Sleepiness in patients with moderate to severe sleep-disordered breathing

BACKGROUND: Population-based studies suggest that complaints of sleepiness are absent in many individuals with sleep-disordered breathing. We investigated the prevalence of sleepiness as well as factors associated with sleepiness in individuals with moderate to severe sleep-disordered breathing (apnea-hypopnea index > or = 15). DESIGN: Cross-sectional study. SETTING: The Sleep Heart Health Study. PARTICIPANTS: Sleep Heart Health Study participants (N = 6440). MEASUREMENTS AND RESULTS: Sleepiness was defined as an Epworth Sleepiness Scale score >10 or a report of at least frequently feeling unrested or sleepy. Forty-six percent of participants with moderate to severe sleep-disordered breathing (n = 1149) reported sleepiness. Characteristics associated with sleepiness after adjustment for confounders included presence of respiratory disease, shorter self-reported weekday and weekend sleep, sleep durations, complaints of insufficient sleep, complaints of sleep maintenance insomnia, early morning awakening, habitual snoring, and complaints of awakening with leg cramps or leg jerks. Some respiratory polysomnography measures were associated with sleepiness, but sleep-stage percentages and measures of sleep disruption were not. CONCLUSIONS: In this community-based cohort, subjective sleepiness is absent in many individuals with significant sleep-disordered breathing. Comorbid conditions, including respiratory disease, sleep restriction, insomnia, and nocturnal leg complaints, are important risk factors for sleepiness in individuals with moderate to severe sleep-disordered breathing.     

Autonomic dysfunction in children with sleep-disordered breathing

STUDY OBJECTIVES: To measure sympathetic responses in children with and without sleep-disordered breathing. DESIGN: Prospective, observational study. SETTING: Kosair Children's Hospital Sleep Medicine and Apnea Center. PARTICIPANTS: Subjects were prospectively recruited from children undergoing overnight polysomnographic assessments and were retrospectively grouped according to the results of the polysomnogram. Sleep-disordered breathing was defined as an apnea-hypopnea index >5 and children were assigned to the control group if their apnea-hypopnea index was < 1. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: During quiet wakefulness, pulse arterial tonometry was used to assess changes in sympathetic activity following vital capacity sighs in 28 children with sleep-disordered breathing and 29 controls. Each child underwent a series of 3 sighs, and the average maximal pulse arterial tonometry signal attenuation was calculated. Further, a cold pressor test was conducted in a subset of 14 children with sleep-disordered breathing and 14 controls. The left hand was immersed in ice cold water for 30 seconds while right-hand pulse arterial tonometry signal was continuously monitored during immersion and 20-minute recovery periods. Signal amplitude changes were expressed as percentage change from corresponding baseline. Results: The magnitude of sympathetic discharge-induced attenuation of pulse arterial tonometry signal was significantly increased in children with sleep-disordered breathing during sigh maneuvers (74.1% +/- 10.7% change compared with 59.2% +/- 13.2% change in controls; P<.0001) and the cold pressor test (83.5% +/- 7.3% change compared with 74.1% +/- 11.4% change in controls; P=.039). Further, recovery kinetics in control children were faster than those of children with sleep-disordered breathing. CONCLUSION: Children with sleep-disordered breathing have altered autonomic nervous system regulation as evidenced by increased sympathetic vascular reactivity during wakefulness.     

