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LA De Backer1, WG Vos2, R Salgado3, JW De Backer2, A Devolder1, SL Verhulst1, R Claes1, PR Germonpré1, WA De Backer11Department of Respiratory Medicine, 2FluidDA, 3Department of Radiology, Antwerp University Hospital, Antwerp, BelgiumBackground: Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD). However, their bronchodilating effect has not yet been compared in the central and distal airways. Functional imaging using computational fluid dynamics offers the possibility of making such a comparison. The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways.Methods: Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments. Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging. Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography.Results: Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product. On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways. Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient. Salbutamol was more effective in the other patients.Conclusion: This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics.Keywords: chronic obstructive pulmonary disease, imaging, computed tomography, computational fluid dynamics, salbutamol, ipratropium

Background: Gravity, and thus body position, can affect the regional distribution of lung ventilation and blood flow. Therefore, body positioning is a potential tool to improve regional ventilation, thereby possibly enhancing the effect of respiratory physiotherapy interventions. In this proof-of-concept study, functional respiratory imaging (FRI) was used to objectively assess effects of body position on regional airflow distribution in the lungs., Methods: Five healthy volunteers were recruited. The participants were asked during FRI first to lie in supine position, afterwards in standardized right lateral position., Results: In right lateral position there was significantly more regional ventilation also described as Imaging Airflow Distribution in the right lung than in the left lung (P < 0.001). Air velocity was significantly higher in the left lung (P < 0.05). In right lateral position there was significantly more airflow distribution in the right lung than in the left lung (P < 0.001). Significant changes were observed in airway geometry resulting in a decrease in imaged airway volume (P = 0.024) and a higher imaged airway resistance (P = 0.029) in the dependent lung. In general, the effect of right lateral position caused a significant increase in regional ventilation (P < 0.001) in the dependent lung when compared with the supine position., Conclusions: Changing body position leads to significant changes in regional lung ventilation, objectively assessed by FRI The volume based on the imaging parameters in the dependent lung is smaller in the lateral position than in the supine position. In right lateral decubitus position, airflow distribution is greater in dependent lung compared to the nondependent lung., Trial Registration: The trial has been submitted to www., Clinicaltrials: gov with identification number NCT01893697 on 07/02/2013., (© 2022. The Author(s).)

Study Objectives: Mandibular advancement devices (MADs) are a noninvasive treatment option for patients with obstructive sleep apnea (OSA) and act by increasing the upper airway volume. However, the exact therapeutic mechanism of action remains unclear. The aim of this study was to assess MAD mechanisms using functional imaging that combines imaging techniques and computational fluid dynamics and assess associations with treatment outcome., Methods: One hundred patients with OSA were prospectively included and treated with a custom-made MAD at a fixed 75% protrusion. A low-dose computed tomography scan was made with and without MADs for computational fluid dynamics analysis. Patients underwent a baseline and 3-month follow-up polysomnography to evaluate treatment efficacy. A reduction in apnea-hypopnea index ≥ 50% defined treatment response., Results: Overall, 71 patients completed both 3-month follow-up polysomnography and low-dose computed tomography scan with computational fluid dynamics analysis. MAD treatment significantly reduced the apnea-hypopnea index (16.5 [10.4-23.6] events/h to 9.1 [3.9-16.4] events/h; P < .001, median [quartile 1-quartile 3]) and significantly increased the total upper airway volume (8.6 [5.4-12.8] cm 3 vs 10.7 [6.4-15.4] cm 3 ; P = .003), especially the velopharyngeal volume (2.1 [0.5-4.1] cm 3 vs 3.3 [1.8-6.0] cm 3 ; P < .001). However, subanalyses in responders and nonresponders only showed a significant increase in the total upper airway volume in responders, not in nonresponders., Conclusions: MAD acts by increasing the total upper airway volume, predominantly due to an increase in the velopharyngeal volume. Responders showed a significant increase in the total upper airway volume with MAD treatment, while there was no significant increase in nonresponders. Findings add evidence to implement functional imaging using computational fluid dynamics in routine MAD outcome prediction., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Predicting Therapeutic Outcome of Mandibular Advancement Device Treatment in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT01532050; Identifier: NCT01532050., Citation: Van Gaver H, Op de Beeck S, Dieltjens M, et al. Functional imaging improves patient selection for mandibular advancement device treatment outcome in sleep-disordered breathing: a prospective study. J Clin Sleep Med. 2022;18(3):739-750., (© 2022 American Academy of Sleep Medicine.)

Purpose: The aim of the present study was to assess the efficacy of a sleep position trainer (SPT) in patients with an established diagnosis of positional obstructive sleep apnea and to evaluate the adherence after 1-year follow-up., Methods: Polysomnography (PSG) was performed at baseline and after 1 year of SPT use. Patients received questionnaires to assess treatment satisfaction and subjective adherence. Data on objective adherence and number of vibrations initiated by the SPT were collected from the SPT device., Results: Nine out of 58 patients stopped using the SPT during the first year of treatment (16%). Thirty-four middle-aged and overweight patients underwent a PSG after 1 year of SPT use (male/female ratio, 28/6; overall apnea/hypopnea index (AHI), 16/h). A significant reduction in overall AHI to 6/h was observed using treatment (p < 0.001). The median percentage of supine sleep decreased significantly to 1% with SPT (p < 0.001). The mean objective SPT use in 28 patients was 7.3 ± 0.9 h/night and 69 ± 26% of the nights. Furthermore, 75% of the patients reported a better sleep quality since the start of SPT treatment., Conclusions: Long-term treatment with the SPT was found to be effective in reducing overall AHI. Time spent sleeping in supine position was reduced to almost zero in the continuing users. Patient satisfaction was high when using the SPT.

