title: Metabolomic Evaluation of Neutrophilic Airway Inflammation in Cystic Fibrosis.
abstract: BACKGROUND
  Metabolomic evaluation of cystic fibrosis (CF) airway secretions could identify metabolites and metabolic pathways involved in neutrophilic airway inflammation that could serve as biomarkers and therapeutic targets.
  
  
  METHODS
  Mass spectrometry (MS)-based metabolomics was performed on a discovery set of BAL fluid samples from 25 children with CF, and targeted MS methods were used to identify and quantify metabolites related to neutrophilic inflammation. A biomarker panel of these metabolites was then compared with neutrophil counts and clinical markers in independent validation sets of lavage from children with CF and adults with COPD compared with control subjects.
  
  
  RESULTS
  Of the 7,791 individual peaks detected by positive-mode MS metabolomics discovery profiling, 338 were associated with neutrophilic inflammation. Targeted MS determined that many of these peaks were generated by metabolites from pathways related to the metabolism of purines, polyamines, proteins, and nicotinamide. Analysis of the independent validation sets verified that, in subjects with CF or COPD, several metabolites, particularly those from purine metabolism and protein catabolism pathways, were strongly correlated with neutrophil counts and were related to clinical markers, including airway infection and lung function.
  
  
  CONCLUSIONS
  MS metabolomics identified multiple metabolic pathways associated with neutrophilic airway inflammation. These findings provide insight into disease pathophysiology and can serve as the basis for developing disease biomarkers and therapeutic interventions for airways diseases.
authors.affiliation: Division of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, NC. Electronic address: Charles_Esther@med.unc.edu.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Esther
authors.affiliation: Cystic Fibrosis and Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Coakley
authors.affiliation: Cystic Fibrosis and Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Ashley G
authors.initials: AG
authors.lastname: Henderson
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Fred A
authors.initials: FA
authors.lastname: Wright
authors.affiliation: Cystic Fibrosis and Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Boucher
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012907:Smoking / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers