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).

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.

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.

Self-setup of home respiratory polygraphy for the diagnosis of sleep apnea syndrome: cost-efficiency study.

PURPOSE: To evaluate the differences in reliability and costs of home respiratory polygraphy (HRP) when installed by the patient and by a nurse, in order to determine the factors affecting and to consider the possible generalization of self-setup procedure. Several HRP devices have been validated for obstructive sleep apnea (OSA) diagnosis but convenience of a nurse intervention in HRP installation has been scarcely studied. METHODS: This is a prospective and interventional study. About 301 participants were assigned to 2 groups: self-setup and nurse intervention. Sleep study, questionnaires, and diagnostic procedures were performed following the clinical practice in 2016. Signals were considered lost above 3 min, and success of the test was established according to guidelines. Costs were calculated according to a previous multicenter study. RESULTS: Both groups (self-setup and nurse intervention) resulted homogeneous in age, gender, BMI, and final diagnosis of OSA. Signal losses during the test were similar in both groups. Slightly higher percentage of unsuccessful tests were obtained in the self-setup procedure (5.3 vs 2.0%, p = 0.121). The costs were similar (107 vs 105 €) in the self-setup group as compared to the nurse setup group. CONCLUSIONS: The setup of HRP by either the patient or nurse had similar costs and data acquisition. Both installation procedures of HRP were similar regarding test reliability and costs. Main findings are that self-installation by the patient could be similarly reliable and economic as installation by a nurse, as far as consensus guidelines are followed. This study demonstrates that self-setup of HRP is a potentially viable option for the diagnosis of OSA.

Nocturnal Oximetry-based Evaluation of Habitually Snoring Children.

RATIONALE: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. METHODS: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. MEASUREMENTS AND MAIN RESULTS: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). CONCLUSIONS: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.

ERS statement on obstructive sleep disordered breathing in 1- to 23-month-old children.

The present statement was produced by a European Respiratory Society Task Force to summarise the evidence and current practice on the diagnosis and management of obstructive sleep disordered breathing (SDB) in children aged 1-23 months. A systematic literature search was completed and 159 articles were summarised to answer clinically relevant questions. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are identified. Morbidity (pulmonary hypertension, growth delay, behavioural problems) and coexisting conditions (feeding difficulties, recurrent otitis media) may be present. SDB severity is measured objectively, preferably by polysomnography, or alternatively polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction during wakefulness, those with abnormal sleep study in combination with SDB symptoms (e.g. snoring) and/or conditions predisposing to SDB (e.g. mandibular hypoplasia) as well as children with SDB and complex conditions (e.g. Down syndrome, Prader-Willi syndrome) will benefit from treatment. Adenotonsillectomy and continuous positive airway pressure are the most frequently used treatment measures along with interventions targeting specific conditions (e.g. supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular hypoplasia). Hence, obstructive SDB in children aged 1-23 months is a multifactorial disorder that requires objective assessment and treatment of all underlying abnormalities that contribute to upper airway obstruction during sleep.

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea.

RATIONALE: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells. OBJECTIVES: To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status. METHODS: Obese children (body mass index z score >1.65) and nonobese children were recruited and underwent polysomnographic testing (PSG), and fasting endothelial function measurements and blood draws in the morning after PSG. Plasma exosomes were isolated from all subjects. Isolated exosomes were then incubated with confluent endothelial cell monolayer cultures. Electric cell-substrate impedance sensing systems were used to determine the ability of exosomes to disrupt the intercellular barrier formed by confluent endothelial cells. In addition, immunofluorescent assessments of zonula occludens-1 tight junction protein cellular distribution were conducted to examine endothelial barrier dysfunction. miRNA and mRNA arrays were also applied to exosomes and endothelial cells, and miRNA inhibitors and mimics were transfected for mechanistic assays. MEASUREMENTS AND MAIN RESULTS: Plasma exosomes isolated from either obese children or nonobese children with OSA were primarily derived from endothelial cell sources and recapitulated ED, or its absence, in naive human endothelial cells and also in vivo when injected into mice. Microarrays identified a restricted signature of exosomal miRNAs that readily distinguished ED from normal endothelial function. Among the miRNAs, expression of exosomal miRNA-630 was reduced in children with ED and normalized after therapy along with restoration of endothelial function. Conversely, transfection of exosomes from subjects without ED with an miRNA-630 inhibitor induces the ED functional phenotype. Gene target discovery experiments further revealed that miRNA-630 regulates 416 gene targets in endothelial cells that include the Nrf2, AMP kinase, and tight junction pathways. CONCLUSIONS: These observations elucidate a novel role of exosomal miRNA-360 as a putative key mediator of vascular function and cardiovascular disease risk in children with underlying OSA and/or obesity, and identify therapeutic targets.

Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management.

This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2-18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea-hypopnoea index (AHI) >5 episodes·h(-1), those with an AHI of 1-5 episodes·h(-1) and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g. Down syndrome and Prader-Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7).

Treatment outcomes of obstructive sleep apnoea in obese community-dwelling children: the NANOS study.

The first line of treatment of obstructive sleep apnoea syndrome (OSAS) in children consists of adenotonsillectomy (T&A). The aim of the present study was to evaluate treatment outcomes of OSAS among obese children recruited from the community.A cross-sectional, prospective, multicentre study of Spanish obese children aged 3-14 years, with four groups available for follow-up: group 1: non-OSAS with no treatment; group 2: dietary treatment; group 3: surgical treatment; and group 4: continuous positive airway pressure treatment.117 obese children (60 boys, 57 girls) with a mean age of 11.3±2.9 years completed the initial (T0) and follow-up (T1) assessments. Their mean body mass index (BMI) at T1 was 27.6±4.7 kg·m(-2), corresponding to a BMI Z-score of 1.34±0.59. Mean respiratory disturbance index (RDI) at follow-up was 3.3±3.9 events·h(-1). Among group 1 children, 21.2% had an RDI ≥3 events·h(-1) at T1, the latter being present in 50% of group 2, and 43.5% in group 3. In the binary logistic regression model, age emerged as a significant risk factor for residual OSAS (odds ratio 1.49, 95% confidence interval 1.01-2.23; p<0.05) in obese children surgically treated, and RDI at T0 as well as an increase in BMI emerged as significant risk factors for persistent OSAS in obese children with dietary treatment (OR 1.82, 95% CI 1.09-3.02 (p<0.03) and OR 8.71, 95% CI 1.24-61.17 (p=0.03)).Age, RDI at diagnosis and obesity are risk factors for relatively unfavourable OSAS treatment outcomes at follow-up.

Inflammatory markers and obstructive sleep apnea in obese children: the NANOS study.

INTRODUCTION: Obesity and obstructive sleep apnea syndrome (OSA) are common coexisting conditions associated with a chronic low-grade inflammatory state underlying some of the cognitive, metabolic, and cardiovascular morbidities. AIM: To examine the levels of inflammatory markers in obese community-dwelling children with OSA, as compared to no-OSA, and their association with clinical and polysomnographic (PSG) variables. Methods. In this cross-sectional, prospective multicenter study, healthy obese Spanish children (ages 4-15 years) were randomly selected and underwent nocturnal PSG followed by a morning fasting blood draw. Plasma samples were assayed for multiple inflammatory markers. RESULTS: 204 children were enrolled in the study; 75 had OSA, defined by an obstructive respiratory disturbance index (RDI) of 3 events/hour total sleep time (TST). BMI, gender, and age were similar in OSA and no-OSA children. Monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in OSA children, with interleukin-6 concentrations being higher in moderate-severe OSA (i.e., AHI > 5/hrTST; P < 0.01), while MCP-1 levels were associated with more prolonged nocturnal hypercapnia (P < 0.001). CONCLUSION: IL-6, MCP-1, and PAI-1 are altered in the context of OSA among community-based obese children further reinforcing the proinflammatory effects of sleep disorders such as OSA. This trial is registered with ClinicalTrials.gov NCT01322763.

Reliability of telemedicine in the diagnosis and treatment of sleep apnea syndrome.

