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儿童中性粒细胞类固醇难治性复发性喘息和嗜酸性粒细胞类固醇难治性哮喘。

Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children.

机构信息

Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris 06, Sorbonne University, Paris, France.

Institute of Mathematics, Toulouse III Paul-Sabatier University, Toulouse, France.

出版信息

J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1351-1361.e2. doi: 10.1016/j.jaip.2017.02.003. Epub 2017 Mar 28.

DOI:10.1016/j.jaip.2017.02.003
PMID:28363401
Abstract

BACKGROUND

Little is known about inflammatory pathways of severe recurrent wheeze in preschool children and severe asthma in children.

OBJECTIVES

The aim of the Severe Asthma Molecular Phenotype cohort was to characterize phenotypes of severe recurrent wheeze and severe asthma during childhood in terms of triggers (allergic or not), involved cells (eosinophil or neutrophil), and corticoid responsiveness.

METHODS

Children with moderate-to-severe asthma and preschool children with moderate-to-severe recurrent wheeze were enrolled prospectively. They underwent standardized clinical and blood workup, and bronchoalveolar lavage (BAL) evaluation. Cluster analysis was applied to 350 children with 34 variables.

RESULTS

Three clusters were identified: cluster 1, Neutrophilic steroid-refractory recurrent wheeze phenotype, with 138 children uncontrolled despite high-dose inhaled corticosteroids (ICS) (92%, P < .001), with more history of pneumonia (31%, P < .001), more gastroesophageal reflux disease (37%, P < .001), and the highest blood neutrophil count (mean 4.524 cells/mm, P = .05); cluster 2, Severe recurrent wheeze with sensitization to a single aeroallergen (12%, P = .002), with 104 children controlled with high-dose ICS (63%, P < .001); cluster 3, Eosinophilic steroid-refractory asthma phenotype, with 108 children uncontrolled despite high-dose ICS (76%, P < .001) with more allergic rhinitis, atopic dermatitis, and food allergies (82%, 40%, 31%, P < .001, respectively). They also had a higher blood eosinophil count and a higher percentage of BAL eosinophil (506/mm, 2.6%, P < .001 respectively).

CONCLUSIONS

Inflammation pathway of asthma and recurrent wheeze are related to eosinophil cells in older children and neutrophil cells in younger children. These results could improve personalized treatments.

摘要

背景

对于学龄前儿童严重复发性哮喘和儿童严重哮喘的炎症途径知之甚少。

目的

严重哮喘分子表型队列的目的是根据诱因(过敏或非过敏)、涉及的细胞(嗜酸性粒细胞或中性粒细胞)和皮质激素反应性,描述儿童期严重复发性哮喘和严重哮喘的表型。

方法

前瞻性纳入中重度哮喘儿童和中重度复发性哮喘学龄前儿童。他们接受了标准化的临床和血液检查以及支气管肺泡灌洗(BAL)评估。对 350 名儿童的 34 个变量进行了聚类分析。

结果

确定了三个聚类:聚类 1,中性粒细胞类固醇难治性复发性哮喘表型,有 138 名儿童尽管使用高剂量吸入皮质激素(ICS)仍未得到控制(92%,P<0.001),肺炎史更多(31%,P<0.001),胃食管反流病更多(37%,P<0.001),血液中性粒细胞计数最高(平均 4.524 个/mm,P=0.05);聚类 2,对单一过敏原过敏的严重复发性哮喘(12%,P=0.002),有 104 名儿童用高剂量 ICS 控制(63%,P<0.001);聚类 3,嗜酸性粒细胞类固醇难治性哮喘表型,有 108 名儿童尽管使用高剂量 ICS 仍未得到控制(76%,P<0.001),过敏性鼻炎、特应性皮炎和食物过敏更多(82%、40%、31%,分别 P<0.001)。他们的血液嗜酸性粒细胞计数和 BAL 嗜酸性粒细胞百分比也更高(506/mm,2.6%,P<0.001)。

结论

哮喘和复发性哮喘的炎症途径与年龄较大的儿童中的嗜酸性粒细胞细胞和年龄较小的儿童中的中性粒细胞细胞有关。这些结果可以改善个体化治疗。

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