Associations of Moderate to Severe Asthma with Obstructive Sleep Apnea

Purpose

This study aimed to evaluate the correlation between associating factors of moderate to severe asthma with obstructive sleep apnea (OSA).

Materials and Methods

One hundred and sixty-seven patients who visited the pulmonary and sleep clinic in Severance Hospital presenting with symptoms of sleep-disordered breathing were evaluated. All subjects were screened with ApneaLink. Thirty-two subjects with a high likelihood of having OSA were assessed with full polysomnography (PSG).

Results

The mean age was 58.8±12.0 years and 58.7% of subjects were male. The mean ApneaLink apnea-hypopnea index (AHI) was 12.7±13.0/hr. The mean ApneaLink AHI for the 32 selected high risk patients of OSA was 22.3±13.2/hr, which was lower than the sleep laboratory-based PSG AHI of 39.1±20.5/hr. When OSA was defined at an ApneaLink AHI ≥5/hr, the positive correlating factors for OSA were age, male gender, and moderate to severe asthma.

Conclusion

Moderate to severe asthma showed strong correlation with OSA when defined at an ApneaLink AHI ≥5/hr.     

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.     

Effect of Continuous Positive Airway Pressure on Sleep Structure in Heart Failure Patients with Central Sleep Apnea

Study Objectives:

At termination of obstructive apneas, arousal is a protective mechanism that facilitates restoration of upper airway patency and airflow. Treating obstructive sleep apnea (OSA) by continuous positive airway pressure (CPAP) reduces arousal frequency indicating that such arousals are caused by OSA. In heart failure (HF) patients with central sleep apnea (CSA), however, arousals frequently occur several breaths after apnea termination, and there is uncertainty as to whether arousals from sleep are a consequence of CSA. If so, they should diminish in frequency when CSA is attenuated. We therefore sought to determine whether attenuation of CSA by CPAP reduces arousal frequency.

Design:

Randomized controlled clinical trial.

Patients and Setting:

We examined data from 205 HF patients with CSA (apnea-hypopnea index [AHI] ≥ 15, > 50% were central) randomized to CPAP or control who had polysomnograms performed at baseline and 3 months later.

Measurements and Results:

In the control group, there was no change in AHI or frequency of arousals. In the CPAP-treated group, the AHI decreased significantly (from [mean ± SD] 38.9 ± 15.0 to 17.6 ± 16.3, P < 0.001) but neither the frequency of arousals nor sleep structure changed significantly.

Conclusion:

These data suggest that attenuation of CSA by CPAP does not reduce arousal frequency in HF patients. We conclude that arousals were not mainly a consequence of CSA, and may not have been acting as a defense mechanism to terminate apneas in the same way they do in OSA.

Citation:

Ruttanaumpawan P; Logan AG; Floras JS; Bradley TD. Effect of Continuous Positive Airway Pressure on Sleep Structure in Heart Failure Patients with Central Sleep Apnea. SLEEP 2009;32(1):91-98.     

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.     

The Relative Impact of Obstructive Sleep Apnea and Hypertension on the Structural and Functional Changes of the Thoracic Aorta

Background:

Recent studies suggest that obstructive sleep apnea (OSA) causes thoracic aortic dilatation; but it is well accepted that hypertension can cause aortic dilatation, and hypertension is a common finding in patients with OSA. We aimed to investigate the relative impact of OSA and hypertension on the structural and functional changes of the thoracic aorta.

Methods:

This was an echocardiography substudy of our prospective OSA study in patients with acute myocardial infarction (AMI). Ninety-four male patients who completed both echocardiography and polysomnography were recruited. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15/hour.

Results:

The patients'' mean age was 53 ± 10 years, and mean body mass index (BMI) was 24.6 ± 3kg/m². Sixty-four (68.1%) patients had OSA; of these, 39 (41.5%) had severe OSA. Thirty-three (52.6%) of the OSA cohort had hypertension. There was no correlation between any of the echocardiographic parameters and thoracic aortic size. Stepwise multivariate regression showed that BMI (P = 0.024), older age (P = 0.044), and hypertension (P = 0.025) were the only determinants. There was no significant independent relationship between OSA/ AHI and thoracic aortic size. Systolic blood pressure but not AHI correlated significantly with aortic distensibility and compliance (r = −0.40 and −0.26, P < 0.001 and 0.022, respectively).

