Comparison between a Single-Channel Nasal Airflow Device and Oximetry for the Diagnosis of Obstructive Sleep Apnea

Rationale:

The most common single channel devices used for obstructive sleep apnea (OSA) screening are nasal airflow and oximetry. No studies have directly compared their role in diagnosing OSA at home.

Study Objectives:

To prospectively compare the diagnostic utility of home-based nasal airflow and oximetry to attended polysomnography (PSG) and to assess the diagnostic value of adding oximetry to nasal airflow for OSA.

Design:

Cross-sectional study

Setting:

Laboratory and home

Participants:

Sleep clinic patients with suspected OSA.

Interventions:

All patients had laboratory PSG and 2 sets of 3 consecutive nights on each device; nasal airflow (Flow Wizard, DiagnoseIT, Australia) and oximetry (Radical Set, Masimo, USA) at home in random order.

Results:

Ninety-eight of the 105 patients enrolled completed home monitoring. The accuracy of nasal airflow respiratory disturbance index (NF RDI) was not different from oximetry (ODI 3%) for diagnosing OSA (area under the ROC curve (AUC) difference, 0.04; 95% CI of difference −0.05 to 0.12; P = 0.43) over 3 nights of at-home recording. The accuracy of NF RDI was higher after 3 nights compared to one night (AUC difference, 0.05; 95% CI of difference, 0.01 to 0.08; P = 0.04). Addition of oximetry to nasal airflow did not increase the accuracy for predicting OSA compared to nasal airflow alone (P > 0.1).

Conclusions:

Nasal flow and oximetry have equivalent accuracy for diagnosing OSA in the home setting. Choice of device for home screening of sleep apnea may depend on logistical and service delivery issues.

Citation:

Makarie Rofail L; Wong KKH; Unger G; Marks GB; Grunstein RR. Comparison between a single-channel nasal airflow device and oximetry for the diagnosis of obstructive sleep apnea. SLEEP 2010;33(8):1106-1114.     

Obstructive Sleep Apnea and Aldosterone

Background:

Obstructive sleep apnea (OSA) is a major risk factor for hypertension and has been associated with increased risk for cardiovascular morbidity. A dysregulated renin-angiotensin-aldosterone system may contribute to excess sodium retention and hypertension and may be activated in OSA. We tested the hypothesis that serum levels of aldosterone and plasma renin activity (PRA) are increased by apneic sleep in subjects without cardiovascular disease, compared to healthy control subjects.

Methods and Results:

Plasma aldosterone level was measured in 21 subjects with moderate to severe OSA and was compared to 19 closely matched healthy subjects. Plasma renin activity (PRA) was measured in 19 OSA patients and in 20 healthy controls. Aldosterone and PRA were measured before sleep (9pm), after 5 hrs of untreated OSA (2am) and in the morning after awakening (6am). There were no baseline (9pm) differences in serum aldosterone levels and PRA between the healthy controls and OSA patients (aldosterone: 55.2 ± 9 vs 56.0 ± 9 pg/mL; PRA: 0.99 ± 0.15 vs 1.15 ± 0.15 ng/mL/hr). Neither several hours of untreated severe OSA nor CPAP treatment affected aldosterone levels and PRA in OSA patients. Diurnal variation of both aldosterone and PRA was observed in both groups, in that morning renin and aldosterone levels were higher than those measured at night before sleep.

Conclusions:

Our study shows that patients with moderate to severe OSA without co-existing cardiovascular disease have plasma aldosterone and renin levels similar to healthy subjects. Neither untreated OSA nor CPAP treatment acutely affect plasma aldosterone or renin levels.

Citation:

Svatikova A; Olson LJ; Wolk R; Phillips BG; Adachi T; Schwartz GL; Somers VK. Obstructive sleep apnea and aldosterone. SLEEP 2009;32(12):1589-1592.     

Endothelial Function in Normotensive Men with Obstructive Sleep Apnea Before and 6 Months After CPAP Treatment

Study Objectives:

To evaluate endothelium-dependent flow-mediated dilation (FMD) and endothelium–independent nitroglycerin (NTG)-induced dilation of the brachial artery with Doppler ultrasound in patients with obstructive sleep apnea (OSA) and impact of six months of continuous positive airway pressure (CPAP) treatment.

Design:

A prospective, controlled, observational study.

Setting:

Single-site, clinic-based.

Patients:

Twenty-nine normotensive men with OSA (apnea-hypopnea index [AHI], mean ± SD, 60.4 ± 22.1-h), and 17 men without OSA (AHI 2.5 ± 0.6-h).

Interventions:

Six months of CPAP therapy in OSA patients.

