The effect of continuous positive airway pressure usage on sleepiness in obstructive sleep apnoea: real effects or expectation of benefit?

RATIONALE: Placebo responses are complex psychobiological phenomena and often involve patient expectation of benefit. With continuous positive airway pressure (CPAP) treatment of obstructive sleep apnoea, greater hours of CPAP use are associated with reduced sleepiness. However, these open-label studies have not controlled for patient expectation of benefit derived from their knowledge of hours of device use. OBJECTIVES: To investigate the relative effectiveness of the use of real or placebo CPAP on daytime sleepiness. METHODS: Patient-level meta-analysis combining data on sleepiness measured by the Epworth Sleepiness Scale from three randomised placebo-controlled crossover trials. Mixed model analysis of variance was used to quantify the effects of real versus placebo device treatment, usage, their interaction and regression to the mean. MEASUREMENTS AND MAIN RESULTS: Duration of real and placebo CPAP use was correlated within patients (r=0.53, p<0.001). High use of real CPAP reduced sleepiness more than high use of placebo (difference 3.0 points; 95% CI 1.7 to 4.3, p<0.001) and more than low use of real CPAP (difference 3.3; 95% CI 1.9 to 4.7, p<0.0001). High use of placebo was superior to low use of placebo (difference 1.5; 95% CI 0.1 to 2.8, p=0.03). Twenty-nine per cent of the effect of high usage of CPAP (4.2 points; 95% CI 3.3 to 5.1) was explained by the expectation of benefit effect associated with high use of placebo (1.2 points ; 95% CI 0.2 to 2.3). CONCLUSIONS: A clinically significant proportion of the effectiveness of high CPAP use in reducing sleepiness is probably caused by patient expectation of benefit.

Nasal versus oronasal continuous positive airway pressure masks for obstructive sleep apnea: a pilot investigation of pressure requirement, residual disease, and leak.

PURPOSE: This single-blinded, randomized, controlled pilot study aimed to investigate whether there is a difference between nasal and oronasal masks in therapeutic continuous positive airway pressure (CPAP) requirement, residual disease, or leak when treating obstructive sleep apnea (OSA) and if differences were related to measures of upper airway size. METHODS: Patients with severe OSA currently using CPAP at ≥4 h/night with a nasal mask were examined (including Mallampati scale, incisal relationship, and mandibular protrusion) and then randomized to receive auto-positive airway pressure (PAP) or fixed CPAP at a manually titrated pressure for 1 week each at home, with immediate crossover. Within each week, a nasal mask and two oronasal masks were to be used for two or three nights each in random order. Data were downloaded from the device. RESULTS: Twelve patients completed the trial (mean ± SD AHI 59.8 ± 28.6 events/h; CPAP 11.1 ± 3.2 cmH(2)O; BMI 37.7 ± 5.0 kg/m(2)). During auto-PAP, the median 95th percentile pressure delivered with all masks was within 0.5 cmH(2)O (p > 0.05). During CPAP, median residual AHI was 0.61 (IQR = 1.18) for the nasal mask, 1.70 (IQR = 4.04) for oronasal mask 1, and 2.48 (IQR = 3.74) for oronasal mask 2 (p = 0.03). The 95th percentile leak was lowest with the nasal mask during both CPAP and auto-PAP (both p < 0.01). Differences in pressure or residual disease were not related to measures of upper airway shape or body habitus. CONCLUSIONS: In obese OSA patients changing from a nasal to oronasal mask increased leak and residual AHI but did not affect the therapeutic pressure requirement. The findings of the current study highlight mask leak as the major difficulty in the use of oronasal masks.

Home set-up polysomnography in the assessment of suspected obstructive sleep apnea.

