Wilfried De Backer

Sleep-disordered breathing in overweight and obese children and adolescents: prevalence, characteristics and the role of fat distribution

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 ⩾1 or obstructive apnoea–hypopnoea index (OAHI) ⩾2, further classified as mild (2⩽OAHI<5) or moderate-to-severe (OAHI⩾5), were used as diagnostic criteria for obstructive sleep apnoea (OSA). Central sleep apnoea was diagnosed when central apnoeas/hypopnoeas ⩾10 s were present accompanied by >1 age-specific bradytachycardia and/or >1 desaturation <89%. Subjects with desaturation ⩽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.

Interleukin 8 (IL-8) in the bronchoalveolar lavage fluid from patients with the adult respiratory distress syndrome (ARDS) and patients at risk for ARDS☆

A sensitive and specific radioimmunoassay was used to measure interleukin 8 (IL-8) in bronchoalveolar lavage fluids from control subjects, patients with the adult respiratory distress syndrome (ARDS) and patients undergoing coronary bypass surgery, a risk factor for developing ARDS. Concentrations of IL-8, albumin, total protein and numbers of neutrophils were higher in both patient groups than in controls. Levels of IL-8 were significantly correlated with the influx of neutrophils, plasma protein extravasation and with the PaO2/FiO2 ratio. These data suggest that IL-8 may mediate the recruitment of neutrophils from the vascular compartment into the alveolar space and may therefore be an important determinant in neutrophil-mediated lung injury. Since increased levels of IL-8 were also found in BAL fluid from patients at risk in whom ARDS did not develop, other factors are likely to be involved and IL-8, as well as other markers of inflammation, are of little prognostic use.

Implanted upper airway stimulation device for obstructive sleep apnea

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.

The prevalence, anatomical correlates and treatment of sleep-disordered breathing in obese children and adolescents

The prevalence of childhood obesity is increasing worldwide. One of the obesity-related complications that has received increasing attention in recent years is sleep-disordered breathing. Obese children are at a higher risk of developing sleep-disordered breathing, including habitual snoring, obstructive sleep apnea syndrome and desaturations preceded by central apneas. Both adiposity and upper airway factors, such as adenotonsillar hypertrophy, modulate the severity of sleep-disordered breathing in these children. Adenotonsillectomy seems to be effective against obstructive sleep apnea syndrome in obese children. On the other hand, there are limited data on the effects of weight loss and of treatment with continuous positive airway pressure on the severity of sleep apnea in obese children and adolescents.

Objective measurement of compliance during oral appliance therapy for sleep-disordered breathing

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/m2; 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.

Electrical stimulation of the hypoglossal nerve in the treatment of obstructive sleep apnea

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.

Validation of Computational Fluid Dynamics in CT-based Airway Models with SPECT/CT

PURPOSE To compare the results obtained by using numerical flow simulations with the results of combined single photon emission computed tomography (SPECT) and computed tomography (CT) and to demonstrate the importance of correct boundary conditions for the numerical methods to account for the large amount of interpatient variability in airway geometry. MATERIALS AND METHODS This study was approved by all relevant institutional review boards. All patients gave their signed informed consent. In this study, six patients with mild asthma (three men; three women; overall mean age, 46 years ± 17 [standard deviation]) underwent CT at functional residual capacity and total lung capacity, as well as SPECT/CT. CT data were used for segmentation and computational fluid dynamics (CFD) simulations. A comparison was made between airflow distribution, as derived with (a) SPECT/CT through tracer concentration analysis, (b) CT through lobar expansion measurement, and (c) CFD through flow computer simulation. Also, the heterogeneity of the ventilation was examined. RESULTS Good agreement was found between SPECT/CT, CT, and CFD in terms of airflow distribution and hot spot detection. The average difference for the internal airflow distribution was less than 3% for CFD and CT versus SPECT/CT. Heterogeneity in ventilation patterns could be detected with SPECT/CT and CFD. CONCLUSION This results of this study show that patient-specific computer simulations with appropriate boundary conditions yield information that is similar to that obtained with functional imaging tools, such as SPECT/CT. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100322/-/DC1.

