Astrid Lindgren Children's Hospital, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
J Allergy Clin Immunol. 2013 Aug;132(2):328-35.e5. doi: 10.1016/j.jaci.2013.03.003. Epub 2013 Apr 26.
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.
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.
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).
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.
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.
儿童重症哮喘包括一组对治疗有抵抗的患者亚群。具体的发病机制尚不清楚，需要新的生物标志物来促进治疗和诊断抵抗性哮喘。几丁质酶样蛋白 YKL-40 与哮喘和气道重塑有关。
比较重度、治疗抵抗性哮喘患儿（n=34）、控制持续哮喘患儿（n=39）和健康对照组（n=27）的血清 YKL-40 水平，并探讨其与炎症和气道重塑生物标志物的相关性。
研究方案包括问卷调查、呼出气一氧化氮测定、血液炎症标志物检测、肺部高分辨率 CT 以识别支气管壁增厚（仅治疗抵抗）。采用 ELISA 法检测血清 YKL-40 水平，所有哮喘患儿均进行 CHI3L1 启动子单核苷酸多态性（rs4950928）的基因分型。
与健康儿童相比，治疗抵抗性哮喘患儿的血清 YKL-40 水平显著升高（19.2ng/ml 比 13.8ng/ml，P=0.03）。在重度、治疗抵抗性哮喘患儿中，YKL-40 水平与呼出气一氧化氮分数（r=0.48，P=0.004）、血中性粒细胞（r=0.63，P＜0.001）和高分辨率 CT 上的支气管壁增厚（r=0.45，P=0.01）相关。校正 CHI3L1 基因型后，治疗抵抗性哮喘患儿的 YKL-40 水平显著高于控制组哮喘患儿。
与健康儿童相比，重度、治疗抵抗性哮喘患儿的血清 YKL-40 水平升高，且校正基因型后，YKL-40 水平也高于控制组哮喘患儿。
