Project description:INTRODUCTION:Obesity hypoventilation syndrome (OHS) is a major respiratory complication caused by severe obesity, being associated with significant morbidity, negative impacts on quality of life and reduced survival if not treated appropriately. Positive airway pressure therapy is the first-line treatment for OHS although the optimal modality remains unclear. The goal of this study is to identify the efficacy of home bilevel positive airway pressure therapy by comparison to continuous positive airway pressure therapy and determine the best strategy for patients with OHS. METHODS AND ANALYSIS:This study will be conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. We will search the following databases: PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Ongoing studies will be identified through the ClinicalTrials.gov and WHO International Clinical Trials Registry Platform Search Portal. Grey literature will be recognised through Google Scholar and other search engines. Only randomised controlled trials meeting the eligibility criteria will be included. The risk of bias of the included studies will be evaluated through the Cochrane Collaboration's tool. RevMan V.5.3.5 software will be used for data analysis. The Q statistic and I2 index will be used for investigating heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence. ETHICS AND DISSEMINATION:Ethics approval is not required because this study contains no primary data collected from humans. This systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER:CRD42017078369.
Project description:Positive airway pressure (PAP) treatment has been shown to have a modest effect on ambulatory blood pressure (BP) in patients with obstructive sleep apnea (OSA). However, there is a paucity of data on the effect of PAP therapy on rapid, yet significant, BP swings during sleep, particularly in obesity hypoventilation syndrome (OHS). The present study hypothesizes that PAP therapy will improve nocturnal BP on the first treatment night (titration PAP) in OHS patients with underlying OSA, and that these improvements will become more significant with 6 wk of PAP therapy. Seventeen adults (7 men, 10 women; age 50.4 ± 10.7 years, BMI 49.3 ± 2.4 kg/m(2)) with OHS and clinically diagnosed OSA participated in three overnight laboratory visits that included polysomnography and beat-to-beat BP monitoring via finger plethysmography. Six weeks of PAP therapy, but not titration PAP, lowered mean nocturnal BP. In contrast, when nocturnal beat-to-beat BPs were aggregated into bins consisting of at least three consecutive cardiac cycles with a >10 mmHg BP surge (i.e., ?10-20, ?20-30, ?30-40, and ?>40 mmHg), titration, and 6-wk PAP reduced the number of BP surges per hour (time × bin, P < 0.05). PAP adherence over the 6-wk period was significantly correlated to reductions in nocturnal systolic (r = 0.713, P = 0.001) and diastolic (r = 0.497, P = 0.043) BP surges. Despite these PAP-induced improvements in nocturnal beat-to-beat BP surges, 6 wk of PAP therapy did not alter daytime BP. In conclusion, PAP treatment reduces nocturnal beat-to-beat BP surges in OHS patients with underlying OSA, and this improvement in nocturnal BP regulation was greater in patients with higher PAP adherence.
Project description:OSA is a highly prevalent condition that is associated with a wide range of long-term morbidities including metabolic, cardiovascular, and cognitive alterations, possibly via activation of systemic inflammatory and oxidative stress pathways. Implementation of positive airway pressure (PAP) is the first-line treatment for OSA, as well as for obesity hypoventilation syndrome (OHS), its most severe phenotype. However, the molecular and cellular mechanisms underlying OHS-induced morbidities and their response to PAP treatment remain unclear, and could be mediated, in part, by OSA-induced epigenetic changes.Blood was collected before starting PAP treatment (PRE group), as well as 6 weeks after PAP treatment (POST group) in 15 adult patients with OHS. DNA methylation profiles were studied by methylated DNA immunoprecipitation coupled to microarrays (MeDIP-chip) in six representative patients and further verified in a cohort of 15 patients by MeDIP-quantitative PCR.We identified 1,847 regions showing significant differential DNA methylation (P < .001; model-based analysis of tiling arrays score, > 4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPARs). Single-locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR-responsive elements (PPAREs) of eight genes in the post-treatment samples (PRE/POST fold changes: ABCA1, 3.11; ABCG1, 1.72; CD36, 5.04; FABP4, 2.49; HMOX, 2.74; NOS2, 7.78; PEPCK, 9.27; and ADIPOQ, 1.73), suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPAR-? complex and downstream gene expression.Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in patients with OHS who are responsive to PAP treatment.
Project description:Heart failure (HF) is a life-threatening disease and is a growing public health concern. Despite recent advances in pharmacological management for HF, the morbidity and mortality from HF remain high. Therefore, non-pharmacological approaches for HF are being developed. However, most non-pharmacological approaches are invasive, have limited indication and are considered only for advanced HF. Accordingly, the development of less invasive, non-pharmacological approaches that improve outcomes for patients with HF is important. One such approach may include positive airway pressure (PAP) therapy. In this review, the role of PAP therapy applied through mask interfaces in the wide spectrum of HF care is discussed.