BACKGROUND: Advances in information technology and telecommunications have provided the option of making it easier to diagnose and treat obstructive sleep apnea syndrome (OSAS) using telemedicine techniques. This study assessed the feasibility and reliability of respiratory polygraphy and prescription of treatment by pressure adjustment with auto-continuous positive airway pressure (CPAP) systems, both being transmitted telematically to the Sleep Unit, with teleconsultation as a support method. SUBJECTS AND METHODS: Forty patients were studied from a population 80 km from the Sleep Unit using respiratory polygraphy transmitted in real time. They were divided into two groups: one was seen by conventional consultation, and the other was seen using teleconsultation. We also estimated satisfaction with this system and its costs. RESULTS: The mean patient age was 53 ± 10.3 years, with a body mass index of 31 ± 6.2 kg/m(2) and an Epworth score of 12 ± 5.3. In total, 35 patients were diagnosed with OSAS, with an Apnea-Hypopnea Index of ≥10, and CPAP treatment was started in 16 of them. The agreement in the Apnea-Hypopnea Index, total apneas and hypopneas, mean oxygen saturation, and time with an oxygen saturation <90% was greater than 90% between the studies transmitted in real time and those stored in the polygraph. The level of compliance with CPAP treatment was 85% for the patients who were seen in a conventional clinic and 75% in those seen by teleconsultation. CONCLUSIONS: The use of telematic techniques is useful to establish a diagnostic and therapeutic strategy for OSAS with the creation of a Wide Core Sleep Laboratory as a process controller.

Sleep apnoea-hypopnoea syndrome in the obese and non-obese: Clinical, polysomnographical and clinical characteristics.

INTRODUCTION: Sleep apnoea-hypopnoea syndrome (SAHS) and childhood obesity are two high prevalence conditions that represent a public health challenge. OBJECTIVE: To analyse the association between both and comparing child groups that had or did not have both conditions. PATIENTS AND METHODS: A prospective study in children (3-14 years), referred to the "Multidisciplinary Sleep Unit" due to suspected SAHS, between 1 November 2015 and 1 August 2017. The following parameters were evaluated: anthropometry, symptoms, blood pressure, ear, nose, and throat examination, polysomnography (nocturnal PSG) and laboratory tests. RESULTS: A total of 67 children were evaluated (64% non-obese (NOb) and 36% obese (Ob). It was observed that the Ob were older (P < .001), slept less hours (P = .028), did less physical exercise (P = .029), ate less in the school dining room (P = .009), had la lower sleep efficiency, and had abnormal values in carbohydrate and lipid metabolism. The children with SAHS were younger (P = .010), a high percentage of daytime sleepiness (P = .001), and breathing through the mouth (P = .006), greater percentile of diastolic blood pressure (P = .019) and a lower IGF-1 (P = .003) than those that did not have SAHS. The comparison of the SAHS NOb and SAHS Ob groups, showed that the first group were younger (P = .010), snored more (P = .012), had a more severe SAHS (IAH 13.1 vs 5.4, P = .041), and a higher GOT (P < .001). In the second group, they slept less hours P = .038) and showed lower values of glucose (P = .039), insulin (P < .001), and HOMA (P < .001). CONCLUSION: The behaviour of SAHS is different in obese children and non-obese children, with differences in age, clinical characteristics, severity of SAHS, and metabolic changes. The children diagnosed with SAHS were in the higher percentile of diastolic blood pressure. Obesity was associated with worse sleep quality, and changes in carbohydrate and lipid metabolism.

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.

[Reliability of respiratory polygraphy for the diagnosis of sleep apnea-hypopnea syndrome in children]. / Fiabilidad de la poligrafía respiratoria para el diagnóstico del síndrome de apneas-hipopneas durante el sueño en niños.

OBJECTIVE: Overnight polysomnography (PSG) is the gold standard diagnostic tool for sleep apnea-hypopnea syndrome (SAHS) in children. The aim of the present study was to evaluate the usefulness of diagnostic respiratory polygraphy in children with clinically suspected SAHS referred to our sleep-disordered breathing clinic. PATIENTS AND METHODS: We studied 53 children referred with clinical suspicion of SAHS; 29 (54.7%) were boys and the mean (SD) age was 6.4 (2.9) years. After a medical history was taken and a physical examination performed, patients underwent respiratory polygraphy (Edentec) simultaneously with overnight PSG in the sleep laboratory. The 2 diagnostic tools were compared using statistical analysis. RESULTS: SAHS was defined by an obstructive apnea-hypopnea index (OAHI) of 3 or more in overnight PSG and a respiratory disturbance index (RDI) of 3 or more in respiratory polygraphy. The rate of diagnostic agreement was 84.9%. The difference between the mean OAHI and RDI values was not significant (0.7 +/- 5.4; P=.34). The intraclass correlation coefficient between the OAHI and RDI was 89.4 (95% confidence interval, 82.4-93.7; P< .001). When receiver operating characteristic curves were calculated for the OAHI cutoff points used for the diagnosis of SAHS (> or =1, > or =3, and > or =5), the best RDI cutoff for all 3 OAHI values considered was found to be 4.6. When age strata were considered, in children 6 years or older the best RDI cutoff for the 3 OAHI values was 2.1. In children younger than 6 years the best RDI cutoff was 3.35 for OAHI > or =1 and 5.85 for OAHI > or =3 and > or =5. CONCLUSIONS: Respiratory polygraphy in the sleep laboratory is a valid method for the diagnosis of SAHS in children.

