title: Analysis of breath volatile organic compounds as a noninvasive tool to diagnose nonalcoholic fatty liver disease in children.
abstract: OBJECTIVE
  Nonalcoholic fatty liver disease (NAFLD) is one of the most common complications of childhood obesity. Our objective was to investigate the association of breath volatile organic compounds with the diagnosis of NAFLD in children.
  
  
  METHODS
  Patients were screened with an ultrasound of the abdomen to evaluate for NAFLD. Exhaled breath was collected and analyzed per protocol using selective ion flow tube mass spectrometry (SIFT-MS).
  
  
  RESULTS
  Sixty patients were included in the study (37 with NAFLD and 23 with normal liver). All children were overweight or obese. The mean age was 14.1±2.8 years and 50% were female. A comparison of the SIFT-MS results of patients with NAFLD with those with normal liver on ultrasound revealed differences in concentration of more than 15 compounds. A panel of four volatile organic compounds can identify the presence of NAFLD with good accuracy (area under the receiver operating characteristic curve of 0.913 in the training set and 0.763 in the validation set). Breath isoprene, acetone, trimethylamine, acetaldehyde, and pentane were significantly higher in the NAFLD group compared with normal liver group (14.7 ppb vs. 8.9 for isoprene; 71.7 vs. 36.9 for acetone; 5.0 vs. 3.2 for trimethylamine; 35.1 vs. 26.0 for acetaldehyde; and 13.3 vs. 8.8 for pentane, P<0.05 for all).
  
  
  CONCLUSIONS
  Exhaled breath analysis is a promising noninvasive method to detect fatty liver in children. Isoprene, acetone, trimethylamine, acetaldehyde, and pentane are novel biomarkers that may help to gain insight into pathophysiological processes leading to the development of NAFLD.
authors.affiliation: Departments of aPediatric Gastroenterology and Hepatology bQuantitative Health Sciences cDepartment of Gastroenterology and Hepatology, Digestive Disease Institute dDepartment of Pathobiology, Lerner Research Institute eDepartment of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Naim
authors.initials: N
authors.lastname: Alkhouri
authors.forename: Frank
authors.initials: F
authors.lastname: Cikach
authors.forename: Katharine
authors.initials: K
authors.lastname: Eng
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moses
authors.forename: Nishaben
authors.initials: N
authors.lastname: Patel
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Hanouneh
authors.forename: David
authors.initials: D
authors.lastname: Grove
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Raed
authors.initials: R
authors.lastname: Dweik
mesh_terms: D000293:Adolescent; D000367:Age Factors; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests; D002648:Child; D003430:Cross-Sectional Studies; D045853:Exhalation; D005234:Fatty Liver / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications; D011237:Predictive Value of Tests; D012372:ROC Curve; D014463:Ultrasonography; D055549:Volatile Organic Compounds / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D055549:Volatile Organic Compounds