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Poor adherence to continuous positive airway pressure (CPAP) commonly affects therapeutic response in obstructive sleep apnea (OSA). We aimed to determine predictors of adherence to CPAP among participants of the Sleep Apnea and cardioVascular Endpoints (SAVE) trial. SAVE was an international, randomized, open trial of CPAP plus usual care versus usual care (UC) alone in participants (45-75 years) with co-occurring moderate-to-severe OSA (≥12 episodes/h of ≥4% oxygen desaturation) and established cardiovascular (CV) disease. Baseline sociodemographic, health and lifestyle factors, OSA symptoms, and 1-month change in daytime sleepiness, as well as CPAP side effects and adherence (during sham screening, titration week, and in the first month), were entered in univariate linear regression analyses to identify predictors of CPAP adherence at 24 months. Variables with p <0.2 were assessed for inclusion in a multivariate linear mixed model with country, age, and sex included a priori and site as a random effect. Significant univariate predictors of adherence at 24 months in 1,121 participants included: early adherence measures, improvement in daytime sleepiness at 1 month, fixed CPAP pressure, some measures of OSA severity, cardiovascular disease history, breathing pauses, and very loud snoring. While observed adherence varied between countries, adherence during sham screening, initial titration, and the first month of treatment retained independent predictive value in the multivariate model along with fixed CPAP pressure and very loud snoring. Early CPAP adherence had the greatest predictive value for identifying those at highest risk of non-adherence to long-term CPAP therapy. SAVE is registered with clinicaltrials.gov (NCT00738179).

The effect of continuous positive airway pressure (CPAP) on mediators of cardiovascular disease and depression in women with obstructive sleep apnea (OSA) is unknown. We aimed to assess the effect of CPAP therapy on a variety of biomarkers of inflammation, antioxidant activity, and depression in women with OSA. We conducted a multicenter, randomized controlled trial in 247 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15). Women were randomized to CPAP (n = 120) or conservative treatment (n = 127) for 12 weeks. Changes in tumor necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were assessed. Additional analyses were conducted in subgroups of clinical interest. Women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index 33.5 (29.0-38.3) kg/m2, and AHI 33.3 (22.8-49.3). No differences were found between groups in the baseline levels of the biomarkers. After 12 weeks of follow-up, there were no changes between groups in any of the biomarkers assessed. These results did not change when the analyses were restricted to sleepy women or to those with severe OSA. In women with CPAP use at least 5 hours per night, only TNFα levels decreased compared to the control group (-0.29 ± 1.1 vs -0.06 ± 0.53, intergroup difference -0.23 [95% CI = -0.03 to -0.50]; p = 0.043). Twelve weeks of CPAP therapy does not improve biomarkers of inflammation, antioxidant activity, or depression compared to conservative treatment in women with moderate-to-severe OSA. NCT02047071.

Background It is not known if the endogenous surfactant pool available early in life is associated with the RDS clinical course in preterm neonates treated with CPAP. We aim to clarify the clinical factors affecting surfactant pool in preterm neonates and study its association with CPAP failure. Methods Prospective, pragmatic, blind, cohort study. Gastric aspirates were obtained (within the first 6 h of life and before the first feeding) from 125 preterm neonates with RDS. Surfactant pool was measured by postnatal automated lamellar body count based on impedancemetry, without any pre-analytical treatment. A formal respiratory care protocol based on European guidelines was applied. Clinical data and perinatal risk factors influencing RDS severity or lamellar body count were real-time recorded. Investigators performing lamellar body count were blind to the clinical data and LBC was not used in clinical practice. Results Multivariate analysis showed gestational age to be the only factor significantly associated with lamellar body count (standardized β:0.233; p  = 0.023). Lamellar body count was significantly higher in neonates with CPAP success (43.500 [23.750–93.750]bodies/μL), than in those failing CPAP (20.500 [12.250–49.750] bodies/μL; p  = 0.0003).LBC had a moderate reliability to detect CPAP failure (AUC: 0.703 (0.615–0.781); p  < 0.0001; best cut-off: ≤30,000 bodies/μL). Upon adjustment for possible confounders, neither lamellar body count, nor its interaction factor with gestational age resulted associated with CPAP failure. Conclusions Early postnatal lamellar body count on gastric aspirates in CPAP-treated preterm neonates with RDS is significantly influenced only by gestational age. Lamellar bodies are not associated with CPAP failure. Thus, the endogenous surfactant pool available early in life only has a moderate reliability to predict CPAP failure.

