哮喘与COPD中甲壳质酶蛋白40 (YKL-40) 和壳三糖酶水平升高
2016/07/07
原理：血清几丁质酶或许是气道炎症与气道重塑的新型生物标志物，但是我们对调节其水平的因素了解甚少。
目的：检测哮喘及慢性阻塞性肺疾病（COPD）患者血清壳三糖酶（chitotriosidase）活性及甲壳质酶蛋白-40（YKL-40）水平，并评估可能影响几丁质酶水平的临床相关因素，包括基因多态性、糖皮质激素治疗、急性发作/加重和过敏原暴露。
方法：对参加欧洲多中心BIOAIR（Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease）研究的三组受试者：轻到中度哮喘（n = 76）、重症哮喘（n = 93）及COPD（n = 64）进行血清壳三糖酶（CHIT1）活性、YKL-40（CHI3L1）水平检测及CHIT1 rs3831317、CHI3L1 rs4950928基因型检测。在2周口服激素干预前后、为期1年时间中6次随访和急性发作/加重时均进行血液标本采集。也对72例健康对照受试者进行基线几丁质酶水平检测。在两组不同的轻度过敏性哮喘受试者中，评估过敏原吸入对血清及痰液YKL-40水平的影响。其中一组接受反复低剂量过敏原刺激（n = 15），另一组接受高剂量过敏原刺激（n = 16）。
测量和主要结果：与健康对照组相比，哮喘及COPD 患者血清壳三糖酶和YKL-40明显升高。基因型和年龄对YKL-40水平及壳三糖酶活性均有十分显著的影响，但在校正基因型和年龄后，升高的YKL-40水平及壳三糖酶活性仍与疾病相关。除外呼出气一氧化氮、血嗜酸粒细胞、骨膜蛋白及IgE在内的其他生物指标，几丁质酶水平仅与肺功能有相关性。急性发作/加重、过敏原诱导的气道阻塞和糖皮质激素治疗均不会影响循环几丁质酶水平。
结论：YKL-40和壳三糖酶水平在哮喘患者中是升高的，在COPD患者中升高更为明显。本研究数据支持YKL-40和壳三糖酶作为相对激素不敏感、非Th2型生物标志物，与慢性炎症性疾病进程具有明显相关性。
关键词：哮喘；壳三糖酶；慢性阻塞性肺疾病；YKL-40
Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease
James AJ, Reinius LE, Verhoek M, Gomes A, Kupczyk M, Hammar U, Ono J, Ohta S, Izuhara K, Bel E, Kere J, Söderhäll C, Dahlén B, Boot RG, Dahlén SE; BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease)
Am J Respir Crit Care Med. 2016; 193: 131–142.
Rationale: Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels.
Objectives: To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically relevant factors that may affect chitinase levels, including genetic variability, corticosteroid treatment, disease exacerbations, and allergen exposure.
Methods: Serum chitotriosidase (CHIT1) activity and YKL-40 (CHI3L1) levels, as well as the CHIT1 rs3831317 and CHI3L1 rs4950928 genotypes, were examined in subsets of patients with mild to moderate asthma (n = 76), severe asthma (n = 93), and COPD (n = 64) taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study. Blood was obtained at baseline, before and after a 2-week oral steroid intervention, up to six times during a 1-year period, and during exacerbations. Baseline chitinase levels were also measured in 72 healthy control subjects. The effect of allergen inhalation on blood and sputum YKL-40 levels was measured in two separate groups of patients with mild atopic asthma; one group underwent repeated low-dose allergen challenge (n = 15), and the other underwent high-dose allergen challenge (n = 16).
Measurements and Main Results: Serum chitotriosidase and YKL-40 were significantly elevated in patients with asthma and those with COPD compared with healthy control subjects. Genotype and age strongly affected both YKL-40 and chitotriosidase activity, but associations with disease remained following adjustment for these factors. Correlations were observed with lung function but not with other biomarkers, including exhaled nitric oxide, blood eosinophils, periostin, and IgE. Generally, acute exacerbations, allergen-induced airway obstruction, and corticosteroid treatment did not affect circulating chitinase levels.
Conclusions: YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes.