Study Objectives: Mandibular advancement device (MAD) outcome varies between patients. We hypothesized that upper airway collapse sites, patterns, and degrees assessed during baseline drug-induced sleep endoscopy (DISE) affect MAD outcome., Methods: One hundred patients with obstructive sleep apnea (OSA) were included and underwent baseline type 1 polysomnography. MAD was fitted intraorally at fixed 75% maximal protrusion. A total of 72 patients completed 3-month follow-up polysomnography and baseline DISE. Response was defined as apnea-hypopnea index (AHI) reduction ≥ 50%, deterioration as AHI increases during MAD treatment compared to baseline., Results: Adjusting for baseline AHI and body mass index, patients with tongue base collapse showed 3.69 higher odds (1.27-10.73; P = .0128) for response. Complete concentric collapse at the level of the palate (5.32 [1.21-23.28]; P = .0234) and complete laterolateral oropharyngeal collapse (6.62 [1.14-38.34]; P = .0330) related to deterioration. Results for tongue base collapse and complete concentric collapse at the level of the palate were confirmed in the moderate to severe OSA subgroup. Applying these results to this selected subgroup increased response rate with 54% and decreased deterioration rate with 53%. These results were confirmed using other response and deterioration definitions., Conclusions: Three baseline DISE phenotypes identified during drug-induced sleep were significantly related to MAD treatment outcome: one beneficial, tongue base collapse, and two adverse, complete concentric collapse at the level of the palate and complete laterolateral oropharyngeal collapse. If confirmed in future prospective studies, these results could guide patient selection for MAD outcome., Clinical Trial Registration: This prospective clinical trial (PROMAD) was registered on Clinicaltrials.gov with identifier: NCT01532050., Citation: Op de Beeck S, Dieltjens M, Verbruggen AE, Vroegop AV, Wouters K, Hamans E, Willemen M, Verbraecken J, De Backer WA, Van de Heyning PH, Braem MJ, Vanderveken OM. Phenotypic labelling using drug-induced sleep endoscopy improves patient selection for mandibular advancement device outcome: a prospective study. J Clin Sleep Med. 2019;15(8):1089-1099., (© 2019 American Academy of Sleep Medicine.)

Study Objectives: To assess the overall clinical effectiveness of a sleep position trainer (SPT) in patients with positional obstructive sleep apnea (POSA) and to evaluate how many patients were willing to continue treatment after a 1-month trial period., Methods: Patients in whom POSA was diagnosed underwent a 1-month trial period with the SPT. Home sleep apnea tests were used to measure baseline data and data following the trial period with the SPT., Results: The 79 patients who completed the study protocol were 81% male, had a mean age of 52 ± 12 years, and a median baseline respiratory event index (REI) of 11 (8, 16) events/h. A significant reduction in overall REI to 5 (3, 10) events/h was observed with the SPT as compared to baseline ( P < .001). The median percentage of sleep time in the supine position decreased significantly from 27 (20, 48) to 7 (2, 20) with the SPT ( P < .001). Adherence was found to be 95 ± 8%. Of the 44 patients who decided to continue treatment, 27 were categorized as responders (having a decrease in REI of at least 50%) and 17 were non-responders. The most important reasons for not purchasing the SPT were poor objective results, intolerance to the vibrations, cost of the device, persistent daytime sleepiness, or patient preference for other treatment options., Conclusions: Treatment with the SPT came with high adherence rates and was effective in reducing REI and supine sleep position. The trial period is in the patients' best interest, as it may prevent those who will not benefit from positional training from purchasing an SPT., (© 2018 American Academy of Sleep Medicine.)

Obstructive sleep apnea (OSA) is a common disease with high morbidity and related mortality. Narrowing and collapse of the pharyngeal airway during sleep characterize the disease, resulting in a decrease (hypopnea) or a complete cessation (apnea) of oronasal airflow. Upper airway stimulation (UAS), using electrical neurostimulation of the hypoglossal nerve (n. XII) synchronized with ventilation, is a novel, evolving treatment option. UAS was found to be an effective treatment in CPAP-intolerant patients. The treatment success is partly due to the strict selection of the patients, based on previous findings. Furthermore, post-operative follow-up is needed in order to maintain or improve treatment outcome. Therefore, a clinical pathway, which provides structure and standardization, is crucial. In this paper, the aim is to discuss the technical aspects of UAS therapy and to describe a clinical pathway to organize the care process of UAS for OSA in a structured and standardized way.

Importance: The main reported reasons for discontinuation of oral appliance therapy for sleep-disordered breathing (SDB) are the presence of self-perceived adverse effects and self-appreciated lack of efficacy. However, these conclusions rely only on subjective compliance data., Objective: To determine which parameters are correlated with objectively measured data on compliance with oral appliance therapy., Design, Setting, and Participants: For 51 outpatients with SDB, a prospective clinical trial using oral appliance therapy was conducted at Antwerp University Hospital from February 7, 2011, to October 8, 2013 (38 [75%] males; mean [SD] age, 49.3 [9.0] years; mean [SD] apnea-hypopnea index, 14.9 [9.3] events per hour of sleep; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 26.3 [2.8]). Analysis was performed November 5, 2014., Intervention: Oral appliance therapy with a custom-made, titratrable mandibular advancement device (OAm)., Main Outcomes and Measures: Possible correlations were assessed between objective compliance and patients’ anthropometric characteristics, polysomnographic parameters, and answers to 3 subjective questionnaires (the visual analog scale for snoring, the Epworth Sleepiness Scale, and an adverse effects questionnaire)., Results: Median oral appliance use was 6.4 hours per night (range, 4.7-7.2 hours per night) at the 3-month follow-up. None of the anthropometric and polysomnographic parameters were correlated with compliance. No correlation was found between objective compliance and reports of excessive daytime sleepiness. However, a significant inverse correlation was found between objective compliance and posttreatment visual analog scale values for snoring (P = .006; ρ = –.40). In addition, objective compliance was correlated significantly with a more pronounced decrease in socially disturbing snoring (P = .005; ρ = 0.39). The presence of dry mouth was the only adverse effect that was negatively correlated with objective compliance at the 3-month follow-up (P < .05; ρ = –.31)., Conclusions and Relevance: Neither the anthropometric and polysomnographic parameters nor reports of excessive daytime sleepiness correlated with compliance during oral appliance therapy. The 2 parameters that were correlated with higher objective compliance during oral appliance therapy were a more pronounced decrease in snoring and the presence of dry mouth during treatment., Trial Registration: clinicaltrials.gov Identifiers: NCT01284881 and NCT01532050.