C-reactive protein and sleep-disordered breathing

STUDY OBJECTIVES: Over a 2-month period, to evaluate serum levels of C-reactive protein (CRP) in new patients with obstructive sleep apnea syndrome (OSAS), upper airway resistance syndrome (UARS), and absence of important comorbidity, as well as in normal controls. DESIGN: Cross-sectional analysis. SETTING: Sleep disorders clinic. PATIENTS: 239 successively monitored subjects: 156 subjects were diagnosed with OSAS, 39 with UARS, and 54 controls. INTERVENTIONS: none. MEASUREMENTS AND RESULTS: Clinical information (neurologic, general medical, and otolaryngology examination), body mass index, neck circumference, hip-waist ratio, Epworth Sleepiness Scale, 3 fatigue scales, Sleep Disorders Questionnaire, serum CRP, and polysomnography were collected. Analysis of variance indicated a significant difference between the groups for diastolic blood pressure, respiratory disturbance index, lowest SaO2, and body mass index. The mean serum CRP level was normal in all 3 groups. Only 15 (14 OSAS and 1 UARS) out of 239 subjects had high serum CRP values. CRP levels were significantly correlated with body mass index, esophageal pressures, hip-waist ratio, neck circumference, and blood pressure. Only body mass index was significantly associated with high CRP values; multiple regression showed: adjusted R2 = 0.115, beta = 0.345, P <.001. When men and women were considered separately, body mass index was again significantly associated with high CRP levels. CONCLUSION: Obesity is a risk factor for high serum CRP levels in patients with sleep-disordered breathing, as in the general population.     

Dream recall after sleep interruption in brain-injured patients

Nineteen patients with unilateral hemispheric lesions of a vascular or neoplastic nature were studied. Before the onset of disease, these patients had experienced dream recall at least once a week. During hospitalization their dream recall was investigated using a morning diary for 10 consecutive days. During this period, seven patients reported having dreamed, whereas 12 had no dream recall. Subsequently, the patients' sleep was interrupted during both stage 2 NREM and REM sleep. With this method, 11 patients reported having dreamed at least once, whereas eight had no dream recall. Patients with lesions in the temporo-parieto-occipital region had a more frequent loss of dream recall than those with lesions outside this area. The agreement between the results obtained using the diary and those from provoked awakening was significant. The results obtained from compilation of a diary on morning awakening appear sufficiently reliable to reveal the presence or absence of dream recall in patients with focal cerebral lesions in the acute phase of the disease.     

Expiratory changes in pressure: flow ratio during sleep in patients with sleep-disordered breathing

OBJECTIVES: The size of the upper airway is smallest during sleep, at the end of expiration. This may favor upper-airway collapse in patients with obstructive sleep apnea. In the respiratory cycles preceding obstructive events during sleep, our hypothesis is that upper-airway resistance (UAR) increased earlier during expiration prior to changes occurring during inspiration. DESIGN: We analyzed the pharyngeal pressure-to-flow ratios in order to determine variations in UAR for both inspiration and expiration during stable respiration and the 4 consecutive breaths preceding upper-airway obstructive events in stage 2 sleep. To assess the variation of resistance throughout the within-breath period during stable respiration and the 4 breaths preceding obstructive events, results were expressed as the instantaneous resistance at fixed points 10%, 30%, 50%, 70%, and 90% of time values of inspiration and expiration. Global inspiratory and expiratory UARs during wakefulness and sleep in stable respiration were expressed by the median of instantaneous UAR values. SETTING: Tertiary-care academic medical center. PATIENTS: Eleven patients with moderate to severe sleep-disordered breathing. INTERVENTION: None. MEASUREMENTS AND RESULTS: During stable respiration, both inspiratory and expiratory resistance increased during sleep, compared to values while awake. The difference between inspiratory and expiratory UAR increased when sleep deepened. During the respiratory cycle, the increase in the end-expiratory UAR occurred earlier than during inspiration; during stable respiration, UAR was much aggravated during the last three breaths preceding an obstructive event. CONCLUSION: Increases in the expiratory UAR occurred earlier than during inspiration in the cycles preceding upper-airway collapse in patients with sleep apnea. This finding suggested an important role of the expiratory phase in promoting upper-airway collapse and is in accordance with the inspiratory pharyngeal instability occurring when lowering the expiratory pressure in patients with obstructive sleep apnea.     

