance index (RDI) of >20/h (range 5.1-91.5) and no patient had central sleep apnoea. After 6 months of octreotide treatment, there was a 28+/-10% decrease in RDI. However, RDI did not correlate with IGF-I or GH levels, but correlated positively with BMI (r=0.58, P=0.001) and age (r=0.46, P=0.02). CONCLUSIONS: Obstructive sleep apnoea but not central sleep apnoea frequently occurs in patients with active acromegaly. Successful treatment with octreotide can decrease tongue volume, which may have benefits for coexisting sleep-disordered breathing.     

Haemodynamic responses to obstructive sleep apnoeas in premenopausal women.

OBJECTIVES: Obstructive apnoeas during sleep are associated with marked cyclical blood pressure fluctuations in men with obstructive sleep apnoea (OSA). Haemodynamic responses to OSA in women are largely unknown. We aimed to investigate haemodynamics during apnoeic events in women with OSA and to assess the influence of the menstrual cycle on these responses. DESIGN AND METHODS: Full overnight polysomnography and continuous non-invasive blood pressure monitoring was performed in 13 women with OSA during follicular and luteal phases of the menstrual cycle. Change in blood pressure (deltaBP) from pre- to post-apnoea termination was measured for each apnoeic cycle. RESULTS: Only 10 of 13 subjects ovulated. In women who ovulated, pressor responses to apnoea termination occurred in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, but substantially increased during the luteal phase of ovulatory cycles [NREM change in mean arterial pressure (deltaMAP) 12 +/- 3 mmHg during the follicular phase and 20 +/- 3 mmHg during the luteal phase, P < 0.001; REM deltaMAP 11 +/- 3 mmHg during the follicular phase and 23 +/- 3 mmHg during the luteal phase, P < 0.001]. Sleep apnoea severity did not change during the cycle in NREM sleep, but was reduced in REM during the luteal phase. Changes in pressor responses were absent in non-ovulating subjects. CONCLUSIONS: Obstructive apnoeas in women were associated with marked blood pressure changes, similar to those previously reported in men. While respiratory events improved slightly in the luteal phase, blood pressure responses to these events increased by approximately 100%. Thus, the menstrual cycle has discordant effects on the respiratory and cardiovascular effects of OSA in women.     

Apnoea characteristics across the night in severe obstructive sleep apnoea: influence of body posture.

Several studies have reported changes in apnoea characteristics across the night in patients with obstructive sleep apnoea (OSA). However, the effect of body posture on these changes has not been evaluated. The purpose of this study was to assess how body posture influences sleep apnoea characteristics across the night in severe OSA. Polysomnograms of 30 patients with severe OSA who had > or = 30 apnoeic episodes in the lateral position and 30 in the supine position during Stage 2 sleep, in the early, middle and late sleep periods were analysed. For each of the 30 events in each body position, the following variables were evaluated: apnoea duration; minimum saturation; change in saturation; duration of arousal; maximum snoring loudness and change in cardiac frequency. Although at any time during the night, apnoeas in the supine posture were more severe than those in the lateral position, a time effect across the night was found only for apnoea duration, change in cardiac frequency and duration of arousal. Body position did not affect the time trend for these variables across the night. The best fit for the changes of these three variables across the night was a quadratic time trend. It was concluded that in severe obstructive sleep apnoea during Stage 2 sleep, body position does not significantly affect the time trends of apnoea characteristics across the night. These data provide support for the participation of sleep-dependent mechanisms (homeostatic and circadian) in the determination of apnoea characteristics across the night.     

Obstructive sleep apnoea

Obstructive sleep apnoea is a disease of increasing importance because of its neurocognitive and cardiovascular sequelae. Abnormalities in the anatomy of the pharynx, the physiology of the upper airway muscle dilator, and the stability of ventilatory control are important causes of repetitive pharyngeal collapse during sleep. Obstructive sleep apnoea can be diagnosed on the basis of characteristic history (snoring, daytime sleepiness) and physical examination (increased neck circumference), but overnight polysomnography is needed to confirm presence of the disorder. Repetitive pharyngeal collapse causes recurrent arousals from sleep, leading to sleepiness and increased risk of motor vehicle and occupational accidents. The surges in hypoxaemia, hypercapnia, and catecholamine associated with this disorder have now been implicated in development of hypertension, but the association between obstructive sleep apnoea and myocardial infarction, stroke, and congestive heart failure is not proven. Continuous positive airway pressure, the treatment of choice for obstructive sleep apnoea, reduces sleepiness and improves hypertension.     

