Combined assessment of serum eosinophil-derived neurotoxin and YKL-40 may identify Asthma-COPD overlap
Combined assessment of serum eosinophil-derived neurotoxin and YKL-40 may identify Asthma-COPD overlap
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血清嗜酸性粒细胞衍生的神经毒素和 YKL-40 的联合评估可能会识别哮喘-慢性阻塞性肺病的重叠
DOI：
10.1016/j.alit.2020.05.007
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发表时间：
2021
影响因子：
6.8
通讯作者：
Hashimoto Shu
中科院分区：
文献类型：
--
作者：
Shirai Toshihiro;Hirai Keita;Gon Yasuhiro;Maruoka Shuichiro;Mizumura Kenji;Hikichi Mari;Itoh Kunihiko;Hashimoto Shu
在我们之前的报告中，1我们表明，血清骨膜蛋白（哮喘2型炎症的生物标志物）和血清YKL-40（COPD的有用生物标志物）的联合评估可能有助于识别ACO。我们发现，在哮喘-COPD重叠（ACO）患者中，血清骨膜蛋白和YKL-40水平均高的患者比例显著高于哮喘或COPD患者：比值比为2.59（95%CI，1.58 e4. 25）; p< 0.001;敏感性，38.3%;特异性，80.7%。为了探索另一种有用的2型生物标志物，我们专注于嗜酸性粒细胞衍生的神经毒素（EDN）。2，3在这项研究中，我们假设使用血清EDN代替骨膜蛋白将有助于识别ACO。研究对象包括2013年2月至2016年8月期间在静冈综合医院或日本大学板桥医院门诊进行常规检查的353名成年患者。参与者被分为三组：哮喘（n = 177），COPD（n = 61）和ACO（n = 115）。哮喘和COPD患者分别符合全球哮喘倡议（GINA）4和全球慢性阻塞性肺疾病倡议（GOLD）5的定义。根据既往报道，6 e8 ACO的诊断条件为：哮喘患者年龄大于40岁，使用支气管扩张剂后1秒用力呼气容积（FEV 1）/用力肺活量（FVC）< 0.7，且满足以下至少一项标准：超过10包-年的吸烟史，肺的一氧化碳弥散量/肺泡容积小于80%，或者在高分辨率计算机断层扫描上存在低衰减区域。如果COPD患者满足以下至少两项标准，则也可诊断为ACO：既往哮喘史，血液嗜酸性粒细胞计数250个细胞/μL，呼出气一氧化氮（FeNO）分数> 35 ppb，或血清总IgE> 100 IU/mL。本研究的队列与我们之前的报告相同，患者流量和临床特征在其他地方显示。1在检查当天，研究受试者依次进行抽血、FeNO和肺功能测定。研究方案由每个机构的伦理委员会批准（批准编号分别为：SGH 15-01-55和RK-130111），并获得患者的书面知情同意书。使用EDN ELISA试剂盒（MBL International，名古屋，日本）测量血清EDN水平。通过人几丁质酶3样1 Quantikine ELISA试剂盒（目录号DC 3L 10，R&D systems，Minneapolis，MN，USA）测定血清YKL-40。根据制造商的说明书使用每个ELISA试剂盒。所有分析均使用R软件（3.6版）进行。2，R统计计算基金会，奥地利维也纳）。双尾P值< 0.05被认为具有统计学显著性。ACO中的血清EDN高于哮喘或COPD（图1A），而COPD和ACO中的血清YKL-40均高于哮喘。115例ACO患者中，哮喘患者86例，COPD患者29例。这些患者中的血清EDN和YKL-40的结果示于补充图1A、B中。COPD患者血清EDN水平显著高于哮喘患者。在哮喘、ACO和COPD患者中，血清EDN水平与血液嗜酸性粒细胞计数相关（图2A）。哮喘患者血清EDN与总IgE之间以及COPD患者血清EDN与FeNO或YKL-40水平之间存在弱相关性，但在ACO患者中未观察到相关性（图2...
In our previous report, 1 we showed that the combined assessment of serum periostin, a biomarker of type 2 inflammation in asthma, and serum YKL-40, a useful biomarker of COPD, may be beneficial for identifying ACO. We found that the proportion of patients with both high serum periostin and YKL-40 levels was significantly higher in asthma-COPD overlap (ACO) than in asthma or COPD: odds ratio, 2.59 (95% CI, 1.58 e4. 25); p< 0.001; sensitivity, 38.3%; and specificity, 80.7%. To explore another useful type 2 biomarker, we focused on eosinophil-derived neurotoxin (EDN). 2, 3 In this study, we hypothesized that using serum EDN instead of periostin would be useful to identify ACO. The study subjects included 353 adult patients who visited outpatient clinics at Shizuoka General Hospital or Nihon University Itabashi Hospital for routine check-ups between February 2013 and August 2016. The participants were classified into three groups: asthma (n ¼ 177), COPD (n ¼ 61), and ACO (n ¼ 115). The asthma and COPD patients fulfilled the definition of the Global Initiative for Asthma (GINA) 4 and the Global Initiative for Chronic Obstructive Lung Disease (GOLD), 5 respectively. According to the previous reports, 6 e8 ACO was diagnosed if the asthma patients were older than 40 years, had post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)< 0.7, and fulfilled at least one of the following criteria: more than 10 pack-years of smoking history, less than 80% of diffusing capacity of the lung for carbon monoxide/alveolar volume, or the presence of a low attenuation area on high-resolution computed tomography. ACO was also diagnosed if the COPD patients fulfilled at least two of the following criteria: a past history of asthma, a blood eosinophil count 250 cells/μL, fractional exhaled nitric oxide (FeNO)> 35 ppb, or serum total IgE> 100 IU/mL. The cohorts of this study were identical to our previous report, and the patient flow and clinical characteristics are shown elsewhere. 1 On the examination day, the study subjects underwent blood draws, FeNO, and spirometry in that order. The study protocols were approved by the ethics committee of each institution (approved number: SGH 15-01-55 and RK-130111, respectively) and written informed consent was obtained from the patients. Serum EDN levels were measured using the EDN ELISA Kit (MBL International, Nagoya, Japan). Serum YKL-40 was determined by theHuman Chitinase 3-like 1 Quantikine ELISA Kit (catalog number DC3L10, R&D systems, Minneapolis, MN, USA). Each ELISA kit was used according to the manufacturer's instructions. All of the analyses were performed with R software (version 3.6. 2, R Foundation for Statistical Computing, Vienna, Austria). A two-tailed P value of< 0.05 was considered statistically significant. Serum EDN was higher in ACO than in asthma or COPD (Fig. 1 A), whereas serum YKL-40 was higher in both COPD and ACO than in asthma. 1 One hundred and fifteen patients with ACO consisted of 86 patients derived from asthma, denoted as ACO (asthma), and 29 derived from COPD, denoted as ACO (COPD). The results of serum EDN and YKL-40 in these patients are shown in Supplementary Figure 1 A, B. Serum EDN levels were significantly higher in patients with ACO (COPD) than in those with ACO (asthma). Serum EDN levels correlated with blood eosinophil counts in patients with asthma, ACO, and COPD (Fig. 2 A). There was a weak correlation between serum EDN and total IgE in patients with asthma and between serum EDN and FeNO or YKL-40 levels in patients with COPD, but no correlation was observed in patients with ACO (Fig. 2 …