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Objective: Obstructive sleep apnea (OSA) is common among overweight and obese children, and it is an independent risk factor for developing metabolic syndrome. However, the mechanisms linking OSA and metabolic syndrome are still unclear, but a role for adipose tissue dysfunction caused by intermittent hypoxia has been suggested. Therefore, the goal of this study was to investigate the relationship between OSA and systemic adipokine concentrations in overweight and obese children., Methods: We included 164 overweight and obese children in a tertiary center and distributed them in groups based on their obstructive apnea-hypopnea index (111 controls, 28 mild OSA, 25 moderate-to-severe OSA). All subjects underwent polysomnography and a blood sample was taken to determine leptin, adiponectin, tumor necrosis factor alpha, and interleukin-6 levels., Results: No significant differences were found in adipokine levels between subjects with or without OSA. Leptin correlated with oxygen desaturation index (r = -0.17, p = 0.03), adiponectin correlated with mean oxygen saturation (r = 0.24, p = 0.002) and with the percentage of sleep time with an oxygen saturation >95% (r = 0.25, p = 0.001). However, these associations did not persist after correction for adiposity. No correlations between interleukin-6 and tumor necrosis factor alpha, and OSA severity were found., Conclusion: These results suggest that serum adipokine levels are mostly dependent on central obesity, while they are not influenced by OSA in an obese pediatric population., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Aim: Obesity is a known risk factor for the development of obstructive sleep apnea (OSA) in children. Early screening is essential because of the possible complications associated with OSA. At present, the gold standard for diagnosing OSA is polysomnography, which however has multiple limitations. The aim of this study is to examine the role of nocturnal oximetry as a screening tool for OSA in obese children and adolescents., Materials and Methods: This retrospective study included obese children who underwent a polysomnography at the Antwerp University Hospital between November 2010 and May 2014. Their oximetries were scored manually, blinded for the polysomnography results, according to Brouilette et al. OSA was defined as an obstructive apnea-hypopnea index (oAHI) ≥ 2 on polysomnography., Results: This study included 130 obese patients (38% boys, mean age 12 years). Polysomnography results determined 44 patients (34%) with a diagnosis of OSA. Oximetry results classified 16 patients as positive, 43 as negative, and 71 as inconclusive. Further analysis of the positive and negative oximetry results showed a sensitivity and specificity of 58% and 88%, respectively, with a negative and positive predictive value of 81% and 69%, respectively. A second analysis, using the oxygen desaturation index, showed inferior results in comparison to the score attained by Brouillette (sensitivity 57%, specificity 73%)., Conclusions: These results suggest that oximetry alone is insufficient as a screening tool for OSA in obese children. Other screening methods need to be explored in the future., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Obese children have an increased risk of developing obstructive sleep apnea syndrome (OSAS) compared to normal-weight children. In obese children, OSAS is more frequently associated with oxygen desaturations, which might be caused by pulmonary function abnormalities. Our goal was to investigate the association between OSAS and pulmonary function in obese children and adolescents., Methods: There were 185 children included and distributed in groups based on their obstructive apnea-hypopnea index (151 controls, 20 mild OSAS, and 14 moderate-to-severe OSAS). All subjects underwent polysomnography and pulmonary function testing., Results: Several differences in pulmonary function were observed between groups. Vital capacity (VC) and forced expired volume in 1s (FEV1) were significantly decreased in patients with moderate-to-severe OSAS, as were expiratory reserve volume (ERV), total lung capacity, and functional residual capacity (FRC). Correlations between FEV1, FRC, and ERV with OSAS severity remained significant independent of the degree of adiposity. Correlations between FEV1/VC and sleep-related respiratory parameters did not persist after correction for adiposity., Conclusion: An association between awake pulmonary function and sleep-related respiratory parameters could be observed in our population of obese children. These results suggest that OSAS severity is correlated with a diminished lung function. However, the level of obesity remains an important confounding factor in both OSAS severity and pulmonary function., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: We aim to investigate if anatomical and functional properties of the upper airway using computerized 3D models derived from computed tomography (CT) scans better predict obstructive sleep apnea (OSA) severity than standard clinical markers., Methods: Consecutive children with suspected OSA underwent polysomnography, clinical assessment of upper airway patency, and a CT scan while awake. A three-dimensional (3D) reconstruction of the pharyngeal airway was built from these images, and computational fluid dynamics modeling of low inspiratory flow was performed using open-source software., Results: Thirty-three children were included (23 boys; mean age, was 6.0±3.2y). OSA was diagnosed in 23 patients. Children with OSA had a significantly lower volume of the overlap region between tonsils and the adenoids (median volume, 1408 mm compared to 2173 mm; p=0.04), a lower mean cross-sectional area at this location (median volume, 69.3mm(2) compared to 114.3mm2; p=0.04), and a lower minimal cross-sectional area (median volume, 17.9 mm2 compared to 25.9 mm2; p=0.05). Various significant correlations were found between several imaging parameters and the severity of OSA, most pronounced for upper airway conductance (r=-0.46) (p<0.01) for correlation between upper airway conductance and the apnea-hypopnea index. No differences or significant correlations were observed with clinical parameters of upper airway patency. Preliminary data after treatment showed that none of the patients with residual OSA had their smallest cross-sectional area located in segment 3, and this frequency was significantly lower than in their peers whose sleep study normalized (64%; p=0.05)., Conclusion: Functional imaging parameters are highly correlated with OSA severity and are a more powerful correlate than clinical scores of upper airway patency. Preliminary data also showed that we could identify differences in the upper airway of those subjects who did not benefit from a local upper airway treatment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep related breathing disorder. A popular treatment is the use of a mandibular repositioning appliance (MRA) which advances the mandibula during the sleep and decreases the collapsibility of the upper airway. The success rate of such a device is, however, limited and very variable within a population of patients. Previous studies using computational fluid dynamics have shown that there is a decrease in upper airway resistance in patients who improve clinically due to an MRA. In this article, correlations between patient-specific anatomical and functional parameters are studied to examine how MRA induced biomechanical changes will have an impact on the upper airway resistance. Low-dose computed tomography (CT) scans are made from 143 patients suffering from OSAHS. A baseline scan and a scan after mandibular repositioning (MR) are performed in order to study variations in parameters. It is found that MR using a simulation bite is able to induce resistance changes by changing the pharyngeal lumen. The change in minimal cross-sectional area is the best parameter to predict the change in upper airway resistance. Looking at baseline values, the ideal patients for MR induced resistance decrease seem to be women with short airways, high initial resistance and no baseline occlusion., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objectives: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services., Methods: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example., Results: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians., Conclusions: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulations, and especially at its medical aspects in the European region., Methods: We obtained data from Transport Authorities in 25 countries (Austria, AT; Belgium, BE; Czech Republic, CZ; Denmark, DK; Estonia, EE; Finland, FI; France, FR; Germany, DE; Greece, GR; Hungary, HU; Ireland, IE; Italy, IT; Lithuania, LT; Luxembourg, LU; Malta, MT; Netherlands, NL; Norway, EC; Poland, PL; Portugal, PT; Slovakia, SK; Slovenia, SI; Spain, ES; Sweden, SE; Switzerland, CH; United Kingdom, UK)., Results: Driving license regulations date from 1997 onwards. Excessive daytime sleepiness is mentioned in nine, whereas sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea syndrome., Conclusion: Despite the available scientific evidence, most countries in Europe do not include sleep apnoea syndrome or excessive daytime sleepiness among the specific medical conditions to be considered when judging whether or not a person is fit to drive. A unified European Directive seems desirable.

