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This is the first study to evaluate the pathogenic role of the novel chitinase-like protein YKL-40 in asthma. In experimental models, YKL-40 and chitinases promoted airway inflammation through type 2 helper T cells. This study investigated serum YKL-40 levels in asthma, including assessing relationships with disease severity, airway YKL-40 levels and airway remodelling.
Serum YKL-40 levels, measured by immunoassay, were investigated in a prospective case-control study involving three separate cohorts of patients with asthma from Yale, Paris and Wisconsin. Serum YKL-40 levels were significantly raised in patients with asthma compared with controls. They correlated with asthma severity assessed by clinical and lung function variables. This significant relationship persisted after adjusting for age, sex, ethnicity and body mass index. It was predominantly due to high serum YKL-40 levels in the subpopulation with severe asthma. Bronchoscopy, only undertaken in the cohort from Paris, showed a positive relationship between serum and airway YKL-40 levels and subepithelial basement membrane thickness.
These findings suggest that YKL-40 has pathogenic importance in some patients with severe asthma, and represents a potential novel therapeutic target. Further research is needed to confirm this because the present study has some limitations. The patient cohorts were relatively small with different inclusion and exclusion criteria. Patients did not receive standard treatments. As the study was cross-sectional, changes over time were not evaluated. The effects of asthma exacerbations were not examined and bronchoscopic data were restricted to one cohort.
Chupp GL, Lee CG, Jarjour N, et al. A chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J Med 2007;357:2016–27