Measurements and Results:

FMD was lower in patients with OSA compared with in controls (7.19 ± 1.78 % vs 10.93 ± 2.59 %; P < 0.001) while NTG-induced vasodilation was similar in both groups (13.75 ± 1.01 % vs 14.25 ± 1.83 %; n.s.). An inverse relationship was found between FMD and AHI adjusted for age and body mass index (BMI) (β = − 0.05, P < 0.001). Following 6 months of CPAP treatment in the OSA group, FMD was increased from 7.38 ± 2.06 % to 10.45 ± 1.68; P = 0.001) in 20 patients compliant with the device whereas the corresponding values did not change in the non-user group (7.08 ± 1.50% vs 7.26 ± 1.01%). No significant changes were observed regarding the NTG–induced vasodilation after CPAP compared with the baseline values.

Conclusion:

Our results confirm the previous reports suggesting impaired endothelium-dependent FMD in OSA, and additionally document the sustained improvement in endothelial function after 6 months of CPAP treatment in complaint patients.

Citation:

Bayram NA; Ciftci B; Keles T; Durmaz T; Turhan S; Bozkurt E; Peker Y. Endothelial function in normotensive men with obstructive sleep apnea before and 6 months after CPAP treatment. SLEEP 2009;32(10):1257-1263.     

Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea: systematic review and meta-analysis

Context:

Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle crash.

Objective:

We performed a systematic review of the literature concerning the impact of continuous positive airway pressure (CPAP) treatment on motor vehicle crash risk among drivers with OSA. The primary objective was to determine whether CPAP use could reduce the risk of motor vehicle crash among drivers with OSA. A secondary objective involved determining the time on treatment required for CPAP to improve driver safety.

Data Sources:

We searched seven electronic databases (MEDLINE, PubMed (PreMEDLINE), EMBASE, PsycINFO, CINAHL, TRIS, and the Cochrane library) and the reference lists of all obtained articles.

Study Selection:

We included studies (before-after, case-control, or cohort) that addressed the stated objectives. We evaluated the quality of each study and the interplay between the quality, quantity, robustness, and consistency of the evidence. We also tested for publication bias.

Data Extraction:

Data were extracted by two independent analysts. When appropriate, data were combined in a fixed or random effects meta-analysis.

Results:

A meta-analysis of 9 observational studies examining crash risk of drivers with OSA pre- vs. post-CPAP found a significant risk reduction following treatment (risk ratio = 0.278, 95% CI: 0.22 to 0.35; P < 0.001). Although crash data are not available to assess the time course of change, daytime sleepiness improves significantly following a single night of treatment, and simulated driving performance improves significantly within 2 to 7 days of CPAP treatment.

Conclusions:

Observational studies indicate that CPAP reduces motor vehicle crash risk among drivers with OSA.

Citation:

Tregear S; Reston J; Schoelles K; Phillips B. Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea. SLEEP 2010;33(10):1373-1380.     

The Utility of Single-Channel Nasal Airflow Pressure Transducer in the Diagnosis Of OSA at Home

Rationale:

Given the high prevalence of obstructive sleep apnea (OSA) and the demand on polysomnography (PSG), there is a need for low cost accurate simple diagnostic modalities that can be easily deployed in primary care to improve access to diagnosis.

Study Objectives:

The aim was to examine the utility of single-channel nasal airflow monitoring using a pressure transducer at home in patients with suspected OSA.

Design:

Cross-sectional study

Setting:

Laboratory and home

Participants:

The study was conducted in two populations. Consecutive patients with suspected OSA were recruited from the sleep disorders clinic at a tertiary referral center and from 6 local metropolitan primary care centers.

Interventions:

All patients answered questionnaires and had laboratory PSG. Nasal airflow was monitored for 3 consecutive nights at home in random order either before or after PSG.

Results:

A total of 193 patients participated (105 sleep clinic patients and 88 from primary care). The mean bias PSG apnea hypopnea index (AHI) minus nasal flow respiratory disturbance index (NF RDI) was –4.9 events per hour with limits of agreement (2 SD) of 27.8. NF RDI monitored over 3 nights had high accuracy for diagnosing both severe OSA (defined as PSG AHI > 30 events per hour) with area under the receiver operating characteristic curve (AUC) 0.92 (95% confidence interval (CI) 0.88-0.96) and any OSA (PSG AHI >5), AUC 0.87 (95% CI 0.80-0.94).

Conclusions:

Single-channel nasal airflow can be implemented as an accurate diagnostic tool for OSA at home in both primary care and sleep clinic populations.

Citation:

Makarie Rofail L; Wong KKH; Unger G; Marks GB; Grunstein RR. The utility of single-channel nasal airflow pressure transducer in the diagnosis of OSA at home. SLEEP 2010;33(8):1097-1105.     