Keywords: asthma; chitotriosidase; chronic obstructive pulmonary disease; YKL-40
目的：检测哮喘及慢性阻塞性肺疾病（COPD）患者血清壳三糖酶（chitotriosidase）活性及甲壳质酶蛋白-40（YKL-40）水平，并评估可能影响几丁质酶水平的临床相关因素，包括基因多态性、糖皮质激素治疗、急性发作/加重和过敏原暴露。
方法：对参加欧洲多中心BIOAIR（Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease）研究的三组受试者：轻到中度哮喘（n = 76）、重症哮喘（n = 93）及COPD（n = 64）进行血清壳三糖酶（CHIT1）活性、YKL-40（CHI3L1）水平检测及CHIT1 rs3831317、CHI3L1 rs4950928基因型检测。在2周口服激素干预前后、为期1年时间中6次随访和急性发作/加重时均进行血液标本采集。也对72例健康对照受试者进行基线几丁质酶水平检测。在两组不同的轻度过敏性哮喘受试者中，评估过敏原吸入对血清及痰液YKL-40水平的影响。其中一组接受反复低剂量过敏原刺激（n = 15），另一组接受高剂量过敏原刺激（n = 16）。
测量和主要结果：与健康对照组相比，哮喘及COPD 患者血清壳三糖酶和YKL-40明显升高。基因型和年龄对YKL-40水平及壳三糖酶活性均有十分显著的影响，但在校正基因型和年龄后，升高的YKL-40水平及壳三糖酶活性仍与疾病相关。除外呼出气一氧化氮、血嗜酸粒细胞、骨膜蛋白及IgE在内的其他生物指标，几丁质酶水平仅与肺功能有相关性。急性发作/加重、过敏原诱导的气道阻塞和糖皮质激素治疗均不会影响循环几丁质酶水平。
结论：YKL-40和壳三糖酶水平在哮喘患者中是升高的，在COPD患者中升高更为明显。本研究数据支持YKL-40和壳三糖酶作为相对激素不敏感、非Th2型生物标志物，与慢性炎症性疾病进程具有明显相关性。
关键词：哮喘；壳三糖酶；慢性阻塞性肺疾病；YKL-40
(张丽 张红萍 王刚 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Am J Respir Crit Care Med. 2016; 193: 131–142.）
（Am J Respir Crit Care Med. 2016; 193: 131–142.）
Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease
James AJ, Reinius LE, Verhoek M, Gomes A, Kupczyk M, Hammar U, Ono J, Ohta S, Izuhara K, Bel E, Kere J, Söderhäll C, Dahlén B, Boot RG, Dahlén SE; BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease)
Am J Respir Crit Care Med. 2016; 193: 131–142.
Rationale: Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels.
Objectives: To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically relevant factors that may affect chitinase levels, including genetic variability, corticosteroid treatment, disease exacerbations, and allergen exposure.
Methods: Serum chitotriosidase (CHIT1) activity and YKL-40 (CHI3L1) levels, as well as the CHIT1 rs3831317 and CHI3L1 rs4950928 genotypes, were examined in subsets of patients with mild to moderate asthma (n = 76), severe asthma (n = 93), and COPD (n = 64) taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study. Blood was obtained at baseline, before and after a 2-week oral steroid intervention, up to six times during a 1-year period, and during exacerbations. Baseline chitinase levels were also measured in 72 healthy control subjects. The effect of allergen inhalation on blood and sputum YKL-40 levels was measured in two separate groups of patients with mild atopic asthma; one group underwent repeated low-dose allergen challenge (n = 15), and the other underwent high-dose allergen challenge (n = 16).
Measurements and Main Results: Serum chitotriosidase and YKL-40 were significantly elevated in patients with asthma and those with COPD compared with healthy control subjects. Genotype and age strongly affected both YKL-40 and chitotriosidase activity, but associations with disease remained following adjustment for these factors. Correlations were observed with lung function but not with other biomarkers, including exhaled nitric oxide, blood eosinophils, periostin, and IgE. Generally, acute exacerbations, allergen-induced airway obstruction, and corticosteroid treatment did not affect circulating chitinase levels.
Conclusions: YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes.
Keywords: asthma; chitotriosidase; chronic obstructive pulmonary disease; YKL-40
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