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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.

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. 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. 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. 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.

Rationale: Obesity hypoventilation syndrome (OHS) is commonly treated with noninvasive ventilation (NIV) or CPAP. NIV is more complex and costly but provides ventilatory support. To date there have been no long-term or cost trials comparing these treatment modalities. Methods: We performed a large, randomized, multicenter, open-label controlled trial in Spain to compare the long-term effectiveness of NIV and CPAP using hospitalization days/year-patient as the primary end point. We carried out a simple cost analysis including effectiveness cost during 3 year of follow-up. We included the following cost groups: visits, adjustment of NIV, tests, medication, therapies and hospital resources utilization. A sensitivity analysis was conducted according to 3 different scenarios guided by the International Gross Domestic Product. Results: In total, 215 patients with untreated OHS and severe obstructive sleep apnea (OSA) were randomized to NIV or CPAP therapy and followed at least 3 years. The effectiveness was close between arms (mean difference NIV-CPAP: -0.19, 95% CI -1.13 to 0.75). The cost per patient/year was lower in the CPAP arm (1,898.2€; SD 1939.5) than the cost in the NIV arm (2,809.3€; SD 2901.6), mean difference -911.1€ (p Conclusions: In stable patients with OHS and severe OSA, despite NIV having a slight advantage in effectiveness, CPAP could be considered the first line of treatment due to its lower cost but, a case-by-case assessment is recommended to detect patients who would benefit from a switch to NIV.

Rationale: Obesity hypoventilation syndrome (OHS) is commonly treated with CPAP or noninvasive ventilation (NIV). NIV is more complex and costly but it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. Methods: We performed a large, multicenter, open-label controlled trial in Spain to compare the long-term effectiveness of NIV and CPAP: respiratory function, Epworth sleepness scale (ESS), other clinical symptoms, blood pressure (BP) and health related quality of life (HRQL). The analysis was performed according to the intention-to-treat principle. Results: In total, 215 patients with untreated OHS and severe obstructive sleep apnea (OSH) were randomized to NIV or CPAP therapy and followed at least 3 years. PaCO2, bicarbonate and pH improved significantly with both treatments without group differences. FEV1 and FVC improved with positive airway pressure (PAP) but without significant group differences. The 6-MWD test did not improve with either PAP modality and there were no significant group differences. ESS and other clinical symptoms like dyspnea or unrefreshing sleep improved similarly with CPAP and NIV therapy. Both systolic and diastolic BP improved significantly with PAP but without group differences. HRQL tests (SF-36 physical and mental, FOSQ and VAWS) improved with PAP without any significant group differences. Conclusions: In stable patients with OHS and severe OSA, NIV and CPAP have similar long-term effectiveness improving respiratory function, symptoms, BP and HRQL. Given that CPAP has lower complexity and cost, CPAP may be the preferred treatment modality until more studies become available.

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 β protein 42 (Aβ42) and pre-senilin 1 (PS1).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 (TA) were assayed for Aβ42 and PS1 levels using commercial enzyme-linked immunosorbent assay kits.286 children (mean age of 7.2 ± 2.7 y) were evaluated. Compared to control subjects, OB children had similar Aβ42 (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 (Aβ42: 186.2 ± 66.7 pg/mL; P0.001; PS1: 3.42 ± 1.46 ng/mL; P0.001), and particularly OSA+OB children had significant elevations in both Aβ42 (349.4 ± 112.9 pg/mL; P0.001) and PS1 (PS1: 4.54 ± 1.16 ng/mL; P0.001) circulating concentrations. In a subset of 24 children, TA resulted in significant reductions of Aβ42 (352.0 ± 145.2 versus 151.9 ± 81.4 pg/mL; P0.0001) and PS1 (4.82 ± 1.09 versus 2.02 ± 1.18 ng/mL; P0.0001).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.

BackgroundObesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions.AimTo examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community.MethodsObese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the two PSGs were assayed for multiple inflammatory and metabolic markers including interleukin (IL)-6, IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), adiponectin, apelin C, leptin and osteocrin.ResultsOut of 122 potential candidates, 100 obese children with OSA completed the study with only one-third exhibiting normalization of their PSG after T&A (that is, apnea-hypopnea index (AHI) ≤1/hour total sleep time). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A-responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (that is, AHI⩾5/hTST).ConclusionsA defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities.