Randomized Controlled Trial Comparing Flexible and Continuous Positive Airway Pressure Delivery: Effects on Compliance,Objective and Subjective Sleepiness and Vigilance

Study Objectives:

Positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) can be limited by suboptimal compliance. C-Flex technology (Philips Respironics, PA, USA) reduces pressure during expiration, aiming to improve comfort and therefore compliance. This may be of particular relevance to patients requiring high pressures. Many studies thus far have suffered from design limitations and small sample sizes. This study aimed to compare compliance with C-Flex and CPAP, as well as analyzing objective and subjective sleepiness and vigilance.

Design:

Three-month, double-blinded, parallel-arm randomized controlled trial.

Setting:

A university-based sleep laboratory.

Patients:

76 consecutive patients with severe OSA (mean ± SD AHI 60.2 ± 32.9 events/hour, ESS 13.6 ± 4.5/24, BMI 35.6 ± 7.8 kg/m²), without significant cardiac, respiratory, psychiatric, or sleep comorbidities.

Interventions:

Patients were randomized to C-Flex (dip level 2) or CPAP.

Measurements and Results:

Patients underwent titration with C-Flex/CPAP (mean pressure 11.6 cm H₂O). Modified maintenance of wakefulness tests (mod-MWT), psychomotor vigilance tasks (PVT) and questionnaires were administered at baseline and after one and 3 months. Median compliance was 5.51 and 5.89 h/ night in the C-Flex and CPAP groups respectively (P = 0.82). There were no significant differences between groups in terms of PVT reaction time, subjective sleepiness, sleep quality, health-related quality of life, or treatment comfort. There was no significant difference between the groups regarding the change in mod-MWT sleep latency values.

Conclusions:

In patients with severe OSA both CPAP and C-Flex resulted in substantial improvements in sleepiness, vigilance, and quality of life. The use of C-Flex did not result in greater compliance, and neither treatment appeared superior.

Citation:

Bakker J; Campbell A; Neill A. Randomized controlled trial comparing flexible and continuous positive airway pressure delivery: effects on compliance, objective and subjective sleepiness and vigilance. SLEEP 2010;33(4):523-529.     

Snoring and the Risk of Obstructive Sleep Apnea in Patients with Pulmonary Embolism

Background:

Obstructive sleep apnea (OSA) is associated with prothrombotic effects that could lead to venous thromboembolic disease. We performed a prospective cross-sectional study to determine the prevalence of snoring and risk of OSA in patients with acute pulmonary embolism (PE).

Methods:

We evaluated 270 consecutive patients who underwent a computed tomographic angiogram for suspected PE. Patients without PE served as a control group. Demographic and clinical characteristics were analyzed. The Berlin Questionnaire was used to determine the presence of snoring and the risk of OSA. A subset of patients also underwent formal nocturnal polysomnography.

Results:

PE was present in 71 (26%) of the 270 patients who underwent a computed tomographic angiogram. When compared with patients without PE, patients with PE had a significantly higher prevalence of snoring (75% vs 50%, odds ratio = 2.91, 95% confidence interval: 1.60, 5.33, P = 0.001) and an increased risk of having OSA, as defined by the Berlin Questionnaire (65% vs 36%, odds ratio = 3.25, confidence interval: 1.84, 5.72, P < 0.001). Results from the multivariate analysis showed that PE was independently associated with risk of OSA (OR = 2.78, P = 0.001).

Conclusions:

We found a higher prevalence of snoring and high risk of OSA in patients diagnosed with acute PE, in comparison with patients in whom PE was suspected but ruled out. This association might be independent of other risks factors common to both OSA and PE. Therefore, OSA may represent a risk factor for the development of PE.

Citation:

Epstein MD; Segal LN; Ibrahim SM; Friedman N; Bustami R. Snoring and the risk of obstructive sleep apnea in patients with pulmonary embolism. SLEEP 2010;33(8):1069-1074.     

Prospective Randomized Study of Patients with Insomnia and Mild Sleep Disordered Breathing

Background:

Patients with insomnia may present with mild and often unrecognized obstructive sleep apnea (OSA).

Objective:

To evaluate both subjective and objective outcomes of patients with complaints of insomnia and mild OSA who receive surgical treatment for OSA versus behavioral treatment with cognitive behavioral therapy for insomnia (CBT-I).

Methods:

Prospective study with crossover design of 30 patients with complaints of insomnia and mild OSA. Thirty subjects, matched for age and gender, were randomized with stratification to receive either CBT-I or surgical treatment of OSA as primary treatment. Patients were reassessed after completing the initial intervention and reassigned if agreeable to the alternative treatment option and assessed again on completion of both treatment arms. Outcome measures included clinical impression, Epworth Sleepiness Scale (ESS) score, Fatigue Severity Scale (FSS) score, and polysomnography (PSG) results.

Results:

Surgery resulted in greater improvements in total sleep time (TST), slow wave sleep and REM sleep duration, respiratory disturbance index, apnea-hypopnea index, minimum oxygen saturation, FSS, and ESS. CBT-I also improved TST and resulted in shorter sleep latency.

