Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea.

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry-based photoplethysmography signals in three prospective cohorts: HypnoLaus (N = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N = 6,367), and "Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP" (ISAACC) (N = 692). The PWAD index was the number of PWADs (>30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ⩾15 or more events per hour or <15/h, respectively, on the apnea-hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07-4.34], P = 0.031; and 2.35 [1.12-4.93], P = 0.024) and in the PLSC (1.36 [1.13-1.63], P = 0.001; and 1.44 [1.06-1.94], P = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08-3.81], P = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73-0.99], P = 0.031; and HR, 0.91 [0.86-0.96], P < 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.

Effectiveness of CPAP vs. Noninvasive Ventilation Based on Disease Severity in Obesity Hypoventilation Syndrome and Concomitant Severe Obstructive Sleep Apnea.

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)≥30events/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 ≥50mmHg). 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.

Documento internacional de consenso sobre apnea obstructiva del sueño / International Consensus Document on Obstructive Sleep Apnea

El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sueño es proporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisiones en la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literatura más actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedades científicas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedades internacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoamericano. El documento consta de un manuscrito principal, con las novedades más relevantes, y una serie de manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los apartados del documento internacional de consenso. Este documento no cubre la edad pediátrica ni el manejo del paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos de consenso aparte). Palabras clave: Apnea obstructiva del sueño Diagnóstico Tratamiento

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). Keywords: Obstructive sleep apnea Diagnosis Treatment

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome.

STUDY OBJECTIVES: 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. METHODS: In a post hoc analysis of the Pickwick trial, we performed a bivariate analysis of baseline characteristics between patients with and without PH. Variables with a P value ≤ .10 were defined as potential risk factors and were grouped by theoretical pathogenic mechanisms in several adjusted models. Similar analysis was carried out for the 2 OHS phenotypes, with and without severe concomitant obstructive sleep apnea. RESULTS: Of 246 patients with OHS, 122 (50%) had echocardiographic evidence of PH defined as systolic pulmonary artery pressure ≥ 40 mm Hg. Lower levels of awake PaO2 and higher body mass index were independent risk factors in the multivariate model, with a negative and positive adjusted linear association, respectively (adjusted odds ratio 0.96; 95% confidence interval 0.93 to 0.98; P = .003 for PaO2, and 1.07; 95% confidence interval 1.03 to 1.12; P = .001 for body mass index). In separate analyses, body mass index and PaO2 were independent risk factors in the severe obstructive sleep apnea phenotype, whereas body mass index and peak in-flow velocity in early/late diastole ratio were independent risk factors in the nonsevere obstructive sleep apnea phenotype. CONCLUSIONS: This study identifies obesity per se as a major independent risk factor for PH, regardless of OHS phenotype. Therapeutic interventions targeting weight loss may play a critical role in improving PH in this patient population. CLINICAL TRIAL REGISTRATION: Registry: Clinicaltrial.gov; Name: Alternative of Treatment in Obesity Hypoventilation Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT01405976; Identifier: NCT01405976. CITATION: Masa JF, Benítez ID, Javaheri S, et al. Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome. J Clin Sleep Med. 2022;18(4):983-992.

Spanish Society of Pulmonology and Thoracic Surgery positioning on the use of telemedine in sleep-disordered breathing and mechanical ventilation / Posicionamiento de la Sociedad Española de Neumología y Cirugía Torácica en el uso del la telemedicina en los trastornos respiratorios del sueño y ventilación mecánica

The rapid introduction of new information and communication technologies into medical practice has prompted the Spanish Society of Pulmonology and Thoracic Surgery to publish a position paper on sleep-disordered breathing, especially in relation to positive pressure treatment. It should be pointed out that the scientific literature is to some extent controversial due to a paucity of large randomized multicenter studies with long-term follow-up. Moreover, the telematics devices and systems on the market vary widely. As a result, the recommendations are based primarily on a consensus of expert professionals. Another very important aspect addressed extensively in this document is the obvious lack of regulations on telemedicine and the operations of commercial companies. The most important recommendations included in this position paper are that telemedicine is primarily advocated in subjects with travel problems or who live far from the hospital, in patients with poor CPAP compliance, and in most cases treated with non-invasive mechanical ventilation. A key element is patient individualization. It is imperative that the relevant technical, legal and ethical requirements (medical device regulations, data protection, and informed consent) are met. Finally, expert professionals from our society must contribute to and become involved in spearheading this technological change. (AU)

