[show abstract][hide abstract] ABSTRACT: EDITORIAL The first ERS School Course on Sleep Medicine was held in Antwerp (Belgium) on November 10–12, 2005, as an initiative from the ERS School and the Sleep and Control of Breathing Group (4.2) of the Clinical Physiology and Integrative Biology Assembly. This course was a 3-day programme designed for anyone who wanted to develop a better understanding of several important areas in sleep medicine. Each topic was addressed by a recognised expert in that specific field. Presentations included a 30-minute formal pre-sentation of the material and a question-and-answer session to ensure faculty–participant interaction. The discussions were always lively and the subjects covered an entire range of sleep and sleep-disordered breathing.
[show abstract][hide abstract] ABSTRACT: INTRODUCTION Nasal CPAP (continuous positive airway pressure) is the preferred treatment for obstructive sleep apnea and mechanical splinting of the upper airway has traditionally been indicated the mechanism of action. Since CPAP can influence lung inflation during the daytime, this could also lead to an improvement of daytime gas exchange. We also wondered whether CPAP therapy could influence the apnea severity of the underlying obstructive sleep apnea syndrome. To explore this hypothesis, we evaluated arterial blood gases in sleep apnea patients after at least one month of CPAP therapy. We also looked at residual effects of CPAP on nocturnal breathing pattern during one night CPAP withdrawal after one year CPAP therapy in a large series of (predominantly obstructive) sleep apnea patients. PATIENTS AND METHODS Gas exchange study 132 patients treated with CPAP were evaluated with arterial blood gas analysis after at least one month of treatment. The characteristics of the patients are shown in Table 1. Measurements were performed in the afternoon before treat-ment, while follow up measurements took place in the morning. Arterial blood gases were processed immediately in an analyzer. The alveolar oxygen tension was calculated according to the ideal alveolar gas equation 1 , which was necessary to derive the alveolo-arterial oxygen difference.
10/2013: pages 135-137; , ISBN: ISBN 90-76906-22-X
[show abstract][hide abstract] ABSTRACT: Sleep-disordered breathing (SDB) is common among overweight and obese children. It is a risk factor for several health complications, including cardiovascular disease. Inflammatory processes leading to endothelial dysfunction are a possible mechanism linking SDB and cardiovascular disease. Elevated C-reactive protein (CRP) is a risk factor for cardiovascular disease and is independently correlated with obstructive sleep apnea syndrome (OSAS) in adults. Our goal is to evaluate the relationship between CRP and OSAS in overweight and obese children and adolescents.
One hundred and twenty children were prospectively studied (85 without OSAS, 20 mild OSAS, 15 moderate-to-severe OSAS). All subjects underwent polysomnography, and a blood sample was taken to determine CRP levels.
No significant differences were found in CRP between subjects with or without OSAS, and no correlations were found between CRP and OSAS severity, despite the relationship between CRP and BMI (r = 0.21, p = 0.015) and between CRP and fat mass (r = 0.31, p < 0.001).
These results suggest that CRP levels are correlated with the level of obesity but are not influenced by SDB in obese children and adolescents; hence, this in contrast to that in adult population.
[show abstract][hide abstract] ABSTRACT: ABSTRACT BACKGROUND Assessment of the overall therapeutic effectiveness of oral appliance therapy can only be realized through objectively measured compliance. The objective is to assess objectively measured compliance during oral appliance therapy at 1-year follow-up, and to compare these objective compliance data with self-reported use. METHODS 51 eligible patients were enrolled in this 1-year prospective clinical study (61% male; age: 49 ± 10 years; AHI: 18.0 ± 11.9/hour sleep; BMI: 26.6 ± 4.1 kg/m2). Objective compliance during oral appliance therapy at 1-year follow-up was assessed using a microsensor thermometer (TheraMon®, Handelsagentur Gschladt, Austria). Subjective compliance was assessed using self-report. Patients with a mean objectively measured use of ≥ 4 hours/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 (ICC = 0.8; 95% CI 0.5; 0.9), showing a mean subjective overestimation of 30 minutes (p = 0.02; 95% CI -3.1; 1.9). The discontinuation rate at 1-year follow-up was 9.8%. The objective mean use rate was 6.4 ± 1.7 hours per night at 1-year follow-up in continuing users, with a regular use rate of 83%. The mean disease alleviation was 54.8%. CONCLUSIONS The present study is the first report on the 1-year results of objectively measured compliance during oral appliance therapy. In addition, a high agreement between objective and subjective compliance data was reported, with a mean subjective overestimation of 30 minutes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01284881.