Home set-up polysomnography (PSG) has advantages over other portable monitoring devices, but remains unendorsed by professional bodies despite excellent utility in the Sleep Heart Health Study (SHHS). The study aims to determine technical reliability and diagnostic accuracy of unattended, home set-up versus attended laboratory-based PSG in patients with suspected obstructive sleep apnea (OSA). Thirty patients with suspected OSA without significant co-morbidity were recruited. After initial lab-PSG (Compumedics S series), patients underwent home set-up PSG (Compumedics Siesta) and lab-based PSG in random order. Studies were compared for study success, signal loss and likelihood ratio for OSA diagnosis [apnea-hypopnea index (AHI) >10]. Thirty subjects (mean age 49±13.8 years, body mass index 31±6.1 kg m(-2) ) completed investigations. SHHS technical acceptability criteria were met by all lab-based PSGs and 90% of home-based PSGs (93% clinically acceptable). Signal loss was higher at home (P=0.008). Sleep efficiency was similar between sites, but more preferred home-based PSG (50%). ancova revealed AHI was significantly different if initial AHI >26 per h (P=0.006), with an average underestimate of 5.1 per h at home. In technically acceptable studies the likelihood ratios to 'rule in' and 'rule out' OSA were 8.1 and 0.1, respectively. Unattended, home set-up PSG is technically reliable and achieves excellent diagnostic utility. Signal loss was higher at home but mitigated by multi-channel redundancy. Success rate was similar to SHHS and superior to laboratory set-up home studies. Home set-up PSG is a valid alternative to laboratory-based PSG for suspected OSA.

Pulse wave analysis in a pilot randomised controlled trial of auto-adjusting and continuous positive airway pressure for obstructive sleep apnoea.

PURPOSE: Non-invasive measurements of arterial stiffness including the augmentation index (AIx) and central blood pressure (BP) have been used to assess the cardiovascular health of patients with obstructive sleep apnoea (OSA), a well-established independent risk factor of cardiovascular disease. Continuous positive airway pressure (CPAP) can significantly reduce the AIx, but no studies have analysed the effect of auto-adjusting PAP (APAP) or studied morbidly obese patients with severe OSA at higher risk of cardiovascular disease. In this randomised, single-blinded crossover pilot trial, we aimed to compare the efficacy of CPAP with APAP (ResMed S8 Autoset II) in improving peripheral BP, central BP and the AIx, using SphygmoCor technology. METHODS: Twelve severe OSA patients (mean±SD; apnoea-hypopnoea index, 75.8 ± 32.7; BMI, 49.9 ± 5.2 kg/m(2)) were consecutively recruited and received CPAP (mean pressure, 16.4 cm H(2)O) or APAP in random order for four nights at home, separated by a four-night washout. Cardiovascular measurements were taken at baseline, post-washout and following each treatment arm. RESULTS: The polysomnographically recorded residual apnoea-hypopnoea index and compliance to treatment were not significantly different between arms (p > 0.05). There were no significant differences in peripheral or central BP between arms (p > 0.05). The AIx was lower with CPAP than APAP (by 5.8%), with a large effect size not reaching statistical significance (r = 0.61, p = 0.14). CONCLUSION: The large effect size evident when comparing the AIx following CPAP and APAP indicates the need to perform an adequately powered trial in order to determine if APAP improves arterial stiffness to the same extent as CPAP.

Clinical Reproducibility of the Epworth Sleepiness Scale for Patients With Suspected Sleep Apnea.

STUDY OBJECTIVES: To determine the reproducibility of the Epworth Sleepiness Scale (ESS) score in a clinical population referred for diagnostic testing with suspected obstructive sleep apnea. METHODS: A retrospective audit of patients referred for a diagnostic sleep study with suspected sleep apnea was undertaken. Data collection was two 3-month time periods from January to March in 2012 and 2014. To evaluate reproducibility, the ESS score at primary care referral was compared to the ESS score at first specialist assessment/sleep assessment. The proportion of scores changing by more than 2, 3, 5, or 7 points was determined. Data were analyzed using Bland-Altman plots and paired t tests. RESULTS: A total of 154 patients (68% male) with a mean ± standard deviation age of 51 ± 13 years, body mass index 36 ± 10 kg/m2, and apnea-hypopnea index 43 ± 40 events/h were included. The average ESS score change was -0.2 with a standard deviation of 3.9 reflecting a wide scatter. A difference between the sequential ESS scores of 5 or more was seen in 21% of subjects. CONCLUSIONS: In a clinical obstructive sleep apnea referral population, the ESS score was variable when administered sequentially. Given this variability the ESS should not be used as the sole tool to prioritize patients for obstructive sleep apnea assessment. COMMENTARY: A commentary on this article appears in this issue on page 711.