Metabolic biomarkers in community obese children: effect of obstructive sleep apnea and its treatment.

OBJECTIVE: Obesity and obstructive sleep apnea in children have been associated with metabolic morbidities. The present study aimed to evaluate the presence of metabolic alterations among obese children recruited from the community, with and without obstructive sleep apnea syndrome (OSAS), and the impact of treatment of OSAS on metabolic profiles. METHODS: A cross-sectional, prospective, multicenter study of Spanish children aged 3-14 years with a body mass index (BMI) ≥95th percentile for age and sex were randomly selected in the first phase. Four groups emerged for follow-up: (1) no treatment; (2) dietary intervention; (3) surgical treatment of OSA; and (4) continuous positive airway pressure (CPAP) treatment of OSA. Fasting blood tests were performed at baseline (T0) and approximately one year after the intervention (T1). RESULTS: A total of 113 obese children with a mean age of 11.3 ± 2.9 years completed T0 and T1 assessments. Their mean BMI z-score at T1 was 1.34 ± 0.59, and mean Respiratory Disturbance Index was 8.6 ± 13.0 at T0 and 3.3 ± 4.0/hour total sleep time at T1. Only glucose fasting levels differed among metabolic parameters in obese children with OSAS and without OSAS at baseline (T0) (p = 0.018). There were statistically significant differences between surgically treated OSAS (p = 0.002), and CPAP-treated OSAS (p = 0.024) versus the non-OSAS group in the glucose levels between baseline (T0) and follow-up (T1) after controlling for age and change in BMI. Significant univariate associations between BMI and C-reactive protein, insulin, and homeostasis model assessment of insulin resistance emerged at both T0 and T1. CONCLUSIONS: Concurrent obesity and OSAS could promote metabolic and inflammatory alterations, and the latter appeared to be sensitive to OSAS treatment outcomes. ClinicalTrials.gov Identifier: NCT01322763.

When and why to treat the child who snores?

Obstructive sleep-disordered breathing (SDB) can result in cardiovascular and neurocognitive morbidity as well as adversely affect behavior, growth, quality of life, and nocturnal continence. This article summarizes the latest evidence regarding the morbidity related to obstructive SDB, commenting on the impact of severity of obstruction, that is, the difference in effects seen of moderate to severe obstructive sleep apnea syndrome (OSAS) compared to those of mild OSAS or primary snoring. The impact of therapy is discussed, focusing on which children are likely to benefit from treatment interventions; namely those with moderate or severe OSAS irrespective of the presence of morbidity, children with mild OSAS with associated morbidity or predictors of SDB persistence such as obesity, and children with complex conditions accompanied by upper airway obstruction like craniosynostosis and Prader-Willi syndrome. The co-existing conditions which may improve when treatment for obstructive SDB is offered are reviewed, while the clinical parameters associated with spontaneous improvement or resolution of obstructive SDB are discussed. The intention being to enable clinicians to make informed decisions on who should be treated, when and why. Pediatr Pulmonol. 2017;52:399-412. © 2016 Wiley Periodicals, Inc.

Biomarkers of Alzheimer Disease in Children with Obstructive Sleep Apnea: Effect of Adenotonsillectomy.

