背景：早期儿童期喘息具有异质性的轨迹，并与后期哮喘发展具有不同的联系。
目的：本研究旨在确定早期喘息轨迹如何影响后期哮喘基因表达。
方法：儿童呼吸环境工作组是由12个出生队列组成的集合，其中7个队列进行了额外的访问，并收集了鼻腔灌洗液，并对其进行了批量RNA测序。早期喘息轨迹通过对纵向早期喘息数据进行潜在类别分析来定义。加权基因关联网络分析被用来将基因表达模式与当前哮喘与早期喘息轨迹联系起来。
结果：共纳入743名儿童（平均年龄17±5.1岁；360名[48.5%]为男性）。识别出了四种早期喘息模式：不常见型、短暂型、晚发型和持续型。早期短暂性喘息与抗病毒反应相关的基因表达模式相关，晚发型喘息与胰岛素信号传导和葡萄糖代谢下降相关。早期持续性喘息与2型炎症和上皮发育的基因表达模块相关，但这些模块无法区分当前是否患有哮喘。与无哮喘的儿童相比，早期持续性喘息和当前哮喘的儿童显示出富集神经元过程和纤毛上皮功能相关基因表达的独特增加。
结论：早期儿童期的纵向喘息轨迹与后期哮喘转录组的特定特征相关。这些数据表明，针对特定的喘息模式进行干预时，早期哮喘预防策略可能是最有效的。
关键词：喘息；哮喘；转录组学；儿科学
目的：本研究旨在确定早期喘息轨迹如何影响后期哮喘基因表达。
方法：儿童呼吸环境工作组是由12个出生队列组成的集合，其中7个队列进行了额外的访问，并收集了鼻腔灌洗液，并对其进行了批量RNA测序。早期喘息轨迹通过对纵向早期喘息数据进行潜在类别分析来定义。加权基因关联网络分析被用来将基因表达模式与当前哮喘与早期喘息轨迹联系起来。
结果：共纳入743名儿童（平均年龄17±5.1岁；360名[48.5%]为男性）。识别出了四种早期喘息模式：不常见型、短暂型、晚发型和持续型。早期短暂性喘息与抗病毒反应相关的基因表达模式相关，晚发型喘息与胰岛素信号传导和葡萄糖代谢下降相关。早期持续性喘息与2型炎症和上皮发育的基因表达模块相关，但这些模块无法区分当前是否患有哮喘。与无哮喘的儿童相比，早期持续性喘息和当前哮喘的儿童显示出富集神经元过程和纤毛上皮功能相关基因表达的独特增加。
结论：早期儿童期的纵向喘息轨迹与后期哮喘转录组的特定特征相关。这些数据表明，针对特定的喘息模式进行干预时，早期哮喘预防策略可能是最有效的。
关键词：喘息；哮喘；转录组学；儿科学
（南方医科大学南方医院 黄海伦 龚钊乾 赵海金）
（Phelan K J, Roskin K M, Burkle J W, et al. Early-life wheeze trajectories are associated with distinct asthma transcriptomes later in life[J]. Journal of Allergy and Clinical Immunology, 2025, 156(3): 640-650. DOI: 10.1016/j.jaci.2025.03.020.）
Abstract
Background: Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later-life asthma development.
Objective: We sought to determine how early-life wheeze trajectories impact later life asthma gene expression.
Methods: The Children’s Respiratory Environmental Workgroup is a collective of 12 birth cohorts, 7 of which conducted an additional visit with a nasal lavage collected and subjected to bulk RNA-sequencing. Early-life wheeze trajectories were defined using latent class analysis of longitudinal early-life wheezing data. Weighted gene correlation network analysis was used to associate gene expression patterns and current asthma with early-life wheeze trajectories.
Results：We investigated 743 children (mean age, 17 ± 5.1 years; 360 [48.5%] male). Four patterns of early-life wheeze were identified: infrequent, transient, late-onset, and persistent. Early-life transient wheeze was associated with gene expression patterns related to increased antiviral response, and late-onset wheeze was associated with decreased insulin signaling and glucose metabolism. Early-life persistent wheeze was associated with gene expression modules of type 2 inflammation and epithelial development, but these modules did not distinguish those with current asthma. Children who had persistent wheeze in early life and current asthma displayed a unique increase in expression of genes enriched for neuronal processes and ciliated epithelial function compared with those without asthma.
Conclusion：Early-life longitudinal wheeze trajectories are associated with specific asthma transcriptomes later in life. These data suggest that early-life asthma prevention strategies may be most beneficial when tailored to the specific wheeze pattern.
Key words: Wheeze; asthma; transcriptomic; spediatrics
Background: Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later-life asthma development.
Objective: We sought to determine how early-life wheeze trajectories impact later life asthma gene expression.
Methods: The Children’s Respiratory Environmental Workgroup is a collective of 12 birth cohorts, 7 of which conducted an additional visit with a nasal lavage collected and subjected to bulk RNA-sequencing. Early-life wheeze trajectories were defined using latent class analysis of longitudinal early-life wheezing data. Weighted gene correlation network analysis was used to associate gene expression patterns and current asthma with early-life wheeze trajectories.
Results：We investigated 743 children (mean age, 17 ± 5.1 years; 360 [48.5%] male). Four patterns of early-life wheeze were identified: infrequent, transient, late-onset, and persistent. Early-life transient wheeze was associated with gene expression patterns related to increased antiviral response, and late-onset wheeze was associated with decreased insulin signaling and glucose metabolism. Early-life persistent wheeze was associated with gene expression modules of type 2 inflammation and epithelial development, but these modules did not distinguish those with current asthma. Children who had persistent wheeze in early life and current asthma displayed a unique increase in expression of genes enriched for neuronal processes and ciliated epithelial function compared with those without asthma.
Conclusion：Early-life longitudinal wheeze trajectories are associated with specific asthma transcriptomes later in life. These data suggest that early-life asthma prevention strategies may be most beneficial when tailored to the specific wheeze pattern.
Key words: Wheeze; asthma; transcriptomic; spediatrics
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