Effects of continuous positive airway pressure treatment on glycaemic control and insulin sensitivity in patients with obstructive sleep apnoea and type 2 diabetes: a meta-analysis

Introduction

Obstructive sleep apnoea (OSA) is a prevalent disorder characterised by repetitive upper-airway obstruction during sleep, and it is associated with type 2 diabetes. Continuous positive airway pressure (CPAP) is the primary treatment for OSA. Prior studies investigating whether CPAP can improve insulin resistance or glucose control in OSA patients have resulted in conflicting findings. This meta-analysis investigated whether CPAP treatment could improve glucose metabolism and insulin resistance in patients with OSA and type 2 diabetes.

Material and methods

We performed a systematic literature search using Medline, Cochrane, EMBASE, and Google Scholar databases for randomised controlled prospective studies that investigated the effect of CPAP on glycaemic control or insulin sensitivity in subjects with type 2 diabetes.

Results

The combined standard (STD) paired difference in mean change in the levels of glycated haemoglobin (HbA_1c) was –0.073% (standard error (SE): 0.126), indicating that CPAP treatment did not alter HbA_1c levels. The combined STD paired difference in mean change of insulin sensitivity was observed as 0.552 µmol/kg • min (SE = 0.196) and indicated insulin sensitivity significantly increased with CPAP treatment (p = 0.005).

Conclusions

We found that the CPAP treatment did not alter HbA_1c levels but did significantly improve insulin resistance, indicating treating OSA can positively impact the symptoms of type 2 diabetes.     

Randomized Controlled Trial of Variable-Pressure Versus Fixed-Pressure Continuous Positive Airway Pressure (CPAP) Treatment for Patients with Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS)

Study Objectives:

To determine whether fixed-pressure or variable-pressure CPAP was preferred by patients and gave better outcomes in patients with the obstructive sleep apnea/hypopnea syndrome (OSAHS).

Design:

Randomized blinded cross-over trial with 6 weeks of fixed and 6 weeks of variable-pressure CPAP

Setting:

Sleep center

Patients:

200 consecutive consenting CPAP naive patients with daytime sleepiness and >15 apneas + hypopneas/h after an attended auto-CPAP titration night.

Interventions:

CPAP therapy using the same device (Autoset Spirit) set for 6 weeks in fixed pressure mode and for 6 weeks in variable pressure mode, the order of therapies being randomized.

Measurements and Results:

All measurements were recorded at the end of each limb by a researcher blind to treatment. These included symptoms, Epworth Score, CPAP usage, objective sleepiness by modified Osler test, vigilance and health related quality of life. A total of 181 of 200 patients completed the study. At the end of the study, patients expressed no significant difference in the primary outcome, patient preference, 72 patients preferring fixed and 69 preferring variable-pressure CPAP. Epworth score was lower on variable (9.5, SEM 0.4) than fixed-pressure CPAP (10.0, SEM 0.3; P = 0.031). Mean CPAP use was higher on variable (4.2, SEM 0.2 h/night) than fixed-pressure CPAP (4.0, SEM 0.2 h/night; P = 0.047). There were no other significant differences between treatments.

Conclusions

This study shows no difference in patient preference and only a marginal benefit of variable over fixed-pressure CPAP in OSAHS in terms of subjective sleepiness and CPAP use. The clinical value of this difference remains to be determined.

Clinical Trial Information:

Variable-pressure versus fixed-pressure continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS); Registration # ISRCTN43085025; http://www.controlled-trials.com/ISRCTN43085025

Citation:

Vennelle M; White S; Riha RL; Mackay T; Engleman HM; Douglas NJ. Randomized controlled trial of variable-pressure versus fixed-pressure continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). SLEEP 2010;33(2):267-271.     

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.     

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.     

Obstructive Sleep Apnea Syndrome Is Associated with Overactive Bladder and Urgency Incontinence in Men

Study Objective:

To investigate the incidence of overactive bladder (OAB) and urgency incontinence (UI) in men with obstructive sleep apnea syndrome (OSAS).

Design:

Prospective questionnaire study

Setting:

Saarland University Hospital

Patients:

All male patients who underwent full-night in-laboratory polysomnography between November 2006 and April 2007.

