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Previous Volume 357:2016-2027 November 15, 2007 Number 20 Next

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ABSTRACT

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.

Source Information

From the Yale University School of Medicine, New Haven, CT (G.L.C., C.G.L., Y.M.S., C.T.H., S.H., J.D.D., M.C., J.A.E.); the University of Wisconsin School of Medicine, Madison (N.J.); MedImmune, Gaithersburg, MD (J.R., A.J.C., P.K.); and INSERM Unité 700, Université Paris 7 (M.G., M.A., M.P.), and Centre Hospitalier Universitaire Bichat Claude Bernard (M.-C.D., M.A.) — both in Paris.

Drs. Pretolani and Elias contributed equally to this article.

Address reprint requests to Dr. Chupp or Dr. Elias at the Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, P.O. Box 208057, 300 Cedar St., TAC 441, New Haven, CT 06520, or at geoffrey.chupp{at}yale.edu or jack.elias{at}yale.edu.

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Related Letters:

Chitinase-like Protein and Asthma
Kuepper M., Bratke K., Virchow J. C., Chupp G., Elias J. A.
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N Engl J Med 2008; 358:1073-1075, Mar 6, 2008. Correspondence

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