Search

Rationale: Primary care clinicians may be well placed to play a greater role in obstructive sleep apnea management. Objectives: To evaluate the outcomes and cost-effectiveness of sleep apnea manage...

We characterized the polysomnography (PSG) parameters associated with alterations in the circadian blood pressure (BP) pattern aiming to identify the main contributors to explain the nondipper profile in obstructive sleep apnea (OSA). This is an observational prospective-multicenter study that included participants referred to the sleep unit for suspected OSA. Following a PSG study, subjects with an apnea–hypopnea index (AHI) ≥5 events/hr were included. Two groups were established based on the 24-hr ambulatory blood pressure monitoring dipping ratio (DR; night/day BP ratio): dippers (DR ≤ 0.9) and nondippers (DR > 0.9). The cohort consisted of 299 patients: 131 (43.8%) dippers and 168 (56.2%) nondippers. A significant increase in the risk of presenting a nondipper BP pattern was found along with AHI gain [odds ratio (OR) (95% CI) = 1.71 (1.28 to 2.28)]. The best AHI cutoff for predicting nondipper status was 25.2 events/hr, increasing the OR (95% CI) to 3.50 (2.02 to 6.07). The hypopnea index [OR (95% CI) = 1.70 (1.27 to 2.26)], TSat90 [OR (95% CI) = 1.41 (1.06 to 1.87)], and respiratory arousal index [OR (95% CI) = 1.74 (1.30 to 2.34)] were individually associated with the risk of a nondipping pattern. Multivariate variable selection processes identified the respiratory arousal index as the most relevant risk factor for the nondipper profile, beyond classical clinical risk factors and usual PSG metrics.

BackgroundThe optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS).MethodsWe searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month’s duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398).FindingsOf 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI −2.15 to 3.38); p=0.68), PaO2 (−0.00 mm Hg (95% CI −4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI −0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome.InterpretationOronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.

STUDY OBJECTIVES: Medium and long-term trials comparing continuous positive airway pressure (CPAP) with noninvasive ventilation in patients with obesity hypoventilation syndrome have shown no differences in outcomes. However, it remains unclear whether CPAP therapy should be prescribed if significant hypoxemia persists during CPAP titration, despite optimization of upper airway obstructive events or if maximum CPAP pressure is reached. We aimed to examine the effects of 6 weeks of home CPAP therapy on gas exchange in patients with obesity hypoventilation syndrome who failed CPAP titration due to persistent hypoxemia. METHODS: This case series is a substudy of a randomized-controlled trial evaluating efficacy of 3 different PAP modalities in obesity hypoventilation syndrome. Patients randomized to CPAP who failed titration and were prescribed CPAP are included. CPAP failure was defined as spending more than 20% of total sleep time with oxygen saturation below 90% despite adequate resolution of apneas and hypopneas. Follow-up data included in-laboratory polysomnogram on prescribed CPAP after 6 weeks of home CPAP therapy. RESULTS: Three of seven participants (43%) randomized to CPAP failed CPAP titration. All were morbidly obese, had severe OSA (apnea-hypopnea index > 90 events/h) and severe sleep hypoxemia (percentage of total sleep time with oxygen saturation < 90% [T90] = 60–89%). Hypoxemia (T90: 43–67%, T80: 0–31%, and T70: 0–11%) and hypercapnia (transcutaneous pressure of CO(2) levels > 50 mm Hg) persisted during CPAP titration polysomnogram. The final polysomnogram after 6 weeks of adherent home CPAP therapy showed effective control of obstructive sleep apnea. Hypoventilation and hypoxemia severity decreased significantly in all 3 participants. CONCLUSIONS: Our data suggest that CPAP titration failure does not equal CPAP treatment failure. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: AVAPS-AE Efficacy Study; URL: https://clinicaltrials.gov/ct2/show/NCT01368614; Identifier: NCT01368614. CITATION: Lastra AC, Masa JF, Mokhlesi B. CPAP titration failure is not equivalent to long-term CPAP treatment failure in patients with obesity hypoventilation syndrome: a case series. J Clin Sleep Med. 2020;16(11):1975–1981.

Background Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe OSA phenotype. Research Question Is NIV effective in OHS without severe OSA phenotype? Study Design and Methods In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index Results Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco2, pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms. Interpretation In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS. Trial Registry ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov

Rationale: Hospitalized patients with acute-on-chronic hypercapnic respiratory failure due to obesity hypoventilation syndrome (OHS) have increased short-term mortality. It is unknown whether prescribing empiric positive airway pressure (PAP) at the time of hospital discharge reduces mortality compared with waiting for an outpatient evaluation (i.e., outpatient sleep study and outpatient PAP titration).Objectives: An international, multidisciplinary panel of experts developed clinical practice guidelines on OHS for the American Thoracic Society. The guideline panel asked whether hospitalized adult patients with acute-on-chronic hypercapnic respiratory failure suspected of having OHS, in whom the diagnosis has not yet been made, should be discharged from the hospital with or without empiric PAP treatment until the diagnosis of OHS is either confirmed or ruled out.Methods: A systematic review with individual patient data meta-analyses was performed to inform the guideline panel's recommendation. Grading of Recommendations, Assessment, Development, and Evaluation was used to summarize evidence and appraise quality.Results: The literature search identified 2,994 articles. There were no randomized trials. Ten studies met a priori study selection criteria, including two nonrandomized comparative studies and eight nonrandomized noncomparative studies. Individual patient data on hospitalized patients who survived to hospital discharge were obtained from nine of the studies and included a total of 1,162 patients (1,043 discharged with PAP and 119 discharged without PAP). Empiric noninvasive ventilation was prescribed in 91.5% of patients discharged on PAP, and the remainder received empiric continuous PAP. Discharge with PAP reduced mortality at 3 months (relative risk 0.12, 95% confidence interval 0.05-0.30, risk difference -14.5%). Certainty in the estimated effects was very low.Conclusions: Hospital discharge with PAP reduces mortality following acute-on-chronic hypercapnic respiratory failure in patients with OHS or suspected of having OHS. Well-designed clinical trials are needed to confirm this finding.