Interventions:

Overactive bladder symptom score (OABSS) and International Consultation on Incontinence Questionnaire, Short-Form (ICIQ-SF).

Measurements and Results:

OSAS severity was assessed according to the apnea-hypopnea-index (AHI). Return rate of questionnaires was 100% (n = 100). Patients with upper airway resistance syndrome (UARS) served as controls. Evaluation of OABSS revealed that patients with moderate and severe OSAS presented with a significantly higher incidence of symptoms of OAB than patients with mild OSAS and UARS (P < 0.05). Further, the ICIQ-SF revealed a higher occurrence of UI in patients with severe OSAS than in those with mild OSAS and UARS (P < 0.05).

Conclusions:

Increasing severity of OSAS appears to be associated with an increasing occurrence of overactive bladder and urgency incontinence in men. This relationship may have clinical implications for the treatment of affected patients.

Citation:

Kemmer H; Mathes AM; Dilk O; Gröschel A; Grass C; Stöckle M. Obstructive Sleep Apnea Syndrome Is Associated with Overactive Bladder and Urgency Incontinence in Men. SLEEP 2009;32(2):271-275.     

Endothelium injury and inflammatory state during abdominal aortic aneurysm surgery: scrutinizing the very early and minute injurious effects using endothelial markers – a pilot study

Introduction

One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Acute kidney injury is an inflammatory process whose pathogenesis involves endothelial cells (EC). The aim of this study was to assess the dynamics of endothelium injury markers measured during elective AAA surgery which might confirm the inflammatory character of AKI.

Material and methods

The study group consisted of 14 patients with AAA. We measured plasma soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin as well as the levels of von Willebrand factor (vWF) before, during (including intra-abdominal vein levels before and after aortic clamp removal) and within 2 days after surgery.

Results

We have found a biphasic response of ICAM-1, VCAM-1 and P-selectin with an initial fall and subsequent rise. However, only VCAM-1 changes were significant compared to its baseline value. The maximum decrease of VCAM-1 was observed in the renal vein 5 min after aortic clamp removal (335.42 ±129.63 ng/ml vs. 488.90 ±169.80 ng/ml baseline value, p < 0.05), and the highest rise 48 h after aortic clamp removal (721.46 ±333.99 vs. baseline, p < 0.05).

Conclusions

Vascular cell adhesion molecule-1 turned out to be the most sensitive indicator of EC injury and inflammatory status after AAA surgery. During AAA surgery, soluble forms of P-selectin, ICAM-1 and VCAM-1 demonstrate a biphasic response with an initial fall and subsequent rise. These soluble forms could have a modulatory effect on the development of inflammation.     

Upper Airway Collapsibility During REM Sleep in Children with the Obstructive Sleep Apnea Syndrome

Study Objectives:

In children, most obstructive events occur during rapid eye movement (REM) sleep. We hypothesized that children with the obstructive sleep apnea syndrome (OSAS), in contrast to age-matched control subjects, would not maintain airflow in the face of an upper airway inspiratory pressure drop during REM sleep.

Design:

During slow wave sleep (SWS) and REM sleep, we measured airflow, inspiratory time, inspiratory time/total respiratory cycle time, respiratory rate, tidal volume, and minute ventilation at a holding pressure at which flow limitation occurred and at 5 cm H₂O below the holding pressure in children with OSAS and in control subjects.

Setting:

Sleep laboratory.

Participants:

Fourteen children with OSAS and 23 normal control subjects.

Results:

In both sleep states, control subjects were able to maintain airflow, whereas subjects with OSAS preserved airflow in SWS but had a significant decrease in airflow during REM sleep (change in airflow of 18.58 ± 12.41 mL/s for control subjects vs −44.33 ± 14.09 mL/s for children with OSAS, P = 0.002). Although tidal volume decreased, patients with OSAS were able to maintain minute ventilation by increasing the respiratory rate and also had an increase in inspiratory time and inspiratory time per total respiratory cycle time

Conclusion:

Children with OSAS do not maintain airflow in the face of upper-airway inspiratory-pressure drops during REM sleep, indicating a more collapsible upper airway, compared with that of control subjects during REM sleep. However, compensatory mechanisms exist to maintain minute ventilation. Local reflexes, central control mechanisms, or both reflexes and control mechanisms need to be further explored to better understand the pathophysiology of this abnormality and the compensation mechanism.

