title: The chitinase-like protein YKL-40: a possible biomarker of inflammation and airway remodeling in severe pediatric asthma.
abstract: BACKGROUND
  Problematic severe childhood asthma includes a subgroup of patients who are resistant to therapy. The specific mechanisms involved are unknown, and novel biomarkers are required to facilitate treatment and diagnosis of therapy-resistant asthma. The chitinase-like protein YKL-40 has been related to asthma and airway remodeling.
  
  
  OBJECTIVE
  To compare serum YKL-40 levels in children with severe, therapy-resistant asthma (n = 34), children with controlled persistent asthma (n = 39), and healthy controls (n = 27), and to investigate correlations with biomarkers of inflammation and airway remodeling.
  
  
  METHODS
  The study protocol included questionnaires, measurement of exhaled nitric oxide in exhaled air, blood sampling for inflammatory biomarkers, and high-resolution computed tomography of the lungs to identify bronchial wall thickening (therapy-resistant only). Serum YKL-40 levels were measured by ELISA, and all asthmatic children were genotyped for a CHI3L1 promoter single nucleotide polymorphism (rs4950928).
  
  
  RESULTS
  Serum YKL-40 levels were significantly higher in children with therapy-resistant asthma than in healthy children (19.2 ng/mL vs 13.8 ng/mL, P = .03). Among children with severe, therapy-resistant asthma, YKL-40 levels correlated with fraction of exhaled nitric oxide in exhaled air (r = 0.48, P = .004), blood neutrophils (r = 0.63, P < .001), and bronchial wall thickening on high-resolution computed tomography (r = 0.45, P = .01). Following adjustment for CHI3L1 genotype, significantly greater levels of YKL-40 were found in children with therapy-resistant asthma than in children with controlled asthma.
  
  
  CONCLUSIONS
  YKL-40 levels are increased in children with severe, therapy-resistant asthma compared to healthy children, and also compared to children with controlled asthma following correction for genotype.
authors.affiliation: Astrid Lindgren Children's Hospital, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. jon.konradsen@karolinska.se
authors.forename: Jon R
authors.initials: JR
authors.lastname: Konradsen
authors.forename: Anna
authors.initials: A
authors.lastname: James
authors.forename: Björn
authors.initials: B
authors.lastname: Nordlund
authors.forename: Lovisa E
authors.initials: LE
authors.lastname: Reinius
authors.forename: Cilla
authors.initials: C
authors.lastname: Söderhäll
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.forename: Asa M
authors.initials: AM
authors.lastname: Wheelock
authors.forename: Asa
authors.initials: A
authors.lastname: Wheelock
authors.forename: Karin C
authors.initials: KC
authors.lastname: Lödrup Carlsen
authors.forename: Marika
authors.initials: M
authors.lastname: Lidegran
authors.forename: Marri
authors.initials: M
authors.lastname: Verhoek
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Boot
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.forename: Sven Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Gunilla
authors.initials: G
authors.lastname: Hedlin
mesh_terms: D054392:Adipokines / Q000097:blood* / Q000235:genetics; D000293:Adolescent; D056151:Airway Remodeling / Q000502:physiology*; D001249:Asthma / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D000071451:Chitinase-3-Like Protein 1; D003430:Cross-Sectional Studies; D045853:Exhalation; D005260:Female; D006133:Growth Substances / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D037102:Lectins / Q000097:blood* / Q000235:genetics; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006133:Growth Substances; D037102:Lectins; D009569:Nitric Oxide
keywords: Asthma; Feno; Fraction of exhaled nitric oxide in exhaled air; HRCT; High-resolution computerized tomography; airway remodeling; children; chitinases; genes; imaging; inflammation