Online Education Improves Confidence in Mechanical Insufflation-Exsufflation.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is a cough augmentation technique used to support people with an ineffective cough. MI-E can be complex due to the number of different pressure, flow, and temporal setting adjustments needed to optimize cough efficacy. Many clinicians identify inadequate training, limited experience, and low confidence as barriers to MI-E use. The purpose of this study was to determine if an online education course could improve confidence and competence in the delivery of MI-E. METHODS: An e-mail invitation to participate was disseminated to physiotherapists with a caseload that involved airway clearance for adults. The exclusion criteria were self-reported confidence and clinical expertise in MI-E. The education was created by physiotherapists with extensive experience in the provision of MI-E. The education material reviewed theoretical and practical components and was designed to take 6 h to complete. Physiotherapists were randomized to either the intervention group, who had 3 weeks of access to the education or the control group who received no intervention. Respondents in both groups completed a baseline and a post-intervention questionnaire by using visual analog scales, 0 to 10, with the primary outcomes being confidence in the prescription and confidence in the application of MI-E. Ten multiple-choice questions that covered key components of MI-E fundamentals were also completed at baseline and post-intervention. RESULTS: The intervention group had a significant improvement in the visual analog scale after the education period with a between-group difference of mean 3.6 (95% CI 4.5 to 2.7) for prescription confidence and mean 2.9 (95% CI 3.9 to 1.9) for application confidence. There was also an improvement in the multiple-choice questions with a between-group difference of mean 3.2 (95% CI 4.3 to 2). CONCLUSIONS: Access to an evidence-based online education course improved confidence in the prescription and application of MI-E, and may be a valuable tool for training clinicians in the application of MI-E.

Does CPAP treat depressive symptoms in individuals with OSA? An analysis of two 12-week randomized sham CPAP-controlled trials.

BACKGROUND: Depression is common in patients with obstructive sleep apnea (OSA). Whether treating OSA with continuous positive airway pressure (CPAP) improves depressive symptoms remains inconclusive. We examined the impact of CPAP on depressive symptoms in OSA patients compared to sham CPAP. METHODS: A sub-analysis of two previous randomized sham-controlled trials was conducted. 126 male OSA patients (age = 51 ± 11 years; BMI = 32.0 ± 5.1 kg/m2; apnea hypopnea index = 42.4 ± 22.6 events/hour) were randomised either to therapeutic CPAP (n = 65) or sham CPAP (n = 61). Depressive symptoms were measured using the Depression, Anxiety and Stress Scale (DASS). The main outcome was the change in the DASS depression score (DASSD) after three months between the therapeutic and sham CPAP arms. RESULTS: The change in DASSD at three months did not differ between therapeutic and sham CPAP (mean difference: 0.5, 95% CI -3.6 to 4.6, p = 0.80). There was no significant between-group differences within the sub-groups of adherent users (device usage≥4hrs/day), or those with baseline depression (DASSD>9). In a secondary analysis of patients with baseline depression, adherent therapeutic CPAP use was associated with a greater reduction in DASSD scores compared to non-adherers (-10.0, 95% CI -18.3 to -1.8, p = 0.019). CONCLUSIONS: Overall, three months of CPAP did not significantly improve depression scores in OSA patients. Adherent use of therapeutic CPAP in patients with baseline depressive symptoms was associated with a reduction in symptom score. Future trials involving OSA patients with higher depressive symptoms will enable us to understand the complex interaction between OSA and depression.

Associations Between Obstructive Sleep Apnea and Measures of Arterial Stiffness.

STUDY OBJECTIVES: The aim of this study was to determine whether severity measures of obstructive sleep apnea (OSA) are associated with arterial stiffness and central blood pressure (two important cardiovascular risk factors) in a large group of patients with OSA. METHODS: Baseline data from six studies on OSA in which arterial stiffness and central aortic blood pressure measures were determined using applanation tonometry were pooled. Associations between measures of arterial stiffness (heart rate corrected augmentation index [AI75]), central aortic blood pressure (central systolic pressure [CSP] and heart rate corrected central augmentation pressure [CAP75]) and measures of OSA severity were explored using stepwise regression modelling. RESULTS: Data from 362 participants (M:F ratio 13:1) with mean (standard deviation) age 49.2 (11.0) years, body mass index 31.9 (5.3) kg/m2, apnea-hypopnea index (AHI) 35.7 (20.7) events/h were included in the analyses. The AHI, oxygen desaturation index (ODI3%), and sleep time with SpO2 < 90% (T90) were all associated with arterial stiffness (AI75), (AHI: adj. ß = .069; P = .01; ODI3%: adj. ß = .072; P = .01; T90: adj. ß = .18; P < .0001) and CAP75 (AHI: adj. ß = .030; P = .01; ODI3%: adj. ß = .027; P = .02; T90: adj. ß = .080; P < .0001). AHI was also associated with CSP (AHI: adj. ß = .11; P = .002). CONCLUSIONS: OSA severity was significantly associated with augmentation index and CAP75 although the relationships were not strong.

