title: Identification of neutrophil activation markers as novel surrogate markers of CF lung disease.
abstract: OBJECTIVE
  Cystic Fibrosis (CF) lung disease is characterized by progressively declining lung function and represents a major factor contributing to the high morbidity and mortality associated with CF. However, apart from spirometry, respiratory disease surrogate markers reliably indicating CF lung disease and the occurrence of pulmonary exacerbations (PEx) are still lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CF lung disease.
  
  
  METHODS
  54 adult and 26 pediatric CF patients were included in the study and serum concentrations of MMP-1, -2, -8, -9, -13, TIMP-1, TIMP-2, YKL-40, hyaluronic acid, procollagen III peptide were quantified by ELISA. CF lung disease was diagnosed by lung function test, PEx was defined based on a clinical scoring established by Rosenfeld in 2001.
  
  
  RESULTS
  Adults and children with moderate to severe CF lung disease exhibited significantly increased serum expression of MMP-8, MMP-9, YKL-40 and TIMP-1. Further, MMP-8, MMP-9 and YKL-40 were significantly increased in adult CF patients suffering from PEx compared to those without clinical signs of respiratory exacerbation. MMP-8, MMP-9, YKL-40, and TIMP-1 serum levels were unaffected by the presence or absence of CF liver disease or pancreatic insufficiency.
  
  
  CONCLUSIONS
  MMP-8, MMP-9, and YKL-40 might serve as novel non-invasive biomarkers of CF lung disease and PEx.
authors.affiliation: Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany; Friedrich Alexander University Erlangen, Department of Medicine 1, Erlangen, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Rath
authors.affiliation: Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zwaschka
authors.affiliation: Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hage
authors.affiliation: Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Kügler
authors.affiliation: Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Menendez
authors.affiliation: Justus-Liebig-University Giessen, Department of Pediatrics, Division of Pulmonology, Giessen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Naehrlich
authors.affiliation: Justus-Liebig-University Giessen, Department of Pulmonology, Giessen, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
authors.affiliation: Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Roderfeld
authors.affiliation: Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Roeb
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D000071451:Chitinase-3-Like Protein 1; D003550:Cystic Fibrosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000378:metabolism; D055815:Young Adult
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9