个人网络推演识别复发性喘息与哮喘高危患儿
2026/04/28
摘要
背景：喘息发作与哮喘急性加重是儿科住院的主要诱因。精准预判患儿是否会出现持续性病情加重，目前仍存在较大挑战。现有研究证实，哮喘急性发作及喘息患儿鼻上皮组织中存在不同免疫内型，各类内型以干扰素与炎症标志物的表达平衡差异为主要特征。其中，干扰素应答水平低下且炎症反应亢进的患儿，反复呼吸道急性加重的发生风险显著升高。
目的：本研究旨在验证基于外周血的基因网络生物标志物，能否检出急性喘息及哮喘患儿的免疫内型，以期为后续病情急性加重风险提供预测依据。
方法：选取因急性喘息、哮喘急性发作入院的儿科患者，采集外周血单个核细胞标本，通过基因芯片开展基因表达谱分析；采用个人网络推演技术解析基因表达模式，据此将患儿疾病划分为不同免疫内型。
结果：KALOS研究入组时间为2020年12月15日至2025年3月21日，LOGOS研究为2021研究共检出三种免疫内型。其中一类内型以干扰素应答不足、固有免疫及适应性免疫通路表达异常升高为核心特征，该内型与患儿远期因呼吸道疾病再次入院风险、长期反复呼吸道加重病程呈显著正相关。
结论：基于外周血单个核细胞的个体化基因网络生物标志物，可有效鉴别与儿童哮喘临床预后密切相关的免疫内型。该高风险免疫内型可作为急性喘息发作阶段的潜在可干预靶点。针对该类患儿，以增强干扰素应答、抑制过度炎症反应为核心的治疗方案，或可改善其临床预后。
Personal network inference identifies children at risk of recurrent wheezing and asthma
Coleman LA, Khoo SK, Bizzintino JA, Franks K, Prastanti F, Borland M, Le Souëf PN, Hancock DG, Karpievitch YV, Bosco A, Laing IA.
Abstract
BACKGROUND:Wheezing and asthma exacerbations are leading causes of pediatric hospital admissions. Predicting which children will experience persistent exacerbations remains challenging. Prior research has identified immune endotypes in the nasal epithelium of children with acute asthma and wheezing, characterized by varying balances of interferons and inflammatory markers. Notably, children exhibiting low interferon responses coupled with high inflammation are at an increased risk for recurrent respiratory exacerbations.
OBJECTIVE:This study aimed to determine if blood-based gene network biomarkers can detect immune endotypes in children presenting with acute wheeze and asthma, potentially serving as predictive tools for future exacerbations.
METHODS:We conducted gene expression analysis using microarrays of peripheral blood mononuclear cell samples from pediatric patients who presented to hospital for acute wheeze and asthma. Personal network inference was used to discern gene expression patterns, facilitating the classification of patients' disease into distinct immune endotypes.
RESULTS:Three immune endotypes were identified. One endotype, characterized by low interferon responses and elevated expression of both innate and adaptive immune pathways, was significantly associated with an increased risk of subsequent hospital respiratory presentations and a persistent pattern of respiratory exacerbations over time.
CONCLUSION:Peripheral blood mononuclear cell-based personal gene network biomarkers can effectively identify immune endotypes correlating with clinical outcomes in pediatric asthma. The high-risk endotype represents a potential treatable trait in acute wheezing episodes. Therapeutic strategies aimed at enhancing interferon responses and/or reducing inflammation may benefit this subgroup.
背景：喘息发作与哮喘急性加重是儿科住院的主要诱因。精准预判患儿是否会出现持续性病情加重，目前仍存在较大挑战。现有研究证实，哮喘急性发作及喘息患儿鼻上皮组织中存在不同免疫内型，各类内型以干扰素与炎症标志物的表达平衡差异为主要特征。其中，干扰素应答水平低下且炎症反应亢进的患儿，反复呼吸道急性加重的发生风险显著升高。
目的：本研究旨在验证基于外周血的基因网络生物标志物，能否检出急性喘息及哮喘患儿的免疫内型，以期为后续病情急性加重风险提供预测依据。
方法：选取因急性喘息、哮喘急性发作入院的儿科患者，采集外周血单个核细胞标本，通过基因芯片开展基因表达谱分析；采用个人网络推演技术解析基因表达模式，据此将患儿疾病划分为不同免疫内型。
结果：KALOS研究入组时间为2020年12月15日至2025年3月21日，LOGOS研究为2021研究共检出三种免疫内型。其中一类内型以干扰素应答不足、固有免疫及适应性免疫通路表达异常升高为核心特征，该内型与患儿远期因呼吸道疾病再次入院风险、长期反复呼吸道加重病程呈显著正相关。
结论：基于外周血单个核细胞的个体化基因网络生物标志物，可有效鉴别与儿童哮喘临床预后密切相关的免疫内型。该高风险免疫内型可作为急性喘息发作阶段的潜在可干预靶点。针对该类患儿，以增强干扰素应答、抑制过度炎症反应为核心的治疗方案，或可改善其临床预后。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2026 Apr 7:S0091-6749(26)00249-6. doi: 10.1016/j.jaci.2026.03.018.）
（J Allergy Clin Immunol. 2026 Apr 7:S0091-6749(26)00249-6. doi: 10.1016/j.jaci.2026.03.018.）
Personal network inference identifies children at risk of recurrent wheezing and asthma
Coleman LA, Khoo SK, Bizzintino JA, Franks K, Prastanti F, Borland M, Le Souëf PN, Hancock DG, Karpievitch YV, Bosco A, Laing IA.
Abstract
BACKGROUND:Wheezing and asthma exacerbations are leading causes of pediatric hospital admissions. Predicting which children will experience persistent exacerbations remains challenging. Prior research has identified immune endotypes in the nasal epithelium of children with acute asthma and wheezing, characterized by varying balances of interferons and inflammatory markers. Notably, children exhibiting low interferon responses coupled with high inflammation are at an increased risk for recurrent respiratory exacerbations.
OBJECTIVE:This study aimed to determine if blood-based gene network biomarkers can detect immune endotypes in children presenting with acute wheeze and asthma, potentially serving as predictive tools for future exacerbations.
METHODS:We conducted gene expression analysis using microarrays of peripheral blood mononuclear cell samples from pediatric patients who presented to hospital for acute wheeze and asthma. Personal network inference was used to discern gene expression patterns, facilitating the classification of patients' disease into distinct immune endotypes.
RESULTS:Three immune endotypes were identified. One endotype, characterized by low interferon responses and elevated expression of both innate and adaptive immune pathways, was significantly associated with an increased risk of subsequent hospital respiratory presentations and a persistent pattern of respiratory exacerbations over time.
CONCLUSION:Peripheral blood mononuclear cell-based personal gene network biomarkers can effectively identify immune endotypes correlating with clinical outcomes in pediatric asthma. The high-risk endotype represents a potential treatable trait in acute wheezing episodes. Therapeutic strategies aimed at enhancing interferon responses and/or reducing inflammation may benefit this subgroup.
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