Metabolomic Profiling of Exhaled Breath Condensate in Patients with Stable and Unstable Cystic Fibrosis

نویسندگان

  • Paolo Montuschi
  • Debora Paris
  • Dominique Melck
  • Vincenzina Lucidi
  • Giovanni Ciabattoni
  • Valeria Raia
  • Cecilia Calabrese
  • Andrew Bush
  • Peter J. Barnes
  • Andrea Motta
چکیده

Background Metabolomics could provide new insights into the pathophysiology of cystic fibrosis (CF) by identifying profiles of endogenous metabolites. Objectives We investigated whether metabolomics of exhaled breath condensate (EBC) could discriminate between patients with unstable CF, stable CF, and healthy subjects, and whether selected metabolites were responsible for between-group differences. Methods Twenty-nine stable CF patients, 24 unstable CF patients, and 31 healthy subjects (age 9-24 years) were studied. Study design was cross-sectional. Metabolomics was performed with high resolution Nuclear Magnetic Resonance (NMR) spectroscopy. Partial least squaresdiscriminant analysis was used as classifier. Results were validated in a second independent study. Results Intraclass correlation coefficients for between-day and technical repeatability were 0.93 and 0.96, respectively. Bland-Altman analysis showed good within-day repeatability. Correct classification rate of CF (n=53) vs healthy subjects (n=31) was 96% (R=0.84; Q=0.79). Model validation with a testing sample set obtained form subjects not included in the primary analysis (CF=23; healthy subjects=25) showed a sensitivity of 91% and a specificity of 96%. Classification rate of stable CF (n=29) vs unstable CF patients (n=24) was 95% (R=0.82; Q=0.78). Model external validation (stable CF=14; unstable CF=16) showed a sensitivity of 86% and a specificity of 94%. Ethanol, acetate, 2-propanol, and acetone are most discriminant between CF patients and healthy subjects, whereas acetate, ethanol, 2-propanol, and methanol

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تاریخ انتشار 2011