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. OBJECTIVES: 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.
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. OBJECTIVES: 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: Reetika Bhardwaj; Jessie W Yester; Sandeep K Singh; Debolina D Biswas; Michael J Surace; Michael R Waters; Kurt F Hauser; Zhenqiang Yao; Brendan F Boyce; Tomasz Kordula Journal: J Immunol Date: 2015-02-13 Impact factor: 5.422
Authors: Cong-Lin Liu; Holger Wemmelund; Yi Wang; Mengyang Liao; Jes S Lindholt; Søren P Johnsen; Henrik Vestergaard; Cleverson Fernandes; Galina K Sukhova; Xiang Cheng; Jin-Ying Zhang; Chongzhe Yang; Xiaozhu Huang; Alan Daugherty; Bruce D Levy; Peter Libby; Guo-Ping Shi Journal: Arterioscler Thromb Vasc Biol Date: 2016-02-11 Impact factor: 8.311