Therapeutic Continuous Positive Airway Pressure Research Articles

Nasal pillow vs. standard nasal mask for treatment of OSA: a systematic review and meta-analysis.

The purpose of this study was to compare the effectiveness of nasal pillows with standard nasal masks in the treatment of patients with obstructive sleep apnea (OSA). A digitalized search was carried out in four different databases including PubMed, Scopus, EMBASE, and CENTRAL using relevant keywords along with a manual search in relevant journals. All comparative studies comparing outcomes of using a nasal pillow with the use of standard nasal masks for continuous positive airway pressure (CPAP) treatment in patients with OSA were included. The qualitative analysis was carried out by tabulating the demographic data. The quantitative data were subjected to meta-analysis. The quality of comparative studies (both retrospective and prospective cohorts) was evaluated using New-castle Ottawa scale (NOS). A total of 14 studies (eight prospective and six retrospective) were included in the review. Of them, five studies were randomized and were of cross-over study design. No significant differences were observed in achieved CPAP and residual apnea-hypopnea index (AHI) levels between the nasal pillow and nasal mask with SMD - 0.05 95% CI [- 0.18, 0.09], p = 0.50 and SMD - 0.13 95% CI [- 0.28, 0.03], p = 0.12, respectively. However, nasal pillow usage was associated with better CPAP adherence with a difference of only + 0.29min/night as compared to a standard nasal mask, with SMD 0.29 95% CI [0.07, 0.50], p = 0.009. Nasal pillow and standard nasal mask were equally effective in terms of residual AHI level and achieved similar therapeutic CPAP pressures. However, the difference in CPAP adherence between groups, though statistically significant, is of questionable clinical significance.

Preterm Neonatal Need for Mechanical Ventilation in Prophylactic Continuous Positive Air Pressure (CPAP) Versus Therapeutic CPAP

Introduction: Preterm birth leads to number of life-threatening complications especially respiratory issues. Continuous Positive Airway Pressure (CPAP) is a conventional method used to keep the airways functional. However, limited literature is available on comparative benefit of prophylactic nasal CPAP vs. therapeutic CPAP specially in terms of preventing need for mechanical ventilation.
 Aims & Objectives: To compare the frequency of need for mechanical ventilation in prophylactic CPAP versus therapeutic CPAP in preterm neonates.
 Place and duration of study: The study was carried out at Neonatal Intensive Care Unit (NICU), Department of Pediatrics, Combined Military Hospital, Lahore between February 1 to August 1, 2019.
 Material & Methods: This randomized controlled trial was conducted on 174 cases using non-probability consecutive sampling. The patients were divided into two groups randomly (group-A and Group -B) using lottery method. Group ‘A’ received therapeutic CPAP only and Group ‘B’ received prophylactic CPAP in the first half an hour after birth. Data was entered and analyzed using the software SPSS version 20. For inferential statistics, p-value ? 0.05 was considered significant.
 Results: The mean age of patients in Therapeutic group was 16.71 ± 13.05 hours and in Prophylactic group the mean age was 12.62 ± 16 hours. In tTherapeutic group 61(70.1%) cases needed mechanical ventilation and in Prophylactic group 23(26.4%) cases needed mechanical ventilation, the frequency of mechanical ventilation was statistically higher in therapeutic CPAP group as compared to Prophylactic CPAP group, p-value < 0.001. There was significant association of need for mechanical ventilation with gender, gestational age and birth weight.
 Conclusion: This study concludes that the frequency of mechanical ventilation was statistically higher in Therapeutic CPAP group as compared to Prophylactic CPAP group in preterm infants between 28-32 weeks of gestation. Hence in future, every expected preterm baby is recommended to be given prophylactic CPAP to minimize the related complications. This can help to reduce the neonatal mortality rate.

