Lung Lavage Granulocyte Patterns and Clinical Phenotypes in Children with Severe, Therapy-Resistant Asthma
Lung Lavage Granulocyte Patterns and Clinical Phenotypes in Children with Severe, Therapy-Resistant Asthma
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DOI：
10.1016/j.jaip.2018.12.027
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发表时间：
2019-07-01
影响因子：
9.4
通讯作者：
Borish, Larry
中科院分区：
文献类型：
--
作者：
Teague, W. Gerald;Lawrence, Monica G.;Borish, Larry
背景：重度哮喘儿童尽管根据指南使用大剂量皮质类固醇治疗，但仍频繁发生急性发作。难治性肺部炎症和感染性物种作为儿童哮喘控制不佳的因素的重要性知之甚少。目的：为了确定流行的粒细胞模式和潜在的病原体作为修订治疗的目标，126名患有严重哮喘的儿童接受了临床指征支气管镜检查。方法：诊断试验包括支气管肺泡灌洗（BAL）细胞计数和分类，细菌和病毒的研究，肺量测定，血嗜酸性粒细胞，总IgE和过敏原特异性IgE的测量。结果：少粒细胞型BAL是最常见的粒细胞类型（52%），与混合粒细胞型BAL相比，少粒细胞型BAL的儿童支气管扩张剂后气流受限较少，血嗜酸性粒细胞增多较少，BAL肠道病毒检出较少。与混合粒细胞BAL相比，孤立性嗜酸性粒细胞BAL的儿童血嗜酸性粒细胞较少，但与少粒细胞BAL相比，潜在细菌病原体的患病率较高。孤立性嗜酸性粒细胞增多性BAL患儿的特征与混合性粒细胞性BAL相似。混合粒细胞BAL的儿童需要更多的维持泼尼松，并有更大的血嗜酸性粒细胞和过敏原致敏性与少粒细胞BAL.CONCLUSIONS相比：在儿童严重，治疗抵抗性哮喘，BAL粒细胞模式和感染性物种与新的表型特征，可以告知特定的路径修改治疗。在32%的儿童中，BAL显示皮质类固醇难治性嗜酸性粒细胞浸润，抗T（H）2生物治疗，12%，可治疗的细菌病原体。(C)2019年美国过敏、哮喘和免疫学会
BACKGROUND: Children with severe asthma have frequent exacerbations despite guidelines-based treatment with high-dose corticosteroids. The importance of refractory lung inflammation and infectious species as factors contributing to poorly controlled asthma in children is poorly understood.OBJECTIVE: To identify prevalent granulocyte patterns and potential pathogens as targets for revised treatment, 126 children with severe asthma underwent clinically indicated bronchoscopy.METHODS: Diagnostic tests included bronchoalveolar lavage (BAL) for cell count and differential, bacterial and viral studies, spirometry, and measurements of blood eosinophils, total IgE, and allergen-specific IgE. Outcomes were compared among 4 BAL granulocyte patterns.RESULTS: Pauci-granulocytic BAL was the most prevalent granulocyte category (52%), and children with pauci-granulocytic BAL had less postbronchodilator airflow limitation, less blood eosinophilia, and less detection of BAL enterovirus compared with children with mixed granulocytic BAL. Children with isolated neutrophilia BAL were differentiated by less blood eosinophilia than those with mixed granulocytic BAL, but greater prevalence of potential bacterial pathogens compared with those with pauci-granulocytic BAL. Children with isolated eosinophilia BAL had features similar to those with mixed granulocytic BAL. Children with mixed granulocytic BAL took more maintenance prednisone, and had greater blood eosinophilia and allergen sensitization compared with those with pauci-granulocytic BAL.CONCLUSIONS: In children with severe, therapy-resistant asthma, BAL granulocyte patterns and infectious species are associated with novel phenotypic features that can inform pathway-specific revisions in treatment. In 32% of children evaluated, BAL revealed corticosteroid-refractory eosinophilic infiltration amenable to anti-T(H)2 biological therapies, and in 12%, a treatable bacterial pathogen. (C) 2019 American Academy of Allergy, Asthma & Immunology