Conclusion:

Surgical intervention for the management of patients with complaints of insomnia and mild OSA demonstrated greater improvement in both subjective and objective outcome measures. Initial treatment of underlying OSA in patients with insomnia was more successful in improving insomnia than CBT-I alone. However CBT-I as initial treatment improved TST compared to baseline; following surgical intervention, it had the additional benefit of further increasing TST and helped to control sleep onset difficulties that may be related to conditioning due to unrecognized symptoms of mild OSA.

Citation:

Guilleminault C; Davis K; Huynh NT. Prospective randomized study of patients with insomnia and mild sleep disordered breathing. SLEEP 2008;31(11):1527–1533     

Prediction of Obstructive Sleep Apnea with Craniofacial Photographic Analysis

Study Objectives:

To develop models based on craniofacial photographic analysis for the prediction of obstructive sleep apnea (OSA).

Design:

Prospective cohort study.

Setting:

Sleep investigation unit in a university teaching hospital.

Patients:

One hundred eighty subjects (95.6% Caucasian) referred for the initial investigation of OSA were recruited consecutively.

Interventions:

Clinical assessment and frontal-profile craniofacial photographic analyses were performed prior to polysomnography. Prediction models for determining the presence of OSA (apnea-hypopnea index [AHI] ≥ 10) were developed using logistic regression analysis and classification and regression trees (CART).

Measurements and Results:

Obstructive sleep apnea was present in 63.3% of subjects. Using logistic regression, a model with 4 photographic measurements (face width, eye width, cervicomental angle, and mandibular length 1) correctly classified 76.1% of subjects with and without OSA (sensitivity 86.0%, specificity 59.1%, area under the receiver operating characteristics curve [AUC] 0.82). Combination of photographic and other clinical data improved the prediction (AUC 0.87), whereas prediction based on clinical assessment alone was lower (AUC 0.78). The optimal CART model provided a similar overall classification accuracy of 76.7%. Based on this model, 59.4% of the subjects were classified as either high or low risk with positive predictive value of 90.9% and negative predictive value of 94.7%, respectively. The remaining 40.6% of subjects have intermediate risk of OSA.

Conclusions:

Craniofacial photographic analysis provides detailed anatomical data useful in the prediction of OSA. This method allows OSA risk stratification by craniofacial morphological phenotypes.

Citation:

Lee RWW; Petocz P; Prvan T; Chan ASL; Grunstein RR; Cistulli PA. Prediction of obstructive sleep apnea with craniofacial photographic analysis. SLEEP 2009;32(1):46-52.     

Slow Wave Sleep and REM Sleep Awakenings Do Not Affect Sleep Dependent Memory Consolidation

Study Objectives:

The effects of REM sleep and slow wave sleep (SWS) deprivation on sleep-dependent motor and declarative memory consolidation.

Design:

Randomized, within-subject, cross-over study

Setting:

Weekly (women: monthly) sleep laboratory visits, with retest 60 hours later

Participants:

Twelve healthy subjects (6 men) aged between 20 and 30 years

Interventions:

REM sleep deprivation, SWS deprivation, or undisturbed sleep

Measurements and Results:

We deprived subjects once each of REM sleep and SWS, and once let them sleep undisturbed through the night. After each night, we tested declarative and procedural memory consolidation. We tested memory performance by a verbal paired associate task and a sequential finger-tapping task at 21:00 on the study night and again 60 hours later. Although REM sleep and SWS awakenings led to a significant reduction of the respective sleep stages, memory consolidation remained unaffected. We also found a significant correlation between the declarative task and sleep spindles in the undisturbed condition, especially the sleep spindles in the first third of the night.

Conclusion:

We suggest that word-pair learning relies on stage 2 sleep spindles and requires little SWS. Their sleep dependent consolidation is not affected by SWS deprivation. Simple motor tasks may either be consolidated in stage 2 sleep or depend on only small amounts of REM sleep. Their sleep dependent consolidation is not influenced by REM sleep deprivation.

Citation:

Genzel L; Dresler M; Wehrle R; Grözinger M; Steiger A. Slow wave sleep and REM sleep awakenings do not affect sleep dependent memory consolidation. SLEEP 2009;32(3):302–310.     

Idiopathic Hypersomnia with and without Long Sleep Time: A Controlled Series of 75 Patients

Objective:

To characterize the clinical, psychological, and sleep pattern of idiopathic hypersomnia with and without long sleep time, and provide normative values for 24-hour polysomnography.

Setting:

University Hospital

Design:

Controlled, prospective cohort

Participants:

75 consecutive patients (aged 34 ± 12 y) with idiopathic hypersomnia and 30 healthy matched controls.

Intervention:

Patients and controls underwent during 48 hours a face-to face interview, questionnaires, human leukocyte antigen genotype, a night polysomnography and multiple sleep latency test (MSLT), followed by 24-h ad libitum sleep monitoring.