15‐Days of Therapeutic Mild Intermittent Hypoxia Improves Cardiovascular, Upper Airway and Motor Limb Function in Participants with Motor Incomplete Spinal Cord Injury and Severe Obstructive Sleep Apnea

IntroductionRepeated exposure to mild intermittent hypoxia (MIH) with sustained hypercapnia improves cardiovascular control in able‐bodied individuals with obstructive sleep apnea. Thus, we aimed to investigate if this treatment can improve cardiovascular function in individuals with motor incomplete spinal cord injuries (SCI). In addition, treatment with MIH improves cortical excitability, as well as, upper airway muscle and limb motor function. Consequently, we also explored if MIH improves upper airway motor function and walking endurance in individuals with motor incomplete SCI with concurrent sleep apnea.MethodsTwo individuals (age 51.0 ± 8.5) with traumatic motor incomplete SCI (T8, C6) and untreated severe obstructive sleep apnea (apnea hypopnea index 53.7 ± 34.0 events/hour) were treated with MIH for 15 days while receiving in‐home continuous positive airway pressure (CPAP) treatment. The MIH protocol consisted of twelve 2‐minute hypoxic exposures (PETO2 ≍ 50 mmHg) with PETCO2 maintained 2 mmHg above baseline. Therapeutic CPAP and the active critical closing pressure were measured before and after the 15‐day exposure period. In addition, blood pressure was measured over 24‐hours before and after the MIH protocol. Beat‐to‐beat blood pressure was measured during baseline (i.e. normoxia) prior to exposure to MIH on day 1 and day 15. Walking endurance was measured on the first and last day of the protocol prior to MIH exposure. Due to the small sample, Cohen’s D effect sizes are presented.Results24‐hour systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressure (unit – mmHg) was reduced following 15 days of MIH (SBP: 131.4 ± 8.5 vs 113.4 ± 9.3, d= 2.0, DBP: 82.3 ± 1.4 vs 75.5 ± 3.9, d= 2.6, MAP: 98.5 ± 1.84 vs 88.0 ± 0.5, d= 9.04). Beat‐to‐beat blood pressure was also reduced following MIH (SBP: 135.3 ± 10.0 vs 116.9 ± 21.5, d= 1.2, DBP: 87.3 ± 0.46 vs 75.6 ± 3.1, d= 6.6, MAP 107.1 ± 0.4 vs 91.3 ± 7.0, d= 4.4). Additionally, an increase in indirect measures of cardiac output at rest (77.6 ± 39.9 vs 84.9 ± 30.2 L/min, d = 0.9) with concurrent reductions in total peripheral resistance (1.3 ± .7 vs 0.6 ± 0.1 mmHg*s/mL, d = 1.8) were found on the day 15. A reduction in therapeutic CPAP (11.0 ± 1.4 vs 9.0 ± 1.4 cmH2O, d= 1.4) and the critical closing pressure (4.5 ± 0.7 vs ‐0.6 ± 1.9 cmH2O, d = 3.9) was also evident following MIH. Lastly, walking endurance (155.8 ± 151.1 vs 240.5 ± 208.0 meters, d = 0.33) and walking velocity (0.4 ± 0.4 vs 0.7 ± 0.6 meters/second, d = 0.33) increased on day 15 compared to day 1.ConclusionFollowing 15 days of therapeutic MIH (i) blood pressure was reduced (ii) upper airway patency was improved and (iii) walking endurance and velocity increased in two individuals with motor incomplete SCI, hypertension and concurrent obstructive sleep apnea.

Duration of positive airway pressure adherence: how much PAP is enough?

Duration of positive airway pressure adherence: how much PAP is enough?

Titration studies overestimate continuous positive airway pressure requirements in uncomplicated obstructive sleep apnea.

