title: Evaluation of circulating markers of hepatic apoptosis and inflammation in obese children with and without obstructive sleep apnea.
abstract: OBJECTIVE
  Hepatocyte apoptosis and macrophage activation contribute to the disease progression of nonalcoholic fatty liver disease (NAFLD). Obstructive sleep apnea (OSA) in obese children is associated with the severity of NAFLD. The aim of this study was to evaluate plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), cytokeratin 18 (CK18) (markers of apoptosis), and soluble CD163 (sCD163) (marker of macrophage activation) in obese children with and without OSA.
  
  
  METHODS
  Consecutive obese children who were evaluated for OSA were recruited. The diagnosis of OSA was made using overnight polysomnography (PSG). Fasting blood samples were used to determine plasma CK18, sFas, sFasL, and sCD163 levels using specific sandwich enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Fifty-eight subjects were included in the analysis with a mean age of 8.9 ± 3.2 years and a mean body mass index (BMI) z-score of 2.4 ± 0.49. Circulating sFas and sFasL levels were significantly lower in subjects with mild and severe OSA compared with those without OSA (p < 0.005 for both). In addition, sCD163 levels increased with an increasing severity of OSA (no OSA = 1.6 ± 0.25 mg/L, mild OSA = 2.3 ± 0.45, and severe OSA = 3.0 ± 0.52; p < 0.001), and they correlated with the apnea-hypopnea index (AHI) [rho (95% confidence interval, CI) of 0.71 (0.41, 1.00), p-value <0.001]. In six patients with severe OSA from whom samples were taken before and after tonsillectomy, the sCD163 level decreased significantly after treatment, and there was a trend toward an increase in sFasL.
  
  
  CONCLUSIONS
  Markers of apoptosis and macrophage activation are altered in obese children with OSA, indicating increased apoptotic and inflammatory pressures.
authors: Department of Pediatric Gastroenterology, Cleveland Clinic, Cleveland, OH 44195, USA; Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: alkhoun@ccf.org.
authors: Naim
authors: N
authors: Alkhouri
authors: Section of Sleep Medicine, Department of Pediatric, Comer Children's Hospital, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, 5721 S. Maryland Avenue, Chicago, IL 60637, USA.
authors: Leila
authors: L
authors: Kheirandish-Gozal
authors: Department of Pediatric Gastroenterology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Ammar
authors: A
authors: Matloob
authors: Sleep Unit, CIBER of Respiratory Diseases, Instituto Carlos III. CIBERES, Hospital Universitario de Burgos (HUBU), Burgos, Spain.
authors: María Luz
authors: ML
authors: Alonso-Álvarez
authors: Section of Sleep Medicine, Department of Pediatric, Comer Children's Hospital, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, 5721 S. Maryland Avenue, Chicago, IL 60637, USA.
authors: Abdelnaby
authors: A
authors: Khalyfa
authors: Sleep Unit, CIBER of Respiratory Diseases, Instituto Carlos III. CIBERES, Hospital Universitario de Burgos (HUBU), Burgos, Spain.
authors: Joaquin
authors: J
authors: Terán-Santos
authors: Department of Pediatric Gastroenterology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Vera
authors: V
authors: Okwu
authors: Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Rocio
authors: R
authors: Lopez
authors: Section of Sleep Medicine, Department of Pediatric, Comer Children's Hospital, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, 5721 S. Maryland Avenue, Chicago, IL 60637, USA.
authors: Alex
authors: A
authors: Gileles-Hillel
authors: Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Pulmonary, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Raed
authors: R
authors: Dweik
authors: Section of Sleep Medicine, Department of Pediatric, Comer Children's Hospital, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, 5721 S. Maryland Avenue, Chicago, IL 60637, USA.
authors: David
authors: D
authors: Gozal
mesh_terms: D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D053538:Keratin-18 / Q000097:blood; D007728:Kupffer Cells / Q000473:pathology; D008262:Macrophage Activation / Q000502:physiology; D008297:Male; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000097:blood; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000150:complications / Q000473:pathology*; D019014:fas Receptor / Q000097:blood; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C488421:KRT18 protein, human; D053538:Keratin-18; D011956:Receptors, Cell Surface; D019014:fas Receptor
keywords: Apoptosis; Inflammation; Nonalcoholic fatty liver disease; Obstructive sleep apnea