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A chitinase-like protein in the lung and circulation of patients with severe asthma.

Authors: Chupp, GL  Lee, CG  Jarjour, N  Shim, YM  Holm, CT  He, S  Dziura, JD  Reed, J  Coyle, AJ  Kiener, P  Cullen, M  Grandsaigne, M  Dombret, MC  Aubier, M  Pretolani, M  Elias, JA 
Citation: Chupp GL, etal., N Engl J Med. 2007 Nov 15;357(20):2016-27.
Pubmed: (View Article at PubMed) PMID:18003958
DOI: Full-text: DOI:10.1056/NEJMoa073600

BACKGROUND: The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3-like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated. METHODS: We quantified serum YKL-40 levels in three cohorts of patients with asthma--one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin--as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated. RESULTS: Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001) and with airway remodeling (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels. CONCLUSIONS: YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.

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CRRD Object Information
CRRD ID: 4892632
Created: 2011-02-28
Species: All species
Last Modified: 2011-02-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.