Project description:Background: Obstructive sleep apnea (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. However, the molecular and cellular mechanisms underlying OSA-induced morbidities and their response to PAP treatment remain unclear. Methods And Results: DNA methylation profiles were examined in blood monocytes of OSA patients before and after PAP treatment. We identified 1,847 regions showing significant differential DNA methylation (p<0.001 and MAT score >4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions (DMRs) were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPAR). Single locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR responsive elements (PPAREs) of 8 genes in the post-treatment samples, suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPARG complex and downstream gene expression. Conclusions: Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in OSA patients that are responsive to PAP treatment. We postulate that differentially methylated regions in blood monocytes may serve as potential biomarkers in clinical practice.
Project description:To evaluate the ability of three indices derived from the airway pressure curve for titrating positive end-expiratory pressure (PEEP) to minimize mechanical stress while improving lung aeration assessed by computed tomography (CT).Prospective, experimental study.University research facilities.Twelve pigs.Animals were anesthetized and mechanically ventilated with tidal volume of 7 ml kg(-1). In non-injured lungs (n = 6), PEEP was set at 16 cmH(2)O and stepwise decreased until zero. Acute lung injury was then induced either with oleic acid (n = 6) or surfactant depletion (n = 6). A recruitment maneuver was performed, the PEEP set at 26 cmH(2)O and decreased stepwise until zero. CT scans were obtained at end-expiratory and end-inspiratory pauses. The elastance of the respiratory system (Ers), the stress index and the percentage of volume-dependent elastance (%E (2)) were estimated.In non-injured and injured lungs, the PEEP at which Ers was lowest (8-4 and 16-12 cmH(2)O, respectively) corresponded to the best compromise between recruitment/hyperinflation. In non-injured lungs, stress index and %E (2) correlated with tidal recruitment and hyperinflation. In injured lungs, stress index and %E (2) suggested overdistension at all PEEP levels, whereas the CT scans evidenced tidal recruitment and hyperinflation simultaneously.During ventilation with low tidal volumes, Ers seems to be useful for guiding PEEP titration in non-injured and injured lungs, while stress index and %E (2) are useful in non-injured lungs only. Our results suggest that Ers can be superior to the stress index and %E (2) to guide PEEP titration in focal loss of lung aeration.
Project description:The authors examined magnitude/variability of residual sleep disordered breathing (SDB) at pressures around the therapeutic continuous positive airway pressure (CPAP), and described a multinight approach to CPAP titration/retitration consisting of recording airflow and summarizing SDB over multiple nights at multiple pressures and choosing an optimal pressure from these summarized data.Prospective, single-center nonblinded study.Ten female/18 male patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) (respiratory disturbance index [RDI] 67/h), 17 newly-initiated, 11 chronic CPAP users.A custom CPAP device (Fisher & Paykel Healthcare) recording airflow and pre-programmed to vary CPAP between 2-3 cm H2O below and 1-2 cm H2O above prescription pressure as determined by a full laboratory titration.Airflow and pressure continuously recorded for multiple nights (15.9 ± 5.1 nights) at four to seven different pressures in each patient. SDB events manually scored from the airflow as apnea (airflow reduction > 90%), hypopnea (airflow reduction > 30% lasting 10 to 120 sec with inspira-tory flow limitation [IFL]) and runs of sustained IFL > 2 min identified. RDI = (apnea + hypopnea)/total sleep time calculated for each night and an obstruction index, including sustained IFL, also was calculated. PressureMultinight was obtained for each patient from multiple nights of data using two mathematical techniques. Night-to-night variability of SDB indices was low in some patients and significant in others. PressureMultinight could be determined in 17 of 28 patients and was similar to the in-laboratory pressure.This study showed that recording multiple nights of CPAP airflow in the home and analyzing these data for residual SDB provided useful information, including the possibility of determining a therapeutic prescription for fixed CPAP in most patients and identification of others with significant physiologic variability of SDB.
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:AbstractThis is a case report of a 60-year-old female with mild obstructive sleep apnea (OSA) who presented to CPAP Alternatives clinic following multiple failed attempts at positive airway pressure (PAP) therapy. She underwent drug-induced sleep endoscopy (DISE) with the concurrent application of PAP via two different mask types. Application of the oronasal mask at low pressures demonstrated soft palate collapse, while high pressures resulted in posterior tongue collapse. In contrast, application of the nasal mask eliminated palatal and tongue obstruction at low pressures, despite mask leak at higher pressures. She was recommended a trial of nasal autoPAP, which with the use of a chinstrap, resulted in both subjective and objective improvement of her OSA.
