Sleep related breathing disorders in older men: A search for underlying mechanisms

—The incidence of sleep-related breathing disorders (SRBDs) associated with hemoglobin desaturation was determined by nocturnal polygraphic evaluations in 26 healthy men, aged 55–70 years. Sixteen subjects (62%) had abnormal rates of at least 12 episodes per hour of sleep: 8 had occlusive, and 8 had central apnea or hypopnea. During waking ten of 16 SRBD subjects and only one subject without SRBDs exhibited either an elevated nasopharyngeal airway resistance (n=4) or a reduced ventilatory response to hypercapnia (n=4) and/or hypoxia (n=3). However, these abnormalities were not related to the type or severity of SRBDs, and 6 subjects with SRBDs demonstrated no respiratory defect. We conclude that SRBDs have a very high incidence in older males and are not usually secondary to pulmonary cardiac, neurological, or behavioral disorders. Additionally, we hypothesize that abnormalities in ventilatory control or upper airway resistance contribute to SRBDs, but depression of brain stem reticular formation activity during sleep plays a primary role in these disorders. Factors related to both aging and SRBDs are reviewed. These include reduced chemoreceptor responses, altered steroid hormone metabolism, and use and metabolism of hypnotic drugs and alcohol.     

Effect of high-fat diet and metformin treatment on ventilation and sleep apnea in non-obese rats

We investigated the effect of insulin resistance on ventilation and the incidence of sleep apnea in non-obese rats and determined whether metformin could change ventilation and occurrence of sleep apneas. Five groups of rats were studied: (1) standard chow; (2) high-fat groups, with 1 with metformin; (2) had type 2 diabetes induced by streptozotocin, with 1 with metformin. Compared to standard rats, ventilatory parameters remained unchanged in the high-fat fed diet as well as in diabetic rats. However, their oxygen consumption was reduced (p相似文献   

Complex sleep apnea and obesity hypoventilation syndrome. Opposite ends of the spectrum of obstructive sleep apnea?

In most cases, the application of continuous positive airway pressure (CPAP) during sleep in patients affected by obstructive sleep apnea (OSA) eliminates upper airway obstruction and makes breathing stable and regular. However, some OSA patients develop periodic breathing and central apneas during CPAP administration, a finding that has been labelled as “complex sleep apnea” (complex SA). Such breathing disorder may occur only acutely after CPAP treatment initiation or sometimes persist with chronic CPAP treatment. We hypothesize that complex SA may be the consequence of mechanisms analogous to those leading to obesity hypoventilation syndrome (OHS), but operating in an opposite direction.Periodic breathing is one of the factors predisposing to OSA and is an essential factor for the recurrence of central apneas in normo or hypocapnic patients. A high ventilatory responsiveness to chemical stimuli enhances breathing periodicity. In subjects with periodic central apneas chemoresponsiveness is high, while in subjects with OSA it spans throughout a wide range, and is correlated to diurnal blood gas levels. In fact, sleep respiratory disorders may be responsible for either an augmentation in ventilatory responses to chemical stimuli consequent to chronic exposure to intermittent hypoxia, or for a decrease in ventilatory responses when prolonged exposure to hypercapnia is experienced. Among OSA subjects, those with OHS show very depressed hypercapnic responses. After chronic OSA treatment, ventilatory responses to chemical stimuli may either decrease, in previously hyperresponsive subjects, or increase, in previously hyporesponsive subjects. Most patients with OHS decrease daytime PCO₂ levels and increase their ventilatory responses after chronic CPAP treatment.Complex SA could appear in those OSA subjects in whom chronic exposure to nocturnal respiratory disorders leads to the highest responsiveness to chemical stimuli, and could disappear after blunting of ventilatory responses following chronic CPAP treatment. Complex SA may be one extreme of evolutionary spectrum of OSA, the opposite end being represented by OHS.     

Correlations among Epworth Sleepiness Scale scores, multiple sleep latency tests and psychological symptoms

The aim of this study was to identify factors other than objective sleep tendency associated with scores on the Epworth Sleepiness Scale (ESS). There were 225 subjects, of whom 40% had obstructive sleep apnoea (OSA), 16% had simple snoring, and 4.9% had snoring with sleep disruption (upper airway resistance syndrome); 9.3% had narcolepsy and 7.5% had hypersomnolence without REM sleep abnormalities; 12% had chronic fatigue syndrome; 7.5% had periodic limb movement disorder and 3% had diurnal rhythm disorders. ESS, the results of overnight polysomnography and multiple sleep latency test (MSLT) and SCL-90 as a measure of psychological symptoms were recorded. The ESS score and the mean sleep latency (MSL) were correlated (Spearman ö =−0.30, P <0.0001). The MSL was correlated with total sleep time (TST) and with sleep efficiency but not with apnoea/hypopnoea index. There was no association between the MSL and any aspect of SCL-90 scores, except a borderline significant association with the somatisation subscale. The ESS was correlated with TST but not with sleep efficiency or apnoea/hypopnoea index. The ESS was correlated with all subscales of the SCL-90 except psychoticism. An ESS≥10 had poor sensitivity and specificity as a predictor of MSL <10 min or MSL <5 min. We conclude that the MSLT and the ESS are not interchangeable. The ESS was influenced by psychological factors by which the MSL was not affected. The ESS cannot be used to demonstrate or exclude sleepiness as it is measured by MSLT.     