The effect of a bronchodilator in asthmatics is only partially described by changes in spirometric values since no information on regional differences can be obtained. Imaging techniques like high-resolution computed tomography (HRCT) provide further information but lack detailed information on specific airway responses. The aim of the present study was to improve the actual imaging techniques by subsequent analysis of the imaging data using computational fluid dynamics (CFD). We studied 14 mild to moderately severe asthmatics. Ten patients underwent HRCT before and 4h after inhalation of a novel long acting beta(2) agonist (LABA) that acts shortly after inhalation. Four patients were studied for chronic effects and underwent CT scans twice after adequate wash-out of bronchodilators. In the active group, a significant bronchodilator response was seen with a forced expiratory volume in 1s (FEV1) increase of 8.78 +/- -6.27% pred vs -3.38 +/- 6.87% pred in the control group. The changes in FEV1 correlated significantly with the changes in distal airway volume (r = 0.69, p = 0.007), total airway resistance (r = -0.73, p = 0.003) and distal airway resistance (r = -0.76, p = 0.002) as calculated with the CFD method. The changes in distal R(aw) were not fully homogeneous. In some patients with normal FEV1 at baseline, CFD-based changes in R(aw) were still detectable. We conclude that CFD calculations, based on airway geometries of asthmatic patients, provide additional information about changes in regional R(aw). All changes in the CFD-based calculated R(aw) significantly correlate with the observed changes in spirometric values therefore validating the CFD method for the studied application.