Conclusions:

Hypertension is a common finding in male AMI patients with OSA. In these patients, increased afterload from systemic hypertension rather than mechanical stress on the aortic wall determines the thoracic aortic size and abnormalities in aortic functional indices. BMI and age were also independent predictors of thoracic aortic dilatation.

Citation:

Lee LC; Torres MC; Khoo SM; Chong EY; Lau C; Than Y; Shi DX; Kailasam A; Poh KK; Lee CH; Yeo TC. The relative impact of obstructive sleep apnea and hypertension on the structural and functional changes of the thoracic aorta. SLEEP 2010;33(9):1173-1176.     

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.     

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.     

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.     

Comparison of Mandibular Advancement Splint and Tongue Stabilizing Device in Obstructive Sleep Apnea: A Randomized Controlled Trial

Study Objectives:

To compare the efficacy of a mandibular advancement splint (MAS) and a novel tongue stabilizing device (TSD) in the treatment of obstructive sleep apnea (OSA).

Design:

A randomized crossover design was used.

Patients:

Twenty-seven patients (20 male, 7 female), recruited from a tertiary hospital sleep clinic.

Measurements and Results:

The apnea-hypopnea index (AHI) was reduced with MAS (11.68 ± 8.94, P = 0.000) and TSD (13.15 ± 10.77, P = 0.002) compared with baseline (26.96 ± 17.17). The arousal index decreased for MAS (21.09 ± 9.27, P = 0.004) and TSD (21.9 ± 10.56, P = 0.001) compared with baseline (33.23 ± 16.41). Sixty-eight percent of patients achieved a complete or partial response with MAS, compared with 45% with TSD. The Epworth Sleepiness Scale (ESS) score was decreased with MAS (P = <0.001) and TSD (P = 0.002). Subjective improvements in snoring and quality of sleep were reported, with a better response for MAS than TSD. Compliance was poorer for TSD, and the side effect profiles of the 2 modalities were different. All patients were satisfied with MAS compared to TSD, and 91% of patients preferred the MAS.

Conclusion:

Objective testing showed the MAS and TSD had similar efficacy in terms of AHI reduction. Patients reported improvements with both devices; however, better compliance and a clear preference for MAS was apparent when both devices were offered. Longer term studies are needed to clarify the role of TSD.

Citation:

Deane SA; Cistulli PA; Ng AT; Zeng B; Petocz P; Darendeliler MA. Comparison of mandibular advancement splint and tongue stabilizing device in obstructive sleep apnea: a randomized controlled trial. SLEEP 2009;32(5):648-653.     

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.     

Development of the FOSQ-10: A Short Version of the Functional Outcomes of Sleep Questionnaire

Introduction:

The Functional Outcomes of Sleep Questionnaire (FOSQ), has been used in research and clinical practice to measure the impact of daytime sleepiness on activities of daily living. The purpose of this study was to develop a shorter version of the instrument (FOSQ-10) that may be more easily implemented in clinical practice.

Methods:

Data from a study of CPAP-treated obstructive sleep apnea (OSA) patients (Sample 1) (n = 155, AHI = 63 ± 31) were used to develop the FOSQ-10. Of the 30 original FOSQ items, 10 questions representing each of the 5 subscales were selected if they had a normal distribution of responses and the largest pre- to post-treatment effect size. The psychometric properties of the instrument were then evaluated with data from a second, independent sample of CPAP-treated OSA patients (n = 51 AH I = 51 ± 28).

Results:

Internal consistency of the FOSQ-10 was α = 0.87. Pre-treatment correlations of the 2 scales was r = 0.96. After 3 months of treatment the correlation was r = 0.97 (P < 0.0001). Subscales were also highly correlated at baseline and following treatment. Effect sizes for both instruments were highly correlated and indicated ability to measure meaningful change. Differences were observed between scores on the FOSQ-10 for normal controls and OSA patients.

Conclusions:

The FOSQ-10 is a psychometrically strong instrument that performs similarly to the long version. The rapidly completed and easily scored FOSQ-10 shows promise for application in the clinical setting.