Purpose: The objective of this randomized controlled trial was to assess the additional effect of a chest-worn sleep position trainer (SPT) in patients with residual supine-dependent obstructive sleep apnea (sdOSA) under mandibular advancement device (MAD) therapy., Methods: Baseline and follow-up polysomnography with MAD were performed. Twenty patients with sdOSA under MAD therapy underwent two consecutive randomized polysomnographies: one with SPT and one with combination of SPT + MAD. Data are presented as median (quartile 1, quartile 3)., Results: The SPT reduced the time spent in supine sleeping position compared to baseline and MAD therapy. Both MAD and SPT were individually effective in reducing the overall apnea/hypopnea index (AHI) significantly when compared to baseline from 20.8 (15.1; 33.6)/h at baseline to 11.0 (6.7; 13.8)/h and to 11.1 (3.5; 17.7)/h with MAD or SPT, respectively. The combination of SPT + MAD further reduced the overall AHI to 5.7 (3.6; 7.4), which was significantly lower than with MAD alone (p < 0.001) and SPT alone (p < 0.008), respectively., Conclusions: The results of this study indicate that combination of SPT + MAD leads to a higher therapeutic efficacy in patients with sdOSA under MAD therapy when compared to one of the treatment modalities alone.

A completely different treatment approach was chosen for 2 patients with unilateral diaphragmatic paralysis and complaints of dyspnea despite similar anatomic and physiologic abnormalities. These decisions were supported by results obtained by functional respiratory imaging (FRI). FRI generated functional information on lobar ventilation and local drug deposition. In the first patient, some lobes were poorly ventilated, and drug deposition simulation showed that some regions were undertreated. This patient underwent diaphragmatic plication to restore ventilation. In the second patient, all lobes were still ventilated. A conservative approach with regular follow-ups was chosen to wait for spontaneous recovery of the diaphragmatic function. Both patients improved subjectively and objectively. These cases demonstrate how novel medical imaging techniques such as FRI can be used to personalize respiratory treatment in patients with unilateral diaphragmatic paralysis., (Copyright © 2014 by Daedalus Enterprises.)

Background: As the upper airway is the most important limiting factor for the deposition of inhalation medication in the lower airways, it is interesting to assess how its morphology varies between different postures. The goal of this study is to compare the upper airway morphology and functionality of healthy volunteers in the upright and supine positions during tidal nasal breathing and to search for baseline indicators for these changes. This is done by performing three-dimensional measurements on computed tomography (CT) and cone beam computed tomography (CBCT) scans., Methods: This prospective study was approved by all relevant institutional review boards. All patients gave their signed informed consent. In this study, 20 healthy volunteers (mean age, 62 years; age range, 37-78 years; mean body mass index, 29.26; body mass index range, 21.63-42.17; 16 men, 4 women) underwent a supine low-dose CT scan and an upright CBCT scan of the upper airway. The (local) average (Savg) and minimal (Smin) cross-sectional area, the position of the latter, the concavity, and the airway resistance were examined to determine if they changed from the upright to the supine position. If changes were found, baseline parameters were sought that were indicators for these differences., Results: There were five dropouts due to movement artifacts in the CBCT scans. Savg and Smin were 9.76% and 26.90% larger, respectively, in the CBCT scan than in the CT scan, whereas the resistance decreased by 26.15% in the upright position. The Savg of the region between the hard palate and the bottom of the uvula increased the most (49.85%). In people with a high body mass index, this value changed the least. The airway resistance in men decreased more than in women., Conclusions: This study demonstrated that there are differences in upper airway morphology and functionality between the supine and upright positions and that there are baseline indicators for these differences.

Background: Assessment of the overall therapeutic effectiveness of oral appliance therapy can only be realized through objectively measured compliance. The aims of this study were to assess objectively measured compliance during oral appliance therapy at 1-year follow-up and to compare these data with self-reported use., Methods: Fifty-one eligible patients were enrolled in this 1-year prospective clinical study (men, 61%; mean age, 49 ± 10 years; apnea-hypopnea index, 18.0 ± 11.9 events/h sleep; BMI, 26.6 ± 4.1 kg/m²). Objective compliance during oral appliance therapy at 1-year follow-up was assessed with a microsensor thermometer. Subjective compliance was assessed by self-report. Patients with a mean objectively measured use of ≥ 4 h/night on 70% of nights monitored were considered regular users. The mean disease alleviation was calculated as a measure of overall therapeutic effectiveness., Results: High agreement between objective and subjective compliance data at 1-year follow-up was reported (intraclass correlation coefficient, 0.8; 95% CI, 0.5-0.9), showing a mean subjective overestimation of 30 min (95% CI, -3.1 to 1.9; P = .02). The discontinuation rate at 1-year follow-up was 9.8%. The objective mean use rate was 6.4 ± 1.7 h/night at 1-year follow-up in continuing users, with a regular use rate of 83%. The mean disease alleviation was 54.9%., Conclusions: This study is the first to our knowledge to report the 1-year results of objectively measured compliance during oral appliance therapy. In addition, a high agreement between objective and subjective compliance data were reported, with a mean subjective overestimation of 30 min., Trial Registry: ClinicalTrials.gov; No.: NCT01284881; URL: www.clinicaltrials.gov.

Objective: Sleep-disordered breathing (SDB) is prevalent in obesity. Weight loss is one of the most effective treatment options. The aim was to assess the association of SDB and metabolic disruption before and after weight loss., Design and Methods: Obese adolescents were included when entering an in-patient weight loss program. Fasting blood analysis was performed at baseline and after 4-6 months. Sleep screening was done at baseline and at follow-up in case of baseline SDB., Results: 224 obese adolescents were included. Median age was 15.5 years (10.1-18.0) and mean BMI z-score was 2.74 ± 0.42. About 30% had SDB at baseline (N = 68). High-density lipoprotein (HDL)-cholesterol was associated with mean nocturnal oxygen saturation () (partial r = 0.21; P = 0.002). Aspartate aminotransferase (ASAT) and alanine aminotransferase were related with oxygen desaturation index (partial r = -0.15; P = 0.03 and partial r = -0.15; P = 0.02), but this became insignificant after correction for sex. After weight loss, 24% had residual SDB. Linear regression showed an association between ASAT and (partial r = -0.34; P = 0.002). There were no significant correlations between improvements in laboratory measurements and sleep parameters. HDL-cholesterol improved in relation with the decrease in BMI z-score., Conclusion: SDB at baseline was associated with higher levels of liver enzymes and lower HDL-cholesterol concentration. Improvements in sleep parameters were not associated with improvements in laboratory measurements., (Copyright © 2013 The Obesity Society.)