Como consecuencia de la rápida introducción de las nuevas tecnologías de información y comunicación (TIC) en la práctica médica, la Sociedad Española de Neumología y Cirugía Torácica ha promovido la elaboración de un documento de posicionamiento aplicado a los trastornos respiratorios del sueño, especialmente en relación con el tratamiento con presión positiva. Cabe mencionar que la literatura científica es en parte controvertida debido a que no existen suficientes estudios multicéntricos aleatorizados, con elevado número de pacientes y seguimiento a largo plazo. Además, los equipos y sistemas telemáticos en el mercado son diferentes. Como consecuencia, las recomendaciones se basan sobre todo en un consenso de profesionales expertos. Otros aspectos muy importantes son la clara ausencia de normativa o las funciones propias de las casas comerciales, que en este trabajo se abordan ampliamente. Las recomendaciones más importantes incluidas en el documento de posicionamiento son que la telemedicina se destina, básicamente, a sujetos con problemas de desplazamiento o con domicilio lejano, a aquellos que no cumplen de forma adecuada el tratamiento con CPAP y a la mayoría de los casos con ventilación mecánica no invasiva. Un elemento clave es la individualización de los pacientes. Es imperativo que se cumplan los requisitos técnicos, legales y deontológicos pertinentes (normativa de los productos sanitarios, protección de datos y consentimiento informado). Por último, los profesionales expertos de nuestra sociedad han de contribuir e implicarse en el liderazgo de este cambio tecnológico. (AU)

Non-invasive Respiratory Support in COVID-19: A Narrative Review.

Acute respiratory failure secondary to COVID-19 pneumonia may require a variety of non-pharmacological strategies in addition to oxygen therapy to avoid endotracheal intubation. The response to all these strategies, which include high nasal flow, continuous positive pressure, non-invasive ventilation, or even prone positioning in awake patients, can be highly variable depending on the predominant phenotypic involvement. Deciding when to replace conventional oxygen therapy with non-invasive respiratory support, which to choose, the role of combined methods, definitions, and attitudes toward treatment failure, and improved case improvement procedures are directly relevant clinical questions for the daily care of critically ill COVID-19 patients. The experience accumulated after more than a year of the pandemic should lead to developing recommendations that give answers to all these questions.

Spanish Society of Pulmonology and Thoracic Surgery positioning on the use of telemedine in sleep-disordered breathing and mechanical ventilation. / Posicionamiento de la Sociedad Española de Neumología y Cirugía Torácica en el uso de la telemedicina en los trastornos respiratorios del sueño y ventilación mecánica.

The rapid introduction of new information and communication technologies into medical practice has prompted Spanish Society of Pulmonology and Thoracic SurgeryR to publish a position paper on sleep-disordered breathing, especially in relation to positive pressure treatment. It should be pointed out that the scientific literature is to some extent controversial due to a paucity of large randomized multicenter studies with long-term follow-up. Moreover, the telematics devices and systems on the market vary widely. As a result, the recommendations are based primarily on a consensus of expert professionals. Another very important aspect addressed extensively in this document is the obvious lack of regulations on legal matters and the operations of commercial companies. The most important recommendations included in this position paper are that telemedicine is primarily advocated in subjects with travel problems or who live far from the hospital, in patients with poor CPAP compliance, and in most cases treated with non-invasive mechanical ventilation. A key element is patient individualization. It is imperative that the relevant technical, legal and ethical requirements (medical device regulations, data protection, and informed consent) are met. Finally, expert professionals from our society must contribute to and become involved in spearheading this technological change.

Long-term Noninvasive Ventilation in Obesity Hypoventilation Syndrome Without Severe OSA: The Pickwick Randomized Controlled Trial.

