痰液2型标志物可预测抗白细胞介素-5治疗的重症哮喘的缓解
2023/02/20
摘要
背景：以白细胞介素-5（IL-5）为靶点的生物疗法可以明显改善哮喘。然而，患者对这些治疗的反应并不相同。即使高血嗜酸性粒细胞计数与靶向IL-5治疗的恶化减少相关，仍缺乏预测这些昂贵治疗后病情缓解的生物标志物。
研究问题：重症嗜酸性粒细胞性哮喘患者的痰液中是否存在靶向IL-5的治疗后缓解的生物标志物？
研究设计和方法：这项观察性研究包括52名重度哮喘患者，他们是从比利时列日CHU的哮喘诊所招募的，使用抗IL-5。缓解定义为患者在治疗后一年内合并：无口服皮质类固醇的慢性治疗，无恶化，哮喘控制问卷低于1.5和/或哮喘控制测试高于19，1秒内用力呼气量（FEV1）≥80%，预计FEV1改善≥10%，血嗜酸性粒细胞计数低于300个细胞/μl。在抗IL-5治疗前，对这些患者的痰液中的嗜酸性粒细胞过氧化物酶（EPX）、免疫球蛋白E（IgE）、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（GM-CSF）、胸腺基质淋巴细胞生成素（TSLP）和嗜酸性粒素-1水平进行了测定。
结果：52例患者中，11例病情缓解。这些患者的特点是痰液嗜酸性粒细胞、巨噬细胞和淋巴细胞计数较高，而痰液中性粒细胞百分比低于未缓解组。此外，缓解组的痰液eotaxin-1、TSLP、IL-5、EPX和IgE蛋白水平在基线时高于其他组。单变量回归分析显示，男性与女性、痰液中性粒细胞百分比、eotaxin-1、IL-5和EPX是缓解的潜在预测因素。
解释：在一组严重嗜酸性粒细胞性哮喘患者中，痰液2型（T2）标记物似乎可以预测抗IL-5后的缓解。这些结果需要在更大的队列中进行验证。
Sputum Type 2 markers could predict remission in severe asthma treated with anti-Interleukin-5
C Moermans, C Brion, G Bock, S Graff, S Gerday, H Nekoee, C Poulet, N Bricmont, M Henket, V Paulus, F Guissard, R Louis, F Schleich
Abstract
Background: Biotherapies targeting interleukin-5 (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 appear 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 severe eosinophilic asthmatics?
Study design and methods: This observational study included 52 severe asthmatics initiated with an anti-IL-5 and recruited from the asthma clinic of the CHU of Liege, Belgium. Remission was defined as patients who combined one year after therapy: no chronic treatment with oral corticosteroids, no exacerbation, asthma control questionnaire lower than 1.5 and/or asthma control test greater than 19, a forced expiration volume in 1s (FEV1) ≥ 80% predicted and/or improvement of FEV1 ≥ 10%, and a blood eosinophil count lower than 300 cells/μl. Eosinophil peroxidase (EPX), Immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), 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 in remission. These patients were characterized by higher sputum eosinophil, macrophage and lymphocyte counts while the sputum neutrophil percentage was lower than in the non-remission group. In addition, the sputum eotaxin-1, TSLP, IL-5, EPX and IgE protein levels were higher at baseline in the remission group compared to the other. Univariate regression analysis revealed that male vs female, sputum neutrophil percentage, eotaxin-1, IL-5 and EPX were potential predictors of remission.
Interpretations: Sputum type-2 (T2) markers appeared to be potentially predictive of remission after anti IL-5 in a cohort of severe eosinophilic asthmatic patients. These results need validation on a larger cohort.
背景：以白细胞介素-5（IL-5）为靶点的生物疗法可以明显改善哮喘。然而，患者对这些治疗的反应并不相同。即使高血嗜酸性粒细胞计数与靶向IL-5治疗的恶化减少相关，仍缺乏预测这些昂贵治疗后病情缓解的生物标志物。
研究问题：重症嗜酸性粒细胞性哮喘患者的痰液中是否存在靶向IL-5的治疗后缓解的生物标志物？
研究设计和方法：这项观察性研究包括52名重度哮喘患者，他们是从比利时列日CHU的哮喘诊所招募的，使用抗IL-5。缓解定义为患者在治疗后一年内合并：无口服皮质类固醇的慢性治疗，无恶化，哮喘控制问卷低于1.5和/或哮喘控制测试高于19，1秒内用力呼气量（FEV1）≥80%，预计FEV1改善≥10%，血嗜酸性粒细胞计数低于300个细胞/μl。在抗IL-5治疗前，对这些患者的痰液中的嗜酸性粒细胞过氧化物酶（EPX）、免疫球蛋白E（IgE）、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（GM-CSF）、胸腺基质淋巴细胞生成素（TSLP）和嗜酸性粒素-1水平进行了测定。
结果：52例患者中，11例病情缓解。这些患者的特点是痰液嗜酸性粒细胞、巨噬细胞和淋巴细胞计数较高，而痰液中性粒细胞百分比低于未缓解组。此外，缓解组的痰液eotaxin-1、TSLP、IL-5、EPX和IgE蛋白水平在基线时高于其他组。单变量回归分析显示，男性与女性、痰液中性粒细胞百分比、eotaxin-1、IL-5和EPX是缓解的潜在预测因素。
解释：在一组严重嗜酸性粒细胞性哮喘患者中，痰液2型（T2）标记物似乎可以预测抗IL-5后的缓解。这些结果需要在更大的队列中进行验证。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Chest. 2023 Feb 3;S0012-3692(23)00169-1. doi: 10.1016/j.chest.2023.01.037.)
(Chest. 2023 Feb 3;S0012-3692(23)00169-1. doi: 10.1016/j.chest.2023.01.037.)
Sputum Type 2 markers could predict remission in severe asthma treated with anti-Interleukin-5
C Moermans, C Brion, G Bock, S Graff, S Gerday, H Nekoee, C Poulet, N Bricmont, M Henket, V Paulus, F Guissard, R Louis, F Schleich
Abstract
Background: Biotherapies targeting interleukin-5 (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 appear 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 severe eosinophilic asthmatics?
Study design and methods: This observational study included 52 severe asthmatics initiated with an anti-IL-5 and recruited from the asthma clinic of the CHU of Liege, Belgium. Remission was defined as patients who combined one year after therapy: no chronic treatment with oral corticosteroids, no exacerbation, asthma control questionnaire lower than 1.5 and/or asthma control test greater than 19, a forced expiration volume in 1s (FEV1) ≥ 80% predicted and/or improvement of FEV1 ≥ 10%, and a blood eosinophil count lower than 300 cells/μl. Eosinophil peroxidase (EPX), Immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), 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 in remission. These patients were characterized by higher sputum eosinophil, macrophage and lymphocyte counts while the sputum neutrophil percentage was lower than in the non-remission group. In addition, the sputum eotaxin-1, TSLP, IL-5, EPX and IgE protein levels were higher at baseline in the remission group compared to the other. Univariate regression analysis revealed that male vs female, sputum neutrophil percentage, eotaxin-1, IL-5 and EPX were potential predictors of remission.
Interpretations: Sputum type-2 (T2) markers appeared to be potentially predictive of remission after anti IL-5 in a cohort of severe eosinophilic asthmatic patients. These results need validation on a larger cohort.
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孟德尔随机化分析揭示特应性皮炎、哮喘和胃食管反流病之间复杂的遗传相互作用
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