Citation:

Chasens ER; Ratcliffe SJ; Weaver TE. Development of the FOSQ-10: a short version of the functional outcomes of sleep questionnaire. SLEEP 2009;32(7):915-919.     

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.     

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.     

Associations Between Obstructive Sleep Apnea,Metabolic Syndrome,and Sleep Duration,As Measured With an Actigraph,in an Urban Male Working Population in Japan

Background:

Severe obstructive sleep apnea (OSA), metabolic syndrome (Mets) and short sleep duration are all risk factors for cardiovascular events. There has been no report which has investigated this relationship in an age- and BMI-matched population-based study. The prevalence of OSA in Mets subjects has not been established, although the converse (i.e., the prevalence of Mets in OSA subjects) has been investigated several times.

Methods:

This home cardiorespiratory (type 3) sleep study, using an actigraph, was conducted in 275 males working for an urban company. Retrospective measurements of fasting blood parameters were obtained from the company''s periodical inspection data. The mean duration between the sleep study and the measurement of blood parameters was 213 days.

Results:

Although there was a significant relationship between OSA severity and the prevalence of Mets (P < 0.001), the association between severity and Mets was not significant after adjustments were made for age and BMI. Severe OSA was 7.8 times as likely to be present in subjects with Mets (16.2% of all 68 Mets subjects) as those without (2.4% of 207 non-Mets) (P < 0.001). Subject with severe OSA had a significantly short sleep duration (P < 0.05). Sleep duration in Mets subjects was also significantly shorter than in those without (P < 0.05).

Conclusions:

Although increased BMI and age both had a significant effect on the prevalence of OSA in patients with Mets, one of 6 subjects with Mets, but only one of 40 without Mets had severe OSA in an urban male population in Japan. Physicians should take into account this high prevalence of severe OSA in patients with Mets. Sleep duration should be taken into consideration as an important factor in studies investigating the prevalence of severe OSA and Mets.

Citation:

Chin K; Oga T; Takahashi K; Takegami M; Nakayama-Ashida Y; Wakamura T; Sumi K; Nakamura T; Horita S; Oka Y; Minami I; Fukuhara S; Kadotani H. Associations between obstructive sleep apnea, metabolic syndrome, and sleep duration, as measured with an actigraph, in an urban male working population in Japan. SLEEP 2010;33(1):89-95.     

Insomnia with Short Sleep Duration and Mortality: The Penn State Cohort

Study Objectives:

Because insomnia with objective short sleep duration is associated with increased morbidity, we examined the effects of this insomnia subtype on all-cause mortality.

Design:

Longitudinal.

Setting:

Sleep laboratory.

Participants:

1,741 men and women randomly selected from Central Pennsylvania.

Measurements:

Participants were studied in the sleep laboratory and were followed-up for 14 years (men) and 10 years (women). “Insomnia” was defined by a complaint of insomnia with duration ≥ 1 year. “Normal sleeping” was defined as absence of insomnia. Polysomnographic sleep duration was classified into two categories: the “normal sleep duration group” subjects who slept ≥ 6 h and the “short sleep duration group” subjects who slept < 6 h. We adjusted for age, race, education, body mass index, smoking, alcohol, depression, sleep disordered breathing, and sampling weight.

Results:

The mortality rate was 21% for men and 5% for women. In men, mortality risk was significantly increased in insomniacs who slept less than 6 hours compared to the “normal sleep duration, no insomnia” group, (OR = 4.00, CI 1.14-13.99) after adjusting for diabetes, hypertension, and other confounders. Furthermore, there was a marginally significant trend (P = 0.15) towards higher mortality risk from insomnia and short sleep in patients with diabetes or hypertension (OR = 7.17, 95% CI 1.41-36.62) than in those without these comorbid conditions (OR = 1.45, 95% CI 0.13-16.14). In women, mortality was not associated with insomnia and short sleep duration.

Conclusions:

Insomnia with objective short sleep duration in men is associated with increased mortality, a risk that has been underestimated.

