Changes in brain morphology in patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common disease that leads to daytime sleepiness and cognitive impairment. Attempts to investigate changes in brain morphology that may underlie these impairments have led to conflicting conclusions. This study was undertaken to aim to resolve this confusion, and determine whether OSA is associated with changes in brain morphology in a large group of patients with OSA, using improved voxel-based morphometry analysis, an automated unbiased method of detecting local changes in brain structure. METHODS: 60 patients with OSA (mean apnoea hypopnoea index 55 (95% CI 48 to 62) events/h, 3 women) and 60 non-apnoeic controls (mean apnoea hypopnoea index 4 (95% CI 3 to 5) events/h, 5 women) were studied. Subjects were imaged using T1-weighted 3-D structural MRI (69 subjects at 1.5 T, 51 subjects at 3 T). Differences in grey matter were investigated in the two groups, controlling for age, sex, site and intracranial volume. Dedicated cerebellar analysis was performed on a subset of 108 scans using a spatially unbiased infratentorial template. RESULTS: Patients with OSA had a reduction in grey matter volume in the right middle temporal gyrus compared with non-apnoeic controls (p<0.05, corrected for topological false discovery rate across the entire brain). A reduction in grey matter was also seen within the cerebellum, maximal in the left lobe VIIIb close to XI, extending across the midline into the right lobe. CONCLUSION: These data show that OSA is associated with focal loss of grey matter that could contribute to cognitive decline. Specifically, lesions in the cerebellum may result in both motor dysfunction and working memory deficits, with downstream negative consequences on tasks such as driving.

Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial.

BACKGROUND: Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease (COPD). A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation (NIV) on survival, lung function and quality of life in patients with severe hypercapnic COPD. METHOD: A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV1.0) <1.5 litres or <50% predicted and ratio of FEV1.0 to forced vital capacity (FVC) <60% with awake arterial carbon dioxide tension (PaCO2) >46 mm Hg and on LTOT for at least 3 months) and age <80 years. Patients with sleep apnoea (apnoea-hypopnoea index >20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood. RESULTS: 144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01-5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV1.0 and PaCO2 measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour. CONCLUSIONS: Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life. TRIAL REGISTRATION NUMBER: ACTRN12605000205639.

Sleep-disordered breathing in Prader-Willi syndrome and its association with neurobehavioral abnormalities.

OBJECTIVES: To determine the prevalence and type of sleep-disordered breathing among patients with Prader-Willi syndrome (PWS) and its relationship to such neurobehavioral abnormalities as mental retardation, obsessive-compulsive behavior, and conduct disorders. STUDY DESIGN: Polysomnography (PSG) studies were conducted in 13 unselected subjects with PWS (age 1.5 to 28 years). PSG results were compared with tests of behavior and cognition (Development Behavior Checklist [DBC], Auditory Continuous Performance Test [ACPT], and Wechsler Intelligence Scale appropriate for age). RESULTS: Nine of 13 (69%) subjects had > 10 apneas and hypopneas per hour of sleep. Apart from a 2-year-old subject with normal body weight who demonstrated severe central hypopnea in rapid eye movement sleep, the sleep-breathing disturbance was due to upper airway obstruction. Age-adjusted body mass index was associated with more severe hypoxemia during sleep (min SaO2, r = -.87, P < .005) and more sleep disruption (arousals/hour of sleep, r = .62, P < .05; sleep efficiency, r = -.66, P < .05). Increasing severity of obstructive sleep apnea (OSA) or sleep disturbance was associated with daytime inactivity/sleepiness and autistic-relating behavior (DBC) and with impulsiveness (ACPT). Unexpectedly, sleep hypoxemia appeared to be predictive of increased performance IQ. CONCLUSIONS: OSA is prevalent among subjects with PWS and is associated with increased body mass, daytime inactivity/ sleepiness, and some behavioral disturbances.

Sleep hypoventilation in hypercapnic chronic obstructive pulmonary disease: prevalence and associated factors.