[show abstract][hide abstract] ABSTRACT: Obstructive sleep apnea/hypopnea syndrome (OSAHS) is characterized by recurrent episodes of partial or complete upper airway collapse during sleep that is highlighted by a reduction in, or complete cessation of, airflow despite documented on going inspiratory efforts. Due to the lack of adequate alveolar ventilation that results from the upper airway narrowing, oxygen saturation may drop and partial pressure of CO2 may occasionally increase. The events are mostly terminated by arousals. Clinical consequences are excessive daytime sleepiness related to the sleep disruption. Minimal diagnostic criteria have been defined for OSAHS. Patients should have excessive daytime sleepiness that can not be better explained by other factors, or experience two or more of the following symptoms, again that are not better explained by other factors: choking or gasping during sleep; recurrent awakenings from sleep; un-refreshing sleep; daytime fatigue; and impaired concentration. All patients should have more than five obstructed breathing events per hour during sleep. An obstructive apnea or hypopnoea can be defined as an event that lasts for ≥10 s and is characterized by an absence or a decrease from baseline in the amplitude of a valid measure of breathing during sleep that either reaches >50% with an oxygen desaturation of 3% or an arousal (alternatively a 30% reduction with 4% desaturation). The American Academy of Sleep Medicine (AASM) recommends these definitions. The Task Force of the AASM also states that there are common pathogenic mechanisms for obstructive apnea syndrome, central apnea syndrome, sleep hypoventilation syndrome and Cheyne-Stokes breathing. It was more preferable to discuss each of these separately; although, they could be placed under the common denominator of "sleep-disordered breathing syndrome". The definition of OSAHS using two components, daytime symptoms and breathing pattern disturbances during sleep, may suggest that there is a tight correlation between the two. However, unfortunately this is not the case. The breathing pattern abnormalities, mostly described by an Apnea/Hypopnoea Index (AHI), only weakly correlate with quantified measures of sleepiness, such as the Epworth Sleepiness Scale (ESS). This probably means that interindividual sensitivity, with some individuals coping better with sleep fragmentation than others, does compromise the relationship between the AHI and daytime sleepiness scores. In addition, epidemiological studies show a broad range of sleepiness in the general population. Obviously, epidemiological studies investigating the prevalence of OSAHS are all biased by the lack of a uniform definition. The prevalence of an AHI of >5 events·h-1 in a general population (without taking into account symptoms of sleepiness) has previously been estimated to be 24% in a male population. When symptoms of sleepiness were also taken into account, the prevalence decreased to 4% in males and 2% in females.
[show abstract][hide abstract] ABSTRACT: Background: Inhaled formulations using extrafine particles of long-acting β2-agonists and corticosteroids were developed to optimize asthma treatment. Findings that these combinations reach and treat smaller airways more effectively are predominantly based on general non-specific outcomes with little information on regional characteristics. Objectives: This study aims to assess long-term effects of extrafine beclomethasone/formoterol on small airways of asthmatic patients using novel functional imaging methods. Methods: Twenty-four stable asthma patients were subdivided into three groups (steroid naive, n = 7; partially controlled, n = 6; well controlled, n = 11). Current treatment was switched to a fixed combination of extrafine beclomethasone/formoterol (Foster®; Chiesi Pharmaceuticals, Parma, Italy). Patients underwent lung function evaluation and thorax high-resolution computerized tomography (HRCT) scan. Local airway resistance was obtained from computational fluid dynamics (CFD). Results: After 6 months, the entire population showed improvement in pre-bronchodilation imaging parameters, including small airway volume (p = 0.0007), resistance (p = 0.011), and asthma control score (p = 0.016). Changes in small airway volume correlated with changes in asthma control score (p = 0.004). Forced expiratory volume in 1 s (p = 0.044) and exhaled nitric oxide (p = 0.040) also improved. Functional imaging provided more detail and clinical relevance compared to lung function tests, especially in the well-controlled group where only functional imaging parameters showed significant improvement, while the correlation with asthma control score remained. Conclusions: Extrafine beclomethasone/formoterol results in a significant reduction of small airway obstruction, detectable by functional imaging (HRCT/CFD). Changes in imaging parameters correlated significantly with clinically relevant improvements. This indicates that functional imaging is a useful tool for sensitive assessment of changes in the respiratory system after asthma treatment.
[show abstract][hide abstract] ABSTRACT: Abstract 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.