Summary Background Despite the improvement in the prognosis of acute coronary syndrome (ACS), substantial morbidity and mortality remain. We aimed to evaluate the effect of obstructive sleep apnoea (OSA) and its treatment with continuous positive airway pressure (CPAP) on the clinical evolution of patients with ACS. Methods We designed a multicentre, open-label, parallel-group, randomised controlled trial of patients with ACS at 15 hospitals in Spain. Eligible non-sleepy patients were men and women aged 18 years and older, admitted to hospital for documented symptoms of ACS. All patients underwent respiratory polygraphy during the first 24–72 h after admission. OSA patients were randomly assigned (1:1) to CPAP treatment plus usual care (CPAP group) or usual care alone (UC group) by a computerised system available 24 h a day. A group of patients with ACS but without OSA was also included as a reference group. Because of the nature of the intervention, the trial intervention could not be masked to either investigators or patients. Patients were monitored and followed for a minimum of 1 year. Patients were examined at the time of inclusion; after 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months; and every 12 months thereafter, if applicable, during the follow-up period. The primary endpoint was the prevalence of a composite of cardiovascular events (cardiovascular death or non-fatal events [Acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack]) in patients followed up for a minimum of 1 year. The primary analysis was done according to the intention-to-treat principle. This study is registered with Clinicaltrials.gov , NCT01335087 and is now closed. Findings Between April 25, 2011, and Feb 2, 2018, a total of 2834 patients with ACS had respiratory polygraphy, of whom 2551 (90·01%) were recruited. 1264 (49·55%) patients had OSA and were randomly assigned to the CPAP group (n=633) or the UC group (n=631). 1287 (50·45%) patients did not have OSA, of whom 603 (46·85%) were randomly assigned to the reference group. Patients were followed up for a median of 3·35 years (IQR 1·50–5·31). The prevalence of cardiovascular events was similar in the CPAP and UC groups (98 events [16%] vs 108 events [17%]; hazard ratio [HR] 0·89 [95% CI 0·68–1·17]; p=0·40) during follow-up. Mean time of adherence to CPAP treatment was 2·78 h/night (SD 2·73). The prevalence of cardiovascular events was similar between patients in the reference group (90 [15%] events) and those in the UC group (102 (17%) events) during follow-up (1·01 [0·76–1·35]; p=0·93). The prevalence of cardiovascular events seem not to be related to CPAP compliance or OSA severity. 464 (74%) of 629 patients in the CPAP group had 1538 serious adverse events and 406 (65%) of 626 patients in the UC group had 1764 serious adverse events. Interpretation Among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence. Funding ResMed (Australia), Fondo de Investigacion Sanitaria (Fondo Europeo de Desarrollo Regional), the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin, Oxigen Salud, and ALLER.

Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS.

Introduction : Respiratory high dependency units (RHDU) set up in European countries in the last decade are based on being a transitional step between the intensive care units (ICU) and the conventional hospital ward in terms of staffing, level of monitoring and patients' severity. In the pre-COVID-19 era, its main use has been the treatment of hypercapnic acute-on-chronic respiratory failure with noninvasive respiratory support and more recently for hypoxemic acute respiratory failure. Areas covered We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, limited to the terms: COVID-19 AND RHDU, Respiratory Intermediate care Unit, acute respiratory distress syndrome (ARDS), non invasive ventilation (NIV), high flow nasal cannula (HFNC), prone position, monitoring. In this review we summarize RHDU´s dual purpose: on one hand, to decrease the number of admissions into ICU, and on the other hand, early discharges of patients from ICU with prolonged admissions due to the need of care or laborious weaning from invasive mechanical ventilation. Although this dual purpose of RHDUs has contributed to decrease the overload of the ICUs during the pandemic, the hundreds of patients admitted in hospitals, with approximately 20% -30% needing critical care, has exceeded the forecasts of many hospitals. Expert opinion It seems clear that a reorganization and optimization of the care of patients with severe COVID-19 is necessary, minimizing admissions to the ICU and facilitating an early discharge. During the pandemic, several hospitals have spontaneously created new RHDUs or extended pre-existing RHDUs or up-graded respiratory wards in order to receive less sick patients requiring lower levels of monitoring and nurse to patient ratios. This article reviews under a European expert perspective this topic and proposes an adaptation and optimization of the RHDUs to meet the emergent needs caused by the pandemic emphasizing the role of the expert application of noninvasive respiratory therapies in preventing intubation and ICU access.

Spanish Sleep Network., [Rationale] Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking. Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking., [Objectives] In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes., [Methods] At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV. Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P, [Conclusions] In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction.

[EN]: [Background]: Large variation in diagnostic procedures and treatment recommendations may hinder the management of obstructive sleep apnea (OSA) and also compromise correct interpretation of the results of multicenter clinical trials, especially in subjects with non-severe OSA. The aim of this study was to analyze the therapeutic decision-making between different sleep physicians in patients with AHI, [ES]: [Introducción]: La gran variedad de procedimientos diagnósticos y recomendaciones de tratamiento puede dificultar el manejo del síndrome de apnea obstructiva del sueño (SAHS), y del mismo modo comprometer la correcta interpretación de los resultados de ensayos clínicos multicéntricos, especialmente en pacientes con SAHS no grave. El objetivo de este estudio fue analizar la decisión terapéutica de distintos médicos expertos en sueño en pacientes con el índice de apnea hipopnea < 40 eventos/h. [Métodos]: Se pidió a seis especialistas con amplia experiencia en sueño de diferentes centros de España que tomaran una decisión terapéutica (terapia de presión positiva continua en las vías respiratorias o CPAP) basada en datos anónimos de los pacientes con sospecha de SAHS en los que previamente se había llevado a cabo un estudio del sueño. Los datos clínicos procedían de una base de datos online e incluían características antropométricas, cuestionarios clínicos, comorbilidades, examen físico y resultados del estudio del sueño. La concordancia intra- e interobservador de la toma de decisiones se analizó mediante el estadístico Fleiss’ Kappa (Kappa). [Resultados]: Se analizaron un total de 720 decisiones médicas para evaluar el consenso entre profesionales del sueño. De manera global, la fiabilidad de la evaluación intraobservador fue casi perfecta (Kappa = 0,83; 95% CI; 0,75 a 0,90, p < 0,001). Sin embargo, la concordancia global interobservador disminuyó hasta alcanzar un grado moderado de consenso (Kappa = 0,46; 95% CI; 0,42 a 0,51, p < 0,001), que fue especialmente bajo cuando se tuvo en cuenta un índice de apnea hipopnea

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS). Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations. Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level

Rationale: Obstructive sleep apnea (OSA) is associated with poor blood pressure (BP) control and resistant hypertension (RH). Nevertheless, studies assessing its prevalence, characteristics, and association with BP control in patients with RH are limited. Objectives: The aim of this multicenter study was to assess the prevalence of OSA in a large cohort of subjects with RH and to evaluate the association of OSA with BP control. Methods: We recruited consecutive subjects with RH from three countries. A formal sleep test and blood pressure measurements, including 24-hour ambulatory blood pressure monitoring, were performed in all participants. Results: In total, 284 subjects with RH were included in the final analysis. Of these, 83.5% (95% confidence interval [CI], 78.7-87.3%) had OSA (apnea-hypopnea index >= 5 events/h); 31.7% (95% CI 26.5-37.3%) had mild OSA, 25.7% (95% CI, 21-31.1%) had moderate OSA, and 26.1% (95% CI, 21.3-31.5%) had severe OSA. Patients with severe OSA had higher BP values than subjects with mild to moderate or no OSA. A greater effect was observed on the average nighttime BP, with an adjusted effect of 5.72 mm Hg (95% CI, 1.08-10.35 mm Hg) in severe OSA compared with participants without OSA. A dose-response association between the severity of OSA and BP values was observed. The prevalence of severe OSA was slightly higher in uncontrolled participants (adjusted odds ratio, 1.69; 95% CI, 0.97-2.99) but was not statistically significant. Conclusions: The present study confirms the high prevalence of OSA in participants with RH. Furthermore, it shows a dose-response association between OSA severity and BP measurements, especially in the nighttime.

