The role of atypical deglutition in children and adolescents with moderate to severe obstructive sleep apnea syndrome.

This cross-sectional study aimed to assess the prevalence of atypical deglutition (tongue thrust) in children diagnosed with moderate to severe obstructive sleep apnea syndrome (OSAS) and to explore its associations, particularly in relation to the type of dentition (mixed or permanent). The study was conducted over a 5 year period at a paediatric hospital in Paris, France. Children aged 6-18 years with moderate to severe OSAS (apnea-hypopnea index ≥5/h) underwent a comprehensive evaluation, including the recording of demographic data, symptoms of snoring and breathing issues, and otolaryngology examination. The swallowing pattern was assessed and orthodontic evaluations were performed. Cephalometric radiography and pharyngometry tests (pharyngeal collapsibility was computed) were conducted. The study found a high prevalence of atypical deglutition in children with mixed 74% [56-87] or permanent 38% [25-51] dentition. In children with mixed dentition and atypical deglutition, the pharyngeal compliance and lower facial dimensions were increased. In children with permanent dentition, atypical deglutition was associated with more severe OSAS and a lower hyoid bone position. Independent of the type of dentition, atypical deglutition was associated with an increase in the apnea-hypopnea index, an increase in the lower facial dimension, increased pharyngeal compliance, and a more caudal hyoid bone position. Atypical deglutition was strongly associated with increased pharyngeal collapsibility, more severe OSAS and altered facial measurements in children. The findings suggest that identifying atypical deglutition in children with OSAS could help to guide a personalised therapeutic approach, including myofunctional therapy.

Obstructive sleep apnea in children with Down syndrome: contribution of upper airway and chemosensitivity.

BACKGROUND: The high prevalence of obstructive sleep apnea syndrome (OSAS) in children with Down syndrome (DS) has been attributed to a reduced upper airway size, while the role of ventilatory control is unclear. The objectives of our case-control study were to evaluate the upper airway reduction in children with DS and moderate to severe OSAS as compared to typically developing (TD) children with similar OSAS severity and to evaluate the degree of chemical loop gain modifications including its components: controller and plant gains (CG, PG). METHODS: Thirteen children with DS were matched for age, sex, OSAS severity and ethnicity with 26 TD children. They had undergone acoustic rhinometry and pharyngometry, chemical LG obtained during awake tidal breathing measurement and hypercapnic-hyperoxic ventilatory response testing. RESULTS: As compared to TD, children with DS depicted reduced oropharyngeal dimensions, significantly lower CG and LG and no different PG. Their hypercapnic ventilatory response slopes were not different. CONCLUSIONS: We concluded that the decreased CG in DS was related to decreased peripheral chemoreceptor sensitivity, and while central chemosensitivity was normal, the former explained the increased end-tidal PCO2 observed in children with DS as compared to TD. Pharyngeal dimensions are reduced in children with DS and OSAS. IMPACT: Reduced upper airway size and nocturnal alveolar hypoventilation in children with Down syndrome (DS) have been previously reported. We confirmed that children with DS and moderate-to-severe OSA have reduced oropharyngeal size as compared to typically developing children with similar OSAS severity and demonstrated decreased peripheral chemosensitivity explaining the alveolar hypoventilation observed in children with DS. Central chemosensitivity appears to be intact in children with DS and moderate to severe OSAS Our results support growing evidence that Down syndrome is associated with autonomic nervous system dysfunction.

Development and validation of moderate to severe obstructive sleep apnea screening test (ColTon) in a pediatric population.

OBJECTIVE: Development and validation of a machine learning algorithm to predict moderate to severe obstructive sleep apnea syndrome (OSAS) in otherwise healthy children. DESIGN: Multivariable logistic regression and cforest algorithm of a large cross-sectional data set of children with sleep-disordered breathing. SETTING: An university pediatric sleep centre. PARTICIPANTS: Children underwent clinical examination, acoustic rhinometry and pharyngometry, and surveying through parental sleep questionnaires, allowing the recording of 14 predictors that have been associated with OSAS. The dataset was nonrandomly split into a training (development) versus test (external validation) set (2:1 ratio) based on the time of the polysomnography. We followed the TRIPOD checklist. RESULTS: We included 336 children in the analysis: 220 in the training set (median age [25th-75th percentile]: 10.6 years [7.4; 13.5], z-score of BMI: 1.96 [0.73; 2.50], 89 girls) and 116 in the test set (10.3 years [7.8; 13.0], z-score of BMI: 1.89 [0.61; 2.46], 51 girls). The prevalence of moderate to severe OSAS was 106/336 (32%). A machine learning algorithm using the cforest with pharyngeal collapsibility (pharyngeal volume reduction from sitting to supine position measured by pharyngometry) and tonsillar hypertrophy (Brodsky scale), constituting the ColTon index, as predictors yielded an area under the curve of 0.89, 95% confidence interval [0.85-0.93]. The ColTon index had an accuracy of 76%, sensitivity of 63%, specificity of 81%, negative predictive value of 84%, and positive predictive value of 59% on the validation set. CONCLUSION: A cforest classifier allows valid predictions for moderate to severe OSAS in mostly obese, otherwise healthy children.

Oropharyngeal obstruction and respiratory system compliance are linked to ventilatory control parameters in pediatric obstructive sleep apnea syndrome.