Citation:

Huang J; Karamessinis LR; Pepe ME; Glinka SM; Samuel JM; Gallagher PR; Marcus CL. Upper airway collapsibility during REM sleep in children with the obstructive sleep apnea syndrome. SLEEP 2009;32(9):1173-1181.     

Upper Airway Sensory Function in Children with Obstructive Sleep Apnea Syndrome

Study Objectives:

Children with the obstructive sleep apnea syndrome (OSAS) have impaired responses to hypercapnia, subatmospheric pressure, and inspiratory resistive loading during sleep. This may be due, in part, to an impairment in the afferent limb of the upper airway sensory pathway. Therefore, we hypothesized that children with OSAS had diminished upper airway sensation compared to controls.

Design:

Case-control

Setting:

Academic hospital

Participants:

Subjects with OSAS aged 6–16 years, and age- and BMI-matched controls.

Interventions:

Two-point discrimination (TPD) was measured during wakefulness with modified calipers in the anterior tongue, right interior cheek, and hard palate.

Results:

Thirteen children with OSAS and 9 controls were tested. The age (mean ± SD) for OSAS and controls was 11 ± 4 vs. 13 ± 2 years (NS); OSAS BMI Z score 2.4 ± 0.5, controls 2.2 ± 0.5 (NS); OSAS apnea hypopnea index 31 ± 48, controls 0.4 ± 0.5 events/hour (P < 0.001). Children with OSAS had impaired TPD in the anterior tongue (median [range]) = 9 [3–14] mm, controls 3 [1–7], P = 0.002) and hard palate (OSAS 6 [3–9] mm, controls 3 [1–4], P < 0.001). TPD in the cheek was similar between the groups (P = 0.12).

Conclusion:

TPD in the anterior tongue and hard palate was impaired in children with OSAS during wakefulness. We speculate that this impairment might be due to a primary sensory function abnormality or secondary to nerve damage and/or hypoxemia caused by OSAS. Further studies after treatment of OSAS are needed.

Citation:

Tapia IE; Bandla P; Traylor J; Karamessinis L; Huang J; Marcus CL. Upper airway sensory function in children with obstructive sleep apnea syndrome. SLEEP 2010;33(7):968–972.     

Determinants of Ventilatory Instability in Obstructive Sleep Apnea: Inherent or Acquired?

Study Objectives:

Certain respiratory control characteristics determine whether patients with collapsible upper airway develop stable or unstable breathing during sleep, thereby influencing the severity of obstructive apnea (OSA). These include arousal threshold (T_A), response to transient hypoxia and hypercapnia (Dynamic Response) and the increase in respiratory drive required for arousal-free airway opening (T_ER). We wished to determine whether these characteristics are inherent or are acquired during untreated OSA.

Design:

T_A, Dynamic Response, and T_ER were measured in patients with severe OSA before and after treatment with continuous positive airway pressure (CPAP). Changes observed after treatment were deemed to have been acquired during untreated OSA.

Setting:

University-based sleep laboratory.

Patients:

15 patients with severe OSA.

Interventions:

(1) 30-sec alterations in inspired gases during sleep on CPAP. (2) Brief dial-downs of CPAP (dial-downs) both during air breathing and when ventilation was increased to different levels.

Measurements and Results:

T_A: the increase in ventilation associated with a 50% probability of arousal (T_A50). Dynamic Response: the increase in ventilation on the 5th breath following breathing 3% CO₂ in 11% to 15% O₂. T_ER: the increase in ventilation prior to dial-downs that was associated with an arousal-free airway opening during dial-down. CPAP therapy (10.5 ± 4.3 months) resulted in marked reduction in Dynamic Response (131% ± 95% to 52% ± 34% baseline ventilation, P < 0.005), a decrease in T_A50 (134% ± 78% to 86% ± 47% baseline ventilation, P < 0.05), and no change in T_ER.