Purpose: This prospective clinical study investigates the efficacy of a specific custom-made titratable mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA). This MAD has attachments in the frontal teeth area that allow for progressive titration of the mandible., Methods: Sixty-one adult OSA patients were included (age, 46.7 ± 9.0 years; male/female ratio, 45/16; apnea-hypopnea index (AHI), 23.2 ± 15.4 events/h sleep; body mass index, 27.9 ± 4.1 kg/m²). After an adaptation period, titration started based on a protocol of symptomatic benefit or upon reaching the physiological limits of protrusion. As a primary outcome, treatment response was defined as an objective reduction in AHI following MAD treatment of ≥50 % compared to baseline, and treatment success as a reduction in AHI with MAD to less than 5 and 10 events/h sleep. Compliance failure was defined as an inability to continue treatment., Results: A statistically significant decrease was observed in AHI, from 23.4 ± 15.7 at baseline to 8.9 ± 8.6 events/h with MAD (p < 0.01). Treatment response was achieved in 42 out of 61 patients (68.8 %), whereas 42.6 % met criteria of AHI < 5 and 63.9 % achieved an AHI < 10 events/h sleep, respectively. Four patients (6.6 %) were considered as "compliance failures.", Conclusions: The present study has evaluated the efficacy of a specific custom-made titratable MAD in terms of sleep apnea reduction.

Background: Oral appliance (OA) therapy is increasingly prescribed as a non-continuous positive airway pressure treatment modality for sleep-disordered breathing (SDB). Although OA therapy is reported to be efficacious for the treatment of SDB, data on compliance remain limited to self-report., Methods: In this 3-month prospective clinical trial, the main outcome was to assess the safety and feasibility of an objective measurement of compliance during OA therapy using an embedded microsensor thermometer with on-chip integrated readout electronics in 51 consecutive patients with an established diagnosis of SDB (AHI 18.0 ± 11.9/h; age 47 ± 10 y; BMI 26.6 ± 4.0 kg/m(2); men/women: 31/20). Patients were unaware of the purpose of the study., Results: No microsensor-related adverse events were recorded. In addition, no problems were encountered during the readout of the compliance data. Out of 51 microsensors, one had a technical defect and was lost to follow-up. In this study, the overall objective mean rate of OA use was 6.6 ± 1.3 h per day with a regular OA users' rate of 82% at the 3-month follow-up. Statistical analysis revealed no significant differences between objective and self-reported OA compliance data in this study. Measurement of the objective OA compliance allowed us to calculate the mean disease alleviation (MDA) as the product of objective compliance and therapeutic efficacy. MDA serves as a measure of the overall therapeutic effectiveness, and turned out to be 51.1%., Conclusions: The results illustrate the safety and feasibility of objective measurement of OA compliance. The objective measurement of OA compliance allows for calculation of the MDA.

Objectives/hypothesis: Previous feasibility studies have shown that electrical stimulation of the hypoglossal nerve can improve obstructive sleep apnea (OSA). The current study examined the safety and preliminary effectiveness of a second generation device, the Upper Airway Stimulation (UAS) system, and identified baseline predictors for therapy success., Study Design: Two consecutive open prospective studies., Methods: UAS systems were implanted in patients with moderate to severe OSA who failed or were intolerant of continuous positive airway pressure (CPAP). The study was conducted in 2 parts. In part 1, patients were enrolled with broad selection criteria. Apnea hypopnea index (AHI) was collected using laboratory-based polysomnography at preimplant and postimplant visits. Epworth Sleepiness Scale (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also collected. In part 2, patients were enrolled using selection criteria derived from the experience in part 1., Results: In part 1, 20 of 22 enrolled patients (two exited the study) were examined for factors predictive of therapy response. Responders had both a body mass index ≤32 and AHI ≤50 (P < .05) and did not have complete concentric palatal collapse. Part 2 patients (n = 8) were selected using responder criteria and showed an improvement on AHI from baseline, from 38.9 ± 9.8 to 10.0 ± 11.0 (P < .01) at 6 months postimplant. Both ESS and FOSQ improved significantly in part 1 and 2 subjects., Conclusions: The current study has demonstrated that therapy with upper airway stimulation is safe and efficacious in a select group of patients with moderate to severe OSA who cannot or will not use CPAP as primary treatment., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Sleep-disordered breathing (SDB) is prevalent in childhood obesity. It may be an independent risk factor for the metabolic syndrome. Possible mechanisms are inflammation and oxidative stress. Adenotonsillectomy in childhood obesity is associated with a high recurrence rate and risk of postoperative weight gain. Therefore, this study assessed the effects of SDB on inflammation and oxidative stress in childhood obesity before and after weight loss. We included 132 obese subjects between 10 and 18 years consecutively. Median age was 15.4 years (10.1-18.0). Mean BMI z-score was 2.72 ± 0.42. Leukocytes and differentiation, high sensitivity C-reactive protein (hs-CRP), and uric acid (UA) were determined at baseline and subjects underwent a sleep assessment. SDB was diagnosed in 39%. Linear regression analysis showed an association between UA(log) and oxygen desaturation index(log) (ODI(log)) (r = 0.20; P = 0.03), between leukocytes(log) and respiratory disturbance index(log) (RDI(log)) (r = 0.23; P = 0.01), and between lymphocytes(log) and RDI(log) (r = 0.19; P = 0.04). Follow-up was organized after 4-6 months of treatment. Median decrease in BMI z-score was 32%. Laboratory measurements were repeated. Subjects with SDB at baseline underwent a second sleep study. Of these 49 subjects, 12 showed residual SDB. This corresponds with a treatment success rate of 71%. Unlike changes in inflammatory markers, improvements in UA were associated with improvements in RDI and ODI (respectively: r = 0.44; P = 0.007, r = 0.41; P = 0.01). In conclusion, weight loss is effective in treating obese children with SDB. At baseline, a link exists between inflammation and SDB. Oxidative stress is reflected by UA at baseline and the concentration decreases after treatment according to improvements in SDB.