Attended manual continuous positive airway pressure (CPAP) titration is the standard practice for determining optimal positive airway pressures for obstructive sleep apnea (OSA) treatment. However, an unattended single night auto-titrating positive airway pressure (APAP) titration is an alternative. The goal of this study was to determine whether therapeutic CPAP pressures determined during manual titrations are higher than APAP-generated surrogate pressures. We conducted a retrospective review of 165 adults with uncomplicated OSA who had full/split-night manual CPAP titrations prior to commencing treatment with APAP. Demographic and clinical data including 30-day APAP compliance data were obtained. We compared the recommended CPAP pressure from manual titrations with the 90th/95th percentile pressure generated from APAP usage over 30 days. The recommended CPAP pressures during the manual titrations were higher than the 90th/95th percentile pressures generated from APAP (11.4 ± 3.4 vs 10.3 ± 2.4 cmH2O; P = .000). Almost half the group (41.9%) had their manually derived titration pressure at least 1.5 cm above the 90th/95th percentile pressure. In multivariate analyses, body mass index was the only variable that predicted higher manual titration pressures. Notably, the average residual apnea-hypopnea index on 30-day APAP data was less than the average residual apnea-hypopnea index observed at the recommended pressure during the manual titration (5.0 ± 4.3 vs 7.2 ± 8.5; P = .006). Manual CPAP titrations may overestimate pressure requirements, particularly in patients with higher body mass index, and may not be necessary in managing patients with uncomplicated OSA. APAP appears to be at least as effective as single-pressure CPAP, while delivering lower positive airway pressure. Fashanu OS, Budhiraja R, Batool-Anwar S, Quan SF. Titration studies overestimate continuous positive airway pressure requirements in uncomplicated obstructive sleep apnea. J Clin Sleep Med. 2021;17(9):1859-1863.

Are there sex-related differences in therapeutic CPAP levels in adults undergoing in-laboratory titration?

The first-choice therapy for adults with moderate/severe obstructive sleep apnea is continuous positive airway pressure (CPAP). However, studies evaluating whether the therapeutic CPAP level obtained from a titration is affected by sex are surprisingly scarce. Our main objective was to verify if sex influenced the optimal CPAP measurement obtained during a titration. This cross-sectional study was conducted in adults diagnosed with moderate/severe obstructive sleep apnea [baseline apnea-hypopnea index (AHI) ≥ 15.0 events/h] who underwent auto-adjusting CPAP titration (S9 or S10 AutoSet ResMed) in a sleep laboratory setting. All participants used a nasal mask during the titration. The optimal pressure, leak, and residual AHI values were registered. Multiple linear regression was used to evaluate if clinical and polysomnographic data influenced the therapeutic CPAP level setting (95th percentile pressure). A total of 1,006 adults were enrolled: 354 women and 652 men. There were no statistically significant sex-related differences in the CPAP requirements and leak values delineated during the titration; all P-values > .005. However, the median residual AHI was significantly higher in males vs females: 2.7 events/h vs 2.2 events/h (P = .008). Body mass index (β: 0.292, P < .001), baseline AHI (β: 0.167, P < .001), and age (β: 0.065, P = .035) were independent predictors of the therapeutic CPAP level settings. Sex does not significantly influence the therapeutic CPAP settings. However, age, BMI, and baseline AHI emerge as independent predictors of the 95thpercentile CPAP requirement during an auto-adjusting CPAP titration. Duarte RLM, Magalhães-da-Silveira FJ, Gozal D. Are there sex-related differences in therapeutic CPAP levels in adults undergoing in-laboratory titration? JClin Sleep Med. 2021;17(9):1815-1820.

Altered K-complex morphology during sustained inspiratory airflow limitation is associated with next-day lapses in vigilance in obstructive sleep apnea.

