通过上皮细胞对鼻病毒的反应识别成人早期哮喘的表型
2022/04/19
摘要
背景：成人哮喘发病机制的研究往往因缺乏该病自然史的准确信息而存在缺陷。与没有持续性喘息的儿童（PW-）相比，在出生后的前6年有持续性喘息且症状在3岁前开始的儿童（PW+）更容易在婴儿期因鼻病毒（RV）而患上喘息性疾病，并在成年前患上哮喘。
目的：确定PW+成人哮喘患者的鼻上皮细胞与PW-成人哮喘患者的鼻上皮细胞相比，是否具有不同的RV暴露激活的生物学机制。
方法：对来自图森儿童呼吸研究中的30名36岁活动性哮喘患者（有或无持续性喘息史，PW+：n=10，PW-：n=20）鼻腔上皮细胞的气液界面（ALI）培养物使用人类RV-a菌株（RV-A16）或对照进行激发，并对其RNA进行测序。
结果：35个参与细胞外重塑和血管生成的差异表达基因在基线和RV-A刺激后将PW+与PW-组区分开来。值得注意的是，22条转录组通路显示PW-与RV相互作用，在PW+患者中始终过度激活，并参与toll样受体和细胞因子介导的反应、重塑和血管生成过程。
结论：在出生后前6年有持续性喘息史的成人哮喘患者对RV-A的反应有特异性的生物分子改变，而在没有这种病史的患者中不存在这种改变。靶向这些机制可能会减缓这些患者的哮喘进展。
Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults
Eugene H Chang, Nima Pouladi, Stefano Guerra, Jana Jandova, Alexander Kim, Haiquan Li, Jianrong Li, Wayne Morgan, Debra A Stern, Amanda L Willis, Yves A Lussier, Fernando D Martinez
Abstract
Background：The study of pathogenic mechanisms in adult asthma is often marred by the lack of precise information about the natural history of the disease. Children who have persistent wheezing during the first 6 years of life and whose symptoms start before age 3 (PW+) are much more likely to have wheezing illnesses due to rhinovirus (RV) in infancy and to have asthma up to adult life than those who do not have persistent wheezing (PW-).
Objective：To determine if nasal epithelial cells from PW+ adult asthmatics as compared with cells from PW- adult asthmatics show distinct biomechanistic processes activated by RV exposure.
Methods：Air-liquid-interface (ALI) cultures derived from nasal epithelial cells of thirty 36-year old participants with active asthma with and without a history of persistent wheeze in childhood (PW+: n=10, PW-: n=20) from the Tucson Children's Respiratory Study were challenged with a human RV-A strain (RV-A16) or control and their RNA was sequenced.
Results：35 differentially expressed genes involved in extracellular remodeling and angiogenesis distinguished the PW+ from the PW- group at baseline and after RV-A stimulation. Notably, 22 transcriptomic pathways showed PW-by-RV interactions, were invariably overactivated in PW+ patients and involved in toll-like receptor and cytokine-mediated responses, remodeling and angiogenic processes.
Conclusions：Adult asthmatics with a history of persistent wheeze in the first 6 years of life have specific biomolecular alterations in responses to RV-A that are not present in patients without such a history. Targeting these mechanisms may slow the progression of asthma in these patients.
背景：成人哮喘发病机制的研究往往因缺乏该病自然史的准确信息而存在缺陷。与没有持续性喘息的儿童（PW-）相比，在出生后的前6年有持续性喘息且症状在3岁前开始的儿童（PW+）更容易在婴儿期因鼻病毒（RV）而患上喘息性疾病，并在成年前患上哮喘。
目的：确定PW+成人哮喘患者的鼻上皮细胞与PW-成人哮喘患者的鼻上皮细胞相比，是否具有不同的RV暴露激活的生物学机制。
方法：对来自图森儿童呼吸研究中的30名36岁活动性哮喘患者（有或无持续性喘息史，PW+：n=10，PW-：n=20）鼻腔上皮细胞的气液界面（ALI）培养物使用人类RV-a菌株（RV-A16）或对照进行激发，并对其RNA进行测序。
结果：35个参与细胞外重塑和血管生成的差异表达基因在基线和RV-A刺激后将PW+与PW-组区分开来。值得注意的是，22条转录组通路显示PW-与RV相互作用，在PW+患者中始终过度激活，并参与toll样受体和细胞因子介导的反应、重塑和血管生成过程。
结论：在出生后前6年有持续性喘息史的成人哮喘患者对RV-A的反应有特异性的生物分子改变，而在没有这种病史的患者中不存在这种改变。靶向这些机制可能会减缓这些患者的哮喘进展。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2022 Mar 31;S0091-6749(22)00440-7. doi: 10.1016/j.jaci.2022.03.020.)
(J Allergy Clin Immunol. 2022 Mar 31;S0091-6749(22)00440-7. doi: 10.1016/j.jaci.2022.03.020.)
Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults
Eugene H Chang, Nima Pouladi, Stefano Guerra, Jana Jandova, Alexander Kim, Haiquan Li, Jianrong Li, Wayne Morgan, Debra A Stern, Amanda L Willis, Yves A Lussier, Fernando D Martinez
Abstract
Background：The study of pathogenic mechanisms in adult asthma is often marred by the lack of precise information about the natural history of the disease. Children who have persistent wheezing during the first 6 years of life and whose symptoms start before age 3 (PW+) are much more likely to have wheezing illnesses due to rhinovirus (RV) in infancy and to have asthma up to adult life than those who do not have persistent wheezing (PW-).
Objective：To determine if nasal epithelial cells from PW+ adult asthmatics as compared with cells from PW- adult asthmatics show distinct biomechanistic processes activated by RV exposure.
Methods：Air-liquid-interface (ALI) cultures derived from nasal epithelial cells of thirty 36-year old participants with active asthma with and without a history of persistent wheeze in childhood (PW+: n=10, PW-: n=20) from the Tucson Children's Respiratory Study were challenged with a human RV-A strain (RV-A16) or control and their RNA was sequenced.
Results：35 differentially expressed genes involved in extracellular remodeling and angiogenesis distinguished the PW+ from the PW- group at baseline and after RV-A stimulation. Notably, 22 transcriptomic pathways showed PW-by-RV interactions, were invariably overactivated in PW+ patients and involved in toll-like receptor and cytokine-mediated responses, remodeling and angiogenic processes.
Conclusions：Adult asthmatics with a history of persistent wheeze in the first 6 years of life have specific biomolecular alterations in responses to RV-A that are not present in patients without such a history. Targeting these mechanisms may slow the progression of asthma in these patients.
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