Highlights
- •We examined the effect of adenotonsillectomy (AT) on flow-mediated dilation (FMD) in children with sleep disorder breathing (SDB).
- •The paper demonstrates that NOX2-derived oxidative stress is implicated in artery dysfunction in SDB children.
- •AT may be a tool to ameliorate endothelial function and NADPH-derived oxidative stress in children with obstructive sleep apnea.
Abstract
Objective
Oxidative stress plays a crucial role in impairing endothelial function in sleep disordered
breathing (SDB) but the underlying mechanism is still undefined. The objective of
this study was to evaluate the interplay between oxidative stress, assessed by serum
isoprostanes (8-iso-PGF2α) and soluble NOX2-dp (sNOX2-dp), and endothelial function,
assessed by flow-mediated dilation (FMD), in children with SDB and healthy controls
(HC).
Methods
One-hundred forty-four children including 45 with primary snoring (PS), 22 with obstructive
sleep apnea (OSA) and 67 HC were recruited in this study; in 15 out of 22 OSA children
FMD, serum 8-iso-PGF2α and sNOX2-dp were assessed before and after one month post
adeno-tonsillectomy (AT).
Results
Compared with HC, OSA and PS children had significantly higher sNOX2-dp and serum
8-iso-PGF2α levels and lower FMD; compared with PS, FMD was significantly lower in
OSA children. No significant difference for sNOX2-dp and serum 8-iso-PGF2α was observed
between OSA and PS children. FMD was inversely correlated with sNOX2-dp levels (p < 0.001)
and with serum 8-iso-PGF2α (p < 0.001). In multiple linear regression analysis, sNOX2-dp
(p < 0.001) and serum 8-iso-PGF2α (p < 0.001) were the only independent predictive
variables associated with FMD.
AT significantly decreased sNOX2-dp and serum 8-iso-PGF2α levels (from 38.2 ± 8.8
to 22.4 ± 11.1 pg/ml, p < 0.001, and from 281.4 ± 69.7 to 226.0 ± 66.4 pg/ml, p < 0.001,
respectively); conversely, FMD significantly increased after AT in OSA children (from
3.0 ± 1.5 to 8.0 ± 2.8%, p < 0.001).
Conclusion
This study suggests that NOX2-derived oxidative stress is involved in artery dysfunction
in SDB children. Such hypothesis is reinforced by FMD improvement after AT coincidentally
with oxidative stress lowering.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02247167.
Keywords
Abbreviations:
SDB (sleep disordered breathing), PS (primary snoring), OSA (obstructive sleep apnea), NADPH oxidase (nicotinamide-adenine dinucleotide phosphate oxidase), AT (adenotonsillectomy), IMT (intima media thickness)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Assessment of atherosclerosis: the role of flow-mediated dilatation.Eur. Heart J. 2010; 31: 2854-2861
- Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force.J. Am. Coll. Cardiol. 2002; 39: 257-265
- Obstructive sleep breathing disorders.Pediatr. Clin. North Am. 2009; 56 (xii): 243-259
- Diagnosis and management of childhood obstructive sleep apnea syndrome.Pediatrics. 2012; 130: e714-755
- Reduced flow-mediated vasodilation of brachial artery in children with primary snoring.Int. J. Cardiol. 2013; 167: 2092-2096
- Topical review: sleep bruxism, headaches, and sleep-disordered breathing in children and adolescents.J. Orofac. Pain. 2012; 26: 267-276
- BP and arterial distensibility in children with primary snoring.Chest. 2003; 123: 1561-1566
- Autonomic alterations and endothelial dysfunction in pediatric obstructive sleep apnea.Sleep. Med. 2010; 11: 714-720
- Does treatment of SDB in children improve cardiovascular outcome?.Sleep. Med. Rev. 2013; 17: 75-85
- Atherosclerosis–an inflammatory disease.N. Engl. J. Med. 1999; 340: 115-126
- Nitric oxide and its role in lipid peroxidation.Diabetes Metab. Res. Rev. 1999; 15: 283-288
- Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study.Circulation. 2009; 120: 1616-1622
- Does NADPH oxidase deficiency cause artery dilatation in humans?.Antioxid. Redox Signal. 2013; 18: 1491-1496
- NADPH oxidases in cardiovascular health and disease.Antioxid. Redox Signal. 2006; 8: 691-728