Dose-dependent effects of continuous positive airway pressure for sleep apnea on weight or metabolic function: Individual patient-level clinical trial meta-analysis.

Therapeutic-continuous positive airway pressure seems to increase weight compared with placebo-continuous positive airway pressure. It is not known whether weight gain with therapeutic-continuous positive airway pressure dose is dependent or whether it causes metabolic dysfunction. Data synthesis of three randomised placebo-continuous positive airway pressure-controlled trials (2-3 months) was performed to test whether there is a dose-dependent effect of continuous positive airway pressure on weight. Fasting glucose, insulin, insulin resistance (homeostatic model assessment), lipids and visceral abdominal fat were also tested to determine any effect on metabolic function. Mixed-model analysis of variance was used to quantify these effects. One-hundred and twenty-eight patients were analysed. Overall there was a small increase in weight with therapeutic-continuous positive airway pressure use compared with placebo-continuous positive airway pressure (difference: 1.17 kg; 0.37-1.97, p = 0.005), which was greater with high-use therapeutic-continuous positive airway pressure compared with high-use placebo-continuous positive airway pressure (1.45 kg; 0.10-2.80, p = 0.04). Continuous positive airway pressure use as a continuous variable was also significantly associated with weight change in continuous positive airway pressure users (0.30 kg hr-1  night-1 ; 0.04-0.56, p = 0.001), but not in placebo users (0.04 kg hr-1  night-1 ; -0.22 to 0.26, p = 0.76). Neither therapeutic-continuous positive airway pressure nor the dose of therapeutic-continuous positive airway pressure caused any changes to metabolic outcomes. The weight gain effects of medium-term therapeutic-continuous positive airway pressure appear modest and are not accompanied by any adverse metabolic effects.

Randomized Trial of CPAP and Vardenafil on Erectile and Arterial Function in Men With Obstructive Sleep Apnea and Erectile Dysfunction.

Context: Erectile function is important for life satisfaction and often impaired in men with obstructive sleep apnea (OSA). Uncontrolled studies show that treating OSA with continuous positive airway pressure (CPAP) improves erectile function. Phosphodiesterase type 5 inhibitors (e.g., vardenafil) are the first-line therapy for erectile dysfunction (ED), but may worsen OSA. Objective: To assess the effects of CPAP and vardenafil on ED. Design: Sixty-one men with moderate-to-severe OSA and ED were randomized to 12 weeks of CPAP or sham CPAP, and 10 mg daily vardenafil or placebo in a two-by-two factorial design. Main Outcome Measures: International Index of Erectile Function (primary end point), treatment and relationship satisfaction, sleep-related erections, sexual function, endothelial function, arterial stiffness, quality of life, and sleep-disordered breathing. Results: CPAP increased the frequency of sleep-related erections, overall sexual satisfaction, and arterial stiffness but did not change erectile function or treatment or relationship satisfaction. Vardenafil did not alter erectile function, endothelial function, arterial stiffness, or sleep-disordered breathing, but did improve overall self-esteem and relationship satisfaction, other aspects of sexual function, and treatment satisfaction. Adherent CPAP improved erectile function, sexual desire, overall sexual, self-esteem, relationship, and treatment satisfaction, as well as sleepiness, and quality of life. Adherent vardenafil use did not consistently change nocturnal erection quality. Conclusion: CPAP improves overall sexual satisfaction, sleep-related erections, and arterial stiffness. Low-dose daily vardenafil improves certain aspects of sexual function and did not worsen OSA. Adherent CPAP or vardenafil use further improves ED and quality of life.

Metabolic and hormonal effects of 'catch-up' sleep in men with chronic, repetitive, lifestyle-driven sleep restriction.