Continuous positive airway pressure treatment for obstructive sleep apnoea: Maori, Pacific and New Zealand European experiences.

INTRODUCTION: Continuous positive airway pressure (CPAP) is an effective treatment of obstructive sleep apnoea (OSA), but can be limited by poor adherence. In New Zealand (NZ), ethnicity has been shown to be a predictor of CPAP adherence. This study aimed to explore Maori , Pacific and NZ European patients' experience of CPAP treatment. METHODS: Patients identifying as Maori , Pacific, or NZ European ethnicity referred for CPAP treatment for OSA attended separate, 1.5-hour group discussions facilitated by a health care worker of the same ethnic group, using an interview template. Thematic analysis was applied to the discussion transcripts independently by two investigators, following published guidelines. FINDINGS: Five Maori , five Pacific, and eight NZ Europeans participated (mean age 47, range 30-71 years, mean ± standard deviation CPAP adherence 6.32 ± 1.25 hours/night). Patients in all three groups reported that they had little knowledge of OSA or CPAP prior to treatment initiation. All groups identified barriers to treatment (both at the CPAP initiation phase and long term), reported feelings of being 'overwhelmed' with information during the initial CPAP education session, and discussed the importance of successful role models. Family and friends were generally reported as being supportive of CPAP therapy. CONCLUSION: The three groups all reported similar initial CPAP experiences, highlighting access barriers to publicly funded assessment and treatment pathways, and sleep health knowledge as key issues. Educational resources to improve access, enable self-management, and increase community awareness of OSA would help overcome some of the issues identified in this study.

Ethnic disparities in CPAP adherence in New Zealand: effects of socioeconomic status, health literacy and self-efficacy.

STUDY OBJECTIVES: We aimed to investigate the influence of ethnicity on adherence with continuous positive airway pressure (CPAP) in a sample of New Zealand patients. DESIGN: Observational study over one month. SETTING: A university-based sleep laboratory. PATIENTS: 126 consecutively consenting CPAP-naïve patients (19.8% Maori, mean±SD apnea-hypopnea index 57.9 ± 38.9 events/h, CPAP 11.1 ± 3.1 cm H2O). INTERVENTIONS: Patients underwent a 4-week supervised home trial of CPAP following pressure titration. MEASUREMENTS AND RESULTS: Self-identified ethnicity (Maori/non-Maori), Epworth Sleepiness Scale, Self-Efficacy Measure for Sleep Apnea, Rapid Estimate of Adult Literacy in Medicine, New Zealand Deprivation Index (calculated from residential address), New Zealand Individual Deprivation Index (validated 8-item questionnaire), educational history, income, and employment assessed at baseline were compared to objective CPAP adherence after one month. Maori demonstrated significantly lower usage than non-Maori (median 5.11, interquartile range 2.24 h/night compared with median 5.71, interquartile range 2.61 h/night, P = 0.05). There were no significant relationships between adherence and subjective sleepiness, health literacy, or self-efficacy. In a multivariate logistic regression model incorporating 5 variables (ethnicity, eligibility for government-subsidized healthcare, individual deprivation scores, income, and education), non-completion of tertiary education, and high individual socioeconomic deprivation remained significant independent predictors of average CPAP adherence not reaching ≥ 4 h (odds ratio 0.25, 95% CI 0.08-0.83, P = 0.02; odds ratio 0.10, 95% CI 0.02-0.86, P = 0.04, respectively). The overall model explained approximately 23% of the variance in adherence. CONCLUSIONS: The disparity in CPAP adherence demonstrated between Maori and non-Maori can be explained in part by lower education levels and socioeconomic status.

