Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.
Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.
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DOI：
10.1016/j.jaci.2017.12.1009
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
National Heart, Lung and Blood Institute Severe Asthma Research Program 3
中科院分区：
文献类型：
--
作者：
Peters MC;Kerr S;Dunican EM;Woodruff PG;Fajt ML;Levy BD;Israel E;Phillips BR;Mauger DT;Comhair SA;Erzurum SC;Johansson MW;Jarjour NN;Coverstone AM;Castro M;Hastie AT;Bleecker ER;Wenzel SE;Fahy JV;National Heart, Lung and Blood Institute Severe Asthma Research Program 3
气道2型炎症通常对皮质类固醇敏感，但2型炎症作为接受大剂量吸入性皮质类固醇（ICS）患者哮喘发病机制的作用尚不确定。我们试图确定接受ICS治疗的患者是否持续存在气道2型炎症，并评估类固醇耐药气道2型炎症患者的临床特征。我们使用定量PCR来产生诱导痰细胞中2型细胞因子基因表达的复合指标（2型基因平均值[T2 GM]），这些诱导痰细胞来自健康对照受试者、接受ICS的重度哮喘患者（n = 174）和接受ICS的非重度哮喘患者（n = 85）。我们探讨了哮喘预后与T2 GM值之间的关系，以及气道T2 GM非侵入性生物标志物的实用性。哮喘患者的痰细胞T2 GM值在肌内注射曲安西龙治疗后显著升高并保持较高水平。我们使用中位T2 GM值作为截止值来分类类固醇治疗的2型-低和类固醇耐药的2型-高（srT 2-高）亚组。与激素治疗的2型低哮喘患者相比，srT 2高哮喘患者年龄更大，哮喘更严重。当体重指数小于40 kg/m2时，血嗜酸性粒细胞计数可预测srT 2高哮喘，但当体重指数大于或等于40 kg/m2时，血嗜酸性粒细胞计数不能预测srT 2高哮喘;而当年龄小于34岁时，血IgE水平可强烈预测srT 2高哮喘，但当年龄大于或等于34岁时，则不能预测srT 2高哮喘。尽管有ICS治疗，许多哮喘患者仍有持续的气道2型炎症（srT 2高哮喘），这些患者年龄更大，病情更严重。体重和年龄会改变气道2型炎症血液生物标志物的表现。
Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients receiving high-dose inhaled corticosteroids (ICSs) is uncertain. We sought to determine whether airway type 2 inflammation persists in patients treated with ICSs and to evaluate the clinical features of patients with steroid-resistant airway type 2 inflammation. We used quantitative PCR to generate a composite metric of type 2 cytokine gene expression (type 2 gene mean [T2GM]) in induced sputum cells from healthy control subjects, patients with severe asthma receiving ICSs (n = 174), and patients with nonsevere asthma receiving ICSs (n = 85). We explored relationships between asthma outcomes and T2GM values and the utility of noninvasive biomarkers of airway T2GM. Sputum cell T2GM values in asthmatic patients were significantly increased and remained high after treatment with intramuscular triamcinolone. We used the median T2GM value as a cutoff to classify steroid-treated type 2–low and steroid-resistant type 2–high (srT2-high) subgroups. Compared with patients with steroid-treated type 2–low asthma, those with srT2-high asthma were older and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when body mass index was less than 40 kg/m2 but not when it was 40 kg/m2 or greater, whereas blood IgE levels strongly predicted srT2-high asthma when age was less than 34 years but not when it was 34 years or greater. Despite ICS therapy, many asthmatic patients have persistent airway type 2 inflammation (srT2-high asthma), and these patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type 2 inflammation.
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影响因子：
--
作者：
Schroeder A;Mueller O;Stocker S;Salowsky R;Leiber M;Gassmann M;Lightfoot S;Menzel W;Granzow M;Ragg T
通讯作者：
Ragg T
影响因子：
24.3
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Teague, W. Gerald
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Seys SF;Scheers H;Van den Brande P;Marijsse G;Dilissen E;Van Den Bergh A;Goeminne PC;Hellings PW;Ceuppens JL;Dupont LJ;Bullens DM
通讯作者：
Bullens DM