Aim: To evaluate the succes rate of surgical treatment and residual OSAS in a cohort of children Methods: We performed an observational, longitudinal, ambispectives study in children referred to the Sleep Unit from 2000 to 2010. In all children included, we performed a clinical history, physical and otorhinolaryngology examination and Nocturnal Polysomnography (NPSG) or Nocturnal Polygraphy (NRP). Obstructive apnea/Hypopnea index (OAHI)≥3 on NPSG and respiratory disturbances index (RDI)≥4.6 on NRP were taken as diagnosis of OSAS. Results: 1139 children were estudied, 672 boys and 467 girls. The average age was 4.85±3.07 years and the average Body Mass Index (BMI) percentile was 52.84±32.39. For the diagnosis, we used NPSG in (50.1%) and NRP in (49.9%) of children included. Snoring and respiratory pauses were reported in 85.9% and 56.9%; Hyperactivity, sleepiness and irritability were reported in 25.5%, 21.8% and 9.2%. 738 (64.8%) of children were diagnosed of OSAS, with an RDI of 9.5±12.6. There were no differences in sex between the OSAS and nonOSAS groups, but there were statistically significant differences in age, weight, neck circunference and BMI. Surgical treatment was performed in 559(75.7%) of OSAS. The success rate was 73.9%; 95% CI:69.01%-78.84% with a statiscally significant improvement in all of clinical and respiratory variables. The prevalence of residual OSAS was 26.1%. In the binary logistic regression model, age BMI, high hard palate and adenotonsillar hypertrophy emerged as a significant risk factors for OSAS. Conclusions: The persistence of disease (26.1%), in spite of treatment, it makes neccessary to follow-up and perform sleep control studies. Funded by SEPAR and FIS

There are no randomized controlled trials assessing the impact of noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) on cardiac function in obesity hypoventilation syndrome (OHS). Objective: To determine the efficacy of 2 months of NIV, CPAP or lifestyle modification (control) on echocardiographic changes. Method: OHS patients (n=302) were sequentially randomized by: 1) severe obstructive sleep apnea (OSA), into NIV, CPAP or control; 2) non-severe OSA, into NIV or control. ABG, spirometry, six-minute walk distance, Epworth sleepiness scale, polysomnography and transthoracic echocardiogram were evaluated. Results: We analyzed 2 groups: 1) with or without severe OSA and NIV or control treatments (entire OHS group; n=222); 2) with severe OSA and NIV, CPAP or control treatments (severe OSA subgroup; n=221). In the entire OHS group, NIV improved the left ventricular (LV) hypertrophy (mass index: -6.6 g/m2; 95%CI -11/-2.1 vs 3.6; 95%CI -1.1/8.3; adjusted p Conclusion: Medium-term NIV therapy is more effective than CPAP and lifestyle modification in improving PAP and LV hypertrophy in OHS

Study Objectives Nucleosomes and cell-free double-stranded DNA (dsDNA) have been suggested as promising biomarkers in cell death-related diseases, such as acute coronary syndrome (ACS). Currently, the impact of obstructive sleep apnea (OSA) in patients with ACS is unclear. Our aim was to evaluate the relationship between OSA, dsDNA, and nucleosomes and to assess their potential implication in the development of ACS. Methods Up to 549 patients were included in the study and divided into four groups (145 ACS; 290 ACS + OSA; 62 OSA; 52 controls). All patients underwent a sleep study, and serum concentrations of dsDNA and nucleosomes were measured. Results Nucleosome and dsDNA levels were higher in patients with OSA than in controls (nucleosomes: 1.47 ± 0.88 arbitary units [AU] vs. 1.00 ± 0.33 AU; p < .001, dsDNA: 315.6 ± 78.0 ng/mL vs. 282.6 ± 55.4 ng/mL; p = .007). In addition, both biomarker levels were higher in patients with ACS than in non-ACS, independently of the presence of OSA. Conclusions Both nucleosomes and dsDNA are increased in patients with OSA and might be related with the high cardiovascular risk seen in these patients. The extensive cell lysis during a myocardial infarction seems to be the major contributor to the high biomarker levels, and OSA does not seem to be implicated in such elevation when this acute event occurs. Clinical trial registration NCT01335087 (clinicaltrials.gov).