OBJECTIVE: Acutely restricting sleep worsens insulin sensitivity in healthy individuals whose usual sleep is normal in duration and pattern. The effect of recovery or weekend 'catch-up' sleep on insulin sensitivity and metabolically active hormones in individuals with chronic sleep restriction who regularly 'catch-up' on sleep at weekends is as yet unstudied. DESIGN: 19 men (mean ± SEM age 28·6 ± 2·0 years, BMI 26·0 ± 0·8 kg/m(2) ) with at least 6 months' history (5·1 ± 0·9 years) of lifestyle-driven, restricted sleep during the working week (373 ± 6·6 min/night) with regular weekend 'catch-up' sleep (weekend sleep extension 37·4 ± 2·3%) completed an in-laboratory, randomized, crossover study comprising two of three conditions, stratified by age. Conditions were 3 weekend nights of 10 hours, 6 hours or 10 hours time-in-bed with slow wave sleep (SWS) suppression using targeted acoustic stimuli. MEASUREMENTS: Insulin sensitivity was measured in the morning following the 3rd intervention night by minimal modelling of 19 samples collected during a 2-h oral glucose tolerance test. Glucose, insulin, c-peptide, leptin, peptide YY (PYY), ghrelin, cortisol, testosterone and luteinizing hormone (LH) were measured from daily fasting blood samples; HOMA-IR, HOMA-ß and QUICKI were calculated. RESULTS: Insulin sensitivity was higher following three nights of sleep extension compared to sustained sleep restriction. Fasting insulin, c-peptide, HOMA-IR, HOMA-ß, leptin and PYY decreased with 'catch-up' sleep, QUICKI and testosterone increased, while morning cortisol and LH did not change. Targeted acoustic stimuli reduced SWS by 23%, but did not alter insulin sensitivity. CONCLUSIONS: Three nights of 'catch-up' sleep improved insulin sensitivity in men with chronic, repetitive sleep restriction. Methods to improve metabolic health by optimizing sleep are plausible.

Does obstructive sleep apnea cause endothelial dysfunction? A critical review of the literature.

Endothelial dysfunction is characterized by impaired endothelium-dependent vasodilatation and is an independent predictor of adverse cardiovascular consequences. The ease with which endothelial function can be assessed has led to it becoming a useful marker of cardiovascular diseases in research studies. Obstructive sleep apnea (OSA) has been independently associated with endothelial dysfunction which may explain the increased risk for cardiovascular and all-cause mortality in this population. One possible mechanism for the development of endothelial dysfunction in OSA is through the cyclical pattern of hypoxia and re-oxygenation. This creates a haemostatic imbalance in which nitric oxide bio-availability is reduced and pro-inflammatory and pro-thrombotic forces prevail. Furthermore the repair capacity of the endothelium to protect itself against this increased damage is diminished. All of these pathways contribute to vascular disease which ultimately gives rise to adverse cardiovascular consequences. This review aims to provide a critical appraisal of the cross-sectional and interventional studies which have investigated micro- and macro-vascular endothelial dysfunction in OSA with emphasis on randomised controlled studies.

To ED or not to ED--is erectile dysfunction in obstructive sleep apnea related to endothelial dysfunction?

Both obstructive sleep apnea (OSA) and erectile dysfunction (ErectD) are highly prevalent and largely under diagnosed medical conditions. These disorders often co-exist, with about half of the male OSA population having ErectD and vice versa. OSA is strongly associated with an increased risk of cardiovascular mortality while ErectD has been proposed as a phenotypic marker of cardiovascular disease. This implies that the two conditions may be linked by a common pathophysiological mechanism. In this review we provide evidence supporting the hypothesis that endothelial dysfunction (EndoD) may be the common pathophysiological mechanism linking OSA with both ErectD and cardiovascular complications. EndoD is one of the earliest markers of cardiovascular disease and substantial evidence suggests that OSA independently causes EndoD. There is also strong evidence that causally links EndoD with organic ErectD. Further research should be directed at determining the value of simultaneously assessing both ErectD and OSA in patients presenting with symptoms of either condition. In both ErectD and OSA clinics, identifying both conditions could improve overall cardiovascular risk stratification whilst treatment of OSA could reduce both ErectD and cardiovascular risk.

Prevalence of patent foramen ovale and its impact on oxygen desaturation in obstructive sleep apnea.