Sleep disturbance and daytime symptoms in wheezing school-aged children.

The aim of the study was to investigate whether wheezing is associated with disturbed sleep and increased daytime symptoms in school‐aged children. A random sample of 1234 children, aged 6–14 years, participated in a respiratory health study in the region of Antwerp. The International Study of Asthma and Allergies in Childhood questionnaire and a separate sleep questionnaire were completed. In the children who wheezed in the last 12 months, sleep quality was more frequently disturbed due to nocturnal awakenings and restless sleep compared with children who did not wheeze. Daytime sleepiness and tiredness were more common in wheezing than in non‐wheezing children. After adjusting for possible confounders a positive association was found between wheeze and: difficulties falling asleep [odds ratio (OR) = 2.0], restless sleep (OR = 5.0), daytime sleepiness (OR = 3.8) and daytime tiredness (OR = 5.1). Chronic cough (OR = 2.4), snoring (OR = 2.0), chronic rhinitis (OR = 2.6) and eczema (OR = 3.3) were associated with disturbed sleep. Chronic cough (OR = 2.5) and rhinitis (OR = 4.1) were related to daytime tiredness. Chronic rhinitis was an important risk factor for snoring (OR = 1.9). In wheezing school‐aged children, decreased quality of sleep and increased daytime tiredness and sleepiness were more often reported. Upper airway symptoms were related to the sleep disturbances.

The Effect of Weight Loss on Sleep‐disordered Breathing in Obese Teenagers

The objective of this study was to assess the effect of weight loss on sleep‐disordered breathing (SDB) in obese teenagers attending a residential treatment center. We also assessed whether the presence of SDB at the start of the weight management therapy was correlated with the amount of weight loss achieved. Obese teenagers were recruited and underwent anthropometry and sleep screening. Subjects with SDB (apnea hypopnea index (AHI) ≥ 2) received a follow‐up screening after weight loss therapy. Sixty‐one obese subjects were included (age = 14.8 ± 2.3; BMI z score = 2.7 ± 0.4). Thirty‐one subjects were diagnosed with SDB with 38% continuing to have residual SDB after a median weight loss of 24.0 kg. Subjects with SDB had a higher median relative decrease in BMI z score compared to subjects without SDB which was 30.5, 33.6, and 50.4% in the group with AHI of the baseline screening study < 2, 2 ≤ AHI < 5, and AHI ≥ 5, respectively (P = 0.02). AHI of the baseline screening study correlated significantly with the relative decrease in BMI z score (partial r = 0.37; P = 0.003), controlling for gender, age, initial BMI z score, and time between both studies. In conclusion, weight loss was successful in treating SDB in obese teenagers. In addition, there was a positive association between the severity of SDB at the start of the treatment and the amount of weight loss achieved. These findings are in favor of considering weight loss as a first‐line treatment for SDB in obese children and adolescents.

Tumour necrosis factor stimulates human skin mast cells to release histamine and tryptase

Besides its effects on tumour cells, tumour necrosis factor (TNF) also acts on a variety of other cells, thus enhancing inflammatory and immune processes. In view of the prominent role of the mast cell in such processes, the aim of the present study was to assess the effects of recombinant TNF‐α on human mast cells. Mast cells from the infant foreskin obtained during circumcision were dispersed by an enzymatic technique using collagenasc and hyaluronidase. Cells thus obtained were pooled, washed and separated by Percoll gradient centrifugation. Mast cells, with a purity of 70 90% were incubated for 60 min with 10‐11 to 10‐7MrTNF‐α. Histamine and tryptase levels were assessed in the cell supernatant by spectrofluorometry and radioimmunoassay (RIA) respectively. A concentration dependent release of histamine was observed, which reached a maximum of 11·5 ± 2·2 nmol/106 cells at 10‐8 MrTNF. Release of tryptase was also concentration dependent and reached a maximum of 293±105 mU/106 cells (10‐8 rTNF). rTNF‐α thus appears to be a direct stimulus for mast cells to degranulale and to release both histamine and tryptase.