Determine if changes in K-complexes associated with sustained inspiratory airflow limitation (SIFL) during N2 sleep are associated with next-day vigilance and objective sleepiness. Data from thirty subjects with moderate-to-severe obstructive sleep apnea who completed three in-lab polysomnograms: diagnostic, on therapeutic continuous positive airway pressure (CPAP), and on suboptimal CPAP (4 cmH2O below optimal titrated CPAP level) were analyzed. Four 20-min psychomotor vigilance tests (PVT) were performed after each PSG, every 2 h. Changes in the proportion of spontaneous K-complexes and spectral characteristics surrounding K-complexes were evaluated for K-complexes associated with both delta (∆SWAK), alpha (∆αK) frequencies. Suboptimal CPAP induced SIFL (14.7 (20.9) vs 2.9 (9.2); %total sleep time, p < 0.001) with a small increase in apnea-hypopnea index (AHI3A: 6.5 (7.7) vs 1.9 (2.3); p < 0.01) versus optimal CPAP. K-complex density (num./min of stage N2) was higher on suboptimal CPAP (0.97 ± 0.7 vs 0.65±0.5, #/min, mean ± SD, p < 0.01) above and beyond the effect of age, sex, AHI3A, and duration of SIFL. A decrease in ∆SWAK with suboptimal CPAP was associated with increased PVT lapses and explained 17% of additional variance in PVT lapses. Within-night during suboptimal CPAP K-complexes appeared to alternate between promoting sleep and as arousal surrogates. Electroencephalographic changes were not associated with objective sleepiness. Sustained inspiratory airflow limitation is associated with altered K-complex morphology including the increased occurrence of K-complexes with bursts of alpha as arousal surrogates. These findings suggest that sustained inspiratory flow limitation may be associated with nonvisible sleep fragmentation and contribute to increased lapses in vigilance.

Upper airway collapsibility in patients with OSA treated with continuous positive airway pressure: a retrospective preliminary study.

To investigate the prevalence of mildly collapsible upper airways (defined by therapeutic continuous positive airway pressure [CPAP] values ≤ 8 cm H₂O) in moderate to severe obstructive sleep apnea patients treated with CPAP and to determine their clinical, functional, and nocturnal polysomnographic characteristics. Eighty-seven patients with moderate to severe obstructive sleep apnea consecutively treated with CPAP were retrospectively investigated. Two nocturnal home sleep portable monitoring studies were performed at baseline and during treatment. Participants were categorized according to therapeutic CPAP values: ≤ 8 cm H₂O (group 1), 8-12 cm H₂O (group 2), ≥ 12 cm H₂O (group 3). Anthropometric, awake respiratory function, symptoms, comorbidities, and nocturnal home sleep portable monitoring studies data were collected. Mild upper airway collapsibility (therapeutic CPAP values ≤ 8 cm H₂O) was present in 25.3% of patients. They showed more favorable apnea-hypopnea index, oxygen desaturation index, mean nocturnal saturation, sleep time with oxygen saturation < 90%, desaturation nadir, and supine position. Oxygen desaturation index showed a weak association with anatomical collapsibility. Using the receiver operating characteristic curve, the area under the curve for the oxygen desaturation index vs CPAP pressure requirements ≤ 8 cm H₂O was low and oxygen desaturation index ≤ 40.8/h showed a sensitivity of 63.3% and a specificity of 69.2% to detect patients with mild collapsibility. A quarter of moderate to severe patients under CPAP therapy had mild collapsibility and were likely to also be good candidates for alternative and better tolerated non-CPAP therapies. Baseline anthropometric, clinical, and respiratory function characteristics did not predict mild upper airway collapsibility determined by CPAP pressure requirements ≤ 8 cm H₂O.

Auto-titrating CPAP for the treatment of obstructive sleep apnea in children.