Instable ventilatory control is an endotypic trait of obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the relationships between the anatomical compromise of the upper (oro- and naso-pharynx) and lower airways and ventilatory control (measured by chemical loop gain) in otherwise healthy children suffering from moderate to severe OSAS (apnea hypopnea index ≥ 5/hour). The children underwent ear, nose and throat examination, measurement of impedance of the respiratory system that allowed characterizing peripheral lung mechanics using the extended Resistance-Inertance-Compliance model. Physiologically constrained analytical model based on tidal breathing analysis allowed for the computation of steady-state plant gain, steady-state controller gain (CG0) and steady-state loop gain (LG0). Medium-frequency components of the feedback control system were then deduced. Fifty children (median age 11.2 years) were enrolled. Oropharyngeal obstruction was associated with decreased CG0 (0.6 [0.2; 1.0] vs 1.5 [0.5; 6.6] L.s- 1.mmHg- 1, p = 0.038) and LG0 (0.4 [0.2; 1.1] vs 1.2 [0.4; 9.3], p = 0.027), while nasal obstruction did not modify ventilatory control parameters. In a multivariate analysis Medium-Frequency PG was negatively related to minute ventilation and respiratory system compliance. Both upper (tonsil hypertrophy) and lower (compliance of respiratory system) airways are linked to ventilatory control in children with moderate to severe OSAS.

Prevalence of mouth breathing, with or without nasal obstruction, in children with moderate to severe obstructive sleep apnea.

BACKGROUND: Mouth breathing (MB) is a symptom of obstructive sleep apnea (OSA) in children, but its diagnosis remains challenging. The main objectives of our study were to evaluate whether parents' and physician's diagnose of MB were concordant and to evaluate the prevalence of nasal obstruction in children with OSA and MB. METHODS: Ninety-three children (median age: 10.6 years, range 3-18) with moderate to severe OSA prospectively underwent otorhinolaryngologist (endoscopy, acoustic rhinometry and pharyngometry allowing calculation of pharyngeal compliance) and orthodontist (clinical exam and cephalometry) assessments together with parental interview (daytime MB: never, sometimes, often, always). MB was also assessed by the otorhinolaryngologist (nasal obstruction on endoscopy) and the orthodontist (incompetent lips or anterior open bite or low tongue position). RESULTS: Thirty-eight children (41%) were mouth (parental criterion: MB often or always, median age 8.2 years) and 55 nasal (11.4 years, p = 0.016) breathers. The agreement of parental and physician diagnosis of MB was slight (orthodontist) to moderate (otorhinolaryngologist). Parental diagnosis of MB was associated with nasal obstruction on acoustic rhinometry and endoscopy (hypertrophy of inferior turbinate, n = 18 or adenoids, n = 15) and with an adenoid facies (increased Frankfort's mandibular plane angle on cephalometry). Eleven children had MB by habit and were characterized by more severe OSA and higher pharyngeal compliance than mouth breathers with nasal obstruction. CONCLUSION: MB diagnosis by parents is acceptable and is mainly related to nasal obstruction. A subset of children had MB by habit associated with worst OSA and increased pharyngeal compliance that could benefit from myofunctional therapy.

Evaluation of Tonsillotomy Effects on Pharyngeal Volume and Compliance in Children.

Our objective was to assess whether adenotonsillotomy improved pharyngeal compliance, which is a risk factor for sleep-disordered breathing. Otherwise healthy children underwent Obstructive Sleep Apnea (OSA)-18 questionnaire and a pre- and postoperative acoustic pharyngometry in both sitting and supine positions, allowing the measurement of the volume of the palatine tonsil region and pharyngeal compliance. Thirty-five children (median age 5.3 years) were enrolled; they were reevaluated at a median of 18 days (25th-75th percentiles, 15-25) after surgery. Participants were compared according to a normal (n = 18) or an increased (n = 17) preoperative pharyngeal compliance. Surgery was associated with a significant decrease in OSA-18 and Brodsky scores, with a median increase in palatine volume of 0.13 cm3 (25th-75th percentiles, 0.00-0.73). A decrease in pharyngeal compliance was observed in children with increased preoperative compliance. The variation of palatine volume after surgery was positively related to the variation of pharyngeal compliance, suggesting that obstruction relief was associated with muscle relaxation in children with normal preoperative compliance.

Pharmacokinetics and tissue diffusion of ganciclovir in mice and rats.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of birth defects, mental retardation and non-genetic sensorineural hearing loss. Murine models have been developed in order to understand the pathophysiological mechanisms underlying these lesions. These models are being proposed for the validation of therapeutic protocols for clinical use. The aim of this preclinical study was to assess the pharmacokinetics of the reference antiviral molecule, ganciclovir, in order to optimize these protocols and confirm the diffusion of the molecule to the appropriate target zones. METHODS: Transplacental and intracochlear diffusion of ganciclovir was evaluated in mice and rats. Pharmacokinetics was assessed in adult mice and pups after 5 consecutive days of intraperitoneal injection of ganciclovir. The occurrence of hematological side effects of ganciclovir was evaluated in the different blood cell lineages. RESULTS: In adult rats, the intracochlear diffusion of ganciclovir was shown to achieve the same concentration as in blood. In gestating mice, transplacental diffusion was observed, with a fetal-to-maternal blood ratio of 0.5. In newborn mice, the plasma concentration profile of ganciclovir showed a peak at 2 h followed by a gradual decrease. In adult mice, the concentration peaked at 1 h, but became undetectable by 2 h after injection. Counts of white blood cells, red blood cells and platelets decreased significantly in ganciclovir-treated newborn mice. CONCLUSION: Our data provide evidence for the intracochlear diffusion of the molecule, which may be relevant for the treatment of sensorineural hearing loss in congenitally-infected children.