Results:

Hypersomniacs had more fatigue, higher anxiety and depression scores, and more frequent hypnagogic hallucinations (24%), sleep paralysis (28%), sleep drunkenness (36%), and unrefreshing naps (46%) than controls. They were more frequently evening types. DQB1*0602 genotype was similarly found in hypersomniacs (24.2%) and controls (19.2%). Hypersomniacs had more frequent slow wave sleep after 06:00 than controls. During 24-h polysomnography, the 95% confidence interval for total sleep time was 493–558 min in controls, versus 672–718 min in hypersomniacs. There were 40 hypersomniacs with and 35 hypersomniacs without long ( > 600 min) sleep time. The hypersomniacs with long sleep time were younger (29 ± 10 vs 40 ± 13 y, P = 0.0002), slimmer (body mass index: 26 ± 5 vs 23 ± 4 kg/m²; P = 0.005), and had lower Horne-Ostberg scores and higher sleep efficiencies than those without long sleep time. MSLT latencies were normal ( > 8 min) in 71% hypersomniacs with long sleep time.

Conclusions:

Hypersomnia, especially with long sleep time, is frequently associated with evening chronotype and young age. It is inadequately diagnosed using MSLT.

Citation:

Vernet C; Arnulf I. Idiopathic Hypersomnia with and without Long Sleep Time: A Controlled Series of 75 Patients. SLEEP 2009;32(6):753-759.     

Enhancing Slow Wave Sleep with Sodium Oxybate Reduces the Behavioral and Physiological Impact of Sleep Loss

Study Objectives:

To investigate whether enhancement of slow wave sleep (SWS) with sodium oxybate reduces the impact of sleep deprivation.

Design:

Double-blind, parallel group, placebo-controlled design

Setting:

Sleep research laboratory

Participants:

Fifty-eight healthy adults (28 placebo, 30 sodium oxybate), ages 18-50 years.

Interventions:

A 5-day protocol included 2 screening/baseline nights and days, 2 sleep deprivation nights, each followed by a 3-h daytime (08:00-11:00) sleep opportunity and a recovery night. Sodium oxybate or placebo was administered prior to each daytime sleep period. Multiple sleep latency test (MSLT), psychomotor vigilance test (PVT), Karolinska Sleepiness Scale (KSS), and Profile of Mood States were administered during waking hours.

Measurements and Results:

During daytime sleep, the sodium oxybate group had more SWS, more EEG spectral power in the 1-9 Hz range, and less REM. Mean MSLT latency was longer for the sodium oxybate group on the night following the first daytime sleep period and on the day following the second day sleep period. Median PVT reaction time was faster in the sodium oxybate group following the second day sleep period. The change from baseline in SWS was positively correlated with the change in MSLT and KSS. During recovery sleep the sodium oxybate group had less TST, SWS, REM, and slow wave activity (SWA) than the placebo group.

Conclusions:

Pharmacological enhancement of SWS with sodium oxybate resulted in a reduced response to sleep loss on measures of alertness and attention. In addition, SWS enhancement during sleep restriction appears to result in a reduced homeostatic response to sleep loss.

Citation:

Walsh JK; Hall-Porter JM; Griffin KS; Dodson ER; Forst EH; Curry DT; Eisenstein RD; Schweitzer PK. Enhancing slow wave sleep with sodium oxybate reduces the behavioral and physiological impact of sleep loss. SLEEP 2010;33(9):1217-1225.     

Differences in Craniofacial Structures and Obesity in Caucasian and Chinese Patients with Obstructive Sleep Apnea

Study Objectives:

To explore differences in craniofacial structures and obesity between Caucasian and Chinese patients with obstructive sleep apnea (OSA).

Design:

Inter-ethnic comparison study.

Setting:

Two sleep disorder clinics in Australia and Hong Kong.

Patients:

150 patients with OSA (74 Caucasian, 76 Chinese).

Interventions:

Anthropometry, cephalometry, and polysomnography were performed and compared. Subgroup analyses after matching for: (1) body mass index (BMI); (2) OSA severity.

Measurements and Results:

The mean age and BMI were similar between the ethnic groups. Chinese patients had more severe OSA (AHI 35.3 vs 25.2 events/h, P = 0.005). They also had more craniofacial bony restriction, including a shorter cranial base (63.6 ± 3.3 vs 77.5 ± 6.7 mm, P < 0.001), maxilla (50.7 ± 3.7 vs 58.8 ± 4.3 mm, P < 0.001) and mandible length (65.4 ± 4.2 vs 77.9 ± 9.4 mm, P < 0.001). These findings remained after correction for differences in body height. Similar results were shown in the BMI-matched analysis (n = 66). When matched for OSA severity (n = 52), Chinese patients had more craniofacial bony restriction, but Caucasian patients were more overweight (BMI 30.7 vs 28.4 kg/m², P = 0.03) and had a larger neck circumference (40.8 vs 39.1 cm, P = 0.004); however, the ratios of BMI to the mandible or maxilla size were similar.