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/m2 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

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.To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status.Obese children (body mass index z score1.65) 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.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.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.

Introduction: Obesity and obstructive sleep apnea syndrome in children have been strongly and independently associated with metabolic and cardiovascular morbidities. Aim: To evaluate the presence of metabolic alterations among obese children recruited from the community. Methods: A cross-sectional, prospective multicenter study of Spanish children aged 3 – 14 years-old with a body mass index (BMI)≥ 95th percentile for age and sex were randomly selected in the first phase of this study. Four groups were obtained for follow-up:(1) No treatment; (2) Dietary intervention; (3) surgical treatment of OSA; (4) CPAP treatment of OSA. We performed fasting blood tests at baseline (T0) and ∼1-year follow-up after the intervention (T1). Results: 113 obese children with a mean age of 11.3±2.9 years completed T0 and T1 assessments within 11.8±4.1 months. Their mean BMI at T0 was 27.6±4.7 kg/m2, and mean respiratory disturbance index was 8.56±12.97 at T0 and 3.29 ± 3.99/hr TST at T1. Significant univariate associations between BMI and C reactive protein (CRP), insulin and HOMA emerged at both T0 and T1 for the whole cohort. To assess potential metabolic characteristics that independently associated with OSA incidence, OSA persistence, or residual OSA, stepwise logisitc regression models were performed, but did not reach statistical significance. However, HOMA index was a predictor of incident (OR: 1.97) and persistent OSA (OR:1.10), while CRP emerged as a predictor of residual OSA (OR:1.41). Conclusions: (1) Concurrent obesity and OSA promotes metabolic and inflammatory alterations. (2) Specific metabolic alterations appear to behave as predictors of incident, persistent and residual OSA in obese children. Funded by SEPAR.

Introduction Home respiratory polygraphy (HRP) is a cost-effectiveness choice to polysomnography (PSG) for diagnosis and treatment in patients with high obstructive sleep apnea (OSA) suspicion what includes 40% of patients needing sleep study. There is not randomized control trial (RCT) focus in the same objective including the entire population needing sleep study (intermediate-high OSA suspicion). Objectives Demonstrate if HRP is a non-inferior effective and a cost-effective alternative to PSG for diagnosis and treatment in most OSA suspicion patients. Method A multicentric, non-inferiority RCT included patients with intermediate-to-high OSA suspicion from 8 centers in Spain. Patients were randomized to be managed (diagnosis and treatment decision-marking) according to PSG or HRP results for 6 months of follow-up. Sleep and quality of life questionnaires, ambulatory 24 hours blood pressure monitoring, CPAP compliance, PSG at 6 months and side effects were collected. An Epworth scale inter-group difference less than -2 in the lower bound of 1-side 95% CI was the non-inferiority premise. QALYS changes were used in a Bayesian cost-effectiveness analysis. Results 430 patients were randomized. At 6 months, changes in the Epworth scale, EuroQol, SF36, FOSQ, analogical scale, PSG and blood pressure were similar between groups. Epworth scale non-inferiority premise was -0.24 adjusted by baseline values and sites. In the cost-effectiveness plane, HRP had similar effectiveness (QALYS different -0.0043) and 421€ lower cost than PSG. Conclusion In this large RCT, HRP was a clear cost-effectiveness alternative to PSG for management of most patients with OSA suspicion. Present results can decrease costs and waiting list across countries.