STUDY OBJECTIVE: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for end-organ morbidities. Both OSA and obesity (OB) have been associated with increased risk for Alzheimer disease (AD). This study aimed to assess whether OSA and OB lead to increased plasma levels of 2 AD markers amyloid ß protein 42 (Aß42) and pre-senilin 1 (PS1). METHODS: Fasting morning plasma samples from otherwise healthy children with a diagnosis of OB, OSA, or both (OSA+OB), and controls, and in a subset of children with OSA after adenotonsillectomy (T&A) were assayed for Aß42 and PS1 levels using commercial enzyme-linked immunosorbent assay kits. RESULTS: 286 children (mean age of 7.2 ± 2.7 y) were evaluated. Compared to control subjects, OB children had similar Aß42 (108.3 ± 31.7 pg/mL versus 83.6 ± 14.6 pg/mL) and PS1 levels (0.89 ± 0.44 ng/mL versus 0.80 ± 0.29 pg/mL). However, OSA children (Aß42: 186.2 ± 66.7 pg/mL; P < 0.001; PS1: 3.42 ± 1.46 ng/mL; P < 0.001), and particularly OSA+OB children had significant elevations in both Aß42 (349.4 ± 112.9 pg/mL; P < 0.001) and PS1 (PS1: 4.54 ± 1.16 ng/mL; P < 0.001) circulating concentrations. In a subset of 24 children, T&A resulted in significant reductions of Aß42 (352.0 ± 145.2 versus 151.9 ± 81.4 pg/mL; P < 0.0001) and PS1 (4.82 ± 1.09 versus 2.02 ± 1.18 ng/mL; P < 0.0001). CONCLUSIONS: Thus, OSA, and particularly OSA+OB, are associated with increased plasma levels of AD biomarkers, which decline upon treatment of OSA in a representative, yet not all- encompassing subset of patients, suggesting that OSA may accelerate AD-related processes even in early childhood. However, the cognitive and overall health-related implications of these findings remain to be defined.

Síndrome de apneas-hipopneas durante el sueño en obesos y no obesos: características clínicas, polisomnográficas y metabólicas / Sleep apnoea-hypopnoea syndrome in the obese and non-obese: clinical, polysomnographical and clinical characteristics

Introducción:El síndrome de apneas-hipopneas del sueño (SAHS) y la obesidad infantil son dos entidades con alta prevalencia que constituyen un problema de salud pública.Objetivo: Analizar la interacción entre ambas, comparando grupos de niños que presentaban o no ambas condiciones.Pacientes y metodología: Estudio prospectivo en niños (3-14 años), remitidos a la «Unidad Multidisciplinar de Sueño» por sospecha de SAHS, entre el 1/11/2015 y el 1/08/2017. Se evaluaron los siguientes parámetros: antropometría, síntomas, tensión arterial, exploración otorrinolaringológica, polisomnografía (PSG nocturna) y estudio analítico.Resultados: Se valoraron 67 niños, 64% no obesos y 36% obesos.Se observó que los obesos tenían más edad (p<0,001), dormían menos horas (p=0,028), realizaban menos ejercicio físico (p=0,029), comían menos en comedor escolar (p=0,009), tenían menor eficiencia del sueño y presentaban valores alterados en el metabolismo hidrocarbonado y lipídico.Los niños que presentaban SAHS tenían menor edad (p=0,010), un mayor porcentaje de somnolencia diurna (p=0,001) y respiración bucal (p=0,006), mayor percentil de tensión arterial diastólica (p=0,019) y menor IGF-1 (p=0,003) que los que no presentaban SAHS.La comparación de los grupos de SAHS no obesos frente SAHS obesos, reveló que los primeros eran de menor edad (p=0,010), roncaban más (p=0,012), tenían mayor severidad del SAHS (IAH 13,1 vs. 5,4, p=0,041) y mayor GOT (p≤0,001) y en el segundo grupo, se objetivó que dormían menos horas (p=0,038) y mostraban valores mayores de glucosa (p=0,039), insulina (p<0,001) y HOMA (p<0,001). (AU)