Project description:STUDY OBJECTIVES:To assess the role of different levels of adherence and long-term effects of positive airway pressure (PAP) therapy on gas exchange, sleepiness, quality of life, depressive symptoms, and all-cause mortality in patients with obesity hypoventilation syndrome (OHS). METHODS:A total of 252 patients with newly diagnosed OHS were followed up for a minimum of 2 years after PAP initiation. PAP adherence (h/night) was monitored. Arterial blood gas samples were taken with patients being alert for more than 4 hours after morning awakening. Subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]), quality of life (Short Form 36 [SF-36]) and patient's depressive symptoms (Beck Depression Inventory [BDI]) were assessed before and at the end of the follow-up period, along with all-cause mortality. RESULTS:At the end of the follow-up period (median duration [25th-75th percentile], 30 [24-52] months), PaO2 increased from baseline (72.7 ± 10.3 versus 63.2 ± 10.6, P < .001) and both PaCO2 and HCO3- decreased (43.0 [39.2-45.0] versus 50.0 [46.7-55.4] and 27.5 ± 3.2 versus 31.4 ± 4.2, respectively, P < .001). In addition, PAP therapy significantly improved ESS (7 [4-9] versus 14 [11-16], P < .001), BDI (8.8 ± 4.9 versus 15.5 ± 7.3, P < .001) and SF-36 (82 [78-87] versus 74 [67-79], P < .001) scores. Over the follow-up period 11 patients died. Patients who used PAP for > 6 h/night had significant improvements (P < .05) in blood gases and SF-36 scores than less adherent patients. CONCLUSIONS:Increased hours of use and long-term therapy with PAP are effective in the treatment of patients with OHS. Clinicians should encourage adherence to PAP therapy in order to provide a significant improvement in clinical status and gas exchange in these patients. COMMENTARY:A commenary on this article appears in this issue on page 1455. CLINICAL TRIAL REGISTRATION:Title: PAP Therapy in Patients With Obesity Hypoventilation Syndrome, Registry: ClinicalTrials.gov, Identifier: NCT03449641, URL: https://clinicaltrials.gov/ct2/show/NCT03449641.
Project description:Structural birth defects are the leading cause of infant mortality in the US and Europe. Among these, congenital heart disease (CHD) is the most common. Historically, Xenopus, mouse, and pig have provided models for CHD. However, it remains unknown what proteins and pathways are conserved between these species and human. Furthermore, the proteome driving the differences between three-chambered (Xenopus) and four-chambered (mammalian) hearts is unknown. Comparative proteomics of heart tissue from species at different evolutionary points can reveal molecular processes underlying heart function. We examined heart tissue proteomes of Xenopus tropicalis, Xenopus laevis, Mus musculus, and Sus scrofa and assessed protein expression changes in the context of pathways and protein complexes, and enrichment of corresponding genes in human heart diseases.
Project description:ImportanceThe association of positive airway pressure (PAP) with reduced mortality in patients with obstructive sleep apnea (OSA) remains uncertain.ObjectiveTo investigate the association between PAP prescription and mortality.Design, setting, and participantsThis multicenter, population-based cohort study evaluated data from the Sleep Heart Health Study (SHHS), a long-term observational cohort study that included participants between 1995 and 1998, with a mean follow-up of 11.1 years. Analyses were performed in September 2018. Within the SHHS, we compared patients with obesity and severe OSA with (n = 81) and without (n = 311) prescription of PAP therapy, after matching patients from each group by age, sex, and apnea-hypopnea index.ExposuresSelf-reported use of PAP.Main outcomes and measuresAll-cause mortality.ResultsOf 392 study participants, 316 (80.6%) were men, and mean (SD) age was 63.1 (11.0) years. Ninety-six deaths occurred; 12 among the prescribed-PAP group and 84 among the nonprescribed-PAP group, yielding crude incidence rates of 12.8 vs 24.7 deaths per 1000 person-years. In Cox multivariate analysis, the hazard ratio (HR) of all-cause mortality for prescribed PAP therapy was 0.38 (95% CI, 0.18-0.81). After propensity matching, the HR of all-cause mortality for prescribed PAP therapy was 0.58 (95% CI, 0.35-0.96). According to survival curves, the difference in mortality appears 6 to 7 years after initiation of PAP therapy.Conclusions and relevancePositive airway pressure prescription is associated with reduced all-cause mortality, and this association appears several years after PAP initiation. If replicated, these findings may have strong clinical implications.
Project description:Study objectivesAdherence to positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA) remains a challenge in children. We hypothesized that the presence of another family member on PAP therapy (parent, sibling, other family member) would be associated with better adherence in the child.MethodsWe conducted a retrospective chart review to identify children < 18 years of age who had a new diagnosis of OSA between Jan 2011 and May 2013. Outcomes were objective PAP adherence at 1 week, 1 month, and 3 months. Potential predictors included family member on PAP therapy, patient demographics, and clinical characteristics. Group differences between children with and without a family member on PAP therapy were determined using χ(2) test and Wilcoxon two-sample test. PAP adherence measures at each time point and patterns of change across time between the two groups were examined using mixed-effects models.ResultsThe final analytic sample included 56 children: age 13.2 ± 3.7 years, 60% male, 67% African American, 65% obese, and 32% with developmental disabilities. The mean obstructive apnea-hypopnea index was 25.2 ± 28.7, and 19 (33%) had a family member on PAP therapy. Overall PAP adherence was 2.8 ± 2.4 h/night at 3 months. At month 3, the group with a family member on PAP therapy had significantly greater average nightly PAP use on all nights (3.6 ± 0.6 vs. 2.3 ± 0.39) and on nights used (4.8 ± 0.6 vs. 3.8 ± 0.40); (p value = 0.04).ConclusionsOverall PAP adherence was low, but having a family member on PAP therapy as a "role model" was associated with better adherence.CommentaryA commentary on this article appears in this issue on page 941.