The relationship of nightmare frequency and nightmare distress to well-being

Nightmares can be defined as very disturbing dreams, the events or emotions of which cause the dreamer to wake up. In contrast, unpleasant dreams can be defined in terms of a negative emotional rating of a dream, irrespective of whether or not the emotions or events of the dream woke the dreamer. This study addresses whether frequency of unpleasant dreams is a better index of low well-being than is frequency of nightmares. A total of 147 participants reported their nightmare frequency retrospectively and then kept a log of all dreams, including nightmares, for 2 weeks, and rated each dream for pleasantness/unpleasantness. Anxiety, depression, neuroticism, and acute stress were found to be associated with nightmare distress (ND) (the trait-like general level of distress in waking-life caused by having nightmares) and prospective frequency of unpleasant dreams, and less so with the mean emotional tone of all dreams, or retrospective or prospective nightmare frequency. Correlations between low well-being and retrospective nightmare frequency became insignificant when trait ND was controlled for, but correlations with prospective unpleasant dream frequency were maintained. The reporting of nightmares may thus be confounded and modulated by trait ND: such confounding does not occur for the reporting of unpleasant dreams in general. Thus there may be attributional components to deciding that one has been awoken by a dream, which can affect estimated nightmare frequency and its relationship with well-being. Underestimation of nightmare frequency by the retrospective questionnaire compared with logs was found to be a function of mean dream unpleasantness and ND.     

Determining optimal sleep position in patients with positional sleep-disordered breathing using response surface analysis

A lateral position (LP) during sleep is effective in reducing sleep disorder symptoms in mild or moderate sleep apnea patients. However, the effect of head and shoulder posture in LP on reducing sleep disorders has not been reported. In this study, effective sleeping positions and a combination of sleep position determinants were evaluated with respect to their ability to reduce snoring and apnea. The positions evaluated included the following: cervical vertebrae support with head tilting (CVS-HT), scapula support (SS), and LP. A central composite design was applied for response surface analysis (RSA). Sixteen patients with mild or moderate positional sleep apnea and snoring who underwent polysomnography for two nights were evaluated. Based on an estimated RSA equation, LP (with a rotation of at least 30°) had the most dominant effect [ P  = 0.0057 for snoring rate, P  = 0.0319 for apnea–hypopnea index (AHI)]. In addition, the LP was found to interact with CVS-HT ( P  = 0.0423) for snoring rate and CVS-HT ( P  = 0.0310) and SS ( P  = 0.0265) for AHI. The optimal sleep position reduced mild snoring by more than 80% (i.e. snoring rate in the supine position was <20%) and the snoring rate was approximately zero with a 40° rotation. To achieve at least 80% reduction of AHI, LP and SS should be >30° and/or 20 mm respectively. To determine an effective sleep position, CVS-HT and SS, as well as the degree of the LP, should be concurrently considered in patients with positional sleep apnea or snoring.     

The effect of sleep-disordered breathing on stages of sleep in patients with Alzheimer's disease

Patients with Alzheimer's disease (AD) commonly have poor sleep and a high reported incidence of sleep-disordered breathing (SDB). This study examined how the presence of SDB affected sleep stages in AD patients. Sixty-six volunteers with mild-moderate AD underwent home polysomnography. Results showed that patients with SDB spent less of the night in REM sleep than those with no SDB, but there were no differences in other sleep stages. The findings suggest that the decreased amount of REM sleep may be due to the presence of AD and SDB. Treating these patients' SDB may increase their amount of REM sleep, which may result in improved daytime functioning. Controlled trials of SDB treatment in AD are needed to answer this question.     

