在使用吸入性糖皮质激素治疗的哮喘患者中的大型亚组中的难治性2型气道炎症
2018/06/04
摘要
背景：2型气道炎症通常对糖皮质激素敏感，但在吸入高剂量糖皮质激素患者中，2型炎症作为哮喘机制的作用尚不确切。
目的：为了明确接受吸入性糖皮质激素（ICS）治疗的哮喘患者中是否存在2型气道炎症，并评估存在激素抵抗的2型气道炎症的患者的临床特征。
方法：我们采用qPCR方法对健康对照、应用ICS的重度哮喘患者（n = 174）和应用ICS的非重度哮喘患者（n = 85）的诱导痰细胞中的2型细胞因子基因表达（2型基因平均值，“T2GM”）情况进行综合评估。并探讨了哮喘结局与T2GM之间的关系，以及气道T2GM作为非侵入性生物标志物的效用。
结果：哮喘患者的痰细胞T2GM显着增加，并且在肌注曲安奈德治疗后仍保持高水平。我们以T2GM的中位数值作为界值来分类，将哮喘患者分为“激素治疗-2型炎症低水平”（stT2低）和“激素抵抗-2型炎症高水平”（srT2高）两个亚组。与stT2-低的哮喘患者相比，srT2-高的患者年龄更大，哮喘程度更重。当BMI <40时，血EOS可预测srT2-高型哮喘，但当BMI≥40时不能。当年龄<34岁时血IgE可预测srT2-高型哮喘，但当年龄≥34时不能。
结论：尽管许多哮喘患者接受ICS治疗但仍存在持续2型气道炎症（srT2-高型哮喘），并且这些患者年龄较大，病情较重。体重和年龄影响2型气道炎症的血液相关生物标志物的作用。
Refractory Airway Type-2 Inflammation in a Large Subgroup of Asthmatics treated with Inhaled Corticosteroids
Michael C. Peters,et al. JACI 2018 Mar 3
Abstract
BACKGROUND：Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients on high dose inhaled corticosteroids (ICS) is uncertain.
OBJECTIVE：To determine if airway type 2 inflammation persists in patients treated with ICS and to evaluate the clinical features of patients with steroid resistant airway type-2 inflammation.
METHODS：We used qPCR to generate a composite metric of type-2 cytokine gene expression (type 2 Gene Mean, “T2GM”) in induced sputum cells from healthy controls, severe asthma patients on ICS (n=174), and non- severe asthma patients on ICS(n=85). We explored relationships between asthma outcomes and the T2GM, and the utility of non-invasive biomarkers of the airway T2GM.
RESULTS：The sputum cell T2GM in asthma subjects was significantly increased in asthma subjects and remained high following treatment with intramuscular triamcinolone. We used the median value for the T2GM as a cutoff to classify “steroid treated type 2-low” (stT2-low) and “steroid-resistant type 2-high” (srT2-high) subgroups. Compared to patients with stT2-low asthma, those with srT2-high asthma were older age and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when BMI was < 40, but not when it was ≥40, whereas, blood IgE strongly predicted srT2-high asthma when age was < 34 years but not when it was ≥34.
CONCLUSION：Despite ICS therapy many asthmatics 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.
背景：2型气道炎症通常对糖皮质激素敏感，但在吸入高剂量糖皮质激素患者中，2型炎症作为哮喘机制的作用尚不确切。
目的：为了明确接受吸入性糖皮质激素（ICS）治疗的哮喘患者中是否存在2型气道炎症，并评估存在激素抵抗的2型气道炎症的患者的临床特征。
方法：我们采用qPCR方法对健康对照、应用ICS的重度哮喘患者（n = 174）和应用ICS的非重度哮喘患者（n = 85）的诱导痰细胞中的2型细胞因子基因表达（2型基因平均值，“T2GM”）情况进行综合评估。并探讨了哮喘结局与T2GM之间的关系，以及气道T2GM作为非侵入性生物标志物的效用。
结果：哮喘患者的痰细胞T2GM显着增加，并且在肌注曲安奈德治疗后仍保持高水平。我们以T2GM的中位数值作为界值来分类，将哮喘患者分为“激素治疗-2型炎症低水平”（stT2低）和“激素抵抗-2型炎症高水平”（srT2高）两个亚组。与stT2-低的哮喘患者相比，srT2-高的患者年龄更大，哮喘程度更重。当BMI <40时，血EOS可预测srT2-高型哮喘，但当BMI≥40时不能。当年龄<34岁时血IgE可预测srT2-高型哮喘，但当年龄≥34时不能。
结论：尽管许多哮喘患者接受ICS治疗但仍存在持续2型气道炎症（srT2-高型哮喘），并且这些患者年龄较大，病情较重。体重和年龄影响2型气道炎症的血液相关生物标志物的作用。
(中国医科大学附属第一医院呼吸与危重症医学科 李文扬 摘译 杨冬 审校)
(Michael C. Peters,et al. JACI 2018 Mar 3 )
(Michael C. Peters,et al. JACI 2018 Mar 3 )
Refractory Airway Type-2 Inflammation in a Large Subgroup of Asthmatics treated with Inhaled Corticosteroids
Michael C. Peters,et al. JACI 2018 Mar 3
Abstract
BACKGROUND：Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients on high dose inhaled corticosteroids (ICS) is uncertain.
OBJECTIVE：To determine if airway type 2 inflammation persists in patients treated with ICS and to evaluate the clinical features of patients with steroid resistant airway type-2 inflammation.
METHODS：We used qPCR to generate a composite metric of type-2 cytokine gene expression (type 2 Gene Mean, “T2GM”) in induced sputum cells from healthy controls, severe asthma patients on ICS (n=174), and non- severe asthma patients on ICS(n=85). We explored relationships between asthma outcomes and the T2GM, and the utility of non-invasive biomarkers of the airway T2GM.
RESULTS：The sputum cell T2GM in asthma subjects was significantly increased in asthma subjects and remained high following treatment with intramuscular triamcinolone. We used the median value for the T2GM as a cutoff to classify “steroid treated type 2-low” (stT2-low) and “steroid-resistant type 2-high” (srT2-high) subgroups. Compared to patients with stT2-low asthma, those with srT2-high asthma were older age and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when BMI was < 40, but not when it was ≥40, whereas, blood IgE strongly predicted srT2-high asthma when age was < 34 years but not when it was ≥34.
CONCLUSION：Despite ICS therapy many asthmatics 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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重症哮喘的气道病理改变与气流阻塞有关，而与症状控制无关
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