title: 1H NMR To Evaluate the Metabolome of Bronchoalveolar Lavage Fluid (BALf) in Bronchiolitis Obliterans Syndrome (BOS): Toward the Development of a New Approach for Biomarker Identification.
abstract: This report describes the application of NMR spectroscopy to the profiling of metabolites in bronchoalveolar lavage fluid (BALf) of lung transplant recipients without bronchiolitis obliterans syndrome (BOS) (stable, S, n = 10), and with BOS at different degrees of severity (BOS 0p, n = 10; BOS I, n = 10). Through the fine-tuning of a number of parameters concerning both sample preparation/processing and variations of spectra acquisition modes, an efficient and reproducible protocol was designed for the screening of metabolites in a pulmonary fluid that should reflect the status of airway inflammation/injury. Exploiting the combination of mono- and bidimensional NMR experiments, 38 polar metabolites, including amino acids, Krebs cycle intermediates, mono- and disaccharides, nucleotides, and phospholipid precursors, were unequivocally identified. To determine which signature could be correlated with the onset of BOS, the metabolites' content of the above recipients was analyzed by multivariate (PCA and OPLS-DA) statistical methods. PCA analysis (almost) totally differentiated S from BOS I, and this discrimination was significantly improved by the application of OPLS-DA, whose model was characterized by excellent fit and prediction values (R2= 0.99 and Q2= 0.88). The analysis of S vs BOS 0p and of BOS 0p vs BOS I samples showed a clear discrimination of considered cohorts, although with a poorer efficiency compared to those measured for S vs BOS I patients. The data shown in this work assess the suitability of the NMR approach in monitoring different pathological lung conditions.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca , 20126 Milan, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Ciaramelli
authors.forename: Marco
authors.initials: M
authors.lastname: Fumagalli
authors.forename: Simona
authors.initials: S
authors.lastname: Viglio
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Bardoni
authors.affiliation: IRCCS Foundation Policlinico San Matteo , Department of Cardiothoracic and Vascular Department, Pneumology Unit, Pavia 27100, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Piloni
authors.affiliation: IRCCS Foundation Policlinico San Matteo , Department of Cardiothoracic and Vascular Department, Pneumology Unit, Pavia 27100, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Meloni
authors.forename: Paolo
authors.initials: P
authors.lastname: Iadarola
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca , 20126 Milan, Italy.
authors.forename: Cristina
authors.identifier: 0000-0002-3670-6262
authors.initials: C
authors.lastname: Airoldi
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000302:isolation & purification / Q000378:metabolism; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism*; D001989:Bronchiolitis Obliterans / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D004187:Disaccharides / Q000302:isolation & purification / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D016040:Lung Transplantation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome / Q000235:genetics*; D008875:Middle Aged; D010743:Phospholipids / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D004187:Disaccharides; D010743:Phospholipids
keywords: BALf (bronchoalveolar lavage fluid); BOS (bronchiolitis obliterans syndrome); CLAD (chronic lung allograft dysfunction); NMR-based metabolomics