Sex influences endothelial function in sleep-disordered breathing

BACKGROUND: The bases for the association between sleep-disordered breathing (SDB) and cardiovascular disease are poorly understood. Endothelial dysfunction, assessed with brachial artery ultrasonography, may predict cardiovascular risk and represent preclinical vascular disease. We determined whether flow-mediated dilation (FMD) and peak blood flow (PBF) increase after cuff occlusion is altered with SDB. METHODS: 193 participants (58% women) in a cohort study were studied with overnight polysomnography and subsequent brachial artery ultrasonography. SDB was quantified using the apnea-hypopnea index (AHI) and indexes of overnight desaturation and arousal frequency. Two-dimensional and Doppler-velocity measurements of the brachial artery were obtained at baseline and after 5 minutes of upper-arm cuff occlusion. FMD and PBF were defined as the percentage changes from baseline in brachial artery diameter and flow, respectively. RESULTS: In the entire sample, the AHI was inversely associated with both FMD (r = -0.30, P < .001) and PBF (r = -0.20, P < .001). However, sex-stratified univariate analyses showed that these relationships were exclusive to women. Specifically, FMD was significantly lower in women with an AHI > or = 15 than in women with lower AHI scores (P < .005), with no relationship between AHI and FMD in men. Additionally, PBF decreased significantly with increasing AHI (r = -0.29, P = .010) in women alone. Statistical modeling, adjusting for body mass index, age, and other covariates, similarly showed that SDB severity significantly influenced FMD and PBF, with significant interactions between sex and AHI, reinforcing that the associations between SDB severity and endothelial function were stronger in women than in men. CONCLUSIONS: Moderate levels of SBD are associated with impaired conduit and resistance endothelial function in women. Women with SDB may be more vulnerable to early SDB-related cardiovascular disease than are men.     

Arousals in sleep-disordered breathing: patterns and implications

STUDY OBJECTIVE: To describe the whole spectrum of electroencephalographic (EEG) transients associated with the termination and recovery of obstructed respiratory events and, thus, widen the recognized spectrum of arousal phenomena from sleep. DESIGN: Retrospective review of diagnostic polysomnograms. SETTING: American Academy of Sleep Medicine (AASM)-accredited multidisciplinary sleep disorders center. PATIENTS: 17 patents with obstructive sleep-disordered breathing. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Nasal airflow using a nasal-cannula-pressure-transducer system and oral flow by a thermistor were used to score apneas and hypopneas; the latter included flow-limitation events. The EEG patterns that crested or occurred within 2 to 3 seconds of respiratory recovery were recorded, and posthoc categories were created for the purpose of tabulation ranging from an AASM 3-second arousal to a single K-complex with no electromyographic increase. Chi-square statistic was calculated to assess the difference in EEG patterns at event termination between apneas and hypopneas. Score-rescore agreement was tested. Apneas were significantly more likely to be associated with a 3-second arousal than were hypopneas, but all types of EEG change were seen with both types of events. Spindles were rarely seen with arousal-linked K-complexes. The majority of events in rapid eye movement sleep were terminated with visible electromyography tone increase. CONCLUSIONS: The spectrum of EEG change associated with the termination of respiratory events identified by using a nasal-cannula-pressure-transducer system is wider than that recognized as arousal phenomena by the 1992 AASM criteria. Scoring arousals with the 3-second rule may falsely minimize the apparent impact of abnormal breathing on sleep. The time may be right to update arousal recognition rules.     

Neurobehavioral correlates of sleep-disordered breathing in children

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.     

Behavioral correlates of sleep-disordered breathing in older women

STUDY OBJECTIVES: To examine the association between SDB and subjective measures of daytime sleepiness, sleep quality, and sleep related quality of life in a large cohort of primarily community-dwelling older women, specifically considering the relative importance of sleep duration in mediating these associations. DESIGN: Cross-sectional. The functional outcome measures of interest were daytime sleepiness (using the Epworth Sleepiness Scale, ESS), sleep-related symptoms (Pittsburgh Sleep Quality Index, PSQI), and sleep related quality of life (Functional Outcomes of Sleep Questionnaire, FOSQ). ANOVA and regression analyses examined the association between SDB severity (measured by indices of breathing disturbances and overnight oxygen saturation) and sleep time (by actigraphy) and these outcome measures. Regression models were adjusted for age, body mass index (BMI), and a medical comorbidity index. We specifically explored whether associations with indices of SDB were mediated by sleep deprivation by adjusting models for actigraphy-determined average total sleep time (TST) during the night. SETTING: Community-based sample examined in home and outpatient settings. PARTICIPANTS: 461 surviving older women from the multicenter Study of Osteoporotic Fractures were examined during Visit 8 from 2002-03. All participants underwent in-home overnight polysomnography for one night and wrist actigraphy for a minimum of 3 24-h periods and completed the above functional outcomes questionnaires. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants were aged 82.9 +/- 3.5 (mean +/- SD) years, had BMI of 27.9 +/- 5.1 kg/m2, and had an apnea-hypopnea index (AHI) of 15.7 +/- 15.1. AHI and TST demonstrated a weak correlation (r = -0.15). ESS score individually demonstrated a modest association with AHI, oxygen desaturation, and TST. The association of ESS score and AHI--but not oxygen desaturation-was attenuated to some extent by adjustment for TST. PSQI and FOSQ scores were not associated with measures of SDB severity or TST. CONCLUSIONS: After adjustment for TST, SDB severity in community-dwelling older women was not independently associated with self-reported daytime sleepiness, although there may be a modest association that is mediated through reduced TST. In older women, SDB severity was not associated with indices of sleep related symptoms or sleep related quality of life.     

Health-related quality of life and sleep-disordered breathing in children

STUDY OBJECTIVES: To assess the extent to which sleep-disordered breathing (SDB) is associated with impairment of health-related quality of life (HRQOL) in children DESIGN: Observational study of pediatric participants in a longitudinal genetic-epidemiologic cohort study of SDB. SETTING: Community-based; studies conducted at participants' homes PARTICIPANTS: 298 children, aged 11.1 years +/- 3.5 SD; 54% females; 61% African-American or Other; 81% with a family member identified with laboratory-confirmed SDB. INTERVENTIONS: Not applicable MEASUREMENTS AND RESULTS: The HRQOL was assessed with the Child Health Questionnaire (CHQ-PF50), a 50-item parent-completed form that measures 14 multidimensional health concepts. Sleep-disordered breathing (SDB) was assessed with ovemight in-home monitoring that recorded nasal-oral airflow, pulse oximetry, chest-wall impedance, and heart rate. Using logistic regression analyses, each CHQ scale outcome was analyzed independently for the effect of SDB, adjusting for other potential confounding variables and for family-correlated data. Significant differences in overall physical health and complaints of bodily pain were observed in children with generally mild levels of SDB. Relationships persisted after adjustment for age, gender, ethnicity, obesity, and asthma. CONCLUSIONS: SDB in children is associated with measurably lower levels of specific dimensions of HRQOL in children. Decrements in HRQOL are measurable even for children with mild SDB, with increasing effects observed with more severe SDB.     

Effects of adaptive servo-ventilation on ventricular arrhythmias in patients with stable congestive heart failure and sleep-disordered breathing

Background

Congestive heart failure patients with reduced left ventricular ejection fraction (HFrEF) and sleep-disordered breathing (SDB) are at an increased risk of nocturnal cardiac arrhythmias. SDB can be effectively treated with adaptive servo-ventilation (ASV). Therefore, we tested the hypothesis that ASV therapy reduces nocturnal arrhythmias and heart rate in patients with HFrEF and SDB.

Methods

In a non-prespecified subanalysis of a multicenter randomized controlled trial (ISRCTN04353156), 20 consecutive patients with stable HFrEF (age 67 ± 9 years; left ventricular ejection fraction, LVEF 32 ± 7?%) and SDB (apnea–hypopnea index, AHI 48 ± 20/h) were randomized to either an ASV therapy (n = 10) or an optimal medical treatment alone group (controls, n = 10). Polysomnography (PSG) with blinded centralized analysis and scoring was performed at baseline and at 12 weeks. The electrocardiograms (ECG) of the PSGs were analyzed with long-term (24-h) Holter ECG software (QRS-Card? Cardiology Suite; Pulse Biomedical Inc., King of Prussia, PA, USA).