Background Obstructive sleep apnea (OSA) is a common disorder, and continuous airway positive pressure (CPAP) is considered to be the gold standard of therapy. CPAP however is known to have problems with adherence, with many patients eventually abandoning the device. The purpose of this paper is to assess secular trends in CPAP adherence over the long term to see if there have been meaningful improvements in adherence in light of the multiple interventions proposed to do so. Methods A comprehensive systematic literature review was conducted using the Medline-Ovid, Embase, and Pubmed databases, searching for data regarding CPAP adherence over a twenty year timeframe (1994–2015). Data was assessed for quality and then extracted. The main outcome measure was reported CPAP non-adherence. Secondary outcomes included changes in CPAP non-adherence when comparing short versus long-term, and changes in terms of behavioral counseling. Results Eighty-two papers met study inclusion/exclusion criteria. The overall CPAP non-adherence rate based on a 7-h/night sleep time that was reported in studies conducted over the twenty year time frame was 34.1 %. There was no significant improvement over the time frame. Behavioral intervention improved adherence rates by ~1 h per night on average. Conclusions The rate of CPAP adherence remains persistently low over twenty years worth of reported data. No clinically significant improvement in CPAP adherence was seen even in recent years despite efforts toward behavioral intervention and patient coaching. This low rate of adherence is problematic, and calls into question the concept of CPAP as gold-standard of therapy for OSA.

Abstract Study Objectives Distinct clinical phenotypes of obstructive sleep apnea (OSA) have been identified: Disturbed Sleep, Minimally Symptomatic, and Sleepy. Determining whether these phenotypes respond differently to standard treatment helps us to create a foundation for personalized therapies. We compared responses to positive airway pressure (PAP) therapy in these clinical OSA phenotypes. Methods The study sample included 706 patients from the Icelandic Sleep Apnea Cohort with moderate-to-severe OSA who were prescribed PAP. Linear and logistic mixed models were used to compare 2-year changes in demographics, comorbid diseases, and sleep-related health issues within and across OSA clinical phenotypes. Relationships between changes in symptoms and PAP adherence were also examined. Results Overall, effect sizes were moderate to large when comparing sleepiness, insomnia-related, and apneic symptom changes in the Sleepy group with changes in other two groups, especially those in the Minimally Symptomatic group. Within the Disturbed Sleep group, PAP users and nonusers demonstrated similar changes in insomnia-related symptoms. The Minimally Symptomatic group remained relatively asymptomatic, but reported significant decreases in daytime sleepiness and physical fatigue; PAP users generally had larger improvements. The Sleepy group had reductions in nearly all measured symptoms, including large reductions in drowsy driving; almost all of these improvements were greater among PAP users than nonusers. Conclusions OSA treatment response patterns differed by initial clinical phenotype and PAP adherence. Individuals with insomnia-related symptoms may require additional targeted therapy for these complaints. These findings underscore the need for a personalized approach to management that recognizes patients with a range of OSA presentations.

Background For some patients, Continuous Positive Airway Pressure (CPAP) remains an uncomfortable therapy despite the constant development of technological innovations. To date, no real life study has investigated the relationship between mask related side-effects (MRSEs) and CPAP-non-adherence (defined as < 4 h/day) or residual-excessive-sleepiness (RES, Epworth-Sleepiness-Scale (ESS) score ≥ 11) in the long-term. Methods The InterfaceVent-CPAP study is a prospective real-life cross-sectional study conducted in an apneic adult cohort undergoing at least 3 months of CPAP with unrestricted mask-access (34 different masks). MRSEs were evaluated using visual-analogue-scales, CPAP-data using CPAP-software, sleepiness using ESS. Results 1484 patients were included in the analysis (72.2% male, median age 67 years (IQ 25–75 : 60–74), initial Apnea–Hypopnea-Index (AHI) of 39 (31–56)/h, residual AHI flow was 1.9 (0.9–4) events/h), CPAP-treatment lasted 4.4 (2.0–9.7) years, CPAP-usage was 6.8 (5.5–7.8) h/day, the prevalence of CPAP-non-adherence was 8.6%, and the prevalence of RES was 16.17%. Leak-related side-effects were the most prevalent side-effects (patient-reported leaks concerned 75.4% of responders and had no correlation with CPAP-reported-leaks). Multivariable logistic regression analyses evaluating explanatory-variable (demographic data, device/mask data and MRSEs) effects on variables-of-interest (CPAP-non-adherence and RES), indicated for patient-MRSEs significant associations between: (i) CPAP-non-adherence and dry-mouth (p = 0.004); (ii) RES and patient-reported leaks (p = 0.007), noisy mask (p < 0.001), dry nose (p < 0.001) and harness pain (p = 0.043). Conclusion In long-term CPAP-treated patients, leak-related side-effects remain the most prevalent side-effects, but patient-reported leaks cannot be predicted by CPAP-reported-leaks. Patient-MRSEs can be independently associated with CPAP-non-adherence and RES, thus implying a complementary role for MRSE questionnaires alongside CPAP-device-reported-data for patient monitoring. Trial registration InterfaceVent is registered with ClinicalTrials.gov (NCT03013283).