Project description:Background and objectivesPrecise BP measurement to exclude hypertension is critical in evaluating potential living kidney donors. Ambulatory BP monitoring is considered the gold standard method for diagnosing hypertension, but it is cumbersome to perform. We sought to determine whether lower BP cutoffs using office and automated BP would reduce the rate of missed hypertension in potential living donors.Design, setting, participants, & measurementsWe measured BP in 578 prospective donors using three modalities: (1) single office BP, (2) office automated BP (average of five consecutive automated readings separated by 1 minute), and (3) ambulatory BP. Daytime ambulatory BP was considered the gold standard for diagnosing hypertension. We assessed both the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) and the American College of Cardiology/American Heart Association (ACC/AHA) definitions of hypertension in the cohort. Empirical thresholds of office BP and automated BP for the detection of ambulatory BP-diagnosed hypertension were derived using Youden index, which maximizes the sum of sensitivity and specificity and gives equal weight to false positive and false negative values.ResultsHypertension was diagnosed in 90 (16%) prospective donors by JNC-7 criteria and 198 (34%) prospective donors by ACC/AHA criteria. Masked hypertension was found in 3% of the total cohort by JNC-7 using the combination of office or automated BP, and it was seen in 24% by ACC/AHA guidelines. Using Youden index, cutoffs were derived for both office and automated BP using JNC-7 (<123/82 and <120/78 mm Hg) and ACC/AHA (<119/79 and <116/76 mm Hg) definitions. Using these lower cutoffs, the sensitivity for detecting hypertension improved from 79% to 87% for JNC-7 and from 32% to 87% by ACC/AHA definition, with negative predictive values of 95% and 87%, respectively. Missed (masked) hypertension was reduced to 2% and 4% of the entire cohort by JNC-7and ACC/AHA, respectively.ConclusionsThe prevalence of hypertension was higher in living donor candidates using ACC/AHA compared JNC-7 definitions. Lower BP cutoffs in the clinic improved sensitivity and led to a low overall prevalence of missed hypertension in prospective living kidney donors.
Project description:ObjectiveThe aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the Fatigue Severity Scale (FSS, preplanned primary outcome), another fatigue measure, sleep quality, somnolence, pain, disability, and quality of life in multiple sclerosis (MS) patients with obstructive sleep apnea-hypopnea (OSAH).MethodsIn a randomized, double-blind trial (NCT01746342), MS patients with fatigue, poor subjective sleep quality, and OSAH (apnea-hypopnea index of ⩾ 15 events per hour/sleep), but without severe OSAH (apnea-hypopnea index > 30, and 4% oxygen desaturation index > 15 events/hour or severe somnolence), were randomized to fixed CPAP or sham CPAP for 6 months. Outcome assessments were performed at 3 and 6 months.ResultsOf 49 randomized patients, 34 completed the protocol. Among completers, FSS did not improve with CPAP compared to sham at 6 months. FSS tended to improve (p = 0.09), and sleepiness (Epworth Sleepiness Scale) improved significantly (p = 0.03) at 3 months with CPAP compared to sham, but there were no other improvements with CPAP at either study evaluation.ConclusionIn non-severe OSAH patients, CPAP did not significantly improve the primary outcome of FSS change at 6 months. In secondary analyses, we found a trend to improved FSS, and a significant reduction in somnolence with CPAP at 3 months.
Project description:Obstructive sleep apnea (OSA) is a highly prevalent condition with major neurocognitive and cardiovascular health effects. Positive airway pressure (PAP) therapy prevents the collapse of the pharyngeal airway to improve hypoxemia, hypercapnia, and sleep fragmentation caused by OSA. While adherence to PAP therapy has been thought to be a barrier to use, consistent usage is likely much higher than commonly thought. In addition, many strategies have been developed to assist providers in improving their patients' PAP adherence.
Project description:ObjectiveAmple behavioral and neurobiological evidence links sleep and affective functioning. Recent self-report evidence suggests that the affective problems associated with sleep loss may be stronger for positive versus negative affective state and that those effects may be mediated by changes in electroencepholographically measured slow wave sleep (SWS). In the present study, we extend those preliminary findings using multiple measures of affective functioning.DesignIn a within-subject randomized crossover experiment, we tested the effects of one night of sleep continuity disruption via forced awakenings (FA) compared to one night of uninterrupted sleep (US) on three measures of positive and negative affective functioning: self-reported affective state, affective pain modulation, and affect-biased attention.SettingThe study was set in an inpatient clinical research suite.ParticipantsHealthy, good sleeping adults (N = 45) were included.Measurement and resultsResults indicated that a single night of sleep continuity disruption attenuated positive affective state via FA-induced reductions in SWS. Additionally, sleep continuity disruption attenuated the inhibition of pain by positive affect as well as attention bias to positive affective stimuli. Negative affective state, negative affective pain facilitation, nor negative attention bias were altered by sleep continuity disruption.ConclusionsThe present findings, observed across multiple measures of affective function, suggest that sleep continuity disruption has a stronger influence on the positive affective system relative to the negative affective affective system.