Results

There was a decrease in ventricular extrasystoles (VES) per hour of recording time in the ASV group compared to the control group (?8.1 ± 42.4 versus +9.8 ± 63.7/h, p = 0.356). ASV reduced the number of ventricular couplets and nonsustained ventricular tachycardias (nsVT) compared to the control group (?2.3 ± 6.9 versus +2.1 ± 12.7/h, p = 0.272 and ?0.1 ± 0.5 versus +0.1 ± 1.1/h, p = 0.407, respectively). Mean nocturnal heart rate decreased in the ASV group compared to the controls (?2.0 ± 2.7 versus +3.9 ± 11.5/min, p = 0.169). The described changes were not significantly different between the groups.

Conclusion

In HFrEF patients with SDB, ASV treatment may reduce nocturnal VES, couplets, nsVT, and mean nocturnal heart rate. The findings of the present pilot study underscore the need for further analyses in larger studies.

     

Mechanisms of sleep-disordered breathing: causes and consequences

Obstructive sleep apnea (OSA) is very common in the general population and is characterized by ineffective inspiratory efforts against a collapsed upper airway during sleep. Collapse occurs mainly at the level of the velopharynx and oropharynx due to a combination of predisposing anatomy and the withdrawal of pharyngeal dilator activity during sleep. Central sleep apnea (CSA) is a manifestation of chemoreflex control instability, leading to periods of inadequate respiratory drive sufficient to trigger breathing, usually alternating with periods of hyperventilation. While both forms of apnea are the result of differing pathophysiology, it has become increasingly clear that OSA and CSA often coexist in the same patient, the existence of one can predispose to the other, and that the two are not as distinct as previously thought. Both OSA and CSA exert a number of acute deleterious effects including intermittent hypoxia, arousals from sleep, and swings in negative intrathoracic pressure, which in turn lead to chronic physiologic consequences such as autonomic dysregulation, endothelial dysfunction, and cardiac remodeling. These underlying pathophysiological mechanisms provide a framework for understanding why OSA and CSA may predispose to cardiovascular diseases like ischemic heart disease and stroke.     

Correlates of respiratory cycle-related EEG changes in children with sleep-disordered breathing

STUDY OBJECTIVES: To explore newly-identified respiratory cycle-related electroencephalographic changes (RCREC), which may represent microarousals, as correlates of neurobehavioral outcomes in children with sleep-disordered breathing (SDB). DESIGN: Retrospective. SETTING: University sleep laboratory. PARTICIPANTS: Ten research subjects, aged 6 to 10 years, with and without SDB. INTERVENTION: Polysomnography, Multiple Sleep Latency Tests, and tests of auditory attention before and after clinically-indicated tonsillectomy (n = 9) or hernia repair (n = 1, control). MEASUREMENTS: For the first 3 hours of nocturnal sleep, a computer algorithm quantified the degree to which delta, theta, and alpha electroencephalographic power varied within non-apneic respiratory cycles. Correlations between the RCREC and standard objective measures of SDB, sleepiness, and attention were explored. RESULTS: Five children had SDB (> 1 obstructive apnea per hour of sleep). Preoperative delta, theta, or alpha RCREC were statistically significant (P < .01) in all subjects except 1 without SDB and the 1 control. Theta RCREC correlated with rates of apneas and hypopneas (P = .01) and decreased after the apnea was treated. Postoperative changes in delta and theta RCREC predicted changes in Multiple Sleep Latency Test scores (rho = -0.84, P = .002; rho = -0.64, P = .05), whereas changes in rates of apneas and hypopneas did not (rho = -0.24, P = .50). Postoperative changes in attention tended to correlate with changes in delta RCREC (rho = -0.54, P = .11) more strongly than with changes in rates of apneic events (rho = -0.07, P = .84). CONCLUSIONS: The RCREC may reflect brief but numerous microarousals that could help to explain neurobehavioral consequences of SDB.