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.

中文翻译：

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吸入皮质类固醇治疗的哮喘亚组中的难治性气道2型炎症

背景

气道2型炎症通常对皮质类固醇敏感，但尚不确定高剂量吸入皮质类固醇（ICS）患者中2型炎症作为哮喘机制的作用。

客观的

为了确定接受ICS治疗的患者中2型气道炎症是否持续存在，并评估类固醇抵抗性2型气道炎症患者的临床特征。

方法

我们使用qPCR生成了来自健康对照，ICS上的重度哮喘患者（n = 174）和非严重哮喘患者的诱导痰细胞中2型细胞因子基因表达的复合指标（2型基因均值，“ T2GM”）在ICS（n = 85）上。我们探讨了哮喘预后与T2GM之间的关系，以及气道T2GM的非侵入性生物标记物的实用性。

结果

哮喘受试者中的痰细胞T2GM在哮喘受试者中显着增加，并且在肌内曲安奈德治疗后仍保持较高水平。我们使用T2GM的中位数作为临界值，对“接受类固醇治疗的2型低位”（stT2低）和“接受类固醇抵抗的2型高位”（srT2高）进行分类。与低stT2哮喘患者相比，高srT2哮喘患者年龄较大，哮喘更为严重。当BMI <40时，血液嗜酸性粒细胞计数预测为srT2高哮喘，而当年龄为<34岁时，血液IgE强烈预测为srT2高哮喘，而当年龄<34岁时，则不是。

结论

尽管进行了ICS治疗，许多哮喘患者仍持续存在2型气道炎症（srT2高哮喘），这些患者年龄较大，病情较重。体重和年龄会改变基于血液的2型气道炎症生物标记物的性能。