In-laboratory titration polysomnography (PSG) is standard to determine optimal therapeutic continuous positive airway pressure (CPAP) in children with obstructive sleep apnea (OSA). The use of auto-titrating CPAP devices (autoCPAP) as an alternative to CPAP titration has not been well studied in children. We hypothesized that autoCPAP-derived pressures (PMEAN, PPEAKMEAN, P90) would be similar to titration PSG pressure (PPSG). This is a retrospective study of children with OSAS initiated on autoCPAP between 2007 and 2017, who used autoCPAP for at least 2 h/night and who had adequate titration PSG were included in the analysis. AutoCPAP-derived pressures were obtained from use downloads and compared with PPSG. PPSG predictive factors were analyzed by median regression. Nonparametric methods were used for analysis. Of 110 children initiated on autoCPAP, 44 satisfied the inclusion criteria. Age (median (interquartile range)) was 13.01 (9.98-16.72) years, and 63.6% were obese. PPSG median (interquartile range) was 8 (7-11) cmH₂O, mean autoCPAP-derived pressure (PMEAN) was 6.2 (5.6-7.6) cmH₂O, peak mean pressure (PPEAKMEAN) was 9.4 (7.7-11.1) cmH₂O, and average device pressure ≤ 90% of the time (P90) was 8.1 (7.2-9.7) cmH₂O. AutoCPAP-derived pressures correlated with PPSG (P < .05). PMEAN was lower than the other 3 pressures (P < .0002). Median regression analysis demonstrated that after adjusting for patient characteristics such as age, sex, and obesity status, autoCPAP-derived pressures remained significant predictors of PPSG (P < .05). There were no significant interactions between these patient characteristics and autoCPAP-derived pressures. This study demonstrates that autoCPAP-derived pressures correlate with the titration PSG-derived pressures. These results indicate that autoCPAP can be used in the pediatric population and can determine pressures that are close to the titration pressures.

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

BackgroundDepression 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. MethodsA 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. ResultsThe 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.

An assessment of a simple clinical technique to estimate pharyngeal collapsibility in people with obstructive sleep apnea.

Quantification of upper airway collapsibility in obstructive sleep apnea (OSA) could help inform targeted therapy decisions. However, current techniques are clinically impractical. The primary aim of this study was to assess if a simple, novel technique could be implemented as part of a continuous positive airway pressure (CPAP) titration study to assess pharyngeal collapsibility. A total of 35 participants (15 female) with OSA (mean ± SD apnea-hypopnea index = 35 ± 19 events/h) were studied. Participants first completed a simple clinical intervention during a routine CPAP titration, where CPAP was transiently turned off from the therapeutic pressure for ≤5 breaths/efforts on ≥5 occasions during stable non-rapid eye movement (non-REM) sleep for quantitative assessment of airflow responses (%peak inspiratory flow [PIF] from preceding 5 breaths). Participants then underwent an overnight physiology study to determine the pharyngeal critical closing pressure (Pcrit) and repeat transient drops to zero CPAP to assess airflow response reproducibility. Mean PIF of breaths 3-5 during zero CPAP on the simple clinical intervention versus the physiology night were similar (34 ± 29% vs. 28 ± 30% on therapeutic CPAP, p = 0.2; range 0%-90% vs. 0%-95%). Pcrit was -1.0 ± 2.5 cmH2O (range -6 to 5 cmH2O). Mean PIF during zero CPAP on the simple clinical intervention and the physiology night correlated with Pcrit (r = -0.7 and -0.9, respectively, p < 0.0001). Receiver operating characteristic curve analysis indicated significant diagnostic utility for the simple intervention to predict Pcrit < -2 and < 0 cmH2O (AUC = 0.81 and 0.92), respectively. A simple CPAP intervention can successfully discriminate between patients with and without mild to moderately collapsible pharyngeal airways. This scalable approach may help select individuals most likely to respond to non-CPAP therapies.

Effects of CPAP on Blood Pressure and Sympathetic Activity in Patients With Diabetes Mellitus, Chronic Kidney Disease, and Resistant Hypertension