Sleep hypoventilation (SH) may be important in the development of hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD). The prevalence of SH, associated factors, and overnight changes in waking arterial blood gases (ABG), were assessed in 54 stable hypercapnic COPD patients without concomitant sleep apnoea or morbid obesity. Lung function assessment, anthropomorphic measurements, and polysomnography with ABG measurement before and after sleep were conducted in all patients. Transcutaneous carbon dioxide tension (Pt,CO2) was measured in sleep, using simultaneous arterial carbon dioxide tension (Pa,CO2) for in vivo calibration and to correct for drift in the sensor. Of the patients, 43% spent > or = 20% of sleep time with Pt,CO2 > 1.33 kPa (10 mmHg) above waking baseline. Severity of SH was best predicted by a combination of baseline Pa,CO2, body mass index and per cent rapid-eye movement (REM) sleep. REM-related hypoventilation correlated significantly with severity of inspiratory flow limitation in REM, and with apnoea/hypopnoea index. Pa,CO2 increased mean+/-SD 0.70+/-0.65 kPa (5.29+/-4.92 mmHg) from night to morning, and this change was highly significant. The change in Pa,CO2 was strongly correlated with severity of SH. Sleep hypoventilation is common in hypercapnic chronic obstructive pulmonary disease, and related to baseline arterial carbon dioxide tension, body mass index and indices of upper airway obstruction. Sleep hypoventilation is associated with significant increases in arterial carbon dioxide tension night-to-morning, and may contribute to long-term elevations in arterial carbon dioxide tension.

Long-term facilitation of ventilation is not present during wakefulness in healthy men or women.

Obstructive sleep apnea (OSA) is more common in men than in women for reasons that are unclear. The stability of the respiratory controller has been proposed to be important in OSA pathogenesis and may be involved in the gender difference in prevalence. Repetitive hypoxia elicits a progressive rise in ventilation in animals [long-term facilitation (LTF)]. There is uncertainty whether LTF occurs in humans, but if present it may stabilize respiration and possibly also the upper airway. This study was conducted to determine 1) whether LTF exists during wakefulness in healthy human subjects and, if so, whether it is more pronounced in women than men and 2) whether inspiratory pump and upper airway dilator muscle activities are affected differently by repetitive hypoxia. Twelve healthy young men and ten women in the luteal menstrual phase were fitted with a nasal mask and intramuscular genioglossal EMG (EMGgg) recording electrodes. After 5 min of rest, subjects were exposed to ten 2-min isocapnic hypoxic periods (approximately 9% O(2) in N(2), arterial O(2) saturation approximately 80%) separated by 2 min of room air. Inspired minute ventilation (Vi) and peak inspiratory EMGgg activity were averaged over 30-s intervals, and respiratory data were compared between genders during and after repetitive hypoxia by using ANOVA for repeated measures. Vi during recovery from repetitive hypoxia was not different from the resting level and not different between genders. There was no facilitation of EMGgg activity during or after repetitive hypoxia. EMGgg activity was reduced below baseline during recovery from repetitive hypoxia in women. In conclusion, we have found no evidence of LTF of ventilation or upper airway dilator muscle activity in healthy subjects during wakefulness.

Effect of CPAP on intrinsic PEEP, inspiratory effort, and lung volume in severe stable COPD.

