title: Endothelial dysfunction and oxidative stress in children with sleep disordered breathing: role of NADPH oxidase.
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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT02247167.
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy. Electronic address: lorenzo.loffredo@uniroma1.it.
authors: Lorenzo
authors: L
authors: Loffredo
authors: Department of Pediatrics, Sapienza University of Rome, Italy.
authors: Anna Maria
authors: AM
authors: Zicari
authors: Department of Pediatrics, Sapienza University of Rome, Italy.
authors: Francesca
authors: F
authors: Occasi
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Ludovica
authors: L
authors: Perri
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Roberto
authors: R
authors: Carnevale
authors: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy.
authors: Francesco
authors: F
authors: Angelico
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Maria
authors: M
authors: Del Ben
authors: Department of Pediatrics, Sapienza University of Rome, Italy.
authors: Francesco
authors: F
authors: Martino
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Cristina
authors: C
authors: Nocella
authors: Department of Pediatrics, Sapienza University of Rome, Italy.
authors: Vincenzo
authors: V
authors: Savastano
authors: Department of Pediatrics, Sapienza University of Rome, Italy.
authors: Azzurra
authors: A
authors: Cesoni Marcelli
authors: Department of Pediatrics, Sapienza University of Rome, Italy.
authors: Marzia
authors: M
authors: Duse
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Francesco
authors: F
authors: Violi
mesh_terms: D000233:Adenoidectomy; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000097:blood*; D018384:Oxidative Stress; D012384:Rome; D015398:Signal Transduction; D012891:Sleep Apnea Syndromes / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D013997:Time Factors; D014068:Tonsillectomy; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: Atherosclerosis; Endothelial function; Oxidative stress; Sleep disorder breathing