Producción Científica, Study Objectives: Nocturnal oximetry has emerged as a simple, readily available, and potentially useful diagnostic tool of childhood obstructive sleep apnea-hypopnea syndrome (OSAHS). However, at-home respiratory polygraphy (HRP) remains the preferred alternative to polysomnography (PSG) in unattended settings. The aim of this study was two-fold: (1) to design and assess a novel methodology for pediatric OSAHS screening based on automated analysis of at-home oxyhemoglobin saturation (SpO2), and (2) to compare its diagnostic performance with HRP. Methods: SpO2 recordings were parameterized by means of time, frequency, and conventional oximetric measures. Logistic regression (LR) models were optimized using genetic algorithms (GAs) for 3 cutoffs for OSAHS: 1, 3, and 5 events per hour (e/h). The diagnostic performance of LR models, manual obstructive apnea-hypopnea index (OAHI) from HRP, and the conventional oxygen desaturation index ≥3% (ODI3) were assessed. Results: For a cutoff of 1 e/h, the optimal LR model significantly outperformed both conventional HRP-derived ODI3 and OAHI: 85.5% Accuracy (HRP 74.6%; ODI3 65.9%) and 0.97 AUC (HRP 0.78; ODI3 0.75) were reached. For a cutoff of 3 e/h, the LR model achieved 83.4% Accuracy (HRP 85.0%; ODI3 74.5%) and 0.96 AUC (HRP 0.93; ODI3 0.85) whereas using a cutoff of 5 e/h, oximetry reached 82.8% Accuracy (HRP 85.1%; ODI3 76.7) and 0.97 AUC (HRP 0.95; ODI3 0.84). Conclusions: Automated analysis of at-home SpO2 recordings provide accurate detection of children with high pre-test probability of OSAHS. Thus, unsupervised nocturnal oximetry may enable a simple and effective alternative to HRP and PSG in unattended settings., This research has been partially supported by the project 153/2015 of the Sociedad Española de Neumología y Cirugía Torácica (SEPAR), the project RTC-2015-3446-1 from the Ministerio de Economía y Competitividad and the European Regional Development Fund (FEDER), and the project VA037U16 from the Consejería de Educación de la Junta de Castilla y León and FEDER. L. Kheirandish-Gozal is supported by NIH grant 1R01HL130984-01. D. Álvarez was in receipt of a Juan de la Cierva grant from the Ministerio de Economía y Competitividad.

Continuous positive airway pressure (CPAP) is the treatment of choice in patients with symptomatic obstructive sleep apnea (OSA). CPAP treatment improves quality of life (QoL) in men with OSA, but its role in women has not yet been assessed.To investigate the effect of CPAP on QoL in women with moderate to severe OSA.We conducted a multicenter, open-label randomized controlled trial in 307 consecutive women diagnosed with moderate to severe OSA (apnea-hypopnea index, ≥15) in 19 Spanish sleep units. Women were randomized to receive effective CPAP therapy (n = 151) or conservative treatment (n = 156) for 3 months. The primary endpoint was the change in QoL based on the Quebec Sleep Questionnaire. Secondary endpoints included changes in daytime sleepiness, mood state, anxiety, and depression. Data were analyzed on an intention-to-treat basis with adjustment for baseline values and other relevant clinical variables.The women in the study had a mean (SD) age of 57.1 (10.1) years and a mean (SD) Epworth Sleepiness Scale score of 9.8 (4.4), and 77.5% were postmenopausal. Compared with the control group, the CPAP group achieved a significantly greater improvement in all QoL domains of the Quebec Sleep Questionnaire (adjusted treatment effect between 0.53 and 1.33; P 0.001 for all domains), daytime sleepiness (-2.92; P 0.001), mood state (-4.24; P = 0.012), anxiety (-0.89; P = 0.014), depression (-0.85; P = 0.016), and the physical component summary of the 12-item Short Form Health Survey (2.78; P = 0.003).In women with moderate or severe OSA, 3 months of CPAP therapy improved QoL, mood state, anxiety and depressive symptoms, and daytime sleepiness compared with conservative treatment. Clinical trial registered with www.clinicaltrials.gov (NCT02047071).

(1) To evaluate the effectiveness of adenotonsillectomy for the treatment of Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in children. (2) To evaluate the usefulness of respiratory polygraphy (RP) for controlling post-adenotonsillectomy effects.The children studied were referred to the Burgos Sleep Unit (SU) with clinical suspicion of OSAHS before undergoing adenotonsillectomy. For all patients, a clinical history was taken and a general physical examination, as well as a specific ear, nose, and throat examination was done. RP before adenotonsillectomy, and seven months afterwards, was also done. OSAHS was diagnosed if the Apnea Hypopnea Index (AHI) was ≥ 4.6.Of the 100 children studied, 68 were male and 32 female, with an age of 4.17 ± 2.05 years. Using RP, 86 of them were diagnosed with OSAHS before undergoing adenotonsillectomy. There was a significant improvement in all clinical and polygraphic variables after adenotonsillectomy. The pre and post surgery AHI index was 11.9 ± 11.0 and 2.6 ± 1.5, respectively, with a significant mean difference (9.4 ± 10.9, p0.01). The residual OSAHS was 11.6% (CI 95%: 4.3-19%).Respiratory polygraphy is a useful tool for monitoring the effectiveness of surgical treatment and the detection of residual OSAHS in children with adenotonsillar hypertrophy.