Objectives Although an association between uric acid (UA) levels and obstructive sleep apnea (OSA) has been reported, the effect of continuous positive airway pressure (CPAP) on this measure is yet unclear. We aimed to investigate the effect of CPAP therapy on serum UA levels in patients with OSA. Methods We conducted a multicenter, open-label, randomized controlled trial in 307 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15) in 19 Spanish Sleep Units. Women were randomized to CPAP (n = 151) or conservative treatment (n = 156) for 12 weeks. Changes in serum UA measures were assessed on an intention-to-treat basis. Additional analyses were conducted in the subgroup of women with CPAP adherence ≥4 h/night and those with UA levels ≥6 mg/dl. Results Women had a mean (SD) age of 57.1 (10.1) years, median (first–third quartile) body mass index of 33.7 (29.0–38.5) mg/kg2 and AHI of 32.0 (22.6–48.5). The average serum UA measure was 5.11 (1.26) mg/dl, and 80 (26.1%) participants had UA ≥ 6 mg/dl. Compared with the control group, the CPAP group did not achieve any reduction in UA levels (non-adjusted intergroup difference −0.03 mg/dl, 95%CI −0.20 to 0.13; p = 0.702) after 12 weeks of follow-up. These results did not change when the analysis was restricted to women with CPAP adherence ≥4 h/night, or the subgroup of women with hyperuricemia. Conclusions Twelve weeks of CPAP therapy does not reduce UA levels compared to conservative treatment in women with moderate-to-severe OSA.

Rationale: Evidence suggests that the physiopathologic consequences of obstructive sleep apnea (OSA) resemble those induced by aging. Some studies report that the deleterious effects associated wit...

[Rationale] Obesity hypoventilation syndrome (OHS) with concomitant severe obstructive sleep apnea (OSA) is treated with CPAP or noninvasive ventilation (NIV) during sleep. NIV is costlier, but may be advantageous because it provides ventilatory support. However, there are no long-term trials comparing these treatment modalities based on OHS severity., [Objective] To determine if CPAP have similar effectiveness when compared to NIV according to OHS severity subgroups., [Methods] Post hoc analysis of the Pickwick randomized clinical trial in which 215 ambulatory patients with untreated OHS and concomitant severe OSA, defined as apnoea-hypopnea index (AHI) ≥ 30 events/h, were allocated to NIV or CPAP. In the present analysis, the Pickwick cohort was divided in severity subgroups based on the degree of baseline daytime hypercapnia (PaCO2 of 45–49.9 or ≥50 mmHg). Repeated measures of PaCO2 and PaO2 during the subsequent 3 years were compared between CPAP and NIV in the two severity subgroups. Statistical analysis was performed using linear mixed-effects model., [Results] 204 patients, 97 in the NIV group and 107 in the CPAP group were analyzed. The longitudinal improvements of PaCO2 and PaO2 were similar between CPAP and NIV based on the PaCO2 severity subgroups., [Conclusion] In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awake hypercapnia, regardless of the severity of baseline hypercapnia. Therefore, in this patient population, the decision to prescribe CPAP or NIV cannot be solely based on the presenting level of PaCO2., [Introducción] El síndrome de hipoventilación-obesidad (SHO) con apnea obstructiva del sueño (AOS) grave concomitante se trata con CPAPo ventilación no invasiva (VNI) durante el sueño. La VNI es más costosa, pero puede ser beneficiosa porque proporciona soporte ventilatorio; sin embargo, no existen estudios a largo plazo que comparen estas modalidades de tratamiento basándose en la gravedad del SHO., [Objetivo] Determinar si la CPAP tiene una eficacia similar a la VNI según los subgrupos de gravedad del SHO., [Métodos] Análisis a posteriori del ensayo clínico aleatorizado Pickwick en el que 215 pacientes ambulatorios con SHO sin tratar y con AOS grave concomitante (definida como un índice de apnea-hipopnea [IAH] ≥ 30 episodios/hora) recibieron tratamiento con VNI o CPAP. En el presente análisis, la cohorte Pickwick se dividió en subgrupos según la gravedad basándose en el grado de hipercapnia diurna al inicio del estudio (PaCO2 de 45-49.9 mm Hg o ≥ 50 mm Hg). Se compararon las mediciones periódicas de PaCO2 y PaO2 durante los 3 años siguientes entre la CPAP y la VNI entre los dos subgrupos de gravedad. Se realizó un análisis estadístico utilizando un modelo lineal mixto., [Resultados] Se analizaron 204 pacientes, 97 en el grupo de VNI y 107 en el grupo de CPAP. Las mejoras lineales de PaCO2 y PaO2 fueron similares entre la CPAP y la NIV según los subgrupos de gravedad en función de la PaCO2., [Conclusión] En los pacientes ambulatorios con SHO y AOS grave concomitante a los que se trató con VNI o CPAP, el tratamiento a largo plazo con VNI resultó similar a la CPAP, en cuanto a la mejora de la hipercapnia en vigilia, independientemente de la gravedad de la hipercapnia de inicio. Por lo tanto, en esta población de pacientes la decisión de prescribir CPAP o VNI no puede basarse exclusivamente en el nivel de partida de PaCO2., Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Madrid, Spain) PI050402, Spanish Respiratory Foundation 2005 (FEPAR) and Air Liquide Spain.

High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558).

Spanish Sleep Network., [Introduction] Short-term treatment with continuous positive airway pressure (CPAP) produces a clinically significant reduction in blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. However, it is unknown whether this effect continues over the long-term. Our objective was to assess the effect of long-term CPAP on BP in patients with OSA and resistant hypertension., [Methods] The study included 161 patients diagnosed with both OSA [apnea--hypopnea index (AHI) ≥15] and resistant hypertension diagnosed via 24-hour ambulatory BP measurement (24-h ABPM), in whom a second analysis via 24-h ABPM was performed at the end of the follow-up., [Results] Patients were followed up within 59 months [interquartile range (IQR): 44–70]. CPAP treatment was prescribed to 82% of the patients (70% with good adherence to CPAP defined as use of CPAP at least 4 h/night). A comparison between the adherent group and nonadherent group (including those with CPAP not prescribed) showed that CPAP adherents had a significant drop in the 24-h BP, both systolic [−3.9 mmHg; 95% confidence interval (CI): −8.1 to 0.3] and diastolic pressure (−3.5 mmHg [95% [CI]: −6.4–0.5]), with a higher magnitude during the night (−5.5 and −4.9 mmHg, respectively). The CPAP adherent group needed a mean of 1.1 less antihypertensive drugs (particularly spironolactone). Finally, there was a positive correlation between the drop in 24-h SBP and the hours of CPAP use (r = 0.24; P = 0.01)., [Conclusion] Good adherence to long-term CPAP treatment largely succeeded in significantly reducing BP in those patients with OSA and resistant hypertension, despite the use of a lower number of antihypertensive drugs.

