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非嗜酸性粒细胞性哮喘中吸入性皮质类固醇的降级:真实生活中的前瞻性试验。

Step-down of inhaled corticosteroids in non-eosinophilic asthma: A prospective trial in real life.

机构信息

Department of Respiratory Medicine, CHU Liege, GIGA I3 Research Group, University of Liege, Liege, Belgium.

Department of Clinical Pharmacy, CIRM (Center for Interdisciplinary Research on Medicines), University of Liege, Liege, Belgium.

出版信息

Clin Exp Allergy. 2018 May;48(5):525-535. doi: 10.1111/cea.13106. Epub 2018 Mar 6.

Abstract

BACKGROUND

While non-eosinophilic asthmatics are usually considered poorly responsive to inhaled corticosteroids (ICSs), studies assessing a step-down of ICS in this specific population are currently lacking.

OBJECTIVES

To assess the proportion of non-eosinophilic asthmatics in whom ICS may be withdrawn without any clinical degradation and to determine the predictive markers of a failure to stop treatment with ICS.

METHODS

This prospective study was completed by 36 non-eosinophilic asthmatics, defined by sputum eosinophils <3% and blood eosinophils <400/μL. In these patients, whichever the baseline asthma control level, the dose of ICS was gradually reduced every 3 months until they met the failure criteria or successfully discontinued ICS for 6 months. The failure criteria were an ACQ score ≥1.5 with an increase from baseline >0.5 or a number of severe exacerbations during the study which was greater than the number during the year prior to the baseline visit. Receiver-operating characteristic (ROC) curves were constructed to assess predictors of a failure to stop ICS. This study is registered with ClinicalTrials.gov, number NCT02169323.

RESULTS

In 14 patients (39%), ICSs were completely withdrawn, and in 10 further patients (28%), ICS were stepped-down to a reduced ICS dose without any deterioration of asthma control and exacerbation rate. Baseline predictors of a failure to stop ICS were a greater age (area under ROC curve [ROC AUC] and [95% CI]: 0.77 [0.62-0.93]) and elevated blood eosinophils (ROC AUC [95% CI]: 0.77 [0.61-0.93]). After the first step-down of ICS, the best predictor was an elevated blood eosinophil count (ROC AUC [95% CI]: 0.85 [0.72-0.99]).

CONCLUSIONS & CLINICAL RELEVANCE: Withdrawing or reducing the dose of ICS is feasible in two-thirds of non-eosinophilic asthmatics irrespective of baseline asthma control. An elevated blood eosinophil count may predict the failure to stop ICS.

摘要

背景

虽然非嗜酸性粒细胞性哮喘患者通常被认为对吸入性皮质类固醇(ICS)反应不佳,但目前缺乏针对这一特定人群ICS 逐步减量的研究。

目的

评估非嗜酸性粒细胞性哮喘患者中可以停用 ICS 而无任何临床恶化的比例,并确定停止 ICS 治疗失败的预测标志物。

方法

这项前瞻性研究纳入了 36 名非嗜酸性粒细胞性哮喘患者,定义为痰嗜酸性粒细胞<3%和血嗜酸性粒细胞<400/μL。在这些患者中,无论基线哮喘控制水平如何,ICS 剂量每 3 个月逐渐减少,直到达到失败标准或成功停用 ICS 6 个月。失败标准为 ACQ 评分≥1.5,与基线相比增加>0.5 或研究期间严重加重次数多于基线就诊前 1 年。构建受试者工作特征(ROC)曲线以评估停止 ICS 失败的预测标志物。本研究在 ClinicalTrials.gov 注册,编号为 NCT02169323。

结果

在 14 名患者(39%)中,完全停用了 ICS,在另外 10 名患者(28%)中,将 ICS 减少至较低剂量,而哮喘控制和加重率没有恶化。停止 ICS 失败的基线预测标志物为年龄较大(ROC 曲线下面积 [AUC]和 [95%CI]:0.77 [0.62-0.93])和血嗜酸性粒细胞升高(ROC AUC [95%CI]:0.77 [0.61-0.93])。ICS 第一次减量后,最佳预测标志物为血嗜酸性粒细胞计数升高(ROC AUC [95%CI]:0.85 [0.72-0.99])。

结论和临床相关性

无论基线哮喘控制如何,三分之二的非嗜酸性粒细胞性哮喘患者可以停用或减少 ICS 剂量。血嗜酸性粒细胞计数升高可能预测停止 ICS 治疗失败。

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