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寻找严重哮喘中的气道骨膜蛋白:它是否可用于 2 型表型聚类?

Looking for Airways Periostin in Severe Asthma: Could It Be Useful for Clustering Type 2 Endotype?

机构信息

Institute of Respiratory Diseases, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy.

出版信息

Chest. 2018 Nov;154(5):1083-1090. doi: 10.1016/j.chest.2018.08.1032. Epub 2018 Oct 15.

Abstract

BACKGROUND

Severe asthma is heterogeneous clinically and biologically and is often difficult to control. In particular, the type 2 (T2) immunity endotype of severe asthma is gaining increasing interest because it is susceptible to newly developed biologic treatments that can transform the quality of life of these patients. The aim of this study was to analyze periostin concentrations in the airways of patients with severe asthma, evaluating its role in clustering the T2 endotype.

METHODS

We enrolled 40 consecutive patients with severe asthma (T2 endotype: n = 25; non-T2 endotype: n = 15), 21 patients with mild to moderate asthma, and 15 healthy control subjects. All subjects enrolled underwent exhaled breath condensate (EBC) and sputum collection, eosinophil count in blood, fractional exhaled nitric oxide, and IgE measurement. Periostin was assessed by an enzyme-linked immunosorbent assay kit on EBC and induced sputum (IS) supernatant.

RESULTS

We were able to detect higher periostin levels in the EBC (0.75 ± 0.46 vs 0.70 ± 0.19 vs 0.11 ± 0.05 ng/mL, P < .05 and P < .01) and in IS (0.55 ± 0.23 vs 0.31 ± 0.13 vs 0.16 ± 0.120 ng/mL, P < .05 and P < .01) of patients with severe asthma compared with patients with mild to moderate asthma and healthy control subjects, respectively. We further found an increase of periostin levels in both samples in T2 endotype compared with non-T2 endotype (EBC: 0.88 ± 0.46 vs 0.52 ± 0.46 ng/mL; IS: 0.69 ± 0.19 vs 0.39 ± 0.16 ng/mL; P < .05) and a correlation between periostin levels in EBC and sputum.

CONCLUSIONS

We found that periostin is measurable in the airways and increased in patients with severe asthma, especially in those from the T2 endotype. Unlike serum periostin, which may be derived from several sources outside the lung, airways periostin is a useful marker of severe eosinophilic asthma and may help to phenotype patients that will respond to the biologic agents.

摘要

背景

严重哮喘在临床上和生物学上具有异质性,通常难以控制。特别是,2 型(T2)免疫表型的严重哮喘越来越受到关注,因为它易受新开发的生物治疗药物的影响,这些药物可以改变这些患者的生活质量。本研究旨在分析严重哮喘患者气道中的骨膜蛋白浓度,评估其在聚类 2 型表型中的作用。

方法

我们纳入了 40 例连续的严重哮喘患者(T2 表型:n=25;非 T2 表型:n=15)、21 例轻度至中度哮喘患者和 15 例健康对照者。所有纳入的受试者均接受呼出气冷凝液(EBC)和痰收集、血液嗜酸性粒细胞计数、呼出一氧化氮分数和 IgE 测量。通过酶联免疫吸附试验试剂盒检测 EBC 和诱导痰(IS)上清液中的骨膜蛋白。

结果

我们能够检测到严重哮喘患者的 EBC(0.75±0.46 比 0.70±0.19 比 0.11±0.05 ng/mL,P<.05 和 P<.01)和 IS(0.55±0.23 比 0.31±0.13 比 0.16±0.12 ng/mL,P<.05 和 P<.01)中骨膜蛋白水平更高,与轻度至中度哮喘患者和健康对照组相比。我们还发现,与非 T2 表型相比,T2 表型患者在两种样本中骨膜蛋白水平均升高(EBC:0.88±0.46 比 0.52±0.46 ng/mL;IS:0.69±0.19 比 0.39±0.16 ng/mL;P<.05),EBC 和痰中骨膜蛋白水平之间存在相关性。

结论

我们发现,骨膜蛋白可在气道中检测到,并在严重哮喘患者中增加,尤其是在 2 型表型患者中。与血清骨膜蛋白不同,后者可能来自肺部以外的多个来源,气道骨膜蛋白是严重嗜酸性粒细胞性哮喘的有用标志物,并可能有助于对生物制剂有反应的患者进行表型分析。

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