Rapid “Breath-Print” of Liver Cirrhosis by Proton Transfer Reaction Time-of-Flight Mass Spectrometry. A Pilot Study

• Published in: PloS one Vol. 8; no. 4; p. e59658
• Main Authors: Morisco, Filomena, Aprea, Eugenio, Lembo, Vincenzo, Fogliano, Vincenzo, Vitaglione, Paola, Mazzone, Giovanna, Cappellin, Luca, Gasperi, Flavia, Masone, Stefania, De Palma, Giovanni Domenico, Marmo, Riccardo, Caporaso, Nicola, Biasioli, Franco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.04.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Agriculture; Alcohol; Alcohols; Alkadienes - metabolism; Biology; Biomarkers - metabolism; Breath Tests - methods; Cancer; Case-Control Studies; Chemistry; Cirrhosis; Clinical medicine; Development and progression; Diabetes; Diagnosis; Diagnostic systems; Etiology; Evidence-based medicine; Exhalation; Female; Food; Food quality; Humans; Insulin resistance; Ketones; Ketones - metabolism; Liver; Liver cirrhosis; Liver Cirrhosis - diagnosis; Liver Cirrhosis - metabolism; Liver diseases; Male; Mass spectrometry; Mass Spectrometry - methods; Mass spectroscopy; Medicine; Metabolism; Middle Aged; Monoterpenes - metabolism; Nitrogen compounds; Nutrition; Organic chemicals; Organic compounds; Patients; Pentanone; Pilot Projects; Reaction time; ROC Curve; Scientific imaging; Spectroscopy; Sulfur; Surgery; Terpenes; Time-of-flight mass spectrometry; VOCs; Volatile organic compounds; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059658

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. 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.