"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM", El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sue˜no esproporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisionesen la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literaturamás actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedadescientíficas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedadesinternacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoame-ricano. El documento consta de un manuscrito principal, con las novedades más relevantes, y una seriede manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los aparta-dos del documento internacional de consenso. Este documento no cubre la edad pediátrica ni el manejodel paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos deconsenso aparte)., The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

Background: The impact of removing the upper airway lymphoid tissue and in particular, tonsillectomy, in adults with OSA has not been demonstrated in large populations. Aims: To compare the severity of OSA and the prevalence of cardiovascular, metabolic and respiratory co-morbidities between patients with OSA who had undergone previous tonsillectomy and those who had not. Methods: The 19,711 participants in this study came from the European sleep apnea database (ESADA) which comprises data from unselected adult patients aged 18–80 years with a history of symptoms suggestive of OSA referred to sleep centers throughout Europe. Results: There were no differences between the two groups in terms of sex ratio and age (146 patients with previous tonsillectomy vs. 19565 patients without). Patients who had undergone tonsillectomy had a lower body mass index (29.3 ± 5.2 kg/m2 vs 32.2 ± 6.6 kg/m2, p < 0.001), lower subjective sleep latency (17.1 ± 17.8 min vs 25.5 ± 30.4 min, p = 0.001), lower ODI (15.7 ± 18.3 events/hour vs 30.7 ± 26.1 events/hour, p < 0.001), and SpO2, European Respiratory Society, ERS, The ESADA network has previously received support from the European Union COST action B26 and the European Respiratory Society. We gratefully acknowledge unrestricted seeding grants from ResMed Inc and Philips Respironics Inc. for establishment of the organisation and the database. Excellent technical assistance in terms of centre monitoring and database maintenance was provided by Ann-Christin Lundquist, RN and Jeanette Norum, RN.

Background Sleep-disordered breathing (SDB) has been associated with a greater incidence and mortality of cancer, although such findings are inconsistent. However, no large studies are currently available to investigate this association in patients with a specific type of cancer. This study seeks to assess potential relationships between SDB severity and aggressiveness markers of cutaneous melanoma. Methods Four hundred and forty-three patients with a diagnosis of melanoma underwent a sleep study within 6 months of diagnosis. General demographics were collected, along with melanoma characteristics and polygraphic parameters consisting of the apnea-hypopnea index (AHI) and indices of both continuous and intermittent night-time oxyhemoglobin desaturation (DI4%). An exploration of independent relationships between SDB and various objective melanoma aggressiveness markers (Breslow index, presence of ulceration, presence of regression, mitotic index, stage of severity, damage to the sentinel lymph, and spreading of the melanoma) was performed. Results Patients in the upper tertiles of AHI or DI4% were 1.94 (95% CI, 1.14-3.32; P = .022) and 1.93 (95% CI, 1.14-3.26; P = .013) times more likely, respectively, to present with aggressive melanoma (Breslow index > 1 mm) than those in the lowest tertiles of these sleep attributes after adjustment for age, sex, tumor location, and BMI. This association was particularly prominent among patients 2 mm. The presence of the additional markers of aggressiveness was also associated with higher AHI and DI4% values. Conclusions The severity of SDB was independently associated with greater aggressiveness of cutaneous melanoma, particularly among younger patients.

Introduction: Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored. The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH. Methods: This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA. Conclusions: This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH. (C) 2018 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.

Obstructive sleep apnea (OSA) is an independent cause of resistant hypertension (RH) but its association with refractory hypertension (RfH), a recently described form of severe hypertension, has not yet been investigated. This study seeks to analyze the association between the presence and severity of OSA/OSA syndrome with RfH and to compare it with a group of patients with OSA/OSA syndrome and RH. We conducted a multicenter, cross-sectional study of consecutive patients diagnosed with RH by means of 24-hour ambulatory blood pressure monitoring. Those patients with blood pressure levels ≥130/80 mm Hg, despite taking at least 5 antihypertensive drugs, were considered to have true RfH. All patients underwent a sleep study and completed a detailed clinical history related to OSA, current medication, and cardiovascular diseases. Overall, 229 patients were included (mean age, 58.3 years; 63% male), of whom 42 (18.3%) satisfied the criteria for RfH. Compared with those with RH, patients with RfH had a higher cardiovascular risk profile, higher blood pressure measurements, and a 2-fold greater risk of having both severe OSA (odds ratio, 2.1, with a prevalence of apnea-hypopnea index ≥15, 95.2% and apnea-hypopnea index ≥30, 64.3%) and OSA syndrome (apnea-hypopnea index ≥5+Epworth Sleepiness Scale >10; odds ratio, 1.9; 52.4% versus 37.3%; P =0.023), as well as higher OSA severity (apnea-hypopnea index, 41.8 versus 33.8 events/h; P =0.026). Patients with RfH had an even greater prevalence and severity of OSA and OSA syndrome than RH patients, highlighting the need to identify these patients to refer them to sleep units on a preferential basis.

ObjectiveTo assess the effectiveness and cost-effectiveness of primary care (PC) and sleep unit (SU) models for the management of subjects with suspected obstructive sleep apnoea (OSA).MethodsMulticentre, open-label, two-arm, parallel-group, non-inferiority randomised controlled trial. A total of 302 subjects with suspected OSA and/or resistant hypertension were consecutively enrolled, 149 were treated at 11 PC units and 153 patients at a SU. The primary outcomes were a 6-month change in the Epworth Sleepiness Scale (ESS) score and Health Utilities Index (HUI). The non-inferiority margin for the ESS score was −2.0.ResultsA total of 80.2% and 70.6% of the PC and SU patients were diagnosed with OSA, respectively, and 59.3% and 60.4% of those were treated with CPAP in PC and SU units, respectively. The Apnoea–Hypopnoea Index was similar between the groups (PC vs SU (median (IQR); 23.1 (26.8) events/h vs 21.8 (35.2) events/h), and the baseline ESS score was higher in the PC than in the SU group (10.3 (6.6) vs 9 (7.2)). After 6 months, the ESS score of the PC group decreased from a mean of 10.1 to 7.6 (−2.49; 95% CI −3.3 to −1.69), and that of the SU group decreased from 8.85 to 5.73 (−3.11; 95% CI −3.94 to 2.28). The adjusted difference between groups for the mean change in the ESS score was −1.25 (one-sided 95% CI −1.88; p=0.025), supporting the non-inferiority of PC management. We did not observe differences in the HUI between groups. The cost analysis showed a median savings of €558.14/patient for the PC setting compared with the SU setting.ConclusionsAmong patients with suspected OSA, the PC model did not result in a worse ESS score or HUI than the specialist model and generated savings in terms of management cost. Therefore, the PC model was more cost-efficient than the SU model.Trial registrationResults; >>NCT02234765, Clinical Trials.gov.

Background An analysis of cardiac injury markers in patients with OSA who sustain an episode of acute coronary syndrome (ACS) may contribute to a better understanding of the interactions and impact of OSA in subjects with ACS. We compared peak cardiac troponin I (cTnI) levels in patients with OSA and patients without OSA who were admitted for ACS. Methods Blood samples were collected every 6 hours from the time of admission until two consecutive assays showed a downward trend in the cTnI assay. The highest value obtained defined the peak cTnI value, which provides an estimate of infarct size. Results We included 89 patients with OSA and 38 patients without OSA with an apnea-hypopnea index of a median of 32 (interquartile range [IQR], 20.8-46.6/h and 4.8 [IQR, 1.6-9.6]/h, respectively. The peak cTnI value was significantly higher in patients without OSA than in patients with OSA (median, 10.7 ng/mL [IQR, 1.78-40.1 ng/mL] vs 3.79 ng/mL [IQR, 0.37-24.3 ng/mL]; P = .04). The multivariable linear regression analysis of the relationship between peak cTnI value and patient group, age, sex, and type of ACS showed that the presence or absence of OSA significantly contributed to the peak cTnI level, which was 54% lower in patients with OSA than in those without OSA. Conclusions The results of this study suggest that OSA has a protective effect in the context of myocardial infarction and that patients with OSA may experience less severe myocardial injury. The possible role of OSA in cardioprotection should be explored in future studies.

