title: Rapid "breath-print" of liver cirrhosis by proton transfer reaction time-of-flight mass spectrometry. A pilot study.
abstract: The aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42-80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35-77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3- pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2-butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance.
  
  
  CONCLUSIONS
  Breath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time.
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. filomena.morisco@unina.it
authors.forename: Filomena
authors.initials: F
authors.lastname: Morisco
authors.forename: Eugenio
authors.initials: E
authors.lastname: Aprea
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lembo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fogliano
authors.forename: Paola
authors.initials: P
authors.lastname: Vitaglione
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mazzone
authors.forename: Luca
authors.initials: L
authors.lastname: Cappellin
authors.forename: Flavia
authors.initials: F
authors.lastname: Gasperi
authors.forename: Stefania
authors.initials: S
authors.lastname: Masone
authors.forename: Giovanni Domenico
authors.initials: GD
authors.lastname: De Palma
authors.forename: Riccardo
authors.initials: R
authors.lastname: Marmo
authors.forename: Nicola
authors.initials: N
authors.lastname: Caporaso
authors.forename: Franco
authors.initials: F
authors.lastname: Biasioli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000466:Alkadienes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests / Q000379:methods; D016022:Case-Control Studies; D045853:Exhalation; D005260:Female; D006801:Humans; D007659:Ketones / Q000378:metabolism; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D039821:Monoterpenes / Q000378:metabolism; D010865:Pilot Projects; D012372:ROC Curve
chemical_list: D000466:Alkadienes; D015415:Biomarkers; D007659:Ketones; D039821:Monoterpenes