Lung cancer is the leading cause of cancer deaths worldwide. Standard chemotherapy has been shown to improve quality of life and has a modest influence on overall survival. This modest improvement in survival is partly due to the choice of chemotherapy regimens that have been based on prognostic factors such as age, performance status and comorbidities of the patient. This underlines the importance of developing a more personalized therapy for patients with non-small cell lung cancer. Such an approach may reduce the variation in how individual patients respond to medications by tailoring therapies to their genetic profile. In this review we focus on several aspects of customized therapy, looking not only at patient characteristics but also to tumor histology and specific tumor biomarkers.

Upper airway occlusion in obstructive sleep apnea has been attributed to a decline in pharyngeal neuromuscular activity occurring in a structurally narrowed airway. Surgical treatment focuses on the correction of anatomic abnormalities, but there is a potential role for activation of the upper airway musculature, especially with stimulation of the hypoglossal nerve and genioglossus muscle. We present evidence from research on upper airway neuromuscular electrical stimulation in animals and humans. We also present results from eight obstructive sleep apnea patients with a fully implanted system for hypoglossal nerve stimulation, demonstrating an improvement in upper airway collapsibility and obstructive sleep apnea severity. Future research, including optimization of device features and stimulation parameters as well as patient selection, is necessary to make hypoglossal nerve stimulation a viable alternative to positive airway pressure therapy and upper airway surgical procedures., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

A multidisciplinary pulmonary rehabilitation program has become an important part of the treatment of chronic obstructive pulmonary disease. It can improve both exercise tolerance and health related quality of life in these patients. Exercise training has to be included for the program to be successful. The intensity of the training is of great importance: there is more physiological benefit in high-intensity training, compared to moderate-intensity training. High-intensity training results in reduced levels of blood lactate and pulmonary ventilation at a given heavy work rate. High-intensity training is limited in COPD patients because of exercise-induced dyspnoea. Flow limitation, as a consequence of increased ventilatory demands of exercise, causes a breathing pattern with greater demands on their inspiratory muscles: this results in a pattern of low tidal volume and high-frequency breathing. Increased inspiratory muscle work causes dyspnoea and limitation in exercise intensity. Artificial ventilatory assistance could improve exercise tolerance and hence help severe COPD patients to achieve a higher level of training. It could help to unload and assist the overburdened ventilatory muscles and give a possibility for higher levels of exercise intensity. In this review article we will discuss the effectiveness and feasibility of training with ventilatory aids.

Introduction: The aim of this retrospective study was to investigate if sleep-disordered breathing (SDB) was an independent predictor of suspected fatty liver disease in a clinical sample of overweight children and adolescents., Materials and Methods: Consecutive overweight and obese children attending a pediatric obesity clinic underwent polysomnography, fasting blood sample, and abdominal ultrasound., Results and Discussion: The respiratory disturbance index, percentage of total sleep time with SO2 < 90%, and SaO2nadir were associated with higher alanine amino-transferases (ALT) independent of abdominal obesity. Multiple logistic regression selected waist circumference (odds ratio = 1.05; p = 0.05) and SaO2nadir (odds ratio = 0.87; p = 0.03) as predictors of suggestive fatty liver disease, defined as ALT > 40 U/L and/or hyperechoic liver on abdominal ultrasound. This study supports the association between the severity of SDB and suspected fatty liver disease in a clinical sample of overweight children and adolescents. We recommend more research on the influence of SDB on the development of fatty liver disease and on the effect of treating sleep apnea on liver function parameters.

This review discusses the pathophysiological aspects of sleep-disordered breathing, with focus on upper airway mechanics in obstructive and central sleep apnoea, Cheyne-Stokes respiration and obesity hypoventilation syndrome. These disorders constitute the end points of a spectrum with distinct yet interrelated mechanisms that lead to substantial pathology, i.e. increased upper airway collapsibility, control of breathing instability, increased work of breathing, disturbed ventilatory system mechanics and neurohormonal changes. Concepts are changing. Although sleep apnoea is considered more and more to be an increased loop gain disorder, the central type of apnoea is now considered as an obstructive event, because it causes pharyngeal narrowing, associated with prolonged expiration. Although a unifying concept for the pathogenesis is lacking, it seems that these patients are in a vicious circle. Knowledge of common patterns of sleep-disordered breathing may help to identify these patients and guide therapy.

Background: To investigate the relationship between obstructive sleep apnea syndrome (OSAS) and exhaled nitric oxide (eNO) in overweight children and adolescents without asthma or atopy and to assess whether obesity per se is associated with increased airway inflammation., Methods: Consecutive overweight subjects without symptoms of asthma or allergy were recruited at a pediatric obesity clinic. A normal-weight control group without OSAS and asthma or allergy was also recruited. All subjects underwent polysomnography and two measurements of eNO (afternoon and morning after polysomnography)., Results: Controlling for age, the mean (+/- SD) afternoon eNO concentration was significantly higher in the snoring group (14.1 +/- 1.1 parts per billion [ppb]) compared with the normal-weight group (10.1 +/- 0.8 ppb; p = 0.03) and with the overweight group with normal polysomnography findings (8.9 +/- 0.8 ppb; p = 0.007). The afternoon eNO concentration was also different between the OSAS group (11.9 +/- 1.0 ppb) and the overweight group with normal polysomnography findings (p = 0.03). Morning eNO values were higher in the OSAS group (12.3 +/- 1.1 ppb) than in the normal weight group (9.9 +/- 0.8 ppb; p = 0.047) and in the overweight control group (9.7 +/- 0.7 ppb; p = 0.02). BMI z score was not significantly correlated with afternoon eNO concentration or with morning eNO concentration., Conclusion: This study illustrates that both habitual snoring and OSAS are associated with increased airway inflammation in overweight children as assessed by higher eNO levels. Furthermore, it was demonstrated that childhood obesity in the absence of sleep-disordered breathing is not associated with increased airway inflammation.