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity. Weight loss is an important component of management based on clinical rationale, but the evidence supporting weight loss has not been summarized and the optimal approach has not been determined.Objectives: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. The panel asked, "Should a weight loss intervention be performed in patients with OHS?"Methods: Medline, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that assessed weight loss interventions in obese adults with confirmed OHS, suspected OHS, or hypercapnia. The quality of the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Results: The search identified 2,994 articles. Six studies were selected, including two randomized trials and four nonrandomized studies without a comparator. Sample size ranged from 16 to 63 subjects. The studies found that a comprehensive weight loss program (including motivational counseling, dieting, and exercise) can reduce weight by 6% to 7% but confers no clinically significant effects compared with standard care. Bariatric surgery, on the other hand, is associated with more robust weight loss (15-64.6%, depending on the type of intervention), reduction of obstructive sleep apnea severity (18-44% reduction of the apnea-hypopnea index), and improvement in gas exchange (17-20% reduction in partial pressure of carbon dioxide in the arterial blood), ultimately leading to the resolution of OHS. Moreover, daytime sleepiness and pulmonary artery pressure also improve with significant weight loss. Bariatric surgery is associated with adverse effects in roughly one-fifth of patients, but serious adverse effects are very rare. The level of certainty in the estimated effects was very low for most outcomes.Conclusions: The guideline panel for which the systematic review was performed made a conditional (i.e., weak) recommendation suggesting a weight loss intervention for patients with OHS, targeting a sustained weight loss of 25% to 30% of actual body weight. This recommendation was based on very low-quality evidence. Although the weight loss target is based on the observation that greater weight loss is associated with better outcomes, there is a need for better-quality studies to ascertain the degree of weight loss necessary to achieve improvement in clinically relevant outcomes in patients with OHS.

Background Obesity hypoventilation syndrome (OHS) is treated with either non-invasive ventilation (NIV) or CPAP, but there are no long-term cost-effectiveness studies comparing the two treatment modalities. Objectives We performed a large, multicentre, randomised, open-label controlled study to determine the comparative long-term cost and effectiveness of NIV versus CPAP in patients with OHS with severe obstructive sleep apnoea (OSA) using hospitalisation days as the primary outcome measure. Methods Hospital resource utilisation and within trial costs were evaluated against the difference in effectiveness based on the primary outcome (hospitalisation days/year, transformed and non-transformed in monetary term). Costs and effectiveness were estimated from a log-normal distribution using a Bayesian approach. A secondary analysis by adherence subgroups was performed. Results In total, 363 patients were selected, 215 were randomised and 202 were available for the analysis. The median (IQR) follow-up was 3.01 (2.91-3.14) years for NIV group and 3.00 (2.92-3.17) years for CPAP. The mean (SD) Bayesian estimated hospital days was 2.13 (0.73) for CPAP and 1.89 (0.78) for NIV. The mean (SD) Bayesian estimated cost per patient/year in the NIV arm, excluding hospitalisation costs, was €2075.98 (91.6), which was higher than the cost in the CPAP arm of €1219.06 (52.3); mean difference €857.6 (105.5). CPAP was more cost-effective than NIV (99.5% probability) because longer hospital stay in the CPAP arm was compensated for by its lower costs. Similar findings were observed in the high and low adherence subgroups. Conclusion CPAP is more cost-effective than NIV; therefore, CPAP should be the preferred treatment for patients with OHS with severe OSA. Trial registration number NCT01405976, Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo) PI050402, Spanish Respiratory Foundation 2005 (FEPAR) and Air Liquide Spain.

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable complication of severe obesity. Although weight loss is an accepted component of management, it is difficult to achieve and sustain the degree of weight loss necessary to reverse OHS. As such, positive airway pressure (PAP) during sleep has become the cornerstone therapy for most patients with OHS. However, the value of PAP therapy remains uncertain.Objective: To perform a systematic review to determine whether adults with OHS should be treated with PAP therapy or not.Methods: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. MEDLINE, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that compared PAP therapy (i.e., continuous PAP or noninvasive ventilation) to no PAP therapy in patients with OHS. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to appraise the quality of evidence.Results: The search identified 2,994 unique articles. The full text of 56 articles was reviewed, and 25 studies were selected, including 3 randomized trials, 12 nonrandomized comparative studies, and 10 randomized and nonrandomized studies without a comparator group. Sample size ranged from 21 to 1,527 patients. PAP was associated with increased resolution of OHS and improvements in mortality, gas exchange, daytime sleepiness, sleep quality, quality of life, and emergency department visits. Nearly half of patients experienced trivial adverse effects related to PAP therapy. Certainty in the estimated effects was low or very low for most outcomes.Conclusions: The panel made a conditional (i.e., weak) recommendation that PAP therapy during sleep be offered to patients with OHS to improve outcomes. This recommendation was based on very low-quality evidence.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity. Treatment consists of weight loss and positive airway pressure (PAP) therapy. However, the preferred mode of PAP is uncertain.Objectives: To perform a systematic review to determine whether PAP therapy should be initiated as noninvasive ventilation (NIV) or continuous PAP (CPAP) in ambulatory patients with OHS.Methods: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. MEDLINE, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that compared initial treatment with NIV to CPAP in OHS. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to appraise the quality of evidence.Results: The search identified 2,994 potentially relevant articles, the full text of 21 articles was reviewed, and five articles were selected. The five articles included three randomized trials (one reported as two articles) and an observational study. The sample size ranged from 36 to 225 subjects. The evidence showed no differences in mortality, cardiovascular events, and healthcare resource use between patients with OHS treated with NIV or CPAP. Both PAP modalities were similarly effective in improving gas exchange, the need for supplemental oxygen, daytime sleepiness, sleep quality, quality of life, dyspnea, and sleep-disordered breathing. There was also no significant difference in adherence to NIV or CPAP therapy. Certainty in the estimated effects was low or very low for some outcomes. Therefore, the conditional recommendation was based on very low-quality evidence.Conclusions: The panel made a conditional (i.e., weak) recommendation that CPAP rather than NIV be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea (OSA). The effectiveness of CPAP is similar to that of NIV, but NIV is more costly and requires more resources than CPAP. Given that approximately 70% of patients with OHS have coexistent severe OSA, this recommendation applies to the great majority of patients with stable OHS, but it should not be extrapolated to patients with OHS without severe OSA. Patients of advanced age, with poor lung function, or with greater or recent acute ventilatory failure may not respond adequately to CPAP.