Introduction: Sleep apnoea-hypopnoea syndrome (SAHS) and childhood obesity are la high prevalence conditions that represent a public health challenge.Objective: To analyse the association between both and comparing child groups that had or did not have both conditions.Patients and methods: A prospective study in children (3-14 years), referred to the “Multidisciplinary Sleep Unit” due to suspected SAHS, between 1 November 2015 and 1 August 2017. The following parameters were evaluated: anthropometry, symptoms, blood pressure, ear, nose, and throat examination, polysomnography (nocturnal PSG) and laboratory tests.Results: A total of 67 children were evaluated (64% non-obese and 36% obese.It was observed that the obese were older (P<.001), slept less hours (P=.028), did less physical exercise (P=.029), ate less in the school dining room (P=.009), had la lower sleep efficiency, and had abnormal values in carbohydrate and lipid metabolism.The children with SAHS were younger (P=.010), a high percentage of daytime sleepiness (P=.001), and breathing through the mouth (P=.006), greater percentile of diastolic blood pressure (P=.019) and a lower IGF-1 (P=.003) than those that did not have SAHS. (AU) The comparison of the SAHS non-obese and SAHS obese groups, showed that the first group were younger (P=.010), snored more (P=.012), had a more severe SAHS (IAH 13.1 vs. 5.4, P=.041), and a higher GOT (P<.001). In the second group, they slept less hours P=.038) and showed lower values of glucose (P=.039), insulin (P<.001), and HOMA (P<.001).

Reliability of home respiratory polygraphy for the diagnosis of sleep apnea in children.

OBJECTIVE: The objective of this study was to evaluate the diagnostic reliability of home respiratory polygraphy (HRP) in children with a clinical suspicion of OSA-hypopnea syndrome (OSAS). METHODS: A prospective blind evaluation was performed. Children between the ages of 2 to 14 years with clinical suspicion of OSAS who were referred to the Sleep Unit were included. An initial HRP followed by a later date, same night, in-laboratory overnight respiratory polygraphy and polysomnography (PSG) in the sleep laboratory were performed. The apnea-hypopnea index (AHI)-HRP was compared with AHI-PSG, and therapeutic decisions based on AHI-HRP and AHI-PSG were analyzed using intraclass correlation coefficients, Bland-Altman plots, and receiver operator curves (ROCs). RESULTS: Twenty-seven boys and 23 girls, with a mean age of 5.3 ± 2.5 years, were studied, and 66% were diagnosed with OSAS based on a PSG-defined obstructive respiratory disturbance index ≥ 3/h total sleep time. Based on the availability of concurrent HRP-PSG recordings, the optimal AHI-HRP corresponding to the PSG-defined OSAS criterion was established as ≥ 5.6/h The latter exhibited a sensitivity of 90.9% (95% CI, 79.6%-100%) and a specificity of 94.1% (95% CI, 80%-100%). CONCLUSIONS: HRP recordings emerge as a potentially useful and reliable approach for the diagnosis of OSAS in children. However, more research is required for the diagnosis of mild OSAS using HRP in children.

Evaluation of circulating markers of hepatic apoptosis and inflammation in obese children with and without obstructive sleep apnea.

OBJECTIVE: Hepatocyte apoptosis and macrophage activation contribute to the disease progression of nonalcoholic fatty liver disease (NAFLD). Obstructive sleep apnea (OSA) in obese children is associated with the severity of NAFLD. The aim of this study was to evaluate plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), cytokeratin 18 (CK18) (markers of apoptosis), and soluble CD163 (sCD163) (marker of macrophage activation) in obese children with and without OSA. METHODS: Consecutive obese children who were evaluated for OSA were recruited. The diagnosis of OSA was made using overnight polysomnography (PSG). Fasting blood samples were used to determine plasma CK18, sFas, sFasL, and sCD163 levels using specific sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty-eight subjects were included in the analysis with a mean age of 8.9 ± 3.2 years and a mean body mass index (BMI) z-score of 2.4 ± 0.49. Circulating sFas and sFasL levels were significantly lower in subjects with mild and severe OSA compared with those without OSA (p < 0.005 for both). In addition, sCD163 levels increased with an increasing severity of OSA (no OSA = 1.6 ± 0.25 mg/L, mild OSA = 2.3 ± 0.45, and severe OSA = 3.0 ± 0.52; p < 0.001), and they correlated with the apnea-hypopnea index (AHI) [rho (95% confidence interval, CI) of 0.71 (0.41, 1.00), p-value <0.001]. In six patients with severe OSA from whom samples were taken before and after tonsillectomy, the sCD163 level decreased significantly after treatment, and there was a trend toward an increase in sFasL. CONCLUSION: Markers of apoptosis and macrophage activation are altered in obese children with OSA, indicating increased apoptotic and inflammatory pressures.