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 < 30 events/h (ie, no severe OSA) to NIV or lifestyle modification (control group) using simple randomization through an electronic database. The primary end point was hospitalization days per year. Secondary end points included other hospital resource utilization, incident cardiovascular events, mortality, respiratory functional tests, BP, quality of life, sleepiness, and other clinical symptoms. Both investigators and patients were aware of the treatment allocation; however, treating physicians from the routine care team were not aware of patients' enrollment in the clinical trial. The study was stopped early in its eighth year because of difficulty identifying patients with OHS without severe OSA. The analysis was performed according to intention-to-treat and per-protocol principles and by adherence subgroups. 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.

Cost-effectiveness of positive airway pressure modalities in obesity hypoventilation syndrome with severe obstructive sleep apnoea.

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.

Intra- and Inter-Physician Agreement in Therapeutic Decision for Sleep Apnea Syndrome / Concordancia intra e inter-médico en la decisión terapéutica para el síndrome de apnea del sueño

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 AHÍ < 40 events/h. Methods: Six experienced senior sleep specialists from different sleep centers of Spain were asked to make a therapeutic decision (CPAP treatment) based on anonymized recordings of patients with suspected OSA that has previously performed a sleep study. The clinical data was shown in an online database and included anthropometric features, clinical questionnaires, comorbidities, physical examination and sleep study results. Intra- and inter-observer decision-making were analyzed by the Fleiss’ Kappa statistics (Kappa). Results: A total of 720 medical decisions were taken to analyze the agreement between sleep professionals. Overall intra-observer evaluation reliability was almost perfect (Kappa = 0.83, 95% CI, 0.75-0.90, p < 0.001). However, overall inter-observer concordance decreased to moderate agreement (Kappa = 0.46, 95% CI, 0.42-0.51, p < 0.001). Nevertheless, it was especially low when considering AHÍ < 15 events/h. Conclusions: This study demonstrates a good intra-observer concordance in the therapeutic decision-making of different sleep physicians treating patients with low/moderate OSA. However, when analyzing inter-observer agreement the results were considerably worse. These findings underline the importance of developing improved consensus management protocols

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 < 15 eventos/h. Conclusiones: Este estudio demuestra una buena concordancia intraobservador en la toma de decisiones terapéuticas de distintos médicos expertos en sueño que tratan a pacientes con SAHS leve o moderado. Sin embargo, los resultados relativos al acuerdo interobservador fueron notablemente peores. Estos hallazgos señalan la importancia de desarrollar mejores protocolos consensuados de manejo

Upcoming Scenarios for the Comprehensive Management of Obstructive Sleep Apnea: An Overview of the Spanish Sleep Network / Escenarios futuros en el manejo integral de la apnea obstructiva del sueño: perspectiva del Spanish Sleep Network

Sleep is considered an essential part of life and plays a vital role in good health and well-being. Equally important as a balanced diet and adequate exercise, quality and quantity of sleep are essential for maintaining good health and quality of life. Sleep-disordered breathing is one of the most prevalent conditions that compromises the quality and duration of sleep, with obstructive sleep apnea (OSA) being the most prevalent disorder among these conditions. OSA is a chronic and highly prevalent disease that is considered to be a true public health problem. OSA has been associated with increased cardiovascular, neurocognitive, metabolic and overall mortality risks, and its management is a challenge facing the health care system. To establish the main future lines of research in sleep respiratory medicine, the Spanish Sleep Network (SSN) promoted the 1st World Café experts' meeting. The overall vision was established by consensus as "Sleep as promoter of health and the social impact of sleep disturbances". Under this leitmotiv and given that OSA is the most prevalent sleep disorder, five research lines were established to develop a new comprehensive approach for OSA management: (1) an integrated network for the comprehensive management of OSA; (2) the biological impact of OSA on comorbidities with high mortality, namely, cardiovascular and metabolic diseases, neurocognitive diseases and cancer; (3) Big Data Analysis for the identification of OSA phenotypes; (4) personalized medicine in OSA; and (5) OSA in children: current needs and future perspectives