BackgroundPatients with obstructive sleep apnea (OSA) have increased sympathetic activity and frequently also have resistant hypertension (HTN). Treatment of OSA with continuous positive airway pressure (CPAP) decreases awake and sleep blood pressure (BP) and sympathetic activity. This study was designed to assess the effect of treatment of OSA with CPAP on sympathetic activity and BP in patients with diabetes mellitus (DM), chronic kidney disease (CKD), and resistant HTN. MethodsThis was a randomized, double-blind, sham-controlled trial. Patients with DM, CKD, and resistant HTN were randomized to treatment with a therapeutic or subtherapeutic CPAP for 6 weeks. They underwent 24-hour ambulatory BP monitoring and assessment of muscle sympathetic nerve activity before and after 6 weeks on treatment. ResultsTreatment with therapeutic CPAP caused significant decreases in awake systolic and diastolic BP from 144 to 136 mm Hg (P = 0.004) and from 79 to 74 mm Hg (P = 0.004) and in sleep BP from 135 to 119 mm Hg (P = 0.045) and from 75 to 65 mm Hg (P = 0.015) compared with treatment with subtherapeutic CPAP. In contrast, treatment with therapeutic CPAP did not decrease sympathetic activity as assessed from muscle sympathetic nerve activity. ConclusionsDecrease in BP by treatment with CPAP in patients with DM, CKD, and OSA indicates the contribution of OSA to severity of HTN in this clinical scenario. Decrease in BP in the absence of changes in sympathetic activity is suggestive that other mechanisms induced by OSA play a larger role in the maintenance of HTN in these patients.

Continuous Positive Airway Pressure Treatment in Patients with Alzheimer's Disease: A Systematic Review.

Background: Epidemiological studies have suggested a pathophysiological relationship between obstructive sleep apnea syndrome (OSAS) and Alzheimer’s disease (AD). The aim of this study is to evaluate the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) in AD and its relationship with neurocognitive function improvement. Methods: Systematic review conducted following PRISMA’s statements. Relevant studies were searched in MEDLINE, PEDro, SCOPUS, PsycINFO, Web of Science, CINAHL and SportDicus. Original studies in which CPAP treatment was developel in AD patients have been included. Results: 5 studies, 3 RCTs (Randomized controlled trials) and 2 pilot studies. In all RCTs the CPAP intervention was six weeks; 3 weeks of therapeutic CPAP vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. The two pilot studies conducted a follow-up in which the impact on cognitive impairment was measured. Conclusions: CPAP treatment in AD patients decreases excessive daytime sleepiness and improves sleep quality. There are indications that cognitive deterioration function measured with the Mini Mental Scale decreases or evolves to a lesser extent in Alzheimer’s patients treated with CPAP. Caregivers observe stabilization in disease progression with integration of CPAP. More research is needed on the topic presented.

DNA methylation changes and improved sleep quality in adults with obstructive sleep apnea and diabetes

ObjectiveObstructive sleep apnea (OSA) is common among adults with diabetes. However, little is known about the impact of OSA treatment on DNA methylation levels. The purpose of this study is...

The effect of torso elevation on minimum effective continuous positive airway pressure for treatment of obstructive sleep apnea

Continuous positive airway pressure (CPAP) is considered the gold standard treatment of obstructive sleep apnea (OSA). However, it can be a challenge in some patients to find an effective CPAP setting that is well tolerated. A lower CPAP setting may improve patient tolerance of the treatment. The objective of this study was to evaluate the effect of approximately 30° torso elevation on minimum effective CPAP for the treatment of OSA. A retrospective chart review was performed to determine the effective CPAP setting required to treat OSA in patients who underwent CPAP titration with torso elevation using a wedge cushion, after having failed during the same titration study to achieve therapeutic results at CPAP of 20cm H2O without torso elevation. Thirty-nine patients who underwent CPAP titration with and without torso elevation utilizing a wedge cushion had statistically significant lowering of the minimum effective CPAP setting with torso elevation, with a mean CPAP reduction of 4.7 (p< 0.001) compared to ineffective treatment at CPAP of 20cm H2O without torso elevation. Apnea hypopnea index (AHI), respiratory disturbance index (RDI), and lowest oxygen saturation (SpO2) were all improved with torso elevation, with a mean AHI difference of 4.4 (p= 0.03), mean RDI difference of 14.2 (p= 0.001), and mean SpO2 difference of 5.9% (p= 0.002). Age and BMI were inversely correlated, and gender had no correlation with therapeutic CPAP settings with use of torso elevation. Torso elevation of approximately 30° resulted in effective CPAP treatment at settings significantly lower than 20cm H2O in all reviewed OSA patients, who had been ineffectively treated without torso elevation at the maximum tested setting of 20cm H2O. This intervention may be a useful adjunct during in-lab titration studies for patients who are not effectively treated at or cannot tolerate high CPAP settings.

