Dataset Information

Neural crest-specific deletion of Bmp7 leads to midfacial hypoplasia, nasal airway obstruction, and disordered breathing modelling Obstructive Sleep Apnea.

ABSTRACT: Pediatric obstructive sleep apnea (OSA), a relatively common sleep-related breathing disorder (SRBD) affecting approximately 1-5% of children, is often caused by anatomical obstruction and/or collapse of the nasal and/or pharyngeal airways. The resulting sleep disruption and intermittent hypoxia lead to various systemic morbidities. Predicting the development of OSA from craniofacial features alone is currently not possible and a controversy remains if upper airway obstruction facilitates reduced midfacial growth or vice-versa. Currently, there is no rodent model that recapitulates both the development of craniofacial abnormalities and upper airway obstruction to address these questions. Here, we describe that mice with a neural crest-specific deletion of Bmp7 (Bmp7^ncko) present with shorter, more acute angled cranial base, midfacial hypoplasia, nasal septum deviation, turbinate swelling and branching defects, and nasal airway obstruction. Interestingly, several of these craniofacial features develop after birth during periods of rapid midfacial growth and precede the development of an upper airway obstruction. We identified that in this rodent model, no single feature appeared to predict upper airway obstruction, but the sum of those features resulted in a reduced breathing frequency, apneas and overall reduced oxygen consumption. Metabolomics analysis of serum from peripheral blood identified increased levels of hydroxyproline, a metabolite upregulated under hypoxic conditions. As this model recapitulates many features observed in OSA, it offers unique opportunities for studying how upper airway obstruction affects breathing physiology and leads to systemic morbidities.

SUBMITTER: Baddam P

PROVIDER: S-EPMC7888714 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Neural crest-specific deletion of <i>Bmp7</i> leads to midfacial hypoplasia, nasal airway obstruction, and disordered breathing modelling Obstructive Sleep Apnea.

Baddam Pranidhi P Biancardi Vivian V Roth Daniela M DM Eaton Farah F Thereza-Bussolaro Claudine C Mandal Rupasri R Wishart David S DS Barr Amy A MacLean Joanna J Flores-Mir Carlos C Pagliardini Silvia S Graf Daniel D

Disease models & mechanisms 20210111

Pediatric obstructive sleep apnea (OSA), a relatively common sleep-related breathing disorder (SRBD) affecting approximately 1-5% of children, is often caused by anatomical obstruction and/or collapse of the nasal and/or pharyngeal airways. The resulting sleep disruption and intermittent hypoxia lead to various systemic morbidities. Predicting the development of OSA from craniofacial features alone is currently not possible and a controversy remains if upper airway obstruction facilitates reduce ...[more]

PMID: 33431521

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Project description:Study objectivesObstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea.MethodsChildren 3-12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5-9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2-30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis.ResultsThe sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30-2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98-5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83-4.34) in children recruited for mild sleep-disordered breathing.ConclusionsAbnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention.Trial registrationPediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859.

Project description:Importance:While functional rhinoplasty has been broadly studied, to our knowledge no systematic review and meta-analysis of lateral wall repair has been done previously. Objective:To evaluate the effectiveness of repair of the lateral nasal wall in adult patients with nasal airway obstruction. Data Sources:Medline, Embase, Cinahl, Central, Scopus, and Web of Science databases and reference lists were searched for clinical and observational studies. Study Selection:The selection criteria were defined according to the PICO (population, intervention, comparison, and outcome) framework. The relevant studies were selected by 2 independent reviewers based on the studies' abstracts and full texts. Data Extraction and Synthesis:Data were extracted using standardized lists chosen by the authors according to Cochrane Collaboration guidelines. The effect sizes were first calculated for each study and then pooled together using random effects synthesis. Heterogeneity was assessed using the I2 statistic, and publication bias was evaluated by the Egger test. Main Outcomes and Measures:The results were reported as pooled row mean differences in changes from preoperative to postoperative Nasal Obstruction Symptom Evaluation scores at different times of follow-up (≤3 months, >3 to 6 months, and >6 months). Results:Of 1522 initial records, 10 studies were considered relevant-all of them observational. The pooled study sample included 324 participants. When combining all the repeated measures together, the pooled effect size for functional rhinoplasty was -47.7 (95% CI, -53.4 to 42.1) points on the Nasal Obstruction Symptom Evaluation scale with high heterogeneity of 72%. The pooled effect size outcomes were similar in short- (-45.0 points [95% CI, -47.8 to -42.2 points]), mid- (-48.4 points [95% CI, -52.5 to -44.4 points]), and long-term (-49.0 points [95% CI, -62.1 to -35.8 points]) follow-ups. Conclusions and Relevance:The pooled effect size of 10 observational studies supported the effectiveness of functional rhinoplasty for the treatment of nasal airway obstruction caused by lateral nasal wall insufficiency. To improve the level of evidence, randomized clinical trials are needed. Level of Evidence:NA.

Dataset Information

Neural crest-specific deletion of Bmp7 leads to midfacial hypoplasia, nasal airway obstruction, and disordered breathing modelling Obstructive Sleep Apnea.

Publications

Neural crest-specific deletion of <i>Bmp7</i> leads to midfacial hypoplasia, nasal airway obstruction, and disordered breathing modelling Obstructive Sleep Apnea.

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