Neurochemical perspectives on the control of breathing during sleep

A specific depression of minute ventilation occurs during sleep in normal subjects. This sleep-related ventilatory depression is partially related to mechanical events and upper airway atonia but some data also indicate that it is likely to be centrally mediated. This paper reviews the anatomical and neurochemical connections between sleep/wake- and respiratory-related areas in an attempt to identify the potential implication of sleep-related neurochemicals (serotonin, catecholamines, GABA, acetylcholine) in the sleep-related hypoventilation. The review of available data suggests that the sleep-related ventilatory depression depends upon the enhanced GABAergic activity together with a loss of suprapontine influence depending on the cessation of activity of the reticular formation. During REM sleep, an additional inhibitory activity emerges from the pontine cholinergic neurons, which contributes to the breathing irregularities and the associated depression of minute ventilation and ventilatory response to chemical stimuli. This model may contribute to a better understanding of the neurochemical environment of respiratory neurons during sleep, which remains a question of importance regarding the numerous pathological states that are linked to specific perturbations of breathing control during sleep.     

Effect of tiagabine on sleep in elderly subjects with primary insomnia: a randomized, double-blind, placebo-controlled study

SUBJECT OBJECTIVE: This study further evaluated the effects of tiagabine on sleep in elderly subjects with primary insomnia. METHODS: Elderly subjects (aged 65-85 years) meeting DSM-IV-TR criteria for primary insomnia were randomly assigned to receive tiagabine 2, 4, 6, or 8 mg or placebo on 2 consecutive nights. Efficacy was assessed using standard polysomnography and a postsleep questionnaire. Additional assessments included the Assessment of Daily Functioning, Digit Symbol Substitution Test (for residual effects), and visual analog scale (for sleepiness/alertness). RESULTS: A total of 207 subjects were randomly assigned to study medication (tiagabine: 2 mg, n = 43; 4 mg, n = 38; 6 mg, n = 45; 8 mg, n = 43; placebo, n = 38). Tiagabine did not significantly effect wake after sleep onset, latency to persistent sleep, or total sleep time compared with placebo (P > .05). Significant increases in Stage 3+4 sleep (i.e., slow-wave sleep) were found for tiagabine 4, 6, and 8 mg versus placebo, with a corresponding significant decrease in Stage 1 sleep (P < .05). At 6 and 8 mg, tiagabine also significantly reduced the number of awakenings and increased the ratio of Stage 3+4/(Stage 1 +wake after sleep onset). In general, there were no significant effects on subjects' ratings of sleep or daily functioning with tiagabine 2, 4, and 6 mg versus placebo. These 3 doses had tolerability profiles comparable with that of placebo and were not associated with significant residual effects or reduced alertness. The 8-mg dose, however, significantly decreased subjective total sleep time and refreshing quality of sleep, as well as daily functioning. This dose was associated with troublesome adverse events, significant residual effects, and reduced alertness. CONCLUSIONS: In elderly subjects with primary insomnia, tiagabine did not have a significant effect on wake after sleep onset, latency to persistent sleep, total sleep time, or the subjective rating of sleep. Tiagabine 4, 6, and 8 mg significantly increased slow-wave sleep, with a corresponding significant decrease in Stage 1 sleep. Tiagabine was generally well tolerated, with doses of less than 6 mg having tolerability profiles generally similar to that of placebo. The 8-mg dose, however, was associated with troublesome adverse events, residual effects, and reduced alertness.     

Treatment of obstructive sleep apnea syndrome in children

Obstructive sleep apnea (OSA) has been identified and recorded in paediatric patients, the potential mechanisms for OSA include anatomical abnormalities that lead to a narrowed airway space, reduced muscle tone and abnormal central ventilatory control. Several treatments have been developed and are routinely used to treat OSA in infants and children. Nasal mask continuous positive airway pressure (CPAP) is an effective non-invasive treatment that prevents the majority of obstructive events, reverses sleep disturbances, improves daytime performance and is associated with increased growth in patients with failure to thrive. Surgery to correct underlying anatomical abnormalities is frequently used and usually results in an improvement in symptoms and in some cases, it is curative. Other forms of treatment include pharmacological interventions, positioning and nasopharyngeal intubation.     