Effects of Suboptimal Adherence of CPAP-Therapy on Symptoms of Obstructive Sleep Apnea: A Randomized, Double-Blind, Controlled Trial

Background: Continuous positive airway pressure (CPAP) is currently the treatment of choice for sleepiness in patients with obstructive sleep apnea (OSA), however, adherence is often thought to be suboptimal. We investigated the effects of suboptimal CPAP-usage on sleepiness parameters in patients with OSA. Methods: In this 2-week, parallel, double-blind, randomized controlled trial we enrolled moderate-to-severe OSA patients with excessive pre-treatment daytime sleepiness (ESS score >10) who had suboptimal CPAP adherence over at least 12 months (mean nightly usage time 3-4 hours). Patients were allocated through minimization to either CPAP-withdrawal (sham-CPAP) or continuation of CPAP (therapeutic-CPAP). A Bayesian analysis with historical priors calculated the posterior probability of superiority. Findings: Between May 27, 2016 and November 10, 2018, 57 patients (60±8 years, 79% men, 93% Caucasian) were allocated in total, and 52 who completed the study (50% in each arm) were included in the final analysis. The unadjusted ESS-score increase was +2.9 points (95% CI +1.3 to +4.7; p=0.001) in the sham-CPAP-group when compared to continuing therapeutic CPAP. The probability of superiority of therapeutic CPAP over sham CPAP was 97.6% for ESS, 90.1% for systolic, and 80.3% for diastolic blood pressure. Conclusion: Patients with moderate-to-severe OSA and daytime sleepiness are still getting a substantial benefit from suboptimal CPAP adherence, albeit not as much as they might get if they adhered more. Whether a similar statement can be made for even lower adherence levels remains to be established in future trials. Trial Registration Number: The trial was pre-registered at ClinicalTrials.gov (NCT02781740) Funding Statement: Swiss National Science Foundation (grant no. 32003B_162534). Declaration of Interests: JRS reports personal fees from Resmed UK, personal fees from Bayer Germany, outside the submitted work. MK reports grants from University of Zurich, grants from Lunge Zurich, during the conduct of the study; grants from Bayer AG, outside the submitted work. TG reports personal fees from Bayer AG, outside the submitted work. All other authors report no conflict of interest. Ethics Approval Statement: All tests were conducted by the University Hospital Zurich and approved by the cantonal ethics committee of Zurich (KEK-ZH-Nr. 2016-00332). All patients provided written informed consent according to the Declaration of Helsinki. Data were obtained according to Good Clinical Practice (GCP) guidelines.

Effects of short-term continuous positive airway pressure withdrawal on cerebral vascular reactivity measured by blood oxygen level-dependent magnetic resonance imaging in obstructive sleep apnoea: a randomised controlled trial.

Impaired cerebral vascular reactivity (CVR) increases long-term stroke risk. Obstructive sleep apnoea (OSA) is associated with peripheral vascular dysfunction and vascular events. The aim of this trial was to evaluate the effect of continuous positive airway pressure (CPAP) withdrawal on CVR.41 OSA patients (88% male, mean age 57±10 years) were randomised to either subtherapeutic or continuation of therapeutic CPAP. At baseline and after 2 weeks, patients underwent a sleep study and magnetic resonance imaging (MRI). CVR was estimated by quantifying the blood oxygen level-dependent (BOLD) MRI response to breathing stimuli.OSA did recur in the subtherapeutic CPAP group (mean treatment effect apnoea-hypopnoea index +38.0 events·h-1, 95% CI 24.2-52.0; p<0.001) but remained controlled in the therapeutic group. Although there was a significant increase in blood pressure upon CPAP withdrawal (mean treatment effect +9.37 mmHg, 95% CI 1.36-17.39; p=0.023), there was no significant effect of CPAP withdrawal on CVR assessed via BOLD MRI under either hyperoxic or hypercapnic conditions.Short-term CPAP withdrawal did not result in statistically significant changes in CVR as assessed by functional MRI, despite the recurrence of OSA. We thus conclude that, unlike peripheral endothelial function, CVR is not affected by short-term CPAP withdrawal.

