Neural network-based automated analyses of nSp recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.
Rationale: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells.Objectives: To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status.Methods: Obese children (body mass index z score .1.65) and nonobese children were recruited and underwent polysomnographic testing (PSG), and fasting endothelial function measurements and blood draws in the morning after PSG. Plasma exosomes were isolated from all subjects. Isolated exosomes were then incubated with confluent endothelial cell monolayer cultures. Electric cellsubstrate impedance sensing systems were used to determine the ability of exosomes to disrupt the intercellular barrier formed by confluent endothelial cells. In addition, immunofluorescent assessments of zonula occludens-1 tight junction protein cellular distribution were conducted to examine endothelial barrier dysfunction. miRNA and mRNA arrays were also applied to exosomes and endothelial cells, and miRNA inhibitors and mimics were transfected for mechanistic assays.Measurements and Main Results: Plasma exosomes isolated from either obese children or nonobese children with OSA were primarily derived from endothelial cell sources and recapitulated ED, or its absence, in naive human endothelial cells and also in vivo when injected into mice. Microarrays identified a restricted signature of exosomal miRNAs that readily distinguished ED from normal endothelial function. Among the miRNAs, expression of exosomal miRNA-630 was reduced in children with ED and normalized after therapy along with restoration of endothelial function. Conversely, transfection of exosomes from subjects without ED with an miRNA-630 inhibitor induces the ED functional phenotype. Gene target discovery experiments further revealed that miRNA-630 regulates 416 gene targets in endothelial cells that include the Nrf2, AMP kinase, and tight junction pathways.Conclusions: These observations elucidate a novel role of exosomal miRNA-360 as a putative key mediator of vascular function and cardiovascular disease risk in children with underlying OSA and/or obesity, and identify therapeutic targets.
OBJECTIVE:Th e objective of this study was to evaluate the diagnostic reliability of home respiratory polygraphy (HRP) in children with a clinical suspicion of OSA-hypopnea syndrome (OSAS). METHODS:A prospective blind evaluation was performed. Children between the ages of 2 to 14 years with clinical suspicion of OSAS who were referred to the Sleep Unit were included. An initial HRP followed by a later date , same night, in-laboratory overnight respiratory polygraphy and polysomnography (PSG) in the sleep laboratory were performed. Th e apneahypopnea index (AHI)-HRP was compared with AHI-PSG, and therapeutic decisions based on AHI-HRP and AHI-PSG were analyzed using intraclass correlation coeffi cients, BlandAltman plots, and receiver operator curves (ROCs). RESULTS:Twenty-seven boys and 23 girls, with a mean age of 5.3 Ϯ 2.5 years, were studied, and 66% were diagnosed with OSAS based on a PSG-defi ned obstructive respiratory disturbance index Ն 3/h total sleep time. Based on the availability of concurrent HRP-PSG recordings, the optimal AHI-HRP corresponding to the PSG-defi ned OSAS criterion was established as Ն 5.6/h Th e latter exhibited a sensitivity of 90.9% (95% CI, 79.6%-100%) and a specifi city of 94.1% (95% CI, 80%-100%).CONCLUSIONS: HRP recordings emerge as a potentially useful and reliable approach for the diagnosis of OSAS in children. However, more research is required for the diagnosis of mild OSAS using HRP in children. ENT 5 ear, nose, and throat; HRP 5 home respiratory polygraphy; ICC 5 interclass correlation coeffi cient; LRP 5 in-laboratory respiratory polygraphy; OAHI 5 obstructive apnea-hypopnea index; ORDI 5 obstructive respiratory disturbance index; OSAS 5 OSAhypopnea syndrome; PSG 5 polysomnography; RDI 5 respiratory disturbance index; ROC 5 receiver operating characteristic; RP 5 respiratory polygraphy; Sp o 2 5 oxygen saturation using pulse oximetry; SU 5 Sleep Unit AFFILIATIONS: From the Sleep Unit (Drs Alonso-Álvarez, Terán-Santos, Ordax Carbajo, Cordero-Guevara, and Navazo-Egüia), the CIBER of Respiratory Diseases (Drs Alonso-Álvarez and Terán-Santos), Instituto Carlos III, CIBERES, and the
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