Phelan Kieran J, Roskin Krishna M, Burkle Jeffrey W, Chang Wan-Chi, Martin Lisa J, Biagini Jocelyn M, Satish Latha, Haslam David B, Spagna Daniel, Jenkins Seth, Parmar Elsie, Bacharier Leonard B, Gebretsadik Tebeb, Gill Michelle, Gold Diane R, Jackson Daniel J, Johnson Christine C, Lynch Susan V, McCauley Kathryn E, McKennan Chris G, Miller Rachel, Ober Carole, Ownby Dennis R, Ryan Patrick H, Schoettler Nathan, Singh Sweta, Visness Cynthia M, Altman Matthew C, Gern James E, Khurana Hershey Gurjit K
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Division of Biomedical Informatics and Division of Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
J Allergy Clin Immunol. 2025 Apr 4. doi: 10.1016/j.jaci.2025.03.020.
Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later-life asthma development.
We sought to determine how early-life wheeze trajectories impact later life asthma gene expression.
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.
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.
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.
儿童早期喘息的特点是具有异质性轨迹，与后期哮喘的发展存在不同的关联。
我们试图确定儿童早期喘息轨迹如何影响后期哮喘的基因表达。
儿童呼吸环境工作组由12个出生队列组成，其中7个队列进行了额外的随访，收集了鼻灌洗样本并进行了批量RNA测序。利用纵向儿童早期喘息数据的潜在类别分析来定义儿童早期喘息轨迹。采用加权基因共表达网络分析将基因表达模式和当前哮喘与儿童早期喘息轨迹相关联。
我们调查了743名儿童（平均年龄17±5.1岁；360名[48.5%]为男性）。确定了四种儿童早期喘息模式：不频繁、短暂性、迟发性和持续性。儿童早期短暂性喘息与抗病毒反应增强相关的基因表达模式有关，迟发性喘息与胰岛素信号传导和葡萄糖代谢降低有关。儿童早期持续性喘息与2型炎症和上皮发育的基因表达模块有关，但这些模块无法区分当前患有哮喘的儿童。与无哮喘儿童相比，儿童早期有持续性喘息且目前患有哮喘的儿童在富含神经元过程和纤毛上皮功能的基因表达上有独特的增加。
儿童早期纵向喘息轨迹与后期特定的哮喘转录组相关。这些数据表明，针对特定喘息模式量身定制的儿童早期哮喘预防策略可能最有益。