Continuous positive airway pressure (CPAP) treatment reduces blood pressure (BP) in obstructive sleep apnoea (OSA) and hypertensive patients, but there is a lack of data about the effects of CPAP on the BP in normotensive patients.The aim of the study was to evaluate BP changes in normotensive OSA individuals receiving CPAP treatment.We selected 131 normotensive outpatients with an apnoea/hypopnoea index (AHI) greater than 15 events/hour who required CPAP treatment. All patients underwent a sleep study and 24-h ambulatory BP monitoring (ABPM) at baseline and after 6 months. In addition, the patients were assessed for the presence of baseline masked hypertension, defined as office BP less than 140/90 mmHg and increased BP on 24-h ABPM (mean 24-h BP ≥130/80 mmHg).After 6 months of CPAP treatment, a mild reduction in all 24-h ABPM variables was observed, but only the mean 24-h DBP [-1.39 mmHg, 95% confidence interval (95% CI), -2.50 to -0.27], mean daytime DBP (-1.39 mmHg, 95% CI -2.56 to -0.22) and the mean 24-h ambulatory BP (-1.80 mmHg, 95% CI, -3.16 to -0.44) reached statistical significance. The reduction was primarily due to BP changes in individuals with masked hypertension who displayed a mean BP reduction of -4.78 mmHg (-7.25 to -2.30 mmHg). Consistent with a circadian BP pattern, a reduction in mean nocturnal BP of -4.73 mmHg (-7.39 to -2.06 mmHg) was observed at 6 months in nondippers; in contrast, the mean nocturnal BP in dippers increased by 2.61 mmHg (0.60-4.62 mmHg).Our findings suggest that the CPAP effects may be different in normotensive outpatients depending on the presence of undiagnosed masked hypertension and the dipping pattern. Therefore, it is important to consider measuring ABPM in this type of patient.

Spanish Sleep Network., [Rationale] Continuous positive airway pressure (CPAP) can significantly reduce blood pressure (BP) levels in patients with resistant hypertension and sleep apnea (OSA); however, the effect on patients with refractory hypertension (RfH) is not known. This study seeks to evaluate the effect of CPAP treatment on BP levels in patients with OSA and RfH, compared with those with OSA and resistant hypertension., [Methods] Post-hoc analysis of the HIPARCO randomized clinical trial on the effect of CPAP treatment on BP levels in patients with resistant hypertension. Those patients with uncontrolled 24-h ambulatory BP monitoring readings (>130 and/or >80 mmHg) in SBP or DBP were considered to have resistant hypertension (if they were taking three or four antihypertensive drugs) or RfH (if they were taking at least five drugs). OSA patients were randomized to receive CPAP or usual care for 3 months. They underwent a second 24-h ambulatory BP monitoring study to establish the effect of CPAP treatment on BP levels in both groups., [Results] A total of 98 patients were randomized to CPAP (19 RfH/79 resistant hypertension) and 96 to usual care (21 RfH/75 resistant hypertension). BP readings dropped more marked in patients with RfH than resistant hypertension, in both 24-h SBP (−9 vs. −1.6 mmHg, P = 0.021) and 24-h DBP (−7.3 vs. −2.3 mmHg, P = 0.074), especially at night (−11.3 vs. −3.8, P = 0.121 and −8.8 vs. −2.2, P = 0.054) respectively. Adjusted difference between groups was statistically significant in 24-h SBP levels (−7.4 mmHg, P = 0.021)., [Conclusion] CPAP lowers BP levels in both resistant hypertension and RfH patients although the degree of this reduction is higher in those with RfH especially during the night.

Introduction Obstructive sleep apnea (OSA) is a prevalent disease associated with significant morbidity and high healthcare costs. Information and communication technology could offer cost-effective management options. Objectives To evaluate an out-of-hospital Virtual Sleep Unit (VSU) based on telemedicine to manage all patients with suspected OSA, including those with and without continuous positive airway pressure (CPAP) therapy. Methods This was an open randomized controlled trial. Patients with suspected OSA were randomized to hospital routine (HR) or VSU groups to compare the clinical improvement and cost-effectiveness in a non-inferiority analysis. Improvement was assessed by changes in the Quebec Sleep Questionnaire (QSQ), EuroQol (EQ-5D and EQ-VAS), and Epworth Sleepiness Scale (ESS). The follow-up was 3 months. Cost-effectiveness was assessed by a Bayesian analysis based on quality-adjusted life-years (QALYs). Results The HR group (n: 92; 78% OSA, 57% CPAP) compared with the VSU group (n: 94; 83% OSA, 43% CPAP) showed: CPAP compliance was similar in both groups, the QSQ social interactions domain improved significantly more in the HR group whereas the EQ-VAS improved more in the VSU group. Total and OSA-related costs were lower in the VSU group than the HR. The Bayesian cost-effectiveness analysis showed that VSU was cost-effective for a wide range of willingness to pay for QALYs. Conclusions The VSU offered a cost-effective means of improving QALYs than HR. However, the assessment of its clinical improvement was influenced by the choice of the questionnaire; hence, additional measurements of clinical improvement are needed. Our findings indicate that VSU could help with the management of many patients, irrespective of CPAP use.

Refractory hypertension (RfH) is defined as a lack of blood pressure control despite the administration of at least 5 anti-hypertensive drugs. The factors associated with its natural history are unknown. This study aimed to evaluate both the incidence of RfH in an cohort of patients with resistant hypertension (RH) and the factors involved in that progression. This was an observational prospective multicenter study (24 centers) with 172 patients with confirmed RH (24-h ABPM) who underwent a further 24 h ABPM study at the end of the follow-up. Prospective information was obtained from all patients in their corresponding Hypertension Units via a standard clinical protocol, and they all underwent a sleep study. Thirty patients were diagnosed with RfH (17.4%) after a mean follow-up of 57 months, despite the prescription of a greater number of long-acting thiazide-like diuretics and mineralocorticoid receptor antagonists. The factors associated with progression to RfH were: a longer period since the diagnosis of RH (OR: 1.06, 95% CI: 1.01–1.1, p = 0.007); the HbA1c concentration (OR: 1.42, 95% CI: 1.42–1.8; p = 0.005); the initial heart rate (OR: 1.05, 95% CI: 1.01–1.09, p = 0.004); and poor adherence to continuous positive airway pressure (CPAP) in cases of obstructive sleep apnea (OR: 3.36, 95% CI: 1.47–7.7, p = 0.004). In conclusion, a considerable percentage of patients evolved from the RH to the RfH phenotype despite changes in their treatment. Some easily measurable variables, such as heart rate, the time since the diagnosis, the HbA1c level, and the presence of untreated obstructive sleep apnea (or poor adherence to CPAP) have been demonstrated to be prognostic factors in the progression to RfH.

