Endothelial Progenitor Cells and Vascular Dysfunction in Children with Obstructive Sleep Apnea

Kheirandish‐Gozal, Leila; Bhattacharjee, Rakesh; Kim, Jinkwan; Clair, Heather B.; Gozal, David

doi:10.1164/rccm.200912-1845oc

Cited by 101 publications

(71 citation statements)

References 46 publications

(36 reference statements)

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“…Th is frequent and highly prevalent pediatric condition is associated with adverse consequences and excessive and costly use of health-care services. [2][3][4][5][6][7][8][9][10][11][12]19 Overnight PSG requires specialized equipment and personnel in a sleep laboratory, 6,18 and for this reason, the ability to diagnose risk of OSAS in children depends on the availability of and accessibility to such usually scarce clinical resources. Accordingly, alternative diagnostic approaches have been sought aiming to expand the accessibility and identify and treat children with OSAS in a timely manner.…”

Section: Discussionmentioning

confidence: 99%

“…Th e true prevalence of OSAS in children is unclear, but is estimated to range between 0.2% and 4.1%. 1 Numerous studies have shown that OSAS in children is associated with signifi cant morbidity, [2][3][4][5][6][7][8][9][10][11] and, therefore, it is critical to recognize and diagnose this condition in a timely manner to reduce the magnitude of OSAS-induced adverse consequences and the attendant increases in direct and indirect health-care costs. 12 Overnight polysomnography (PSG) remains the gold standard for the diagnosis of OSAS.…”

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confidence: 99%

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Reliability of Home Respiratory Polygraphy for the Diagnosis of Sleep Apnea in Children

Alonso-Álvarez

Terán-Santos

Carbajo

et al. 2015

Chest

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135

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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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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Reliability of Home Respiratory Polygraphy for the Diagnosis of Sleep Apnea in Children

Alonso-Álvarez

Terán-Santos

Carbajo

et al. 2015

Chest

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135

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“…18 Recent evidence indicates that exosomes derived from specific endothelial progenitor cell lineages can protect the endothelium against acute hypoxia-reoxygenation injury, 19 a finding that may account for the heterogeneity of vascular dysfunction in children with OSA. 20 Exosomes can carry signaling molecules to activate local target cells in tissues, including cardiomyocytes, endothelial cells, fibroblasts, and stem cells, as well as distant organs, e.g., bone marrow. 21 Exosomes have recently emerged as novel elements of intercellular communication in the cardiovascular system.…”

Section: Introductionmentioning

confidence: 99%

Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults

Khalyfa

Zhang

Khalyfa

et al. 2016

Sleep

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Study Objective: Intermittent hypoxia (IH) is associated with increased risk of cardiovascular disease. Exosomes are secreted by most cell types and released in biological fluids, including plasma, and play a role in modifying the functional phenotype of target cells. Using an experimental human model of IH, we investigated potential exosome-derived biomarkers of IH-induced vascular dysfunction. Methods: Ten male volunteers were exposed to room air (D0), IH (6 h/day) for 4 days (D4) and allowed to recover for 4 days (D8). Circulating plasma exosomes were isolated and incubated with human endothelial monolayer cultures for impedance measurements and RNA extracted and processed with messenger RNA (mRNA) arrays to identify gene targets. In addition, immunofluorescent assessments of endothelial nitric oxide synthase (eNOS) mRNA expression, ICAM-1 cellular distribution were conducted. Results: Plasma exosomal micro RNAs (miRNAs) were profiled. D4 exosomes, primarily from endothelial sources, disrupted impedance levels compared to D0 and D8. ICAM-1 expression was markedly upregulated in endothelial cells exposed to D4 exosomes along with significant reductions in eNOS expression. Microarray approaches identified a restricted and further validated signature of exosomal miRNAs in D4 exosomes, and mRNA arrays revealed putative endothelial gene target pathways. Conclusions:In humans, intermittent hypoxia alters exosome cargo in the circulation which promotes increased permeability and dysfunction of endothelial cells in vitro. A select number of circulating exosomal miRNAs may play important roles in the cardiovascular dysfunction associated with OSA by targeting specific effector pathways.

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“…Crucially, if left untreated, it can lead to adverse neurocognitive/behavioral, cardiovascular, and metabolic consequences. [1][2][3][4][5] It is, therefore, of utmost importance that accurate diagnosis is made in a timely manner so that appropriate treatment can be initiated and potential resultant morbidities minimized.…”

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confidence: 99%

Pediatric Home Sleep Apnea Testing

Tan

Kheirandish‐Gozal

Gozal

2015

Chest

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105

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Endothelial Progenitor Cells and Vascular Dysfunction in Children with Obstructive Sleep Apnea

Abstract: Endothelial dysfunction is frequently present in OSAS. Variance in endothelial functional phenotype may not only reside in the individual susceptibility but also in the ability to recruit endothelial repair mechanisms.

Cited by 101 publications

References 46 publications

Reliability of Home Respiratory Polygraphy for the Diagnosis of Sleep Apnea in Children

Reliability of Home Respiratory Polygraphy for the Diagnosis of Sleep Apnea in Children

Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults

Pediatric Home Sleep Apnea Testing

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