BACKGROUND: Intrinsic positive end expiratory pressure (PEEPi) constitutes an inspiratory threshold load on the respiratory muscles, increasing work of breathing. The role of continuous positive airway pressure (CPAP) in alleviating PEEPi in patients with severe stable chronic obstructive pulmonary disease is uncertain. This study examined the effect of CPAP on the inspiratory threshold load, muscle effort, and lung volume in this patient group. METHODS: Nine patients were studied at baseline and with CPAP increasing in increments of 1 cm H(2)O to a maximum of 10 cm H(2)O. Breathing pattern and minute ventilation (I), dynamic PEEPi, expiratory muscle activity, diaphragmatic (PTPdi/min) and oesophageal (PTPoes/min) pressure-time product per minute, integrated diaphragmatic (EMGdi) and intercostal EMG (EMGic) and end expiratory lung volume (EELV) were measured. RESULTS: Expiratory muscle activity was present at baseline in one subject. In the remaining eight, PEEPi was reduced from a mean (SE) of 2.9 (0.6) cm H(2)O to 0.9 (0.1) cm H(2)O (p<0.05). In two subjects expiratory muscle activity contributed to PEEPi at higher pressures. There were no changes in respiratory pattern but I increased from 9.2 (0.6) l/min to 10.7 (1.1) l/min (p<0.05). EMGdi remained stable while EMGic increased significantly. PTPoes/min decreased, although this did not reach statistical significance. PTPdi/min decreased significantly from 242.1 (32.1) cm H(2)O.s/min to 112.9 (21.7) cm H(2)O.s/min). EELV increased by 1.1 (0.3) l (p<0.01). CONCLUSION: High levels of CPAP reduce PEEPi and indices of muscle effort in patients with severe stable COPD, but only at the expense of substantial increases in lung volume.

Genioglossus muscle activity at rest and in response to brief hypoxia in healthy men and women.

Obstructive sleep apnea (OSA) is more common in men than in women for reasons that are not clearly understood. An underlying difference between men and women in the respiratory-related neural control of upper airway dilator muscles has been suggested as a possible reason for the gender difference. We have compared three aspects of upper airway dilator muscle function in healthy men and women: 1) resting inspiratory genioglossus electromyogram (EMGgg) activity, 2) the respiratory EMGgg "afterdischarge" after a brief hypoxic stimulus, and 3) the relationship between the EMGgg and pharyngeal airway pressure. Inspired minute ventilation (VI), epiglottic pressure (P(epi)), and EMGgg and diaphragm EMG (EMGdi) activity were measured in 24 subjects (12 men, 12 women in the luteal menstrual phase) and were compared between genders while lying supine awake. Every 7-8 min over 2 h, subjects were exposed to 45-s periods of isocapnic hypoxia (9% O(2) in N(2)) that were abruptly terminated with one breath of 100% O(2). The relationship between P(epi) and EMGgg activity was also compared between genders. The results of 117 trials with satisfactory end-tidal PCO(2) control and no sighs or swallows are reported. There was no gender difference in the resting level of peak inspiratory EMGgg [3.7 +/- 0.8 (women) vs. 3.2 +/- 0.6% maximal activity (men)]. Repeated-measures ANOVA showed no gender or gender-by-time interaction effect between men and women in VI or EMGgg or EMGdi activity during or after the hypoxic stimulus. The relationship between P(epi) and EMGgg was not different between men (slope -0.63 +/- 0.20) and women (slope -0.69 +/- 0.33). These results do not support the hypothesis that the higher prevalence of OSA in men is related to an underlying gender difference in respiratory neural control of upper airway dilator muscles.

Ventilatory decline after hypoxia and hypercapnia is not different between healthy young men and women.

The gradual decay in ventilation after removal of a respiratory stimulus has been proposed to protect against cyclic breathing disorders such as obstructive sleep apnea (OSA). The male predominance of OSA, and the increased incidence of OSA in women after menopause, indicates that the respiratory-stimulating effect of progesterone may provide protection against OSA by altering the rate of poststimulus ventilatory decline (PSVD). It was therefore hypothesized that PSVD is longer in premenopausal women than in men and is longer in the luteal menstrual phase compared with the follicular phase. PSVD was measured in 12 men and in 11 women at both their luteal and follicular phases, after cessation of isocapnic hypoxia and normoxic hypercapnia. PSVD was compared between genders and between women in the luteal and follicular phases by repeated-measures ANOVA. There were no significant differences in PSVD between any of the groups after either respiratory stimulus. This suggests that the higher occurrence of OSA in men does not reflect an underlying gender difference in PSVD and implies the increased prevalence of OSA in women after menopause is not representative of an effect of progesterone on PSVD.