Child Health Research Center, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va; Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.
Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va; Division of Allergy, Asthma, and Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
J Allergy Clin Immunol Pract. 2021 Jul;9(7):2792-2801.e4. doi: 10.1016/j.jaip.2021.03.059. Epub 2021 Apr 24.
Preschool children with treatment-refractory wheeze often require unscheduled acute care. Current guidelines advise treatment of persistent wheeze with inhaled corticosteroids. Alternative treatments targeting structural abnormalities and specific inflammatory patterns could be more effective.
To apply unsupervised analysis of lung lavage (bronchoalveolar lavage [BAL]) variables to identify clusters of preschool children with treatment-refractory wheeze.
A total of 155 children 6 years or younger underwent bronchoscopy with BAL for evaluation of airway structure, inflammatory markers, and pathogens. Variables were screened with factor analysis and sorted into clusters by Ward's method, and membership was confirmed by discriminant analysis.
The model was repeatable in a 48-case validation sample and accurately classified 86% of cases. Cluster 1 (n = 60) had early-onset wheeze, 85% with structural abnormalities, mostly tracheamalacia, with low total IgE and agranulocytic BAL. Cluster 2 (n = 42) had later-onset wheeze, the highest prevalence of gastroesophageal reflux, little atopy, and two-third had increased BAL lipid-laden macrophages. Cluster 3 (n = 46) had mid-onset wheeze, low total IgE, and two-third had BAL viral transcripts, predominately human rhinovirus, with BAL neutrophilia. Cluster 4 (n = 7) was older, with high total IgE, blood eosinophilia, and mixed BAL eosinophils and neutrophils.
Preschool children with recurrent wheeze refractory to inhaled corticosteroid treatment include 4 clusters: airway malacia, gastroesophageal reflux, indolent human rhinovirus bronchoalveolitis, and type-2 inflammation. The results support the risk and cost of invasive bronchoscopy to diagnose causes of treatment-refractory wheeze and develop novel therapies targeting airway malacia, human rhinovirus infection, and BAL neutrophilia in preschool children.
治疗抵抗性喘息的学龄前儿童常需要非计划的急性护理。目前的指南建议对持续性喘息采用吸入皮质类固醇治疗。针对结构异常和特定炎症模式的替代治疗可能更有效。
应用未监督的肺灌洗（支气管肺泡灌洗[BAL]）变量分析，以确定治疗抵抗性喘息的学龄前儿童聚类。
共有 155 名 6 岁或以下的儿童接受支气管镜检查和 BAL，以评估气道结构、炎症标志物和病原体。采用因子分析筛选变量，并采用 Ward 法对其进行聚类，通过判别分析确认成员资格。
该模型在 48 例验证样本中具有可重复性，准确分类了 86%的病例。聚类 1（n=60）有早发性喘息，85%有结构异常，主要为气管软化，总 IgE 和无粒细胞 BAL 低。聚类 2（n=42）有晚发性喘息，胃食管反流患病率最高，很少有特应性，三分之二有增加的 BAL 脂质载巨噬细胞。聚类 3（n=46）有中间性喘息，总 IgE 低，三分之二有 BAL 病毒转录物，主要是人鼻病毒，伴有 BAL 中性粒细胞增多。聚类 4（n=7）年龄较大，总 IgE 高，血嗜酸性粒细胞增多，BAL 嗜酸性粒细胞和中性粒细胞混合。
反复喘息且对吸入皮质激素治疗抵抗的学龄前儿童包括 4 个聚类：气道软化、胃食管反流、慢性人类鼻病毒细支气管炎和 2 型炎症。这些结果支持进行有创性支气管镜检查以诊断治疗抵抗性喘息的病因，并为治疗学龄前儿童气道软化、人类鼻病毒感染和 BAL 中性粒细胞增多开发新的治疗方法的风险和成本。