Citation:

Vgontzas AN; Liao D; Pejovic S; Calhoun S; Karataraki M; Basta M; Fernández-Mendoza J; Bixler EO. Insomnia with short sleep duration and mortality: the Penn State Cohort. SLEEP 2010;33(9):1159-1164.     

Sleep Disorders and their Association with Laboratory Pain Sensitivity in Temporomandibular Joint Disorder

Study Objectives:

We characterized sleep disorder rates in temporomandibular joint disorder (TMD) and evaluated possible associations between sleep disorders and laboratory measures of pain sensitivity.

Design:

Research diagnostic examinations were conducted, followed by two consecutive overnight polysomnographic studies with morning and evening assessments of pain threshold.

Setting:

Orofacial pain clinic and inpatient sleep research facility

Participants:

Fifty-three patients meeting research diagnostic criteria for myofascial TMD.

Interventions:

N/A

Measurements and Results:

We determined sleep disorder diagnostic rates and conducted algometric measures of pressure pain threshold on the masseter and forearm. Heat pain threshold was measured on the forearm; 75% met self-report criteria for sleep bruxism, but only 17% met PSG criteria for active sleep bruxism. Two or more sleep disorders were diagnosed in 43% of patients. Insomnia disorder (36%) and sleep apnea (28.4%) demonstrated the highest frequencies. Primary insomnia (PI) (26%) comprised the largest subcategory of insomnia. Even after controlling for multiple potential confounds, PI was associated with reduced mechanical and thermal pain thresholds at all sites (P < 0.05). Conversely, the respiratory disturbance index was associated with increased mechanical pain thresholds on the forearm (P < 0.05).

Conclusions:

High rates of PI and sleep apnea highlight the need to refer TMD patients complaining of sleep disturbance for polysomnographic evaluation. The association of PI and hyperalgesia at a non-orofacial site suggests that PI may be linked with central sensitivity and could play an etiologic role in idiopathic pain disorders. The association between sleep disordered breathing and hypoalgesia requires further study and may provide novel insight into the complex interactions between sleep and pain-regulatory processes.

Citation:

Smith MT; Wickwire EM; Grace EG; Edwards RR; Buenaver LF; Peterson S; Klick B; Haythornthwaite JA. Sleep disorders and their association with laboratory pain sensitivity in temporomandibular joint disorder. SLEEP 2009;32(6):779–790.     

Hypoadiponectinemia is Related to Sympathetic Activation and Severity of Obstructive Sleep Apnea

Study Objectives:

Hypoadiponectinemia is associated with cardiovascular morbidity and diabetes mellitus. We hypothesize that adiponectin may be downregulated in sleep apnea through various mechanisms, contributing to cardiometabolic risks. This study investigated the relationship between serum adiponectin and sleep disordered breathing and its potential determinants.

Design:

Cross-sectional study.

Subjects and setting:

Adult men without prevailing medical comorbidity from the sleep clinic in a teaching hospital.

Measurements & Results:

One hundred thirty-four men underwent polysomnography, with mean age of 43.9 (9.8) years, and median apnea-hypopnea index (AHI) of 17.1 (5.7, 46.6). Overnight urine samples for catecholamines and blood samples for analyses of insulin, glucose and adiponectin levels from fasting subjects were taken. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). Magnetic resonance imaging was performed to quantify the amount of abdominal visceral fat. Serum adiponectin level, adjusted for age, body mass index, and visceral fat volume, was significantly lower in subjects with severe obstructive sleep apnea (AHI ≥ 30) compared with those with an AHI of less than 30: 4.0 (3.1, 5.4) versus 5.4 (3.6, 7.9) μg/mL, P = 0.039. After we adjusted for adiposity, adiponectin levels remained negatively correlated with AHI (P = 0.037), arousal index (P = 0.022), HOMA-IR/fasting insulin (P < 0.001), and urinary norepinephrine and normetanephrine (P < 0.008). In a multiple stepwise regression model, the independent determinants of adiponectin after adjustment for adiposity were HOMA-IR (P < 0.001) and urinary norepinephrine and normetanephrine (P = 0.037).

Conclusions:

Adiponectin was suppressed in subjects with severe obstructive sleep apnea, independent of obesity. Adiponectin levels were determined by insulin resistance and sympathetic activation, factors that may be totally or partially attributed to sleep disordered breathing.