Conclusions:

Craniofacial factors and obesity contribute differentially to OSA in Caucasian and Chinese patients. For the same degree of OSA severity, Caucasians were more overweight, whereas Chinese exhibited more craniofacial bony restriction.

Citation:

Lee RWW; Vasudavan S; Hui DS; Prvan T; Petocz P; Darendeliler MA; Cistulli PA. Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea. SLEEP 2010;33(8):1075-1080.     

Airway Dilator Muscle Activity and Lung Volume During Stable Breathing in Obstructive Sleep Apnea

Study Objectives:

Many patients with obstructive sleep apnea (OSA) have spontaneous periods of stable flow limited breathing during sleep without respiratory events or arousals. In addition, OSA is often more severe during REM than NREM and more severe during stage 2 than slow wave sleep (SWS). The physiological mechanisms for these observations are unknown. Thus we aimed to determine whether the activity of two upper airway dilator muscles (genioglossus and tensor palatini) or end-expiratory lung volume (EELV) differ between (1) spontaneously occurring stable and cyclical breathing and (2) different sleep stages in OSA.

Design:

Physiologic observation.

Setting:

Sleep physiology laboratory.

Study Participants:

15 OSA patients with documented periods of spontaneous stable breathing.

Intervention:

Subjects were instrumented with intramuscular electrodes for genioglossus and tensor palatini electromyograms (EMG_GG and EMG_TP), chest and abdominal magnetometers (EELV measurement), an epiglottic pressure catheter (respiratory effort), and a mask and pneumotachograph (airflow/ventilation). Patients slept supine overnight without CPAP.

Measurements and Results:

Peak and Tonic EMG_GG were significantly lower during cyclical (85.4 ± 2.7 and 94.6 ± 4.7 % total activity) than stable breathing (109.4 ± 0.4 and 103 ± 0.8 % total activity, respectively). During respiratory events in REM, tonic EMG_GG activity was lower than during respiratory events in stage 2 (71.9 ± 5.1 and 119.6 ± 5.6 % total activity). EMG_GG did not differ between stable stage 2 and stable SWS (98.9 ± 3.2 versus 109.7 ± 4.4 % total activity), nor did EMG_TP or EELV differ in any breathing condition/sleep stage.

Conclusions:

Increased genioglossus muscle tone is associated with spontaneous periods of stable flow limited breathing in the OSA subjects studied. Reductions in genioglossus activity during REM may explain the higher severity of OSA in that stage. Increased lung volume and tensor palatini activity do not appear to be major mechanisms enabling spontaneous stable flow limited breathing periods.

Citation:

Jordan AS; White DP; Lo YL; Wellman A; Eckert DJ; Yim-Yeh S; Eikermann M; Smith SA; Stevenson KE; Malhotra A. Airway dilator muscle activity and lung volume during stable breathing in obstructive sleep apnea. SLEEP 2009;32(3):361–368.     

Relationship Between Obstructive Sleep Apnea Severity and Brain Activation During a Sustained Attention Task

Study Objectives:

The objectives of this study were to (1) characterize cognitive and cerebral correlates of attention and response speed in patients with obstructive sleep apnea (OSA) and (2) assess the association of performance and brain activation with measures of OSA severity.

Design:

Patients with OSA and controls were compared on performance and brain activation during a sustained attention task. The association of reaction time and brain activation with apnea-hypopnea index, nocturnal hypoxia, and arousals was assessed.

Setting:

Functional magnetic resonance imaging was conducted while participants performed a Go–No-Go task. The ‘Go’ trials of the Go–No-Go task were used to index attention processing.

Participants:

Fourteen patients with OSA and 14 normal control subjects with equivalent age, body mass index, blood pressure, and education.

Interventions:

N/A.

Measurements and Results:

Patients with OSA showed decreased brain activation in cingulate, frontal, and parietal regions typically involved in attention tasks, compared with control subjects. Within the patients with OSA, increasing arousal index, but not desaturation index, was associated with slower mean reaction time and with decreased brain activation in areas involved in arousal and attention, response selection, motor response, and decision making. The apnea-hypopnea index, by itself, was not associated with changes in cerebral response.

Conclusions:

Patients with OSA showed decreased brain activation compared with control subjects during an attention task. The association of arousal index (but not hypoxia) with slow reaction times and brain activation suggests that alertness and reaction times show greater correlations with measures of sleep disruption than with measures of hypoxia.

Citation:

Ayalon L; Ancoli-Israel S; Aka AA; McKenna BS; Drummond SPA. Relationship between obstructive sleep apnea severity and brain activation during a sustained attention task. SLEEP 2009;32(3):373–381.     