Background Acute coronary syndrome (ACS) is a major cause of death and closely related with obstructive sleep apnea (OSA). Our hypothesis is that several cardiovascular-related biomarkers could have a differential prognostic value for ACS severity in patients with OSA, and could also help (individually or combined) in the detection of OSA in patients after a coronary event. Methods Up to 361 consecutive individuals admitted due to ACS were included in the study. All of them were evaluated for ACS severity (Killip score, number of diseased vessels, ejection fraction) and further classified as OSA or non-OSA. Medical records were registered and eleven blood biomarkers were measured, including heart-type fatty acid-binding globulin, N-terminal pro-brain natriuretic peptide, matrix metalloproteinase-9 (MMP9), placental growth factor (PlGF) and high-sensitivity C-reactive protein. Odds ratios of every biomarker for ACS severity-related parameters were calculated and adjusted for age, gender, body-mass index (BMI), hypertension, diabetes, smoking and drinking. The use of clinical measures and biomarkers for the diagnosis of OSA in ACS patients was evaluated both alone and combined using ROC curves. Results Several biomarkers showed a significant association with ACS severity, which remained after adjusting for OSA and other potentially confounding variables. The mathematical combination of age, BMI, PlGF and MMP9 showed an area under the ROC curve (AUC) for OSA identification of 0.741, which was greater than any individual parameter or combination assessed: AUC(BMI):0.687, AUC(age):0.576, AUC(PlGF):0.584, AUC(MMP9):0.555. Conclusions The usefulness of biomarkers in the assessment of ACS severity was independent of OSA and the other variables evaluated. In patients admitted after a coronary event, the combination of clinical measures and biomarkers showed a significant discriminating power for the detection of OSA. Clinical trial registration: NCT01335087 ( clinicaltrials.gov ).

Obstructive sleep apnea (OSA) is an independent cause of resistant hypertension (RH) but its association with refractory hypertension (RfH), a recently described form of severe hypertension, has not yet been investigated. This study seeks to analyze the association between the presence and severity of OSA/OSA syndrome with RfH and to compare it with a group of patients with OSA/OSA syndrome and RH. We conducted a multicenter, cross-sectional study of consecutive patients diagnosed with RH by means of 24-hour ambulatory blood pressure monitoring. Those patients with blood pressure levels ≥130/80 mm Hg, despite taking at least 5 antihypertensive drugs, were considered to have true RfH. All patients underwent a sleep study and completed a detailed clinical history related to OSA, current medication, and cardiovascular diseases. Overall, 229 patients were included (mean age, 58.3 years; 63% male), of whom 42 (18.3%) satisfied the criteria for RfH. Compared with those with RH, patients with RfH had a higher cardiovascular risk profile, higher blood pressure measurements, and a 2-fold greater risk of having both severe OSA (odds ratio, 2.1, with a prevalence of apnea-hypopnea index ≥15, 95.2% and apnea-hypopnea index ≥30, 64.3%) and OSA syndrome (apnea-hypopnea index ≥5+Epworth Sleepiness Scale10; odds ratio, 1.9; 52.4% versus 37.3%; P=0.023), as well as higher OSA severity (apnea-hypopnea index, 41.8 versus 33.8 events/h; P=0.026). Patients with RfH had an even greater prevalence and severity of OSA and OSA syndrome than RH patients, highlighting the need to identify these patients to refer them to sleep units on a preferential basis.

Resumen El proyecto Pickwick es un estudio prospectivo, aleatorizado, abierto y controlado con grupos en paralelo que intenta dar respuesta a los interrogantes del sindrome de hipoventilacion-obesidad (SHO), una enfermedad creciente en los paises desarrollados. Para ello, pacientes con SHO fueron divididos en pacientes con indice de apneas-hipoapneas (IAH) ≥ 30 y Su objetivo ha sido evaluar la eficacia del tratamiento con ventilacion VNI, CPAP y estilo de vida saludable (control) a medio y largo plazo en el SHO, analizando como variable primaria la PaCO2 y los dias de hospitalizacion, respectivamente, y como variables operativas el porcentaje de abandonos por razones medicas y mortalidad. Los objetivos secundarios a medio plazo fueron: 1) evaluar la eficacia clinica-funcional, en calidad de vida, en variables polisomnograficas y ecocardiograficas; 2) investigar la importancia de los episodios apneicos y de la leptina en la genesis de la hipoventilacion alveolar diurna y el cambio con los diferentes tratamientos; 3) investigar si las alteraciones metabolicas, bioquimicas y disfuncion endotelial vascular dependen de la presencia de apneas e hipoapneas, y 4) cambio de marcadores inflamatorios y de dano endotelial con los tratamientos. Los objetivos secundarios a largo plazo fueron: 1) evaluar la eficacia clinico-funcional y en calidad de vida con VNI y CPAP; 2) cambio de la leptina, marcadores inflamatorios y de dano endotelial con los tratamientos; 3) cambio de la hipertension pulmonar y otras variables ecocardiograficas, asi como en la hipertension arterial e incidencia de episodios cardiovasculares, y 4) frecuencia de abandonos y mortalidad.

Despite the fact that metanalyses and clinical guidelines do not recommend the routine use of domiciliary non-invasive ventilation (NIV) for patients diagnosed with severe stable Chronic Obstructive Pulmonary Disease (COPD) and with chronic respiratory failure, it is common practice in some countries.We conducted an international web-survey of physicians involved in provision of long-term NIV to examine patterns of domiciliary NIV use in patients diagnosed with COPD.The response rate was 41.6%. A reduction of hospital admissions, improvements in quality of life and dyspnea relief were considered as the main expected benefits for patients. Nocturnal oxygen saturation assessment was the principal procedure performed before NIV prescription. Recurrent exacerbations (>3) requiring NIV and failed weaning from in hospital NIV were the most important reasons for starting domiciliary NIV. Pressure support ventilation (PSV) was the most common mode, with low intensity settings (PSV-low) the most popular (44.4 30.1%) compared with high intensity (PSV-high) strategies (26.9 +/- 25.9%), with different geographical preferences.COPD is confirmed to be a common indication for domiciliary NIV. Recurrent exacerbations and failed weaning from in-hospital NIV were the main reasons for its prescription.

The incidence of obesity hypoventilation syndrome (OHS) may be increasing in parallel with the present obesity epidemic. Despite extensive noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) use in patients with OHS, information regarding efficacy is limited.We performed a large, multicenter randomized controlled study to determine the comparative efficacy of NIV, CPAP, and lifestyle modification (control group) using daytime PaCO2 as the main outcome measure.Sequentially screened patients with OHS with severe sleep apnea were randomized into the above-mentioned groups for a 2-month follow up. Arterial blood gas parameters, clinical symptoms, health-related quality-of-life assessments, polysomnography, spirometry, 6-minute-walk distance, dropouts, compliance, and side effects were evaluated. Statistical analysis was performed using intention-to-treat analysis, although adjustments for CPAP and NIV compliance were also analyzed.In total, 351 patients were selected, and 221 were randomized. NIV yielded the greatest improvement in PaCO2 and bicarbonate, with significant differences relative to the control group but not relative to the CPAP group. In the CPAP group, PaCO2 improvement was significantly different than in the control group only after CPAP compliance adjustment. Additionally, clinical symptoms and polysomnographic parameters improved similarly with NIV and CPAP relative to the control. However, some health-related quality-of-life assessments, the spirometry, and 6-minute-walk distance results improved more with NIV than with CPAP. Dropouts were similar between groups, and compliance and secondary effects were similar between NIV and CPAP.NIV and CPAP were more effective than lifestyle modification in improving clinical symptoms and polysomnographic parameters, although NIV yielded better respiratory functional improvements than did CPAP. Long-term studies must demonstrate whether this functional improvement has relevant implications. Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

