Bronchoalveolar lavage cytokine patterns in children with severe neutrophilic and paucigranulocytic asthma.
Bronchoalveolar lavage cytokine patterns in children with severe neutrophilic and paucigranulocytic asthma.
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重症中性粒细胞性哮喘和少粒细胞性哮喘患儿的支气管肺泡灌洗细胞因子模式
DOI：
10.1016/j.jaci.2020.05.039
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发表时间：
2021-03
影响因子：
14.2
通讯作者：
Borish, Larry
中科院分区：
文献类型：
--
作者：
Steinke, John W.;Lawrence, Monica G.;Teague, W. Gerald;Braciale, Thomas J.;Patrie, James T.;Borish, Larry
关键词：
哮喘是一种复杂的异质性疾病，发生在成人和儿童中，其特征在于不同的炎症模式。虽然已经在成人中进行了许多研究，但对儿童严重哮喘的异质性知之甚少，特别是涉及空气空间的炎症特征。确定根据嗜中性与非嗜中性支气管肺泡灌洗（BAL）炎性细胞模式分层的严重治疗抵抗性哮喘儿童中支气管肺泡灌洗（BAL）细胞因子/趋化因子表达模式的关系。尽管进行了治疗，但症状控制不佳的重度哮喘儿童接受了诊断性支气管镜检查和BAL。使用多重蛋白质珠测定法测定炎性细胞因子/趋化因子浓度。用无偏聚类方法分析BAL组分揭示了不同的细胞因子/趋化因子模式，这些模式与2型先天性淋巴细胞、单核细胞、中性粒细胞运输和T效应细胞相关的途径一致。与非嗜肺性哮喘相比，除一个例外（VEGF）外，所有检测的细胞因子（27）在BAL嗜肺性哮喘中均过表达，这在交叉验证分析中得到证实。在嗜中性粒细胞队列中，特异性负责Th 17（IL-17、IL-6、G-CSF）和Th 1分化和表达（IL-12、TNF-α、IFN-γ）的细胞因子增强。中性粒细胞组的特征还在于细菌和病毒病原体的较高患病率，然而，细胞因子表达模式独立于病原体表达。结果表明，患有难治性哮喘和嗜酸性炎症的儿童具有与混合Th 17/Th 1/Th 2应答一致的BAL细胞因子模式。与此相反，非嗜中性粒细胞性哮喘独立的细胞因子过度表达。患有难治性哮喘和嗜酸性炎症的儿童具有与混合炎症反应一致的BAL细胞因子模式。与此相反，非嗜中性粒细胞性哮喘独立的细胞因子过度表达。
Asthma is a complex heterogeneous disease occurring in adults and children that is characterized by distinct inflammatory patterns. While numerous studies have been performed in adults, little is known regarding the heterogeneity of severe asthma in children, particularly inflammatory signatures involving the air spaces. To determine the relationship of bronchoalveolar lavage (BAL) cytokine/chemokine expression patterns in children with severe-therapy resistant asthma stratified according to neutrophilic versus non-neutrophilic BAL inflammatory cell patterns. Children with severe asthma with inadequate symptom control despite therapy, underwent diagnostic bronchoscopy and BAL. Inflammatory cytokine/chemokine concentrations were determined using a multiplex protein bead assay. Analysis of BAL constituents with an unbiased clustering approach revealed distinct cytokine/chemokine patterns and these aligned with pathways associated with type 2 innate lymphoid cells, monocytes, neutrophil trafficking, and T effector cells. All cytokines examined (27) with one exception (VEGF) were over-expressed with BAL neutrophilia compared to non-neutrophilic asthma and this was confirmed in a cross-validation analysis. Cytokines specifically responsible for Th17 (IL-17, IL-6, G-CSF) and Th1 differentiation and expression (IL-12, TNF-α, IFN-γ) were enhanced in the neutrophilic cohorts. Neutrophilic groups were also characterized by higher prevalence of bacterial and viral pathogens, however, cytokine expression patterns manifested independently of pathogen expression. The results demonstrate that children with refractory asthma and neutrophilic inflammation had a BAL cytokine pattern consistent with a mixed Th17/Th1/Th2 response. In contrast, non-neutrophilic asthma presented independently of cytokine overexpression. Children with refractory asthma and neutrophilic inflammation have a BAL cytokine pattern consistent with a mixed inflammatory response. In contrast, non-neutrophilic asthma presented independently of cytokine overexpression.
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影响因子：
14.2
作者：
Moore, Wendy C.;Hastie, Annette T.;Li, Xingnan;Li, Huashi;Busse, William W.;Jarjour, Nizar N.;Wenzel, Sally E.;Peters, Stephen P.;Meyers, Deborah A.;Bleecker, Eugene R.
通讯作者：
Bleecker, Eugene R.
DOI：
10.1016/j.jaip.2018.12.027
发表时间：
2019-07-01
影响因子：
9.4
作者：
Teague, W. Gerald;Lawrence, Monica G.;Borish, Larry
通讯作者：
Borish, Larry
DOI：
10.1001/jama.2015.13896
发表时间：
2015-11-17
期刊：
JAMA
影响因子：
--
作者：
Bacharier LB;Guilbert TW;Mauger DT;Boehmer S;Beigelman A;Fitzpatrick AM;Jackson DJ;Baxi SN;Benson M;Burnham CD;Cabana M;Castro M;Chmiel JF;Covar R;Daines M;Gaffin JM;Gentile DA;Holguin F;Israel E;Kelly HW;Lazarus SC;Lemanske RF Jr;Ly N;Meade K;Morgan W;Moy J;Olin T;Peters SP;Phipatanakul W;Pongracic JA;Raissy HH;Ross K;Sheehan WJ;Sorkness C;Szefler SJ;Teague WG;Thyne S;Martinez FD
通讯作者：
Martinez FD
影响因子：
9.6
作者：
Gibson, PG;Simpson, JL;Saltos, N
通讯作者：
Saltos, N
影响因子：
32.4
作者：
Woytschak, Janine;Keller, Nadia;Boyman, Onur
通讯作者：
Boyman, Onur