BACKGROUND: A possible association between patent foramen ovale (PFO) and obstructive sleep apnea has been suggested (OSA), whereby right-to-left shunting may exacerbate the severity of nocturnal oxygen desaturation. However, the interaction between these two conditions has not been well characterised. METHODS: A case-control study was conducted to evaluate the epidemiological association between PFO and OSA. Subjects were recruited prospectively from a sleep laboratory population, and 102 OSA subjects (mean age 51.5 ± 13 years) were compared to 50 controls without OSA (mean age 49.9 ± 12.4). The presence and size of right-to-left shunting were determined by contrast transcranial Doppler ultrasonography with Valsalva provocation. Using the 21,749 obstructive breathing events recorded at polysomnography from the OSA group, a mixed-effects linear regression model was developed to evaluate the impact of right-to-left shunting on nocturnal oxygen desaturation (ΔSpO2). RESULTS: A higher prevalence of PFO was present in the OSA group compared to the control group (47.1% vs. 26.0%, OR 2.53, CI 1.20 to 5.31, p=0.014). From the regression model, right-to-left shunt size did not exert a significant influence on the severity of ΔSpO2 (coefficient 0.85, CI -0.62 to 2.32, p=0.254); whereas sleep state, event type, body position, event duration, awake oxygen saturation, apnea-hypopnea index and body mass index were all independent predictors of ΔSpO2. CONCLUSION: A higher prevalence of PFO is found in OSA subjects. However, the degree of right-to-left shunting, characterised by Valsalva provocation, is not associated with an increased severity of nocturnal oxygen desaturation.

Two randomized placebo-controlled trials to evaluate the efficacy and tolerability of mirtazapine for the treatment of obstructive sleep apnea.

OBJECTIVE: Mirtazapine is an a2A antagonist and mixed 5-HT2/5-HT3 antagonist that has been proposed as a potential treatment for obstructive sleep apnea (OSA). A small, randomized, controlled trial has previously found an approximate halving in the severity of OSA with daily doses of 4.5 and 15 mg. We aimed to confirm and extend these findings in 2 randomized placebo-controlled, proof-of-concept trials. METHODS: Two randomized, double-blind, placebo-controlled trials of mirtazapine for OSA (apnea-hypopnea index 10-40/h). Study 1: 3-way crossover, dose-finding study testing the self-administration of mirtazapine (7.5, 15, 30, and/or 45 mg) or placebo 30 minutes prior to bedtime for 2 weeks at each dose. Twenty patients were randomly assigned to 1 of 6 different dose-sequence groups, with each patient exposed to a maximum of 3 doses. Study 2: 3-arm, randomized, parallel-group trial of mirtazapine at 15 mg or mirtazapine 15 mg + Compound CD0012 or placebo for 4 weeks in 65 patients with OSA. RESULTS: Two patients withdrew from Study 1 after complaints of unacceptable lethargy. Fifteen patients were withdrawn from study 2, 7 after complaints of unacceptable lethargy or other side-effects. No measurement of sleep apnea improved due to mirtazapine in either study. Weight gain was significantly greater on mirtazapine than on placebo in both trials. CONCLUSIONS: Mirtazapine did not improve sleep apnea in either trial. Mirtazapine caused weight gain, which may further worsen OSA. Therefore, mirtazapine is not recommended for the treatment of OSA.

Effects of short-term CPAP withdrawal on neurobehavioral performance in patients with obstructive sleep apnea.

STUDY OBJECTIVE: Changes in sleep parameters and neurobehavioral functioning were systematically investigated after an acute (1 night) and short-term (7 nights) period of withdrawal from continuous positive airway pressure (CPAP) treatment and 1 subsequent night of CPAP reintroduction in patients with obstructive sleep apnea. DESIGN: Repeated-measurement within-subject design. SETTING: Sleep laboratory, university teaching hospital. PARTICIPANTS: Twenty participants receiving optimal CPAP therapy for > or = 12 months. INTERVENTIONS: CPAP withdrawal. MEASUREMENTS AND RESULTS: Polysomnograms were performed on Night 0 (with CPAP), Night 1 and Night 7 (without CPAP) and Night 8_R (with CPAP). Acute CPAP withdrawal resulted in the recurrence of sleep-disordered breathing with sleep disruption, hypoxemia, and increased subjective sleepiness. Short-term CPAP withdrawal exacerbated hypoxemia, increased subjective and objective sleepiness and poor mood ratings. Neurobehavioral functioning assessed using the Psychomotor Vigilance Task was impaired following Night 7 and associated with hypoxemia and changes in morning levels of tumor necrosis factor-alpha. However, other neurobehavioral measures were not affected. Autonomic arousals measured via respiratory-related reductions in finger blood volume by peripheral arterial tonometry decreased from Night 1 to Night 7. On Night 8_R, reintroduction of CPAP treatment eliminated most airway obstruction, maintained oxygenation, and reversed daytime sleepiness and some vigilance decrements. CONCLUSION: Despite recurrence of sleep-disordered breathing with increased sleepiness and impaired vigilance, most neurobehavioral variables were unaffected by CPAP withdrawal. The reduction in vigilance appeared to be associated with worsened hypoxemia and changed levels of tumor necrosis factor-alpha. Resumption of CPAP treatment had immediate benefits on sleep consolidation and subjective sleepiness.