Obstructive Sleep Apnea: A Risk Factor for Work Disability

Study Objective:

To examine obstructive sleep apnea (OSA) as a risk factor for work disability.

Patients and Setting:

Consecutive patients referred to the University of California San Francisco Sleep Disorders Center with suspected OSA (n = 183).

Design:

All patients underwent overnight polysomnography after completing a written survey which assessed work disability due to sleep problems, occupational characteristics and excessive daytime sleepiness (EDS) defined as an Epworth Sleepiness Scale score > 10.

Results:

Among 150 currently employed patients, 83 had OSA on polysomnography (apnea-hypopnea index ≥ 5). Compared with patients in whom both OSA and EDS were absent, patients with the combination of OSA and EDS were at higher risk of both recent work disability (adjusted odds ratio [OR], 13.7; 95% confidence interval [CI], 3.9–48) and longer-term work duty modification (OR, 3.6; CI, 1.1–12). When either OSA or EDS were absent, the strength of the association with work disability was less than when both OSA and EDS were present. When OSA was examined without respect to EDS, patients with OSA were at increased risk of recent work disability relative to patients without OSA (OR 2.6; 95% CI 1.2–5.8), but the association of OSA with longer-term work duty modification did not meet standard criteria for statistical significance (OR = 2.0, 95% CI 0.8–5.0).

Conclusions:

The combination of OSA and EDS contributes to work disability, and OSA by itself contributes to recent work disability. These findings should highlight to employers and clinicians the importance of OSA in the workplace to encourage patients to be screened for OSA, particularly in situations of decreased productivity associated with EDS.

Citation:

Omachi TA; Claman DM; Blanc PD; Eisner MD. Obstructive sleep apnea: a risk factor for work disability. SLEEP 2009;32(6):791-798.     

The association between sleep disordered breathing, academic grades, and cognitive and behavioral functioning among overweight subjects during middle to late childhood

Study Objectives:

(1) to determine the associations of sleep disordered breathing (SDB) with behavioral functioning, cognitive test scores, and school grades during middle- to late-childhood, an under-researched developmental period in the SDB literature, and (2) to clarify whether associations between SDB and school grades are mediated by deficits in cognitive or behavioral functioning.

Design:

Cross-sectional correlative study.

Setting:

Office/hospital, plus reported functioning at home and at school.

Participants:

163 overweight subjects aged 10-16.9 years were divided into 4 groups based upon their obstructive apnea+hypopnea index (AHI) during overnight polysomnography and parent report of snoring: Moderate-Severe OSA (AHI > 5, n = 42), Mild OSA (AHI = 1-5, n = 58), Snorers (AHI < 1 + snoring, n = 26), and No SDB (AHI < 1 and nonsnoring, n = 37).

Measurements:

Inpatient overnight polysomnography, parent- and self-report of school grades and sleep, parent- and teacher-report of daytime behaviors, and office-based neuropsychological testing.

Results:

The 4 groups significantly differed in academic grades and parent- and teacher-reported behaviors, particularly inattention and learning problems. These findings remained significant after adjusting for subject sex, race, socioeconomic status, and school night sleep duration. Associations with SDB were confined to reports of behavioral difficulties in real-world situations, and did not extend to office-based neuropsychological tests. Findings from secondary analyses were consistent with, but could not definitively confirm, a causal model in which SDB affects school grades via its impact on behavioral functioning.

Conclusions:

SDB during middle- to late-childhood is related to important aspects of behavioral functioning, especially inattention and learning difficulties, that may result in significant functional impairment at school.

Citation:

Beebe DW; Ris MD; Kramer ME; Long E; Amin R. The association between sleep disordered breathing, academic grades, and cognitive and behavioral functioning among overweight subjects during middle to late childhood. SLEEP 2010;33(11):1447-1456.     

Obstructive Sleep Apnea and Aging Effects on Macrovascular and Microcirculatory Function

Study Objectives:

Many patients with obstructive sleep apnea (OSA) are obese, and whether obesity itself explains the increased prevalence of cardiovascular disease in OSA is unknown.We hypothesize that OSA, independent of obesity, contributes to abnormal vascular function.

Design:

Physiology study.

Setting:

Academic medical centers.

Patients:

Obese subjects, free of known comorbidities, were enrolled.

Measurements and Results:

Vascular function was assessed with brachial artery ultrasound for flow-mediated dilation (FMD) and in skin microcirculation by laser Doppler flowmetry. Arterial stiffness was measured by arterial tonometry. Seventy-two subjects (43/72 women, 38/72 with OSA) were studied. FMD was impaired in patients with OSA, compared with control subjects (5.7% ± 3.8% vs 8.3% ± 4.1%, P = 0.005). In step-forward regression analysis inclusive of age, sex, and body mass index, age (P = 0.013) was a significant independent predictor of FMD. In a subgroup of subjects younger than 50 years of age (n = 59), however, OSA was the only independent predictor of FMD (P = 0.04), adjusted for known covariates. OSA did not significantly influence vascular function in the skin microcirculation. The augmentation index, a measure of arterial stiffness, was similar between the OSA and control groups (16.2% ± 11.4% vs 20.4% ± 10.1%, respectively, P = 0.10). In step-forward regression analysis of younger men (≤ 50 years old, 23 subjects), OSA independently predicted the augmentation index in men only (P = 0.001).