Citation:

Lam JCM; Xu A; Tam S; Khong PL; Yao TJ; Lam DCL; Lai AYK; Lam B; Lam KSL; Ip MSM. Hypoadiponectinemia is related to sympathetic activation and severity of obstructive sleep apnea. SLEEP 2008;31(12):1721–1727.     

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.     

Reduced Brain Gray Matter Concentration in Patients With Obstructive Sleep Apnea Syndrome

Study Objectives:

To investigate differences in brain gray matter concentrations or volumes in patients with obstructive sleep apnea syndrome (OSA) and healthy volunteers.

Designs:

Optimized voxel-based morphometry, an automated processing technique for MRI, was used to characterize structural differences in gray matter in newly diagnosed male patients.

Setting:

University hospital

Patients and Participants:

The study consisted of 36 male OSA and 31 non-apneic male healthy volunteers matched for age (mean age, 44.8 years).

Interventions:

Using the t-test, gray matter differences were identified. The statistical significance level was set to a false discovery rate P < 0.05 with an extent threshold of k_E > 200 voxels.

Measurements and Results:

The mean apnea-hypopnea index (AHI) of patients was 52.5/ h. On visual inspection of MRI, no structural abnormalities were observed. Compared to healthy volunteers, the gray matter concentrations of OSA patients were significantly decreased in the left gyrus rectus, bilateral superior frontal gyri, left precentral gyrus, bilateral frontomarginal gyri, bilateral anterior cingulate gyri, right insular gyrus, bilateral caudate nuclei, bilateral thalami, bilateral amygdalo-hippocampi, bilateral inferior temporal gyri, and bilateral quadrangular and biventer lobules in the cerebellum (false discovery rate P < 0.05). Gray matter volume was not different between OSA patients and healthy volunteers.

Conclusions:

The brain gray matter deficits may suggest that memory impairment, affective and cardiovascular disturbances, executive dysfunctions, and dysregulation of autonomic and respiratory control frequently found in OSA patients might be related to morphological differences in the brain gray matter areas.

Citation:

Joo EY; Tae WS; Lee MJ; Kang JW; Park HS; Lee JY; Suh M; Hong SB. Reduced brain gray matter concentration in patients with obstructive sleep apnea syndrome. SLEEP 2010;33(2):235-241.     

Sleep Stage Dynamics Differ Between Children With and Without Obstructive Sleep Apnea

Study Objectives:

Analysis of sleep dynamics—distributions of contiguous sleep and sleep stage durations—reveal exponential distributions and potential clinical utility in adults. We sought to examine these polysomnographic variables for the first time in children, and in the context of childhood sleep disordered breathing (SDB).

Design and Setting:

Analysis of polysomnographic data available from the Washtenaw County Adenotonsillectomy Cohort.

Participants:

Selected subjects were 48 children aged 5–12 years with SDB (pediatric apnea/hypopnea index ≥ 1.5) who were scheduled for adenotonsillectomy and 20 control subjects of similar ages without SDB. Subjects were studied at enrollment and again one year later in almost all cases.

Results:

Durations of sleep and specific sleep stage bouts generally followed exponential distributions. At baseline, the number of sleep stage changes, proportion of total sleep time occupied by stage 1 sleep, proportion stage 2 sleep, mean stage 2 duration, and mean stage REM duration each distinguished subjects with and without SDB (P < 0.05), but only mean stage 2 duration did so independently after accounting for the other variables (P = 0.03). At one-year follow-up, changes in total sleep time, mean stage 2 duration, and mean stage REM duration distinguished SDB from control subjects, but again only changes in mean stage 2 duration did so independently (P = 0.01)

Conclusions:

Durations of uninterrupted sleep and specific sleep stages appear to follow exponential distributions in children with or without SDB. Parameters that describe these distributions—particularly mean duration of stage 2 sleep periods—may provide useful additions to standard sleep stage analyses.

Citation:

Chervin RD; Fetterolf JL; Ruzicka DL; Thelen BJ; Burns JW. Sleep stage dynamics differ between children with and without obstructive sleep apnea. SLEEP 2009;32(10):1325-1332.