Treatment of obstructive sleep apnea in achondroplasia: Evaluation of sleep,breathing, and somatosensory-evoked potentials

The occurrence of obstructive sleep apnea (OSA) in achondroplasia has been linked to brain stem compression. Overnight sleep studies (11 subjects) and somatosensoryevoked potentials (SEP's, 10 subjects) were recorded before and after conventional treatment of OSA in achondroplasia. The two groups were derived from 30 subjects who underwent diagnostic sleep studies and SEPs, including 15 females and 15 males with a median age 6.6 of years (range 1.0–47.6) at the time of the first study. In 30 initial studies there was no correlation between severity of OSA and abnormalities on SEP evaluation. Treatment of 17 subjects included adenotonsillectomy (n = 3), weight loss (n = 1), and nasal-mask continuous positive airway pressure (CPAP) (n = 13). Sleep studies in 11 subjects after a delay of 8.8 ± 2.8 months showed a reduction in respiratory disturbance index (RDI) from 38.4 ± 6.9 to 6.5 ± 1.8 events hr^?1 (p < 0.001) and movements/arousals fell from 10.4 ± 2.2 to 4.8 ± 0.2 hr^?1 (p < 0.04). Obstructive events were reduced from 33.7 ± 6.9 to 2.4 ± 1.0 hr^?1 (p < 0.001). Improvement of respiratory indices was associated with an increased proportion of slow-wave sleep from 25.2 ± 4.0% to 32.3 ± 2.4% (p = 0.01), and decrease in stage 1–2 sleep from 59.3 ± 5.8% to 46.6 ± 1.9% (p = 0.03). There was no increase in the percentage of REM sleep (15.2% to 21.2%). Repeat SEP studies in 10 subjects, after clinically effective treatment of OSA, showed improvement of SEP score of at least 1 grade, in 5 of 7 (71%) with initially abnormal values. We conclude that treatment to relieve upper airway obstruction improves OSA in achondroplasia, accompanied by changes in sleep structure and, in some cases, improved studies of neurological function. © 1995 Wiley-Liss, Inc.     

Sleep duration as a risk factor for diabetes incidence in a large U.S. sample

STUDY OBJECTIVES: To explore the relationship between sleep duration and diabetes incidence over an 8- to 10-year follow-up period in data from the First National Health and Nutrition Examination Survey (NHANES I). We hypothesized that prolonged short sleep duration is associated with diabetes and that obesity and hypertension act as partial mediators of this relationship. The increased load on the pancreas from insulin resistance induced by chronically short sleep durations can, over time, compromise beta-cell function and lead to type 2 diabetes. No plausible mechanism has been identified by which long sleep duration could lead to diabetes. DESIGN: Multivariate longitudinal analyses of the NHANES I using logistic regression models. SETTING: Probability sample (n=8992) of the noninstitutionalized population of the United States between 1982 and 1992. PARTICIPANTS: Subjects between the ages of 32 and 86 years. MEASUREMENTS AND RESULTS: Between 1982 and 1992, 4.8% of the sample (n=430) were determined by physician diagnosis, hospital record, or cause of death to be incident cases of diabetes. Subjects with sleep durations of 5 or fewer hours (odds ratio = 1.47, 95% confidence interval 1.03-2.09) and subjects with sleep durations of 9 or more hours (odds ratio = 1.52, 95% confidence interval 1.06-2.18) were significantly more likely to have incident diabetes over the follow-up period after controlling for covariates. CONCLUSIONS: Short sleep duration could be a significant risk factor for diabetes. The association between long sleep duration and diabetes incidence is more likely to be due to some unmeasured confounder such as poor sleep quality.     

Excessive daytime somnolence and increased rapid eye movement pressure in myotonic dystrophy

STUDY OBJECTIVES: Sleep studies at Duke University Medical Center were retrospectively reviewed to investigate causes of excessive daytime sleepiness (EDS) in our myotonic dystrophy1 (DM1) patient population, identified by an abnormal CTG expansion on chromosome 19. Excessive daytime sleepiness, an accentuated desire for sleep or the occurrence of sleep episodes that interfere with normal wakefulness, is common in patients with DM1. Sleep abnormalities, such as central and obstructive sleep apnea, have been extensively reported; however, many DM1 patients suffer from EDS in the absence of any identified respiratory dysrhythmia. DESIGN: Nineteen DM1 patients, with the clinical diagnosis and genetic confirmation in the proband or a related family member, had a sleep evaluation. Polysomnogram (PSG) and mean sleep latency test (MSLT) results were retrospectively reviewed. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Most DM1 patients demonstrated grade 3 (distal weakness) or grade 4 (mild to moderate proximal weakness) on the myotonic dystrophy impairment rating scale. All patents had a PSG, with 13 patients having an MSLT the following day. Clinically significant respiratory abnormalities on PSG, defined in this study as a respiratory disturbance index > 15 and/or upper airway resistance syndrome, could not explain the EDS observed in 14 of 19 patients. Decreased mean sleep latency was observed in 12 of 13 patients evaluated by MSLT, while sleep onset REM sleep was seen in 8 of 13 patients. Pathologic REM onset (2 or more SOREMs on MSLT) was seen in 5 of 13 patients, with 3 of those 5 patients having a PSG with RDI < or = 5. CONCLUSIONS: Most DM1 patients did not have significant respiratory abnormalities on PSG to explain the manifested EDS. Objective sleepiness is common in DM1, and pathologic REM pressure can be commonly observed. These observations imply an intrinsic hypersomnolence sometimes accompanied by abnormal REM pressure may be an integral part of EDS in DM1 patients.