Rationale: General practitioners play a passive role in obstructive sleep apnea (OSA) management. Simplification of the diagnosis and use of a semiautomatic algorithm for treatment can facilitate the integration of general practitioners, which has cost advantages.Objectives: To determine differences in effectiveness between primary health care area (PHA) and in-laboratory specialized management protocols during 6 months of follow-up.Methods: A multicenter, noninferiority, randomized, controlled trial with two open parallel arms and a cost-effectiveness analysis was performed in six tertiary hospitals in Spain. Sequentially screened patients with an intermediate to high OSA probability were randomized to PHA or in-laboratory management. The PHA arm involved a portable monitor with automatic scoring and semiautomatic therapeutic decision-making. The in-laboratory arm included polysomnography and specialized therapeutic decision-making. Patients in both arms received continuous positive airway pressure treatment or sleep hygiene and dietary treatment alone. The primary outcome measure was the Epworth Sleepiness Scale. Secondary outcomes were health-related quality of life, blood pressure, incidence of cardiovascular events, hospital resource utilization, continuous positive airway pressure adherence, and within-trial costs.Measurements and Main Results: In total, 307 patients were randomized and 303 were included in the intention-to-treat analysis. Based on the Epworth Sleepiness Scale, the PHA protocol was noninferior to the in-laboratory protocol. Secondary outcome variables were similar between the protocols. The cost-effectiveness relationship favored the PHA arm, with a cost difference of €537.8 per patient.Conclusions: PHA management may be an alternative to in-laboratory management for patients with an intermediate to high OSA probability. Given the clear economic advantage of outpatient management, this finding could change established clinical practice.Clinical trial registered with www.clinicaltrials.gov (NCT02141165).

Background: Previous population-based studies have suggested that lung function impairment (LFI) could be associated with an increase in the mortality of cardiovascular events. Methods: We evaluated the association between LFI and the severity and short-term prognosis of acute coronary syndrome (ACS). LFI was established through presence of a forced expiratory volume in one second (FFV1) and/or a forced vital capacity (FVC) less than 80% of predicted. Results: Seventy-one LFI subjects (61.45 +/- 10.70 years, 83.10% males) and 247 non-LFI subjects (58.98 +/- 11.18 years, 80.57% males) with ACS were included. Subjects with LFI exhibited a higher prevalence of systemic hypertension (57.75% vs. 40.89%, P=0.02) and tobacco exposure (28.50 +/- 26.67 vs. 18.21 +/- 19.83 pack-years, P=0.007). No significant differences between groups were found regarding the severity of ACS (ejection fraction, Killip class, number of affected vessels, and peak plasma troponin). However, in comparison to non-LFI subjects, a significantly shorter length of stay in the coronary care unit (CCU) was observed in the LFI group (1.83 +/- 1.10 vs. 2.24 +/- 1.21 days, P=0.01) and this was even shorter in subjects with obstructive LFI (1.62 +/- 1.17 days, P=0.009). When considering obstructive sleep apnea (OSA), an interaction with length of stay was found, revealing that OSA subjects with obstructive LFI had the shortest length of stay in the CCU (0.60 +/- 0.89 days, P=0.05) also in comparison to non-LFI. Conclusions: This study indicates a possible association between LFI and a shorter length of stay in the CCU but docs not show a significant association with ACS severity.

Background: Sleep-disordered-breathing (SDB), which is characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), is a prevalent condition that promotes metabolic dysfunction, particularly among patients suffering from obstructive hypoventilation syndrome (OHS). Exosomes are generated ubiquitously, are readily present in the circulation, and their cargo may exert substantial functional cellular alterations in both physiological and pathological conditions. However, the effects of plasma exosomes on adipocyte metabolism in patients with OHS or in mice subjected to IH or SF mimicking SDB are unclear. Methods: Exosomes from fasting morning plasma samples from obese adults with polysomnographically-confirmed OSA before and after 3 months of adherent CPAP therapy were assayed. In addition, C57BL/6 mice were randomly assigned to (1) sleep control (SC), (2) sleep fragmentation (SF), and (3) intermittent hypoxia (HI) for 6 weeks, and plasma exosomes were isolated. Equivalent exosome amounts were added to differentiated adipocytes in culture, after which insulin sensitivity was assessed using 0 nM and 5 nM insulin-induced pAKT/AKT expression changes by western blotting. Results: When plasma exosomes were co-cultured and internalized by human naive adipocytes, significant reductions emerged in Akt phosphorylation responses to insulin when compared to exosomes obtained after 24 months of adherent CPAP treatment (n = 24; p < 0.001), while no such changes occur in untreated patients (n = 8). In addition, OHS exosomes induced significant increases in adipocyte lipolysis that were attenuated after CPAP, but did not alter pre-adipocyte differentiation. Similarly, exosomes from SF- and IH-exposed mice induced attenuated p-AKT/total AKT responses to exogenous insulin and increased glycerol content in naive murine adipocytes, without altering pre-adipocyte differentiation. Conclusions: Using in vitro adipocyte-based functional reporter assays, alterations in plasma exosomal cargo occur in SDB, and appear to contribute to adipocyte metabolic dysfunction. Further exploration of exosomal miRNA signatures in either human subjects or animal models and their putative organ and cell targets appears warranted.

In recent decades, the study of sleep breathing disorders has accelerated and increased our overall knowledge of sleep disorders in general. This now represents a real challenge to the health system due to the high prevalence, morbidity and mortality with concomitant social and economic repercussions [1]., Sleep medicine: a new approach http://ow.ly/qzVh30iVkWL

Background: Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea (OSA), but compliance and variables involved in CPAP adherence in women are unknown. Objectives: To analyse CPAP adherence and variables associated with CPAP compliance in women with OSA. Methods: We analysed 151 women with moderate-to-severe OSA (AHI≥15) who participated in a randomized controlled trial (NCT02047071) and received CPAP for 3 months. Good adherence was defined as an objective average use ≥ 4 hours/night. To identify independents predictors of adherence, multivariate logistic regression analyses were performed. Results: Nine women were excluded from the analyses because they did not begin CPAP, two women dropped out, and 140 were still on CPAP therapy at the end of the follow-up. The mean CPAP use was 5.09±2.05 hours/night at the end of the first month and 5.24±1.99 hours/night at the end of the follow-up. 73.9% (105/142) of the women had good CPAP adherence at the end of the first month, and 79.6% (113/142) at the end of follow-up. Independent baseline predictors of good adherence were the number of hour of sleep (OR 1.34, 95%CI: 1.01 to 1.76, p=0.038) and the use of antidepressant drugs (OR 0.27, 95%CI: 0.11 to 0.67, p=0.005). In addition, a fewer number of side-effects during the follow-up period was also a predictor of good CPAP adherence (1.8±1.4vs 2.6±1.7, p=0.010). Conclusions: In women with moderate-severe OSA, CPAP adherence at 3 months was adequate. Longer sleep duration predicted better adherence , whereas antidepressant therapy and greater number of side -effects were associated with poorer CPAP adherence.