title: Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.
abstract: Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear.
  
  
  
  The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF.
  
  
  
  Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed.
  
  
  
  Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF.
  
  
  
  Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease.
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hector
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Sanjay H
authors.initials: SH
authors.lastname: Chotirmall
authors.affiliation: Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Lavelle
authors.affiliation: Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Bojana
authors.initials: B
authors.lastname: Mirković
authors.affiliation: Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Horan
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Eichler
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Mezger
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Anurag
authors.initials: A
authors.lastname: Singh
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Anjai
authors.initials: A
authors.lastname: Ralhan
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Sina
authors.initials: S
authors.lastname: Berenbrinker
authors.affiliation: Department of Paediatrics, University of Basel, Basel, Switzerland.
authors.forename: Ines
authors.initials: I
authors.lastname: Mack
authors.affiliation: Experimental Pediatrics, Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, and the Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Ensenauer
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Riethmüller
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Graepler-Mainka
authors.affiliation: Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Murray
authors.affiliation: Dr von Hauner Children's Hospital, Ludwig-Maximilians-Universität, Munich, and Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.affiliation: Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: N Gerry
authors.initials: NG
authors.lastname: McElvaney
authors.affiliation: CF Center, Children's Hospital, University of Tübingen, Tübingen, Germany. Electronic address: dominik.hartl@med.uni-tuebingen.de.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000150:complications; D002176:Candida albicans / Q000302:isolation & purification / Q000378:metabolism; D002177:Candidiasis / Q000150:complications* / Q000201:enzymology; D002688:Chitinases / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D002688:Chitinases
keywords: Candida species; Cystic fibrosis; chitinases; chitotriosidase; fungi; lung disease; neutrophils; proteases