- The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology.Physiol. Rev. 2007; 87: 245-313
- Oxidant stress and inflammation in the snoring child: confluent pathways to upper airway pathogenesis and end-organ morbidity.Sleep. Med. Rev. 2006; 10: 83-96
- Urinary concentration of 8-isoprostane as marker of severity of pediatric OSAS.Sleep. Breath. 2014; 18: 23-29
- Neurocognitive and endothelial dysfunction in children with obstructive sleep apnea.Pediatrics. 2010; 126: e1161-e1167
- Urinary F2-isoprostane metabolite levels in children with sleep-disordered breathing.Sleep. Breath. 2006; 10: 211-215
- National UK survey on the assessment and surgical management of suspected paediatric obstructive sleep apnoea syndrome.Int. J. Pediatr. Otorhinolaryngology. 2013; 77: 1689-1696
- An update on childhood snoring.Acta Paediatr. 2006; 95: 1029-1035
- A randomized trial of adenotonsillectomy for childhood sleep apnea.N. Engl. J. Med. 2013; 368: 2366-2376
- A diagnostic approach to suspected obstructive sleep apnea in children.J. Pediatr. 1984; 105: 10-14
- Inability of clinical history to distinguish primary snoring from obstructive sleep apnea syndrome in children.Chest. 1995; 108: 610-618
- Adenoid tissue rhinopharyngeal obstruction grading based on fiberendoscopic findings: a novel approach to therapeutic management.Int. J. Pediatr. Otorhinolaryngol. 2003; 67: 1303-1309
- A comparison of tonsillar size and oropharyngeal dimensions in children with obstructive adenotonsillar hypertrophy.Int. J. Pediatr. Otorhinolaryngol. 1987; 13: 149-156
- Serum resistin levels in children with primary snoring.Int. J. Immunopathol. Pharmacol. 2014; 27: 449-454
- Cephalometric pattern and nasal patency in children with primary snoring: the evidence of a direct correlation.PLoS One. 2014; 9: e111675
- Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force.J. Am. Coll. Cardiol. 2002; 39: 257-265
- Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease.Eur. Heart J. 2007; 28: 608-612
- Impaired flow mediated dilatation as evidence of endothelial dysfunction in chronic atrial fibrillation: relationship to plasma von Willebrand factor and soluble E-selectin levels.Thrombosis Res. 2008; 122: 85-90
- Atorvastatin inhibits gp91phox circulating levels in patients with hypercholesterolemia.Arterioscler. Thromb. Vasc. Biol. 2010; 30: 360-367
- A reliable and sensitive enzyme immunoassay method for measuring 8-isoprostaglandin F2 alpha: a marker for lipid peroxidation after experimental brain injury.J. Neurosci. Methods. 1996; 68: 133-136
- Obesity and hypercholesterolemia are associated with NOX2 generated oxidative stress and arterial dysfunction.J. Pediatr. 2012; 161: 1004-1009
- Oxidative stress is associated with arterial dysfunction and enhanced intima-media thickness in children with hypercholesterolemia: the potential role of nicotinamide-adenine dinucleotide phosphate oxidase.Pediatrics. 2008; 122: e648-655
- The conundrum of primary snoring in children: what are we missing in regards to cognitive and behavioural morbidity?.Sleep. Med. Rev. 2014; 18: 463-475
- Oxidative stress in the airways of children with asthma and allergic rhinitis.Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol. 2012; 23: 556-561
- Cysteinyl leukotriene levels correlate with 8-isoprostane levels in exhaled breath condensates of atopic and healthy children.Pediatr. Res. 2013; 74: 584-591
- Oxidative stress mediated arterial dysfunction in patients with obstructive sleep apnoea and the effect of continuous positive airway pressure treatment.BMC Pulm. Med. 2012; 12: 36
- Obstructive sleep apnea syndrome and cardiovascular diseases.Semin. Thromb. Hemost. 2011; 37: 280-297
- Endothelial function in children with OSA and the effects of adenotonsillectomy.Chest. 2015; 147: 132-139
Article info
Publication history
Published online: March 18, 2015
Accepted:
March 17,
2015
Received in revised form:
March 9,
2015
Received:
January 25,
2015
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