Background Obesity hypoventilation syndrome (OHS) is associated with a high burden of cardiovascular morbidity (CVM) and mortality. The majority of patients with OHS have concomitant OSA, but there is a paucity of data on the association between CVM and OSA severity in patients with OHS. The objective of our study was to assess the association between CVM and OSA severity in a large cohort of patients with OHS. Methods In a cross-sectional analysis, we examined the association between OSA severity based on tertiles of oxygen desaturation index (ODI) and CVM in 302 patients with OHS. Logistic regression models were constructed to quantify the independent association between OSA severity and prevalent CVM after adjusting for various important confounders. Results The prevalence of CVM decreased significantly with increasing severity of OSA based on ODI as a continuous variable or ODI tertiles. This inverse relationship between OSA severity and prevalence of CVM was seen in the highest ODI tertile and it persisted despite adjustment for multiple confounders. Chronic heart failure had the strongest negative association with the highest ODI tertile. No significant CVM risk change was observed between the first and second ODI tertiles. Patients in the highest ODI tertile were younger, predominantly male, more obese, more hypersomnolent, had worse nocturnal and daytime gas exchange, lower prevalence of hypertension, better exercise tolerance, and fewer days hospitalized than patients in the lowest ODI tertile. Conclusions In patients with OHS, the highest OSA severity phenotype was associated with reduced risk of CVM. This finding should guide the design of future clinical trials assessing the impact of interventions aimed at decreasing cardiovascular morbidity and mortality in patients with OHS. Trial Registry Clinicaltrial.gov; No.: NCT01405976 ; URL: www.clinicaltrials.gov

Introduction: Apparent life threatening event (ALTE), is an apnea event with an alteration of muscle tone and skin coloration, with appearance of imminent death. Aims: To analyze polysomnographic findings in patients with ALTE. Methods: A descriptive, retrospective study of 12 infants with ALTE. Medical history, blood test, brain doppler ultrasound, electroencephalogram, echocardiogram, magnetic resonance imaging, Phmetry, upper airway exploration and sleep study were performed. Results: Five of them were men and 7 women, with a mean age of 54.25 ± 36.89 days. Four were premature and 5 with underweight at born. Mean Apgar was 7.9 and 9. 33% had sudden death family history. More frequent symptoms were coloration change (75%), apnea (33.33%) and stiffness (33.33%). 25% of them presented respiratory acidosis, 33.33% showed an increase in lactic acid and 50% mild or moderate gastroesophageal reflux (GER). Sleep study were performed in all infants: 7 by Polygraphy and 5 by polysomnography. The mean values obtained were: respiratory events 157.42±255.23, apnea-hypopnea index (AHI): 17.63±33.96, Central AHI:10.84, Obstructive AHI: 6.70±11.2, respiratory disturbance index (RDI): 21.96±40.16, minimum heart rate 95.11±17.48, minimum oxygen saturation 88.18±3.28 and CO2 peak 46.50±4.45. The final diagnosis were: GER (1,33%), central sleep apnea (41.7%); obstructive sleep apnea (33.3%), and idiophatic (16.66%). Sleep-disordered breathing associated with GER were present in 60% of infants. 50% of infants received anti-reflux treatment, 33.3% caffeine, and two infants non invasive ventilation. Conclusion: Sleep-Disordered breathing are frequent in ALTE and GER is frequently associated with obstructive sleep events.

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.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).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-value0.001]. 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.Markers of apoptosis and macrophage activation are altered in obese children with OSA, indicating increased apoptotic and inflammatory pressures.