El sueño se considera una parte esencial de la vida y es vital para una buena salud y para el bienestar. De igual importancia que una dieta equilibrada y una adecuada actividad física, la calidad y la cantidad del sueño son esenciales para mantener una buena salud y calidad de vida. Las alteraciones respiratorias del sueño son los trastornos más prevalentes que comprometen la calidad y duración del sueño, siendo el síndrome de la apnea obstructiva del sueño (SAHS) el más frecuente. El SAHS es una enfermedad de elevada prevalencia que se considera un problema de salud pública. Se ha asociado con aumento del riesgo cardiovascular, neurocognitivo, metabólico y especialmente de mortalidad, y su manejo representa un reto para el sistema de salud. Para establecer las principales líneas futuras de investigación en medicina respiratoria del sueño, el Spanish Sleep Network promovió la primera edición del World Cafe experts' meeting. El mensaje principal «El sueño como promotor de la salud y el impacto social de los trastornos del sueño» se estableció por consenso. Bajo este lema y dado que el SAHS es el trastorno del sueño más prevalente, se establecieron cinco líneas de investigación para desarrollar una aproximación completa para el manejo de este síndrome: 1) Una red integrada para el manejo del SAHS; 2) El impacto biológico del SAHS en las comorbilidades con elevada mortalidad como la enfermedad cardiovascular, las enfermedades metabólicas y neurocognitivas y el cáncer; 3) El análisis de grandes bases de datos para la identificación de fenotipos del SAHS; 4) Medicina personalizada en el SAHS, y 5) El SAHS en niños: necesidades actuales y perspectivas futuras

Upcoming Scenarios for the Comprehensive Management of Obstructive Sleep Apnea: An Overview of the Spanish Sleep Network.

Sleep is considered an essential part of life and plays a vital role in good health and well-being. Equally important as a balanced diet and adequate exercise, quality and quantity of sleep are essential for maintaining good health and quality of life. Sleep-disordered breathing is one of the most prevalent conditions that compromises the quality and duration of sleep, with obstructive sleep apnea (OSA) being the most prevalent disorder among these conditions. OSA is a chronic and highly prevalent disease that is considered to be a true public health problem. OSA has been associated with increased cardiovascular, neurocognitive, metabolic and overall mortality risks, and its management is a challenge facing the health care system. To establish the main future lines of research in sleep respiratory medicine, the Spanish Sleep Network (SSN) promoted the 1st World Café experts' meeting. The overall vision was established by consensus as "Sleep as promoter of health and the social impact of sleep disturbances". Under this leitmotiv and given that OSA is the most prevalent sleep disorder, five research lines were established to develop a new comprehensive approach for OSA management: (1) an integrated network for the comprehensive management of OSA; (2) the biological impact of OSA on comorbidities with high mortality, namely, cardiovascular and metabolic diseases, neurocognitive diseases and cancer; (3) Big Data Analysis for the identification of OSA phenotypes; (4) personalized medicine in OSA; and (5) OSA in children: current needs and future perspectives.

Echocardiographic Changes with Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome. Long-Term Pickwick Randomized Controlled Clinical Trial.

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 < 0.0001 for longitudinal intragroup changes for both treatment arms). However, there were no significant differences between groups. NIV and CPAP therapies similarly improved left ventricular diastolic dysfunction and reduced left atrial diameter. Both NIV and CPAP improved respiratory function and dyspnea.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.Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

Intra- and Inter-Physician Agreement in Therapeutic Decision for Sleep Apnea Syndrome.

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<40events/h. METHODS: Six experienced senior sleep specialists from different sleep centers of Spain were asked to make a therapeutic decision (CPAP treatment) based on anonymized recordings of patients with suspected OSA that has previously performed a sleep study. The clinical data was shown in an online database and included anthropometric features, clinical questionnaires, comorbidities, physical examination and sleep study results. Intra- and inter-observer decision-making were analyzed by the Fleiss' Kappa statistics (Kappa). RESULTS: A total of 720 medical decisions were taken to analyze the agreement between sleep professionals. Overall intra-observer evaluation reliability was almost perfect (Kappa=0.83, 95% CI, 0.75-0.90, p<0.001). However, overall inter-observer concordance decreased to moderate agreement (Kappa=0.46, 95% CI, 0.42-0.51, p<0.001). Nevertheless, it was especially low when considering AHI<15events/h. CONCLUSIONS: This study demonstrates a good intra-observer concordance in the therapeutic decision-making of different sleep physicians treating patients with low/moderate OSA. However, when analyzing inter-observer agreement the results were considerably worse. These findings underline the importance of developing improved consensus management protocols.