Rationale: The efficacy of immediate adaptation of mandibular advancement devices made of thermoplastic material as a treatment option for sleep-disordered breathing (SDB) has been demonstrated in clinical studies. To date, there have been no studies comparing the efficacy of such prefabricated devices with custom-made devices., Objectives: Our purpose was to compare the efficacy of both types of devices in patients with SDB., Methods: A randomized controlled cross-over trial, comprising 4 months of treatment with a thermoplastic and a custom-made device, with a 1-month washout interval., Measurements and Main Results: A total of 35 patients (29 males; age, 49 +/- 9 yr; apnea-hypopnea index [AHI], 13 +/- 11 events/h; body mass index, 28 +/- 4 kg/m(2)) completed the protocol. AHI was only reduced with the custom-made device (P = 0.005). In addition, this device reduced snoring to a greater extent than the thermoplastic device. The success rate was higher with the custom-made device (60 vs. 31%; P = 0.02). One-third of the patients demonstrated compliance failure with the thermoplastic device, mainly because of insufficient overnight retention. Total failure rate with the thermoplastic device was 69%, whereas the majority (63%) of these were successfully treated with the custom-made device. At the end of the study, 82% of the patients preferred the custom-made device, and 9% had no preference (P < 0.0001)., Conclusions: In this study, a custom-made device turned out to be more effective than a thermoplastic device in the treatment of SDB. Our results suggest that the thermoplastic device cannot be recommended as a therapeutic option nor can it be used as a screening tool to find good candidates for mandibular advancement therapy.

Objective: To assess if the severity of sleep-disordered breathing (SDB) and mainly intermittent hypoxia is associated with increased peripheral leukocytes in overweight children and adolescents, controlling for adiposity and obesity-related metabolic abnormalities., Methods: Consecutive subjects were recruited at a pediatric obesity clinic. All subjects underwent polysomnography and a fasting blood sample., Results: In total, 95 subjects were included ( =11.1+/-2.6, 43 boys, body mass index, =2.3+/-0.5, 29 subjects were overweight and 66 obese). Total white blood cell count increased significantly by worsening of intermittent hypoxia. Total white blood cell count was correlated with the maximal degree of desaturation, independent of puberty, HOMA and HDL-cholesterol. Neutrophil levels were associated with the degree of desaturation, while controlling for puberty and HOMA., Conclusion: This study supports the hypothesis of an independent interaction between intermittent hypoxia and nocturnal desaturation during sleep, and increased white blood cell and neutrophil levels in overweight and obese children and adolescents. This finding may contribute to the mechanisms linking SDB with increased cardiovascular morbidity.

Objective: The aim of this study was to determine whether the severity of sleep-disordered breathing (SDB) was associated with increased levels of uric acid (UA), both in serum and in urine, as a marker of tissue hypoxia, in a sample of overweight and obese subjects, irrespective of indexes of adiposity., Methods: Consecutive subjects underwent polysomnography, fasting blood sampling, and 24-h urine collection. Outcome parameters were serum UA, UA excretion ([24-h urinary UA x serum creatinine]/urine creatinine) and urinary UA/creatinine ratio., Results: A total of 93 subjects were included (44% boys; mean [+/- SD] age = 11.1 +/- 2.5; 73% obese). A fasting measurement of serum UA levels was available for 62 patients. The respiratory disturbance index was a significant covariate (beta = 0.09 +/- 0.03; p = 0.01) in the regression model for serum UA, controlling for sex (beta = 0.32 +/- 0.29; p = 0.3), puberty (beta = 0.87 +/- 0.34; p = 0.01), and waist circumference (beta = 0.04 +/- 0.01; p = 0.005). The percentage of total sleep time with arterial oxygen saturation < or = 89% (beta = 0.94 +/- 0.45; p = 0.04) was also significantly associated with serum UA level, controlling for sex (beta = 0.22 +/- 0.30; p = 0.5), puberty (beta = 0.83 +/- 0.35; p = 0.02), and waist circumference (beta = 0.04 +/- 0.02; p = 0.02). None of the SDB variables correlated with UA excretion or with urinary UA/creatinine ratio., Conclusion: This study in overweight children and adolescents demonstrated a relationship between the severity of sleep apnea and increased levels of serum UA, independent of abdominal adiposity. In view of the known associations between UA and cardiovascular risk, this finding may contribute to the mechanisms linking SDB with cardiovascular morbidity.

Aim: To investigate the association between wheezing and impaired sleep in Sri Lankan children, aged 6-12 years; and, to report the prevalence of asthma-related symptoms in these subjects., Methods: The International Study of Asthma and Allergies in Childhood questionnaire and a separate sleep questionnaire were completed., Results: Of 800 originally distributed questionnaires, 652 were analyzed. Wheezing was present in 89 children (14%). Within this group, 66% reported wheezing in the last 12 months. Wheezing children had a significantly higher presence of snoring, restless sleep, nocturnal awakenings and daytime tiredness. Wheezing was found to be independently associated with restless sleep (odds ratio (OR) = 2.4). There was no association between wheezing and difficulties falling asleep, nocturnal awakenings, apneas, and daytime sleepiness and tiredness. After adjusting for possible confounders, the following significant associations were present: snoring and apneas (OR = 1.6), chronic rhinitis and apneas (OR = 1.6), snoring and restless sleep (OR = 3.2), chronic rhinitis and restless sleep (OR = 2.1), and hayfever and daytime tiredness (OR = 4.3). Wheezing was related to an increased risk of snoring (OR = 2.8) and subjects with chronic rhinitis had also an increased risk of snoring (OR = 1.7), adjusting for possible confounders., Conclusion: The sleep of wheezing children was impaired compared with their non-wheezing peers, resulting in an increased prevalence of daytime tiredness. Upper airway symptoms, such as chronic rhinitis or hayfever, should be carefully considered in these children, as they might be responsible for these sleep problems.