Producción Científica, The obstructive sleep apnea syndrome (OSAS) greatly affects both the health and the quality of life of chil-dren. Therefore, an early diagnosis is crucial to avoid their severe consequences. However, the standarddiagnostic test (polysomnography, PSG) is time-demanding, complex, and costly. We aim at assessinga new methodology for the pediatric OSAS diagnosis to reduce these drawbacks. Airflow (AF) and oxy-gen saturation (SpO2) at-home recordings from 50 children were automatically processed. Informationfrom the spectrum of AF was evaluated, as well as combined with 3% oxygen desaturation index (ODI3)through a logistic regression model. A bootstrap methodology was conducted to validate the results.OSAS significantly increased the spectral content of AF at two abnormal frequency bands below (BW1)and above (BW2) the normal respiratory range. These novel bands are consistent with the occurrenceof apneic events and the posterior respiratory overexertion, respectively. The spectral information fromBW1 and BW2 showed complementarity both between them and with ODI3. A logistic regression modelbuilt with 3 AF spectral features (2 from BW1 and 1 from BW2) and ODI3 achieved (mean and 95% confi-dence interval): 85.9% sensitivity [64.5–98.7]; 87.4% specificity [70.2–98.6]; 86.3% accuracy [74.9–95.4];0.947 area under the receiver-operating characteristics curve [0.826–1]; 88.4% positive predictive value[72.3–98.5]; and 85.8% negative predictive value [65.8–98.5]. The combination of the spectral informationfrom two novel AF bands with the ODI3 from SpO2is useful for the diagnosis of OSAS in children., Ministerio de Economía y Competitividad (project TEC2011-22987), Junta de Castilla y León (project VA059U13)

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.

INTRODUCTION Obesity in children is assumed to serve as a major risk factor in pediatric obstructive sleep apnea syndrome (OSAS). However, the prevalence of OSAS in otherwise healthy obese children from the community is unknown. AIM To determine the prevalence of OSAS in obese children identified and recruited from primary care centers. METHODS A cross-sectional, prospective, multicenter study. Spanish children ages 3-14 y with a body mass index (BMI) greater than or equal to the 95th percentile for age and sex were randomly selected, and underwent medical history, snoring, and Pediatric Sleep Questionnaire (PSQ) assessments, as well as physical examination, nasopharyngoscopy, and nocturnal polysomnography (NPSG) recordings. RESULTS Two hundred forty-eight children (54.4% males) with mean age of 10.8 ± 2.6 y were studied with a BMI of 28.0 ± 4.7 kg/m(2) corresponding to 96.8 ± 0.6 percentile when adjusted for age and sex. The mean respiratory disturbance index (RDI), obstructive RDI (ORDI), and obstructive apnea-hypopnea index (OAHI) were 5.58 ± 9.90, 5.06 ± 9.57, and 3.39 ± 8.78/h total sleep time (TST), respectively. Using ≥ 3/h TST as the cutoff for the presence of OSAS, the prevalence of OSAS ranged from 21.5% to 39.5% depending on whether OAHI, ORDI, or RDI were used. CONCLUSIONS The prevalence of obstructive sleep apnea syndrome (OSAS) in obese children from the general population is high. Obese children should be screened for the presence of OSAS. ClinicalTrials.gov identifier: NCT01322763.

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. Leila Kheirandish-Gozal and David Gozal are supported by a Grant HL-65270 from the National Institutes of Health. The NANOS study was supported by the Spanish Respiratory Society (SEPAR) and Mutua Madrilena. The authors thank the subjects and their parents for their participation and the Basque Biobank For Research-OEHUN for their collaboration. The authors would like to thank the members of the Spanish Sleep Network: Estrella Ordax Carbajo, M. D. (Hospital Universitario de Burgos); Ana Isabel Navazo-Eguia, M. D. (Hospital Universitario de Burgos); Marian Martinez Martinez, M. D. (Hospital Universitario Valdecilla, Santander); Odile Romero Santo-Tomas, MD (Hospital Val D'Hebron); Fernando Masa-Jimenez, M. D. (Hospital San Pedro de Alcantara, Caceres); Cristina Martinez Null (Hospital Universitario Araba, Vitoria); Antonia Barcelo-Bennassar, Ph.D. (Hospital Son Dureta, Palma de Mallorca).

Influence od obstructive sleep apnea on professional activities ogf transport workers, with special considerations of professional drivers