Conclusions:

T_ER may be an inherent characteristic. Untreated OSA results in an increase in dynamic response to asphyxia and an increase in arousal threshold.

Citation:

Loewen A; Ostrowski M; Laprairie J; Atkar R; Gnitecki J; Hanly P; Younes M. Determinants of Ventilatory Instability in Obstructive Sleep Apnea: Inherent or Acquired? SLEEP 2009;32(10):1355-1365.     

Neighborhood of Residence is Associated with Daily Adherence to CPAP Therapy

Study Objectives:

Adherence to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea is poor. Risk factors for nonadherence are not well understood but may reflect individual or neighborhood socioeconomic factors. We sought to determine the association of socioeconomic status and initial CPAP adherence.

Design:

Retrospective cohort study, 2005 to 2006.

Setting:

Philadelphia VA Medical Center.

Participants:

Of 330 consecutive veterans who met study criteria for initiation of CPAP therapy for newly diagnosed sleep apnea, 266 had complete data for study inclusion.

Interventions:

N/A.

Measurements:

Through a multivariable logistic regression model, using an outcome of objectively measured CPAP use ≥ 4 h daily during the first week of treatment, we tested whether patients from higher socioeconomic neighborhoods had higher CPAP adherence. We measured neighborhood socioeconomic status with an index derived from the 2000 U.S. Census at the block group-level composed of median household income, male and female employment, adult high school completion, married households, and minority composition.

Results:

CPAP adherence ≥ 4 h occurred on 48.9% of 1,805 patient-days observed for the 266 subjects. After adjustment for individual sociodemographic characteristics and medical comorbidity, the probability of daily CPAP use ≥ 4 h ranged from 34.1% (95% CI, 26.4–42.7) for subjects from a low socioeconomic neighborhood (5th percentile) to 62.3% (95% CI, 53.8–70.1) for subjects from a high (95th percentile) neighborhood.

Conclusions:

In a retrospective cohort of veterans, initial CPAP adherence was closely associated with higher neighborhood socioeconomic factors. Future investigation should target specific impediments to adherence in the home and neighborhood environment.

Citation:

Platt AB; Field SH; Asch DA; Chen Z; Gupta R; Roche DF; Gurubhagavatula I; Christie JD; Kuna ST. Neighborhood of residence is associated with daily adherence to CPAP therapy. SLEEP 2009;32(6):799-806.     

Expenditure on Health Care in Obese Women with and without Sleep Apnea

Study Objectives:

To determine the effect of obesity and sleep apnea on health care expenditure in women over 10 years.

Design:

Retrospective observational study

Setting:

Tertiary university-based medical center

Patients and controls:

Three groups of age-matched women: 223 obese women with OSAS (body mass index: 39.3 ± 0.6 kg/m²), and from the general population, 223 obese controls (BMI 36.3 ± 0.4) and 223 normal weight controls (BMI 23.9 ± 0.4).

Interventions:

None

Measurements and Results:

We examined health care utilization in the 3 matched groups for the 10 years leading up to the documentation of OSAS. The mean physician fees and the number of physician visits were significantly higher in obese controls than in normal weight controls during the observed period. Physician fees and physician visits progressively increased in the 10 years before diagnosis in the OSAS cases and were significantly higher than in the matched obese controls. Physician fees, in Canadian dollars, one year before diagnosis in the OSAS cases were higher than in obese controls: $547.49 ± 34.79 vs $246.85 ± 20.88 (P < 0.0001). More was spent for OSAS cases on physician fees for circulatory, endocrine and metabolic diseases, and mental disorders than the obese controls. Physician visits one year before diagnosis in the OSAS cases were more frequent than in the obese controls: 13.2 ± 0.73 visits vs 7.26 ± 0.49 visits (P < 0.0001).

Conclusions:

Obese women are heavier users of health services than normal weight controls. Obese women with OSAS use significantly more health services than obese controls. Since OSAS imposes a greater financial burden, treatment of OSAS may reduce other comorbidities and lower overall medical costs.