Randomised trial of compliance with flexible (C-Flex) and standard continuous positive airway pressure for severe obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is often treated with continuous positive airway pressure (CPAP) but the effectiveness of treatment is probably limited by poor compliance. CPAP manufacturers are thus attempting to devise more comfortable PAP devices in an effort to improve compliance. An example of such a novel device is Flexible expiratory-modulated PAP (C-Flex mode Respironics REMstar Pro, Murraysville, PA, USA). MATERIALS AND METHODS: We aimed to compare compliance between C-Flex and standard CPAP in patients with severe OSA in a randomised controlled trial. Nineteen patients with severe OSA (mean +/- SD Apnea Hypopnea Index = 78 +/- 33/h, Epworth 14 +/- 4, PAP 8-17 cm H2O, BMI = 39 +/- 10 kg/m2) and aged 20-63 years were randomly assigned to 4 weeks of either C-Flex (setting II, n = 9) or CPAP (n = 10). RESULTS: Patients treated with C-Flex exhibited a trend toward higher compliance with their PAP devices compared to patients treated with standard CPAP (4.7 +/- 2.9 vs. 3.0 +/- 2.1 h/night, p = 0.15, effect size = 0.68). Paradoxically, improvements in subjective sleepiness (Epworth Sleepiness Scale) were greater in those who received CPAP than C-Flex (8.1 + 4.9 vs. 2.1 + 4.0 points, p = 0.014, effect size = 1.46). Improvements in objective wakefulness (Modified Maintenance of Wakefulness Test) and simple reaction times (Psychomotor Vigilance Task) were not significantly different between treatments. This randomised trial provides some evidence that C-Flex might increase initial treatment compliance, compared to CPAP, in patients with severe OSA. However, this trend toward greater compliance was not associated with better short-term treatment outcomes for patients. These findings need to be confirmed in a larger, longer-term trial.

A randomized controlled trial of continuous positive airway pressure in mild obstructive sleep apnea.

A common clinical dilemma faced by sleep physicians is in deciding the level of severity at which patients with obstructive sleep apnea (OSA) should be treated. There is particular uncertainty about the need for, and the effectiveness of, treatment in mild cases. To help define the role of nasal continuous positive airway pressure (CPAP) treatment in mild OSA we undertook a randomized controlled cross-over trial of CPAP in patients with an apnea- hypopnea index (AHI) of 5 - 30 (mean, 12.9 +/- 6.3 SD). Twenty-four-hour blood pressure and neurobehavioral function were measured at baseline, after 8 wk of treatment with CPAP, and after 8 wk of treatment with an oral placebo tablet. Twenty-eight of 42 patients enrolled in the study completed both treatment arms. Baseline characteristics were not different between those who completed the study and those who did not complete the study. Patients used CPAP for a mean (SD) of 3.53 (2.13) h per night and the mean AHI on the night of CPAP implementation was 4.24 (2.9). Nasal CPAP improved self-reported symptoms of OSA, including snoring, restless sleep, daytime sleepiness, and irritability (in-house questionnaire), more than did placebo, but did not improve objective (Multiple Sleep Latency Test) or subjective (Epworth Sleepiness Scale) measures of daytime sleepiness. We found no benefit of CPAP over placebo in any tests of neurobehavioral function, generic SF-36 (36-item Short Form Medical Outcomes Survey) or sleep-specific (Functional Outcomes of Sleep Questionnaire) quality of life questionnaires, mood score (Profile of Moods States and Beck Depression Index), or 24-h blood pressure. However, the placebo tablet resulted in a significant improvement in a wide range of functional variables compared with baseline. This placebo effect may account for some of the treatment responses to CPAP observed previously in patients with mild OSA.