Mandibular advancement devices (MADs) have emerged as a popular alternative for the treatment of sleep-disordered breathing. These devices bring the mandibula forward in order to increase upper airway (UA) volume and prevent total UA collapse during sleep. However, the precise mechanism of action appears to be quite complex and is not yet completely understood; this might explain interindividual variation in treatment success. We examined whether an UA model, that combines imaging techniques and computational fluid dynamics (CFD), allows for a prediction of the treatment outcome with MADs. Ten patients that were treated with a custom-made mandibular advancement device (MAD), underwent split-night polysomnography. The morning after the sleep study, a low radiation dose CT scan was scheduled with and without the MAD. The CT examinations allowed for a comparison between the change in UA volume and the anatomical characteristics through the conversion to three-dimensional computer models. Furthermore, the change in UA resistance could be calculated through flow simulations with CFD. Boundary conditions for the model such as mass flow rate and pressure distributions were obtained during the split-night polysomnography. Therefore, the flow modeling was based on a patient specific geometry and patient specific boundary conditions. The results indicated that a decrease in UA resistance and an increase in UA volume correlate with both a clinical and an objective improvement. The results of this pilot study suggest that the outcome of MAD treatment can be predicted using the described UA model.

Determination of the apnea hypopnea index (AHI) as a measure of the severity of obstructive sleep apnea/hypopnea syndrome (OSAHS) is a widely accepted methodology. However, the outcome of such a determination depends on the method used, is time consuming and insufficient for prediction of the effect of all treatment modalities. For these reasons more methods for evaluating the severity of OSAHS, based on different imaging modalities, have been looked into and recent studies have shown that anatomical properties determined from three-dimensional (3D) computed tomography (CT) images are good markers for the severity of the OSAHS. Therefore, we correlated anatomical measurements of a 3D reconstruction of the upper airway together with flow simulation results with the severity of OSAHS in order to find a combination of variables to indicate the severity of OSAHS in patients. The AHI of 20 non-selected, consecutive patients has been determined during a polysomnography. All patients also underwent a CT scan from which a 3D model of the upper airway geometry was reconstructed. This 3D model was used to evaluate the anatomical properties of the upper airway in OSAHS patients as well as to perform computational fluid dynamics (CFD) computations to evaluate the airflow and resistance of this upper airway. It has been shown that a combination of the smallest cross-sectional area and the resistance together with the body mass index (BMI) form a set of markers that predict very well the severity of OSAHS in patients within this study. We believe that these markers can be used to evaluate the outcome of an OSAHS treatment.

Objective: To investigate the pre-and postoperative pattern of upper airway obstruction in obstructive sleep apnea (OSA) patients treated by uvulopalatopharyngoplasty (UPPP).Background: The response rate to UPPP in unselected OSA patients is generally about 50%.Methods: Intraluminal pressure measurements during sleep were employed to analyze the pattern of upper airway obstruction before and after surgery.Results: Ten patients with mild to moderate OSA (respiratory disturbance index 19.7 (16.9-27.5) events/hr underwent a full night polysomnography before and 114 (6 1-138) days after UPPP. UPPP resulted in a significant improvement in subjective snoring and daytime sleepiness, but did not significantly alter the severity of sleep-disordered breathing. Preoperatively, the major site of obstruction was located at the oropharynx in nine patients, seven of them had additional minor obstruction sites outside the oropharynx. Complete relief of upper airway obstruction was only observed in those two patients with collapse confined to the oropharynx.Conclusions: In unselected OSA patients, UPPP improved subjective snoring and daytime sleepiness but did not result in a significant improvement in RDI or sleep architecture. Our results emphasize the need for a pre-operative investigation of the upper airway during sleep to select patients with collapse confined to the oropharynx.

Human alveolar type II cells are thought to play a role in the pathogenesis of lung injury. Patterns of mediator release of arachidonic acid metabolism by type II cells were therefore studied after challenge with calcium ionophore A23187, opsonized zymosan and hydrogen peroxide. A time- and concentration dependent release of cyclooxygenase products was observed, with release of PGE2 greater than 6-keto-PGF1 alpha greater than TxB2. Addition of glutathione or bicarbonate further increased the production of PGE2. N-ethylmaleimide, a sulfhydryl (SH) reactant, induced a dose-dependent increase in the release of TxB2 and 6-keto-PGF1 alpha, but not of PGE2. This relates most likely to the SH-dependency and glutathione requirement of the PGE2 isomerase and SH-independence of thromboxane and prostacyclin isomerase.