Citation:

Banno K; Ramsey C; Walld R; Kryger MH. Expenditure on health care in obese women with and without sleep apnea. SLEEP 2009;32(2):274–252.     

CSF Histamine Contents in Narcolepsy,Idiopathic Hypersomnia and Obstructive Sleep Apnea Syndrome

Study Objective:

To (1) replicate our prior result of low cerebrospinal fluid (CSF) histamine levels in human narcolepsy in a different sample population and to (2) evaluate if histamine contents are altered in other types of hypersomnia with and without hypocretin deficiency.

Design:

Cross sectional studies.

Setting and Patients:

Sixty-seven narcolepsy subjects, 26 idiopathic hypersomnia (IHS) subjects, 16 obstructive sleep apnea syndrome (OSAS) subjects, and 73 neurological controls were included. All patients were Japanese. Diagnoses were made according to ICSD-2.

Results:

We found significant reductions in CSF histamine levels in hypocretin deficient narcolepsy with cataplexy (mean ± SEM; 176.0 ± 25.8 pg/mL), hypocretin non-deficient narcolepsy with cataplexy (97.8 ± 38.4 pg/mL), hypocretin non-deficient narcolepsy without cataplexy (113.6 ± 16.4 pg/mL), and idiopathic hypersomnia (161.0 ± 29.3 pg/mL); the levels in OSAS (259.3 ± 46.6 pg/mL) did not statistically differ from those in the controls (333.8 ± 22.0 pg/mL). Low CSF histamine levels were mostly observed in non-medicated patients; significant reductions in histamine levels were evident in non-medicated patients with hypocretin deficient narcolepsy with cataplexy (112.1 ± 16.3 pg/mL) and idiopathic hypersomnia (143.3 ± 28.8 pg/mL), while the levels in the medicated patients were in the normal range.

Conclusion:

The study confirmed reduced CSF histamine levels in hypocretin-deficient narcolepsy with cataplexy. Similar degrees of reduction were also observed in hypocretin non-deficient narcolepsy and in idiopathic hypersomnia, while those in OSAS (non central nervous system hypersomnia) were not altered. The decrease in histamine in these subjects were more specifically observed in non-medicated subjects, suggesting CSF histamine is a biomarker reflecting the degree of hypersomnia of central origin.

Citation:

Kanbayashi T; Kodama T; Kondo H; Satoh S; Inoue Y; Chiba S; Shimizu T; Nishino S. CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome. SLEEP 2009;32(2):181–187.     

Day/Night Rhythm of Hemostatic Factors in Obstructive Sleep Apnea

Study Objectives:

To investigate the hypothesis that day/night patterns of prothrombotic activity differ between patients with obstructive sleep apnea (OSA) and individuals with no OSA.

Design:

Prothrombotic markers'' day/night rhythms recorded over one 24-h period.

Setting:

General clinical research center.

Patients:

38 untreated OSA patients as verified by polysomnography (apnea-hypopnea index ≥10/h sleep) and 22 non-OSA controls.

Measurements and Results:

Blood samples were collected every 2 h to measure plasma levels of fibrinolysis-inhibiting plasminogen activator inhibitor (PAI)-1 and the primary fibrin degradation product D-dimer. Day/night variation in hemostasis factors was examined using a cosinor analysis. Mesor (mean) PAI-1 over the 24-h period was higher (P = 0.015), and mesor of D-dimer was lower (P = 0.001) in patients with OSA than in the non-OSA controls. These group differences stayed significant when controlling for age and gender. After further adjustment for body mass index, mean arterial pressure, and smoking, the relationship between OSA and PAI-1 became non-significant, but the relationship between OSA and D-dimer continued to be significant (P = 0.006). In the fully adjusted analysis, the amplitude (peak) for D-dimer was lower in OSA patients than in non-OSA controls (P = 0.048). The acrophase (time of the peak) for PAI-1 and D-dimer did not significantly differ between groups.

Conclusions:

The relatively higher average level of PAI-1 and lower average level of D-dimer across the 24-h in OSA patients might reflect decreased fibrinolytic capacity and fibrin degradation, respectively. The findings provide some evidence for a prothrombotic state in OSA, but were only partially independent of metabolic variables.