High Mallampati score and nasal obstruction are associated risk factors for obstructive sleep apnoea.

Induced nasal obstruction can cause obstructive apnoeas in healthy subjects during sleep, but the relationship between nasal resistance measured during wakefulness and obstructive sleep apnoea syndrome (OSAS) is weak. It was postulated that if the subjects could not breathe through the nose, the oral airway must be used, but if this airway is narrowed as well, then it could precipitate sleep-disordered breathing (SDB). Nasal patency, Mallampati score (MS), neck circumference and body mass index were measured in 202 subjects referred to the authors' hospital to undergo a full-night polysomnography for suspicion of SDB. A significant correlation was found between the MS and apnoea/hypopnoea index measured during sleep. However, the relationship between these parameters was only significant in patients with nasal obstruction. The relative risk of having OSAS with a MS of III or IV was 1.95 for the whole group and 2.45 in patients with nasal obstruction. In conclusion, a high Mallampati score represents a predisposing factor for obstructive sleep apnoea syndrome, especially if it is associated with nasal obstruction. These patients merit special attention from both the sleep physician and the anaesthetist.     

Heart failure and central respiratory dysregulation. Cheyne-Stokes respiration during sleep in advanced left heart failure

Central sleep apnoea, especially Cheyne-Stokes respiration, is found in 45 to 66% of patients with congestive heart failure (CHF) in functional classes NYHA II to IV. Cheyne-Stokes breathing cycles are characterised by central apnoeas, followed by a crescendo--like increase of tidal volume into hyperventilation and a subsequent decline of tidal volume, ending in another central apnoea. Cheyne-Stokes respiration has been shown to be a poor prognostic factor for patients with CHF. Apnoeas and hypopnoeas cause marked oxygen desaturation and rises of carbon dioxide concentrations in the blood. The resumption of breathing is frequently associated with arousals, which might cause daytime symptoms like fatigue and sleepiness as well as persistent activation of the sympathetic nervous system. Elevated concentrations of catecholamines increase cardiac work, adversely affecting cardiac function. Serum catecholamines are known to augment the chemoreceptor susceptibility for carbon dioxide. This might be one reason for the permanent mild hyperventilation found in these patients during wakefulness. Increased chemoreceptor responsiveness destabilises the feedback control of breathing, and hyperventilation below the apnoeic threshold grows more likely. Other contributing factors for the development of Cheyne-Stokes respiration include alterations in the control of breathing during sleep and the increased circulation time between the lung and chemoreceptors in CHF patients. The feedback regulation of breathing might be less dampened since carbon dioxide levels are reduced in these patients. Treatment includes nCPAP, but in many cases this is poorly tolerated in patients with central sleep apnoea. Future approaches to Cheyne-Stokes respiration might focus on improving ventilatory pattern and pharmacological manipulation of carbon dioxide receptor susceptibility.     