Objective: To assess whether sleep-disordered breathing (SDB) is a risk factor of the metabolic syndrome (MS) in children and adolescents who are overweight and to examine whether the severity of SDB was independently associated with glucose intolerance, insulin resistance, and/or dyslipidemia., Study Design: Consecutive subjects who were overweight or obese underwent polysomnography, fasting blood sample, and oral glucose tolerance test (for calculation of area under the curve [AUC]). SDB was defined as a respiratory disturbance index > or = 2. MS was present when > or = 3 of these factors were present: waist circumference > or = 90th percentile; fasting glucose level > or = 110 mg/dL; triglyceride level > or = 110 mg/dL; high-density lipoprotein cholesterol level < or = 40 mg/dL; blood pressure > or = 90th percentile., Results: A total of 104 subjects were included in the study (44% boys; 58% prepubertal; mean age, 11.1 +/- 2.6 years; 69% obese). Mean SaO2 (odds ratio, 0.54) and SaO2nadir (odds ratio, 0.89) were independent, significant predictors of the presence of MS. Multiple regression showed significant associations between SaO2nadir and high-density lipoprotein cholesterol level, mean SaO2 and both AUC glucose and triglyceride levels, and between the percentage of total sleep time with SaO2 > or = 95% and cholesterol level, while controlling for adiposity and sex, puberty, or both., Conclusion: This study supports the hypothesis of an interaction between SDB and metabolic abnormalities, independent of estimates of body fat distribution, in children and adolescents who are overweight and obese.

Aims: To determine the prevalence of sleep-disordered breathing (SDB) in a clinical sample of overweight and obese children and adolescents, and to examine the contribution of fat distribution., Methods: Consecutive subjects without chronic lung disease, neuromuscular disease, laryngomalacia, or any genetic or craniofacial syndrome were recruited. All underwent measurements of neck and waist circumference, waist-to-hip ratio, % fat mass and polysomnography. Obstructive apnoea index > or =1 or obstructive apnoea-hypopnoea index (OAHI) > or =2, further classified as mild (2< or =OAHI<5) or moderate-to-severe (OAHI> or =5), were used as diagnostic criteria for obstructive sleep apnoea (OSA). Central sleep apnoea was diagnosed when central apnoeas/hypopnoeas > or =10 s were present accompanied by >1 age-specific bradytachycardia and/or >1 desaturation <89%. Subjects with desaturation < or =85% after central events of any duration were also diagnosed with central sleep apnoea. Primary snoring was diagnosed when: snoring was detected by microphone and normal obstructive indices and saturation., Results: 27 overweight and 64 obese subjects were included (40 boys; mean (standard deviation (SD)) age 11.2 (2.6) years). Among the obese children, 53% were normal, 11% had primary snoring, 11% had mild OSA, 8% had moderate-to-severe OSA and 17% had central sleep apnoea. Half of the patients with central sleep apnoea had desaturation <85%. Only enlarged tonsils were predictive of moderate-to-severe OSA. On the other hand, higher levels of abdominal obesity and fat mass were associated with central sleep apnoea., Conclusion: SDB is very common in this clinical sample of overweight children. OSA is not associated with abdominal obesity. On the contrary, higher levels of abdominal obesity and fat mass are associated with central sleep apnoea.

Aim: Only a limited number of studies, designed to establish normal values for sleep-related respiratory variables in children, have been reported, and all are non-European. The aim of this study was to expand the knowledge on normative data in children., Methods: Subjects ranging from 6 to 16 years were recruited and underwent full polysomnography. Only subjects without sleep disordered breathing or other sleep problems as assessed by clinical history were included., Results: Sixty subjects were studied ( = 11.7 +/- 2.6 years; 28 boys; = 118.8 +/- 30.6%). was 0.85 +/- 1.06 (range: 0.0-5.5). was 0.06 +/- 0.16 (range: 0.0-0.9); 11 patients had a total of 31 obstructive apneas. Only five obstructive hypopneas were detected with = 0.08 +/- 0.17 (range: 0.0-0.9). was 1.98 +/- 1.39 (range: 0.1-7.2). was 97.0 +/- 0.6% (range: 96.0-98.0); was 91.8 +/- 2.7% (range: 82.0-96.0); <% of total sleep time with SaO2 >or= 95%> was 98.7 +/- 2.1% (range: 90.8-100.0); was 0.8 +/- 0.9 (range: 0.0-4.9) and was 6.1 +/- 1.8 (range: 2.7-10.9). Snoring was detected in 15 patients (4 overweight subjects), with no difference in patient characteristics and sleep-related respiratory variables between snorers and non-snorers. Subjects in the overweight group (n = 22) had a lower SaO2nadir (90.8 +/- 2.7 vs. 92.4 +/- 2.6; P = 0.01) and a higher ODI (1.3 +/- 1.3 vs. 0.4 +/- 0.4; P = 0.0002) than their normal weight peers., Conclusion: Our data are in agreement with other non-European studies, designed to establish normal values in children., ((c) 2006 Wiley-Liss, Inc.)

Inhaled corticosteroids (ICS) are the standard of care in asthma and are widely used in the treatment of patients with COPD. The influence of steroids on inflammatory processes has long been established since glucocorticoids and their receptor belong to the regulatory network involved in inhibition of several inflammatory pathways. Inflammatory processes are usually accompanied by an increased oxidative burden followed by a depletion of antioxidants. Therefore, the effects of steroids on antioxidant status have been investigated revealing possible positive effects on the reduced antioxidant enzyme activity. Nevertheless, the mechanisms of this modulation have not been fully elucidated yet. It is possible that antioxidant enzyme activity is regulated at the level of transcription. Additionally, because of the fact that antioxidant enzymes are trace element dependent, steroids may affect their activity through influence on trace element accumulation. This review summarizes the effects of steroids on the antioxidant enzymes activity in vitro and in vivo in relation to asthma and COPD.

