title: Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels.
  
  
  OBJECTIVE
  To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically relevant factors that may affect chitinase levels, including genetic variability, corticosteroid treatment, disease exacerbations, and allergen exposure.
  
  
  METHODS
  Serum chitotriosidase (CHIT1) activity and YKL-40 (CHI3L1) levels, as well as the CHIT1 rs3831317 and CHI3L1 rs4950928 genotypes, were examined in subsets of patients with mild to moderate asthma (n = 76), severe asthma (n = 93), and COPD (n = 64) taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study. Blood was obtained at baseline, before and after a 2-week oral steroid intervention, up to six times during a 1-year period, and during exacerbations. Baseline chitinase levels were also measured in 72 healthy control subjects. The effect of allergen inhalation on blood and sputum YKL-40 levels was measured in two separate groups of patients with mild atopic asthma; one group underwent repeated low-dose allergen challenge (n = 15), and the other underwent high-dose allergen challenge (n = 16).
  
  
  RESULTS
  Serum chitotriosidase and YKL-40 were significantly elevated in patients with asthma and those with COPD compared with healthy control subjects. Genotype and age strongly affected both YKL-40 and chitotriosidase activity, but associations with disease remained following adjustment for these factors. Correlations were observed with lung function but not with other biomarkers, including exhaled nitric oxide, blood eosinophils, periostin, and IgE. Generally, acute exacerbations, allergen-induced airway obstruction, and corticosteroid treatment did not affect circulating chitinase levels.
  
  
  CONCLUSIONS
  YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes.
authors.affiliation: 1 Institute of Environmental Medicine.|2 Center for Allergy Research.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: James
authors.affiliation: 2 Center for Allergy Research.|3 Center for Innovative Medicine, and.|4 Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lovisa E
authors.initials: LE
authors.lastname: Reinius
authors.affiliation: 5 Department of Biochemistry, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
authors.forename: Marri
authors.initials: M
authors.lastname: Verhoek
authors.affiliation: 1 Institute of Environmental Medicine.|2 Center for Allergy Research.
authors.forename: Anna
authors.initials: A
authors.lastname: Gomes
authors.affiliation: 1 Institute of Environmental Medicine.|2 Center for Allergy Research.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kupczyk
authors.affiliation: 1 Institute of Environmental Medicine.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hammar
authors.affiliation: 6 Shino-Test Corporation, Sagamihara, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ono
authors.affiliation: 7 Department of Laboratory Medicine and.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ohta
authors.affiliation: 8 Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga University, Saga, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.affiliation: 9 Department of Pulmonology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bel
authors.affiliation: 2 Center for Allergy Research.|3 Center for Innovative Medicine, and.|4 Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.affiliation: 2 Center for Allergy Research.|3 Center for Innovative Medicine, and.|4 Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cilla
authors.initials: C
authors.lastname: Söderhäll
authors.affiliation: 2 Center for Allergy Research.|10 Department of Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.affiliation: 5 Department of Biochemistry, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Boot
authors.affiliation: 1 Institute of Environmental Medicine.|2 Center for Allergy Research.
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
mesh_terms: D054392:Adipokines / Q000097:blood* / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D000071451:Chitinase-3-Like Protein 1; D018450:Disease Progression; D005060:Europe; D005260:Female; D006596:Hexosaminidases / Q000097:blood* / Q000235:genetics / Q000276:immunology; D006801:Humans; D037102:Lectins / Q000097:blood* / Q000235:genetics / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D012044:Regression Analysis; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects / Q000097:blood; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D013256:Steroids; D006596:Hexosaminidases; C086400:chitotriosidase
keywords: YKL-40; asthma; chitotriosidase; chronic obstructive pulmonary disease