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痰液蛋白质组学分析揭示了各种哮喘表现的新型生物标志物。

Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma.

机构信息

Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

State Key Lab. for Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

出版信息

J Transl Med. 2017 Aug 4;15(1):171. doi: 10.1186/s12967-017-1264-y.

Abstract

BACKGROUND

It is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features.

METHODS

30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry.

RESULTS

There were no significant differences in atopy and FEV among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls.

CONCLUSIONS

Patients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes. Trial registration http://www.chictr.org.cn (ChiCTR-OOC-15006221).

摘要

背景

现在已经认识到,哮喘可以表现为不同的形式。通常,哮喘的症状包括喘息、呼吸困难和咳嗽。哮喘的非典型形式,如咳嗽变异性哮喘(CVA)或胸闷变异性哮喘(CTVA),则不喘息。我们假设这些不同形式的哮喘可能具有不同的细胞和分子特征。

方法

本前瞻性研究纳入了 30 例典型或经典哮喘(CA)患者、27 例 CVA 患者、30 例 CTVA 患者和 30 例健康对照成年人。我们测量了血清 IgE、肺功能、痰嗜酸性粒细胞、呼出气一氧化氮(FeNO)。我们通过质谱法对诱导痰上清液进行了蛋白质组学分析。

结果

CA、CVA 和 CTVA 患者之间的特应性和 FEV 没有显著差异。与健康对照组相比,哮喘患者的三种表现形式的血清 IgE、痰嗜酸性粒细胞百分比、FeNO、焦虑和抑郁评分均显著升高,但哮喘组之间没有差异。综合质谱分析显示,CA、CVA 和 CTVA 患者的痰中存在超过 1000 种蛋白质,其中 23 种分泌蛋白在患者中高于对照组。

结论

CA、CVA 或 CTVA 患者具有相似的嗜酸性气道炎症的临床特征。更重要的是,他们的痰样本由共同的因素组成,只有细微的区别。这些发现支持这样一种观点,即这三种不同表现形式的哮喘在增强的 Th2 相关嗜酸性粒细胞方面具有相似的发病机制。此外,本研究还确定了一组用于哮喘诊断和标记其亚型的新型生物标志物。

试验注册

http://www.chictr.org.cn(ChiCTR-OOC-15006221)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3737/5544989/c581d63fb91b/12967_2017_1264_Fig1_HTML.jpg

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