Recurrent Severe Preschool Wheeze: From Prespecified Diagnostic Labels to Underlying Endotypes.
Recurrent Severe Preschool Wheeze: From Prespecified Diagnostic Labels to Underlying Endotypes.
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反复发作的严重学龄前喘息：从预先指定的诊断标签到潜在的内在型。
DOI：
10.1164/rccm.202009-3696oc
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发表时间：
2021-09-01
影响因子：
24.7
通讯作者：
Saglani S
中科院分区：
文献类型：
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作者：
Robinson PFM;Fontanella S;Ananth S;Martin Alonso A;Cook J;Kaya-de Vries D;Polo Silveira L;Gregory L;Lloyd C;Fleming L;Bush A;Custovic A;Saglani S
理由：学龄前喘息具有异质性，但其潜在机制却知之甚少。目的：调查不同临床诊断的学龄前儿童接受选择性支气管镜检查和支气管肺泡灌洗（BAL）时的下呼吸道炎症和感染情况。方法：我们招募了 136 名 1-5 岁儿童（105 名患有复发性严重喘息 [RSW]；31 名患有非喘息性呼吸道疾病 [NWRD]）。患有 RSW 的儿童被分为阵发性病毒性喘息 (EVW) 或多触发性喘息 (MTW)。我们比较了不同临床诊断中的下呼吸道炎症和感染，并进行了数据驱动的分析以确定病理生理学特征的集群，并研究了它们与预先指定的诊断标签的关系。测量和主要结果：RSW 儿童的血液嗜酸性粒细胞计数和百分比以及过敏致敏程度显着高于 NWRD 儿童。各组之间的血液中性粒细胞计数和百分比、BAL 嗜酸性粒细胞和中性粒细胞百分比以及阳性细菌培养和病毒检出率相似。然而，病原体分布存在显着差异，RSW 儿童中鼻病毒的检出率较高，RSW 致敏儿童中莫拉氏菌的检出率较高。患有 EVW 的儿童和患有 MTW 的儿童在血液或 BAL 样本炎症、细菌或病毒检测方面没有差异。 Medoids 算法的分区揭示了四组病理生理学特征：1）特应性（17.9％），2）非特应性，感染率低且大量使用吸入皮质类固醇（31.3％），3）非特应性，感染率高（23.1％），4）非特应性，感染率低且不使用吸入皮质类固醇（27.6％）。 RSW 组和 NWRD 组之间的聚类分配存在显着差异（RSW 均匀分布在各个聚类中，NWRD 组的 60% 被分配到聚类 4；P < 0.001）。 EVW 组和 MTW 组之间的簇成员资格没有差异。簇1以莫拉氏菌检测为主(P = 0.04)，簇3以嗜血杆菌或葡萄球菌或链球菌检测为主(P = 0.02)。结论：我们确定了四组严重学龄前喘息，通过致敏、外周嗜酸性粒细胞增多、下呼吸道中性粒细胞增多和细菌学进行区分。
Rationale: Preschool wheezing is heterogeneous, but the underlying mechanisms are poorly understood. Objectives: To investigate lower airway inflammation and infection in preschool children with different clinical diagnoses undergoing elective bronchoscopy and BAL. Methods: We recruited 136 children aged 1–5 years (105 with recurrent severe wheeze [RSW]; 31 with nonwheezing respiratory disease [NWRD]). Children with RSW were assigned as having episodic viral wheeze (EVW) or multiple-trigger wheeze (MTW). We compared lower airway inflammation and infection in different clinical diagnoses and undertook data-driven analyses to determine clusters of pathophysiological features, and we investigated their relationships with prespecified diagnostic labels. Measurements and Main Results: Blood eosinophil counts and percentages and allergic sensitization were significantly higher in children with RSW than in children with a NWRD. Blood neutrophil counts and percentages, BAL eosinophil and neutrophil percentages, and positive bacterial culture and virus detection rates were similar between groups. However, pathogen distribution differed significantly, with higher detection of rhinovirus in children with RSW and higher detection of Moraxella in sensitized children with RSW. Children with EVW and children with MTW did not differ in terms of blood or BAL-sample inflammation, or bacteria or virus detection. The Partition around Medoids algorithm revealed four clusters of pathophysiological features: 1) atopic (17.9%), 2) nonatopic with a low infection rate and high use of inhaled corticosteroids (31.3%), 3) nonatopic with a high infection rate (23.1%), and 4) nonatopic with a low infection rate and no use of inhaled corticosteroids (27.6%). Cluster allocation differed significantly between the RSW and NWRD groups (RSW was evenly distributed across clusters, and 60% of the NWRD group was assigned to cluster 4; P < 0.001). There was no difference in cluster membership between the EVW and MTW groups. Cluster 1 was dominated by Moraxella detection (P = 0.04), and cluster 3 was dominated by Haemophilus or Staphylococcus or Streptococcus detection (P = 0.02). Conclusions: We identified four clusters of severe preschool wheeze, which were distinguished by using sensitization, peripheral eosinophilia, lower airway neutrophilia, and bacteriology.