Journal of Aerosol Medicine and Pulmonary Drug Delivery 03/2013; · 2.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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, 1408mm compared to 2173mm; p=0.04), a lower mean cross-sectional area at this location (median volume, 69.3mm2 compared to 114.3mm2; p=0.04), and a lower minimal cross-sectional area (median volume, 17.9mm2 compared to 25.9mm2; 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.
[show abstract][hide abstract] ABSTRACT: Previous studies have demonstrated the potential beneficial effect of N-acetylcysteine (NAC) in chronic obstructive pulmonary disease (COPD). However, the required dose and responder phenotype remain unclear. The current study investigated the effect of high-dose NAC on airway geometry, inflammation, and oxidative stress in COPD patients. Novel functional respiratory imaging methods combining multislice computed tomography images and computer-based flow simulations were used with high sensitivity for detecting changes induced by the therapy.
Twelve patients with Global Initiative for Chronic Obstructive Lung Disease stage II COPD were randomized to receive NAC 1800 mg or placebo daily for 3 months and were then crossed over to the alternative treatment for a further 3 months.
Significant correlations were found between image-based resistance values and glutathione levels after treatment with NAC (P = 0.011) and glutathione peroxidase at baseline (P = 0.036). Image-based resistance values appeared to be a good predictor for glutathione peroxidase levels after NAC (P = 0.02), changes in glutathione peroxidase levels (P = 0.035), and reduction in lobar functional residual capacity levels (P = 0.00084). In the limited set of responders to NAC therapy, the changes in airway resistance were in the same order as changes induced by budesonide/formoterol.
A combination of glutathione, glutathione peroxidase, and imaging parameters could potentially be used to phenotype COPD patients who would benefit from addition of NAC to their current therapy. The findings of this small pilot study need to be confirmed in a larger pivotal trial.
[show abstract][hide abstract] ABSTRACT: Urban atmospheres in modern cities carry characteristic mixtures of particulate pollution which are potentially aggravating for chronic respiratory patients (CRP). Although air quality surveys can be detailed, the obtained information is not always useful to evaluate human health effects. This paper presents a novel approach to estimate particle deposition rates in airways of CRP, based on real air pollution data. By combining computational fluid dynamics with physical-chemical characteristics of particulate pollution, deposition rates are estimated for particles of different toxicological relevance, that is, minerals, iron oxides, sea salts, ammonium salts, and carbonaceous particles. Also, it enables some qualitative evaluation of the spatial, temporal, and patient specific effects on the particle dose upon exposure to the urban atmosphere. Results show how heavy traffic conditions increases the deposition of anthropogenic particles in the trachea and lungs of respiratory patients (here, +0.28 and +1.5 μg·h(-1), respectively). In addition, local and synoptic meteorological conditions were found to have a strong effect on the overall dose. However, the pathology and age of the patient was found to be more crucial, with highest deposition rates for toxic particles in adults with a mild anomaly, followed by mild asthmatic children and adults with severe respiratory dysfunctions (7, 5, and 3 μg·h(-1), respectively).
[show abstract][hide abstract] ABSTRACT: Nocturnal gastroesophageal reflux (nGER) is associated with asthma and obstructive sleep apnoea (OSA). Our aim was to investigate whether nGER is a risk factor for onset of asthma and onset of respiratory and OSA symptoms in a prospective population based study.We invited 2640 subjects from Iceland, Sweden and Belgium for two evaluations over a nine years interval. They participated in structured interviews, answered questionnaires, underwent spirometries and methacholine challenge testing. nGER was defined by reported symptoms.Subjects with persistent nGER (n=123) had an independent increased risk of new asthma at follow-up [OR (95% CI): 2.3 (1.1-4.9)]. Persistent nGER was independently related to onset of respiratory symptoms [OR (95% CI): 3.0 (1.6-5.6)]. The risk of developing symptoms of OSA was increased in subjects with new and persistent nGER [OR (95% CI): 2.2 (1.3-1.6) and 2.0 (1.0-3.7), respectively]. No significant association was found between nGER and lung function or bronchial responsiveness.Persistent symptoms of nocturnal gastroesophageal reflux contributes to the development of asthma and respiratory symptoms. New onset of OSA symptoms is higher among subjects with symptoms of nGER. These findings support that nGER may play a role in the genesis of respiratory symptoms and diseases.
European Respiratory Journal 09/2012; · 6.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
Two consecutive open prospective studies.
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.
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.
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.
The Laryngoscope 03/2012; 122(7):1626-33. · 1.98 Impact Factor