Conclusions:

In obesity, both OSA and aging impair endothelial function and increase arterial stiffness. The influence of OSA on vascular function is most pronounced in young subjects. OSA, therefore, may be associated with functional impairment (“a premature aging effect”) on the endothelium and on arterial stiffness (in men), although skin microcirculatory function appears preserved.

Citation:

Yim-Yeh S; Rahangdale S; Nguyen ATD; Jordan AS; Novack V; Veves A; Malhotra A. Obstructive sleep apnea and aging effects on macrovascular and microcirculatory function. SLEEP 2010;33(9):1177-1183.     

Night Shift Performance is Improved by a Compromise Circadian Phase Position: Study 3. Circadian Phase after 7 Night Shifts with an Intervening Weekend Off

Study Objective:

To produce a compromise circadian phase position for permanent night shift work in which the sleepiest circadian time is delayed out of the night work period and into the first half of the day sleep period. This is predicted to improve night shift alertness and performance while permitting adequate late night sleep on days off.

Design:

Between-subjects.

Setting:

Home and laboratory.

Participants:

24 healthy subjects.

Interventions:

Subjects underwent 3 simulated night shifts, 2 days off, and 4 more night shifts. Experimental subjects received five, 15 minute bright light pulses from light boxes during night shifts, wore dark sunglasses when outside, slept in dark bedrooms at scheduled times after night shifts and on days off, and received outdoor afternoon light exposure (the “light brake”). Control subjects remained in normal room light during night shifts, wore lighter sunglasses, and had unrestricted sleep and outdoor light exposure.

Measurements and Results:

The final dim light melatonin onset (DLMO) of the experimental group was ∼04:30, close to our target compromise phase position, and significantly later than the control group at ∼00:30. Experimental subjects performed better than controls, and slept for nearly all of the allotted time in bed. By the last night shift, they performed almost as well during the night as during daytime baseline. Controls demonstrated pronounced performance impairments late in the night shifts, and exhibited large individual differences in sleep duration.

Conclusions:

Relatively inexpensive and feasible interventions can produce adaptation to night shift work while still allowing adequate nighttime sleep on days off.

Citation:

Smith MR; Eastman CI. Night shift performance is improved by a compromise circadian phase position: study 3. Circadian phase after 7 night shifts with an intervening weekend off. SLEEP 2008;31(12):1639–1645.     

Prospective Trial of Efficacy and Safety of Ondansetron and Fluoxetine in Patients with Obstructive Sleep Apnea Syndrome

Study Objective:

Incremental withdrawal of serotonin during wake to sleep transition is postulated as a key mechanism that renders the pharyngeal airway collapsible. While serotonin promotion with reuptake inhibitors have demonstrated modest beneficial effects during NREM sleep on obstructive sleep apnea (OSA), animal studies suggest a potential therapeutic role for selective serotonin receptor antagonists (5-HT₃) in REM sleep. We aimed to test the hypothesis that a combination of ondansetron (Ond) and fluoxetine (Fl) may effectively reduce expression of disordered breathing during REM and NREM sleep in patients with OSA.

Design and Setting:

A prospective, parallel-groups, single-center trial in patients with OSA.

Participants:

35 adults with apnea hypopnea index (AHI) > 10; range 10-98.

Intervention:

Subjects were randomized to placebo, n = 7; Ond (24 mg QD), n = 9; Fl (5 mg QD) + Ond (12 mg QD), n = 9; and Fl (10 mg QD) + Ond (24 mg QD), n = 10.

Measurements and Results:

AHI was measured by in-lab polysomnography after a 7-day no-treatment period (Baseline) and on days 14 and 28 of treatment. The primary endpoint was AHI reduction at days 14 and 28. OND+FL resulted in approximately 40% reduction of baseline AHI at days 14 and 28 (unadjusted P < 0.03 for each) and improved oximetry trends. This treatment-associated relative reduction in AHI was also observed in REM and supine sleep.

Conclusions:

Combined treatment with OND+FL is well-tolerated and reduces AHI, yielding a potentially therapeutic response in some subjects with OSA.

Citation:

Prasad B; Radulovacki M; Olopade C; Herdegen JJ; Logan T; Carley DW. Prospective trial of efficacy and safety of ondansetron and fluoxetine in patients with obstructive sleep apnea syndrome. SLEEP 2010;33(7):982-989.