In order to develop efficient therapeutic regimes for chronic obstructive pulmonary disease (COPD), N-acetylcysteine (NAC) has been tested as a medication which can suppress various pathogenic processes in this disease. Besides its well-known and efficient mucolytic action, NAC meets these needs by virtue of its antioxidant and anti-inflammatory modes of action. NAC is a thiol compound which by providing sulfhydryl groups, can act both as a precursor of reduced glutathione and as a direct ROS scavenger, hence regulating the redox status in the cells. In this way it can interfere with several signaling pathways that play a role in regulating apoptosis, angiogenesis, cell growth and arrest and inflammatory response. Overall, the antioxidant effects of NAC are well documented in in vivo and in vitro studies. It successfully inhibits oxidative stress at both high and low concentrations, under acute (in vitro) and chronic administration (in vivo). With regard to its anti-inflammatory action, in contrast, the effects of NAC differ in vivo and in vitro and are highly dose-dependent. In the in vitro settings anti-inflammatory effects are seen at high but not at low concentrations. On the other hand, some long-term effectiveness is reported in several in vivo studies even at low dosages. Increasing the dose seems to improve NAC bioavailability and may also consolidate some of its effects. In this way, the effects that are observed in the clinical and in vivo studies do not always reflect the success of the in vitro experiments. Furthermore, the results obtained with healthy volunteers do not always provide incontrovertible proof of its usefulness in COPD especially when number of exacerbations and changes in lung function are chosen as the primary outcomes. Despite these considerations and in view of the present lack of effective therapies to inhibit disease progression in COPD, NAC and its derivatives, because of their multiple molecular modes of action, remain promising medication once doses and route of administration are optimized.

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.

Objective and Background: Existence of an increased oxidative stress has been confirmed in patients with acute exacerbation of COPD. This study aims to examine the extent and time-course of antioxidant defence in patients with an acute exacerbation of COPD in comparison with stable patients., Methods: Twelve patients with acute exacerbation were studied at admission, and then 24 h and 48 h following admission and at discharge. The antioxidants assessed were the endogenous antioxidants: glutathione peroxidase, superoxide dismutase, oxidized and reduced glutathione, albumin and exogenous antioxidants: alpha-tocopherol and retinol. Trolox equivalent antioxidant capacity as a marker of antioxidant status was also measured., Results: There was an increase in glutathione peroxidase and superoxide dismutase 48 h after admission (P<0.05). Alpha-tocopherol was the lowest 24 h after admission and increased significantly at discharge (P<0.05)., Conclusions: There is an increase in antioxidant defence during acute exacerbation of COPD reaching a maximum at 48 h after admission. This rise in the antioxidant defence is not sufficient to prevent depletion of non-enzymatic antioxidants such as alpha-tocopherol.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. The initial step in the inflammatory process is overexpression of adhesion molecules, which leads to excessive transmigration of neutrophils. One of these adhesion molecules is ICAM-1 which is elevated in COPD patients. In this study we evaluated the influence of N-acetylcysteine (NAC) (0.01 mM-30 mM) on the cytokine-induced (TNF-alpha/IL-1 beta) expression of the ICAM-1 adhesion molecule and on IL-8 release in endothelial (ECV-304) and bronchial epithelial (H292) cell lines. The methodology used consisted of immunochemistry for the assessment of surface ICAM-1 and ELISA method for that of soluble ICAM-1 and IL-8. NAC inhibited the TNF-alpha/IL-1 beta-stimulated ICAM-1 expression and IL-8 release from both cell lines in a concentration dependent manner. The most effective concentrations were 30 mM and 20 mM (99 and 90% inhibition respectively, P<0.01). We conclude that NAC is an effective inhibitor of TNF-alpha/IL-1 beta- stimulated ICAM-1 and IL-8 release in endothelial and epithelial cells. This fact highlights the anti-inflammatory potential of NAC in COPD.

Inhaled corticosteroids have a high level of topical anti-inflammatory activity. However, in patients with COPD these drugs have been reported to exert limited effects. A reduction in histone deacetylase (HDAC) activity is suggested to prevent the anti-inflammatory action of corticosteroids. Cigarette smoke is known to reduce HDAC expression. The aim of this study is to compare the outcome of corticosteroid therapy in both smoking and non-smoking COPD patients. Twenty-three smoking patients and 18 ex-smoking patients with COPD were treated with inhaled corticosteroids for a period of 2 months. Blood and induced sputum samples were collected before and after treatment. Values of FEV(1) %-predicted did not change upon the therapy, but there was a trend to improve in the ex-smokers (63.1 -> 64.8%-pred.), compared with a decrease in the smokers (63.3 -> 61.6%-pred.). The levels of the pro-inflammatory cytokine IL-8 increased in the group of smokers from 379 +/-78 to 526 +/-118 ng/ml. Although not significant, a slight decrease from 382 +/-70 to 342 +/-62 ng/ml was observed in the group of ex-smokers. The neutrophil related elastase activity showed similar effects after steroid treatment, it went up from 36.4 +/-12.0 to 113.5 +/-9.7 nmol/l in smokers, and decreased from 346.2 +/-72.1 to 131.1 +/-6.5 nmol/l in ex-smokers with COPD. These results support the evidence that inhaled corticosteroids have no anti-inflammatory effects in COPD patients, but only when these patients are still smoking. Smoking cessation seems the best therapy for COPD patients.

Aims: To assess the presence of a first night effect (FNE) in children and adolescents and to examine if a single night polysomnography (PSG) is sufficient for diagnosing obstructive sleep apnoea syndrome (OSAS)., Methods: Prospective case study of 70 patients (group 1: 2-6 years, n = 22; group 2: 7-12 years, n = 32; group 3: 13-17 years, n = 16) referred for OSAS. Diagnostic criteria for OSAS: one or more of the following: (1) obstructive apnoea index (OAI) > or =1; (2) obstructive apnoea hypopnoea index (oAHI) > or =2; (3) SaO2 < or =89% in association with obstruction., Results: In all age groups, but mainly in the oldest children, REMS increased during the second night, mainly at the expense of stage 2 sleep. The first night PSG correctly identified OSAS in 86%, 91%, and 100% of the children for groups 1, 2, and 3 respectively. This represents 9% false negatives for OSAS when only the first night PSG was used. All cases missed had mild OSAS, except for one with oAHI >5 on night 2. There were also seven patients with OSAS on night 1 but with a normal PSG on night 2: all had oAHI <5., Conclusion: There is a FNE in children and adolescents. A single night PSG is sufficient for diagnosing OSAS, but in cases with a suggestive history and examination and with a negative first night, a second night study might be advisable.