Prevalence of sleep apnoea in patients undergoing operation

Obstructive sleep apnoea (OSA) is defined as episodes of obstructive apnoeas and hypopnoeas during sleep with daytime somnolence. The gold standard in diagnostic tool patients with these symptoms is polisomnography. The goals of this study were to determine the frequency of OSA symptoms and the prevalence of OSA in patients undergoing operation. Patients were asked questions pertaining to symptoms of sleep apnoea. The patients who had two major symptoms or one major and two minor symptoms were invited to undergo a sleep study. Patients were diagnosed as OSA when they had apnoea–hypopnoea index higher than five. Forty-one patients with two major or one major and two minor symptoms of 433 patients were referred to the sleep laboratory. The most frequent major symptom was snoring, and the most frequent minor symptom was morning tiredness. In this connection, 18 (43.9%) patients accepted to be studied in the sleep laboratory (14 with two major, 4 with one major and two minor symptoms). Obstructive sleep apnoea was finally diagnosed in 14 patients or 3.2% of the initial entire population. Thirteen of them had two major symptoms, and only one of the 14 had one major and two minor symptoms. Six of the OSA patients were women. High percentage of OSA focus attention on anaesthesiology concerns of OSA. The exact management of each sleep apnoea patient with regard to intubation, extubation and pain control requires judgement and is a function of many anaesthesia, medical and surgical considerations. Therefore, we suggest that all patients should be asked for OSA symptoms, and patients with two major OSA symptoms must be evaluated with polisomnography.     

Changes in heart rate during obstructive sleep apnoea.

The mechanisms behind the decrease in heart rate during apnoeas in patients with obstructive sleep apnoea (OSA) are little known. Recent findings in animal experiments indicate that stimulation of the upper airway activates postinspiratory and cardiac vagal neurones in the medullary respiratory centre, causing alterations in heart rate and respiratory rhythm. Since OSA leads to a collapse of the airway and consequent stimulation of upper airway receptors, we studied the interrelations between heart rate and respiratory rhythm during apnoea and during negative intrathoracic pressure generated by the Mueller manoeuvre (MM). Fifteen patients with OSA (apnoea hypopnoea index (AHI) 45 +/- 28.h-1) were studied by polysomnography, during a MM and a Valsalva manoeuvre, each of 15 s duration. The heart rate decrease (delta HRA) and the increase in total respiratory cycle duration (TOT) were evaluated during apnoea in non-rapid eye movement (REM) sleep. Patients with OSA demonstrated a decrease in heart rate during apnoea (-14.4 +/- 9.0 beats.min-1), and during MM (-11.5 +/- 13.5 in OSA vs 3.1 +/- 7.8 beats.min-1 in a control group). TOT increased during apnoea (4.6 +/- 3.1 s). There was a significant correlation between delta HRA and AHI (r = -0.64) as well as between delta HRA and increase in TOT (r = 0.62). These findings indicate that upper airway obstruction may cause an activation of receptors at the site of airway collapse or distortion leading to changes in heart rate and respiratory rhythm.     

The accuracy of subjective sleep time in sleep apnoea recordings

Total sleep time is important in investigations of obstructive sleep apnoea, since the diagnosis is usually based on the average number of apnoeas per hour of sleep. Sleep estimates instead of exact EEG-recorded total sleep time is often used in the clinical setting. However, an overestimated sleep time would underestimate the degree of the disease and vice versa. The purpose of this study was to investigate the accuracy of subjective sleep time and time-in-bed as sleep estimates. One hundred patients undergoing diagnostic polysomnography for suspected obstructive sleep apnoea were asked to estimate their sleep time in a questionnaire. Seventy-five patients were diagnosed as suffering from obstructive sleep apnoea syndrome. The mean difference between self-scored and EEG-recorded total sleep time was 4 +/- 74 min. However, 30% scored with a difference greater than 1 h. The intra-class correlation coefficient was fair (0.58, CI: 0.43-0.70). Fifty-three patients overestimated their sleep time and 47 patients underestimated it. All but four patients underestimated their number of awakenings (P<0.001). The mean difference between time-in-bed and EEG-recorded total sleep time was 110 +/- 63 min. This difference was significantly larger than the difference between subjective sleep time and EEG-recorded total sleep time (P<0.001). The intra-class correlation coefficient was poor (0.38, CI: 0.20-0.54). Mean AHI was 27 +/- 27 using subjective sleep time and did not change significantly compared with the mean AHI of 25 +/- 21 based on EEG-recorded total sleep time. Mean AHI decreased significantly to 20 +/- 17 (P<0.001) when time-in-bed was used. In conclusion, 'time-in-bed' time is a poor predictor of total sleep time and should not be used when calculating the apnoea-hypopnoea index. Subjective sleep time is better as an approximation, but the individual differences are large.     

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.