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抗白细胞介素-5 治疗重度哮喘时,痰 2 型标志物可预测缓解

Sputum Type 2 Markers Could Predict Remission in Severe Asthma Treated With Anti-IL-5.

机构信息

Giga I3, Pneumology Research Group, Liege University, Liege, Belgium; Department of Pneumology-Allergology, CHU of Liege, Liege, Belgium.

Haute École de la Province de Liège, Liege, Belgium.

出版信息

Chest. 2023 Jun;163(6):1368-1379. doi: 10.1016/j.chest.2023.01.037. Epub 2023 Feb 3.

DOI:10.1016/j.chest.2023.01.037
PMID:36740095
Abstract

BACKGROUND

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments. Even if high blood eosinophil counts seem to be associated with a reduction in exacerbations with treatment targeting IL-5, we lack biomarkers for the prediction of remission after these very expensive treatments.

RESEARCH QUESTION

Are there biomarkers of remission after therapy targeting IL-5 in the sputum of patients with severe eosinophilic asthma?

STUDY DESIGN AND METHODS

This observational study included 52 patients with severe asthma initiated with anti-IL-5 therapy and recruited from the asthma clinic of the Centre Hospitalier Universitaire of Liege, Belgium. Remission was defined as patients who combined the following at 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire score < 1.5, asthma control test score > 19, or both; FEV of ≥ 80% predicted, improvement of FEV of ≥ 10%, or both; and a blood eosinophil count < 300 cells/μL. Eosinophil peroxidase (EPX), IgE, IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor, thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels were measured in the sputum of these patients before anti-IL-5 treatment.

RESULTS

Among the 52 patients, 11 were classified as being in remission. These patients were characterized by higher sputum eosinophil, macrophage, and lymphocyte counts, whereas the sputum neutrophil percentage was lower than in the nonremission group. In addition, the sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein levels were higher at baseline in the remission group compared with the nonremission group. Univariate regression analysis revealed that male vs female sex, sputum neutrophil percentage, eotaxin-1, IL-5, and EPX were potential predictors of remission.

INTERPRETATION

Sputum type 2 markers seemed to be potentially predictive of remission after anti-IL-5 therapy in a cohort of patients with severe eosinophilic asthma. These results need validation on a larger cohort.

摘要

背景

针对白细胞介素 5(IL-5)的生物疗法可显著改善哮喘症状。然而,并非所有患者对这些治疗的反应都相同。尽管血液嗜酸性粒细胞计数升高似乎与针对 IL-5 的治疗后减少恶化有关,但我们缺乏这些昂贵治疗后缓解的预测生物标志物。

研究问题

在重度嗜酸性粒细胞性哮喘患者的痰中,针对白细胞介素 5 的治疗后缓解是否存在生物标志物?

研究设计和方法

这项观察性研究纳入了 52 名从比利时列日大学附属医院哮喘诊所开始接受抗白细胞介素 5 治疗的重度哮喘患者。缓解定义为治疗 1 年后患者同时满足以下条件:无慢性口服皮质类固醇治疗;无恶化;哮喘控制问卷评分<1.5、哮喘控制测试评分>19 或两者均满足;FEV1 占预计值的比例≥80%,FEV1 改善率≥10%或两者均满足;且血液嗜酸性粒细胞计数<300 个/μL。在开始抗白细胞介素 5 治疗前,测量这些患者痰中的过氧化物酶(EPX)、免疫球蛋白 E(IgE)、白细胞介素 3(IL-3)、IL-4、IL-5、IL-13、IL-25、IL-33、粒细胞-巨噬细胞集落刺激因子、胸腺基质淋巴生成素(TSLP)和嗜酸性粒细胞趋化因子-1(eotaxin-1)水平。

结果

在 52 名患者中,有 11 名被归类为缓解组。与未缓解组相比,这些患者的痰中嗜酸性粒细胞、巨噬细胞和淋巴细胞计数较高,而痰中性粒细胞百分比较低。此外,与未缓解组相比,缓解组患者的痰 eotaxin-1、TSLP、IL-5、EPX 和 IgE 蛋白水平在基线时更高。单变量回归分析显示,男性与女性、痰中性粒细胞百分比、eotaxin-1、IL-5 和 EPX 是缓解的潜在预测因子。

解释

在重度嗜酸性粒细胞性哮喘患者队列中,针对白细胞介素 5 的治疗后缓解似乎与痰 2 型标志物有关。这些结果需要在更大的队列中进行验证。

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