Citation:

von Käanel R; Natarajan L; Ancoli-Israel S; Mills PJ; Loredo JS; Dimsdale JE. Day/night rhythm of hemostatic factors in obstructive sleep apnea. SLEEP 2010;33(3):371-377.     

Irregular Respiration as a Marker of Wakefulness During Titration of CPAP

Study Objectives:

Regularity of respiration is characteristic of stable sleep without sleep disordered breathing. Appearance of respiratory irregularity may indicate onset of wakefulness. The present study examines whether one can detect transitions from sleep to wakefulness using only the CPAP flow signal and automate this recognition.

Design:

Prospective study with blinded analysis

Setting:

Sleep disorder center, academic institution.

Participants:

74 subjects with obstructive sleep apnea/hypopnea syndrome (OSAHS)

Interventions:

n/a

Measurements and Results:

74 CPAP titration polysomnograms in patients with OSAHS were examined. First we visually identified characteristic patterns of ventilatory irregularity on the airflow signal and tested their relation to conventional detection of EEG defined wake or arousal. To automate recognition of sleep-wake transitions we then developed an artificial neural network (ANN) whose inputs were parameters derived exclusively from the airflow signal. This ANN was trained to identify the visually detected ventilatory irregularities. Finally, we prospectively determined the accuracy of the ANN detection of wake or arousal against EEG sleep/wake transitions. A visually identified irregular respiratory pattern (IrREG) was highly predictive of appearance of EEG wakefulness (Positive Predictive Value [PPV] = 0.89 to 0.98 across subjects). Furthermore, we were able to automate identification of this irregularity with an ANN which was highly predictive for wakefulness by EEG (PPV 0.66 to 0.86).

Conclusions:

Despite not detecting all wakefulness, the high positive predictive value suggests that analysis of the respiration signal alone may be a useful indicator of CNS state with potential utility in the control of CPAP in OSAHS. The present study demonstrates the feasibility of automating the detection of IrREG.

Citation:

Ayappa I; Norman RG; Whiting D; Tsai AHW; Anderson F; Donnely E; Silberstein DJ; Rapoport DM. Irregular respiration as a marker of wakefulness during titration of CPAP. SLEEP 2009;32(1):99-104.     

Evaluation of Sham-CPAP as a Placebo in CPAP Intervention Studies

Study Objectives:

To evaluate the use of sham-continuous positive airway pressure (CPAP) treatment as a placebo intervention.

Design and Setting:

Analysis of polysomnograms performed in fixed order without sham-CPAP and on the first night of the sham-CPAP intervention in participants in the CPAP Apnea Trial North American Program (CATNAP), a randomized, placebo controlled trial evaluating the effects of CPAP treatment on daytime function in adults with newly diagnosed mild to moderate obstructive sleep apnea (apnea hypopnea index (AHI) 5 - 30).

Participants:

The first 104 CATNAP participants randomized to the sham-CPAP intervention arm.

Measurements and Results:

Compared to the polysomnographic measures without sham-CPAP, the study on the first night with sham-CPAP had statistically significant differences that suggested a decrease in sleep quality: decreased sleep efficiency, increased arousal index, increased time in stage 1 NREM sleep, and prolonged latency to REM sleep. However, all of these differences had a relatively small effect size. Compared to the polysomnogram without sham-CPAP, the number of hypopneas on the sham-CPAP polysomnogram was significantly increased and the number of apneas significantly decreased. Relatively minor differences in AHI with and without sham-CPAP were present and were dependent on the criteria used to score hypopneas.

Conclusion:

Comparison of polysomnograms with and without sham-CPAP revealed differences that, although statistically significant, were small in magnitude and had relatively low effect sizes suggesting minimal clinical significance. The results support the use of sham-CPAP as a placebo intervention in trials evaluating the effects of CPAP treatment in patients with obstructive sleep apnea.

Clinical Trial Information:

This paper was a secondary analysis of clinical trial data. CATNAP: CPAP Apnea Trial North American Program, the trial from which the data were obtained, is registered with clinicaltrial.gov. Registration #{"type":"clinical-trial","attrs":{"text":"NCT00089752","term_id":"NCT00089752"}}NCT00089752.