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 (2-3months) 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: 1.17kg; 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 (1.45kg; 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 (0.30kghr-1 night-1 ; 0.04-0.56, p=0.001), but not in placebo users (0.04kghr-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.

A randomised crossover trial comparing nasal masks with oronasal masks: No differences in therapeutic pressures or residual apnea-hypopnea indices.

In treating obstructive sleep apnea (OSA), the use of oronasal masks with continuous positive airway pressure (CPAP) has been reported to increase pressure levels and reduce compliance. These reports come mostly from large observational studies. In this study, we examined the impact that oronasal masks have on 95th centile pressures, the residual apnea-hypopnea index (AHI) and compliance compared with nasal masks. A randomised crossover design was implemented. Participants already established on CPAP were randomly allocated to a nasal mask or oronasal mask with auto-titrating positive airway pressure (APAP) for 2weeks. Participants then crossed over to use the alternate mask for another 2weeks. Seventy-one participants were recruited but only 60 completed the trial. There were no differences in median 95th centile pressure (nasal, 11.5cm H2 O; oronasal, 11.7cm H2 O; p=0.115), median residual AHI (nasal, 4.9 events/hr; oronasal, 5.3 events/hr; p=0.234) or median compliance (nasal, 7.3hr/night; oronasal, 7.3hr/night; p=0.961). Only four patients had 95th centile pressures that were at least 1.5cm H2 O greater with oronasal masks. Oronasal masks do not systematically increase therapeutic CPAP requirements. Rather, a small subset of patients display significant differences in CPAP levels.

Effect of continuous positive airway pressure therapy on circadian patterns of cardiac repolarization in patients with obstructive sleep apnoea: data from a randomized trial.

Obstructive sleep apnoea (OSA) has been proposed as an independent risk factor for sudden cardiac death (SCD). This study takes advantage of a previous randomized trial and seeks to evaluate circadian patterns of the QTc-interval, a marker of cardiac repolarization and biomarker for SCD, in patients with OSA. We hypothesized that patients with OSA would exhibit longest QTc during the night-time and that continuous positive airway pressure (CPAP) therapy would reverse this. One hundred eighteen patients diagnosed with moderate-to-severe OSA were randomized to receive therapeutic or subtherapeutic CPAP for 4 weeks. Of these, 84 had full 24 h-Holter monitoring data at baseline and follow-up. Weighted means of all QTc-intervals were analysed over 24 h, during four time-periods (12 pm-6 am, 6 am-12 am, 12 am-6 pm, 6 pm-12 pm) as well as during each individual hour. A two-sided P value <0.05 was considered to be of statistical significance. QTc-intervals at baseline [mean (SD) over 24 h: 407.8 ms (36.6)] were highest from 6 pm-12 pm [411.7 ms (42.0)] and shortest from 6 am-12 am [405.4 ms (39.5)]. Overall 24 h CPAP treatment effect on QTc was -11.3 ms [95% confidence interval (CI), -22.1 to -0.6; P=0.039] and was estimated to be greater from 6 pm-12 pm than from 12 pm-6 am (P=0.068). The CPAP treatment effect on QTc was driven by those patients in the highest QTc decile at baseline (all >430 ms). In these patients, CPAP led to reductions in QTc, allowing reclassification into lower risk-associated values of QTc (<430 ms). In this exploratory study, CPAP treatment led to an overall reduction in the QTc-interval compared with subtherapeutic CPAP. This reduction seems more pronounced during evening hours and in patients with a QTc above 430 ms.