Preterm birth complications are the leading cause of neonatal deaths. Malawi has high rates of preterm birth, with 18.1 preterm births per 100 live births. More than 50% of preterm neonates develop respiratory distress which if left untreated, can lead to respiratory failure and death. Term and preterm neonates with respiratory distress can often be effectively managed with Continuous Positive Airway Pressure (CPAP) and this is considered an essential intervention for the management of preterm neonates by the World Health Organization. Bubble CPAP may represent a safe and cost-effective method for delivering CPAP in low-income settings. The study explored the factors that influence the implementation of bubble CPAP among health care professionals in secondary and tertiary hospitals in Malawi. This was a qualitative study conducted in three district hospitals and a tertiary hospital in southern Malawi. We conducted 46 in-depth interviews with nurses, clinicians and clinical supervisors, from June to August 2018. All data were digitally recorded, transcribed verbatim and thematically analyzed. Factors that influenced implementation of bubble CPAP occurred in an interconnected manner and included: inadequate healthcare provider training in preparation for use, rigid division of roles and responsibilities among providers, lack of effective communication among providers and between providers and newborn's caregivers, human resource constraints, and inadequate equipment and infrastructure. There are provider, caregiver and health system level factors that influence the implementation of bubble CPAP among neonates in Malawian health facilities. Ensuring adequate staffing in the nurseries, combined with ongoing training for providers, team cohesion, improved communication with caregivers, and improved hospital infrastructure would ensure optimal utilization of bubble CPAP and avoid inadvertent harm from inappropriate use.

Background Obstructive sleep apnea (OSA) is highly prevalent in patients with coronary artery disease (CAD) and is associated with recurrent cardiovascular risk. However, whether treatment with continuous positive airway pressure (CPAP) reduces this risk remains unclear. We performed a systematic review and meta-analysis to assess the effect of CPAP on long-term cardiovascular outcomes in patients with concomitant CAD and OSA. Methods We searched the PubMed, EMBASE, and Cochrane library from their inceptions to October 7, 2017. We included observational studies and randomized controlled trials (RCTs) that described the association of CPAP treatment with cardiovascular events in patients with CAD and OSA. The primary outcome of interest was major adverse cardiovascular event (MACE), including all-cause or cardiovascular death, myocardial infarction, stroke, repeat revascularization, or hospitalization for heart failure. Outcomes data were pooled using random effects models and heterogeneity assessed with the I 2 statistic. Results We identified 9 studies (2 RCTs and 7 observational studies) with 1430 participants. The median follow-up duration was from 36 to 86.5 months. Treatment with CPAP was associated with a significantly lower risk of MACE in 6 observational studies (RR 0.61, 95% CI: 0.39–0.94, P  = 0.02), but this was not reproduced in 2 RCTs (RR 0.57, 95% CI: 0.32–1.02, P  = 0.06). Similarly, CPAP significantly reduced the risk of all-cause death (4 observational studies) and cardiovascular death (3 observational studies), which were also not confirmed in RCTs. Conclusions The use of CPAP in patients with CAD and OSA might prevent subsequent cardiovascular events, which was only demonstrated in observational studies, but not in RCTs. The value of CPAP therapy as second prevention for CAD needs further investigation.

The Alertapnée study followed 555 adults with obstructive sleep apnea treated with CPAP and found that the occurrence of Cheyne-Stokes respiration (CSR) was linked to a 14-fold increase in the risk of significant cardiac events (SCE) after one year. However, the progression and clinical significance of CSR episodes over time remain unclear. This ancillary study aimed to assess CSR progression and clinical outcomes during a second year of follow-up in 66 patients who had experienced at least one CSR episode in the first year. The study focused on the number of nights with CSR, percentage of CSR, SCEs. Results showed that 62 of 66 patients with CSR in the first year also experienced CSR in the second year, with a significant increase in the median number of CSR nights, particularly when CSR was related to cardiovascular conditions (37 vs. 19 nights, p  = 0.006). Patients who experienced a SCE in year 2 had significantly more nights with CSR (median 48/90nights; IQR = 35) and a significantly greater mean percentage of CSR (median 13.8%; interquartile range (IQR) = 13.7) as compared with patients free of SCE (median 9.5/90 nights IQR = 27.8 ( p  = 0.012); 6.1% IQR = 4.5 ( p  = 0.008), respectively). In conclusion, CSR occurrence and severity depend on the underlying condition. CSR related to cardiovascular aetiology increases over time and is associated with SCEs, whereas CSR linked to non-cardiovascular conditions does not indicate a poor prognosis. Identifying CSR patterns related to cardiovascular aetiologies could enable early detection of SCEs through telemonitoring in CPAP-treated patients.