Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults.
Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults.
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上皮细胞对鼻病毒的反应确定了成人早期发病的哮喘表型。
DOI：
10.1016/j.jaci.2022.03.020
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发表时间：
2022-09
影响因子：
14.2
通讯作者：
Martinez, Fernando D.
中科院分区：
文献类型：
--
作者：
Chang, Eugene H.;Pouladi, Nima;Guerra, Stefano;Jandova, Jana;Kim, Alexander;Li, Haiquan;Li, Jianrong;Morgan, Wayne;Stern, Debra A.;Willis, Amanda L.;Lussier, Yves A.;Martinez, Fernando D.
关键词：
对成人哮喘发病机制的研究常常由于缺乏关于疾病自然史的精确信息而受到损害。在生命的前6年内有持续喘息且症状在3岁之前开始的儿童（PW+）在婴儿期因鼻病毒（RV）而更有可能患有喘息疾病，并且比没有持续喘息的儿童（PW-）更有可能患有哮喘直至成年。确定PW+成人哮喘患者的鼻上皮细胞与PW−成人哮喘患者的细胞相比是否显示出RV暴露激活的不同生物力学过程。采用人RV-A株（RV-A16）或对照株激发30例36岁Tucson儿童呼吸研究中有或无儿童期持续喘息史的活动性哮喘参与者（PW+：n=10，PW-：n=20）的鼻上皮细胞的气液界面（ALI）培养物，并对其RNA进行测序。在基线和RV-A刺激后，35个参与细胞外重塑和血管生成的差异表达基因将PW+与PW−组区分开来。值得注意的是，22个转录组通路显示PW-RV相互作用，在PW+患者中总是过度激活，并参与toll样受体和精氨酸介导的反应、重塑和血管生成过程。在出生后6年内有持续喘息病史的成人哮喘患者对RV-A的反应有特定的生物分子改变，而没有这种病史的患者则没有这种改变。针对这些机制可能会减缓这些患者的哮喘进展。呼吸道上皮细胞对人鼻病毒感染的反应改变是一种常见的特异性哮喘亚型的特征，其在学龄前开始为持续喘息，并持续到成年哮喘。
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−). 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. 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. 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. 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. Alterations in response to human rhinovirus infection by airway epithelial cells characterize a common specific asthma subtype that starts in the preschool years as persistent wheezing and continues into adult life with asthma.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
母乳喂养对成年后反复咳嗽的保护作用。
影响因子：
10
作者：
Gerhart KD;Stern DA;Guerra S;Morgan WJ;Martinez FD;Wright AL
通讯作者：
Wright AL
DOI：
10.1093/infdis/jiy629
发表时间：
2019-06-19
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Gern JE;Lee WM;Swenson CA;Nakagome K;Lee I;Wolff M;Grindle K;Sigelman S;Liggett SB;Togias A;Evans M;Denlinger L;Gangnon R;Bochkov YA;Crisafi G
通讯作者：
Crisafi G
DOI：
10.1136/amiajnl-2012-001519
发表时间：
2013-07
期刊：
Journal of the American Medical Informatics Association : JAMIA
影响因子：
--
作者：
Lee Y;Li H;Li J;Rebman E;Achour I;Regan KE;Gamazon ER;Chen JL;Yang XH;Cox NJ;Lussier YA
通讯作者：
Lussier YA
影响因子：
14.2
作者：
Baines, Katherine J.;Simpson, Jodie L.;Gibson, Peter G.
通讯作者：
Gibson, Peter G.