Citation:

Rodway GW; Weaver TE; Mancini C; Cater J; Maislin G; Staley B; Ferguson KA; George CFP; Schulman DA; Greenberg H; Rapoport DM; Walsleben JA; Lee-Choing T; Kuna ST. Evaluation of sham-CPAP as a placebo in CPAP intervention studies. SLEEP 2010;33(2):260-266.     

Obstructive Apneas Induce Early Release of Mesenchymal Stem Cells into Circulating Blood

Study Objectives:

To investigate whether noninvasive application of recurrent airway obstructions induces early release of mesenchymal stem cells into the circulating blood in a rat model of obstructive sleep apnea.

Design:

Prospective controlled animal study.

Setting:

University laboratory.

Patients or Participants:

Twenty male Sprague-Dawley rats (250–300 g).

Interventions:

A specially designed nasal mask was applied to the anesthetized rats. Ten rats were subjected to a pattern of recurrent obstructive apneas (60 per hour, lasting 15 seconds each) for 5 hours. Ten anesthetized rats were used as controls.

Measurements and Results:

Mesenchymal stem cells from the blood and bone marrow samples were isolated and cultured to count the total number of colony-forming unit fibroblasts (CFU-F) of adherent cells after 9 days in culture. The number of CFU-F from circulating blood was significantly (P = 0.02) higher in the rats subjected to recurrent obstructive apneas (5.00 ± 1.16; mean ± SEM) than in controls (1.70 ± 0.72). No significant (P = 0.54) differences were observed in CFU-F from bone marrow.

Conclusions:

Application of a pattern of airway obstructions similar to those experienced by patients with sleep apnea induced an early mobilization of mesenchymal stem cells into circulating blood.

Citation:

Carreras A; Almendros I; Acerbi I; Montserrat JM; Navajas D; Farré R. Obstructive apneas induce early release of mesenchymal stem cells into circulating blood. SLEEP 2009;32(1):117-119.     

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.     

Model-Based Assessment of Cardiovascular Autonomic Control in Children with Obstructive Sleep Apnea

Study Objectives:

To quantitatively assess daytime autonomic cardiovascular control in pediatric subjects with and without obstructive sleep apnea syndrome (OSAS).

Design:

Respiration, R-R intervals, and noninvasive continuous blood pressure were monitored in awake subjects in the supine and standing postures, as well as during cold face stimulation.

Setting:

Sleep disorders laboratory in a hospital setting.

Participants:

Ten pediatric patients (age 11.4 ± 3.6 years) with moderate to severe OSAS (obstructive apnea-hypopnea index = 21.0 ± 6.6/ h) before treatment and 10 age-matched normal control subjects (age 11.5 ± 3.7 years).

Measurements and Results:

Spectral analysis of heart rate variability revealed that high-frequency power was similar and the ratio of low- to high-frequency power was lower in subjects with OSAS vs control subjects. The closed-loop minimal model allowed heart rate variability to be partitioned into a component mediated by respiratory-cardiac coupling and a baroreflex component, whereas blood pressure variability was assumed to result from the direct effects of respiration and fluctuations in cardiac output. Baroreflex gain was lower in subjects with OSAS vs control subjects. Under orthostatic stress, respiratory-cardiac coupling gain decreased in both subject groups, but baroreflex gain decreased only in controls. The model was extended to incorporate time-varying parameter changes for analysis of the data collected during cold face stimulation: cardiac output gain increased in controls but remained unchanged in OSAS.

Conclusions:

Our findings suggest that vagal modulation of the heart remains relatively normal in pediatric subjects with OSAS. However, baseline cardiovascular sympathetic activity is elevated, and reactivity to autonomic challenges is impaired.

Citation:

Chaicharn J; Lin Z; Chen ML; Ward SLD; Keens T; Khoo MCK. Model-based assessment of cardiovascular autonomic control in children with obstructive sleep apnea. SLEEP 2009;32(7):927-938.     

Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

OBJECTIVE:

Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide.

METHODS:

The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples.

RESULTS:

Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05).

CONCLUSION:

Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels.