title: Elevated peptides in lung lavage fluid associated with bronchiolitis obliterans syndrome.
abstract: OBJECTIVE
  The objective of this discovery-level investigation was to use mass spectrometry to identify low mass compounds in bronchoalveolar lavage fluid from lung transplant recipients that associate with bronchiolitis obliterans syndrome.
  
  
  METHODS
  Bronchoalveolar lavage fluid samples from lung transplant recipients were evaluated for small molecules using ESI-TOF mass spectrometry and correlated to the development of bronchiolitis obliterans syndrome. Peptides associated with samples from persons with bronchiolitis obliterans syndrome and controls were identified separately by MS/MS analysis.
  
  
  RESULTS
  The average bronchoalveolar lavage fluid MS spectrum profile of individuals that developed bronchiolitis obliterans syndrome differed greatly compared to controls. Controls demonstrated close inter-sample correlation (R = 0.97+/-0.02, average+/-SD) while bronchiolitis obliterans syndrome showed greater heterogeneity (R = 0.86+/-0.09, average+/-SD). We identified 89 features that were predictive of developing BOS grade 1 and 66 features predictive of developing BOS grade 2 or higher. Fractions from MS analysis were pooled and evaluated for peptide content. Nearly 10-fold more peptides were found in bronchiolitis obliterans syndrome relative to controls. C-terminal residues suggested trypsin-like specificity among controls compared to elastase-type enzymes among those with bronchiolitis obliterans syndrome.
  
  
  CONCLUSIONS
  Bronchoalveolar lavage fluid from individuals with bronchiolitis obliterans syndrome has an increase in low mass components detected by mass spectrometry. Many of these features were peptides that likely result from elevated neutrophil elastase activity.
authors.affiliation: Waters Corporation, Milford, Massachusetts, United States of America ; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Stone
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Harvey
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Nelsestuen
authors.affiliation: Department of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Cavan
authors.initials: C
authors.lastname: Reilly
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Marshall I
authors.initials: MI
authors.lastname: Hertz
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America ; Department of Medicine, Veterans Administration Medical Center, University of Minnesota, Minneapolis, Minnesota, United States.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Wendt
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000737:chemistry; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry*; D013577:Syndrome; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D010455:Peptides