Comprehensive management of obstructive sleep apnea by telemedicine: Clinical improvement and cost-effectiveness of a Virtual Sleep Unit. A randomized controlled trial.

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.

Differential blood pressure response to continuous positive airway pressure treatment according to the circadian pattern in hypertensive patients with obstructive sleep apnoea.

Continuous positive airway pressure (CPAP) has a heterogeneous effect on blood pressure (BP) in hypertensive patients. However, the effect of CPAP on BP in hypertensive subjects regarding circadian BP pattern has never been explored. This study aimed to assess the effect of CPAP on BP, taking into consideration the circadian BP pattern in untreated hypertensive patients.This study is a post hoc analysis of the Spanish Cohort for the Study of the Effect of CPAP in Hypertension (CEPECTA), a multicentre, randomised trial of CPAP versus sham-CPAP in patients with new-onset systemic hypertension and an apnoea-hypopnoea index >15 events·h-1 We included patients for whom 24-h ambulatory BP monitoring (ABPM) data were available at baseline and 12 weeks after the intervention. Subjects were classified based on the dipping ratio (dipper/non-dipper). We evaluated the effect of CPAP on ABPM parameters after 12 weeks of treatment.Overall, 272 hypertensive subjects were included in the analysis (113 dippers and 159 non-dippers). Baseline clinical and polysomnographic variables were similar between the groups. CPAP treatment in non-dipper patients was associated with reductions in 24-h ambulatory BP variables and night-time ambulatory BP measurements. However, a nonsignificant effect was reported in the dipper group. The differential effects of CPAP between the groups were -2.99 mmHg (95% CI -5.92-- -0.06 mmHg) for the mean 24-h ambulatory BP and -5.35 mmHg (95% CI -9.01- -1.69 mmHg) for the mean night-time ambulatory BP.Our results show a differential effect of CPAP treatment on BP in hypertensive patients depending on the circadian pattern. Only non-dipper patients benefited from CPAP treatment in terms of BP reduction.

Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep. Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. We therefore aimed to determine the long-term comparative effectiveness of both treatment modalities. METHODS: We did a multicentre, open-label, randomised controlled trial at 16 clinical sites in Spain. We included patients aged 15-80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We randomly assigned patients, using simple randomisation through an electronic database, to receive treatment with either non-invasive ventilation or continuous positive airway pressure. Both investigators and patients were aware of the treatment allocation. The research team was not involved in deciding hospital treatment, duration of treatment in the hospital, and adjustment of medications, as well as adjudicating cardiovascular events or cause of mortality. Treating clinicians from the routine care team were not aware of the treatment allocation. The primary outcome was the number of hospitalisation days per year. The analysis was done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01405976. FINDINGS: From May 4, 2009, to March 25, 2013, 100 patients were randomly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group, of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis. The median follow-up was 5·44 years (IQR 4·45-6·37) for all patients, 5·37 years (4·36-6·32) in the continuous positive airway pressure group, and 5·55 years (4·53-6·50) in the non-invasive ventilation group. The mean hospitalisation days per patient-year were 1·63 (SD 3·74) in the continuous positive airway pressure group and 1·44 (3·07) in the non-invasive ventilation group (adjusted rate ratio 0·78, 95% CI 0·34-1·77; p=0·561). Adverse events were similar between both groups. INTERPRETATION: In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea, non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness. Given that continuous positive airway pressure has lower complexity and cost, continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available. FUNDING: Instituto de Salud Carlos III, Spanish Respiratory Foundation, and Air Liquide Spain.

Los trastornos respiratorios durante el sueño 2018: una nueva dimensión / Respiratory Disorders During Sleep: A New Dimension for 2018

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Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes.

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.