Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures.

Acute respiratory illness (ARI) is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular mechanisms driving ARI-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of ARI amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. We found that ARI is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during ARI. Most strikingly, we report that asthmatics that experience ARI-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair and the expression of a newly described exacerbation-specific signature. Findings from our study represent a significant contribution towards clarifying the complex molecular interactions which typify ARI-induced asthma exacerbations. Upon the onset of ‘common cold’, volunteers were instructed to attend the first of three required visits to the study clinic. The first and second visits were designed to obtain samples and clinical data during the early and late stages of symptomatic illness respectively, whereas the third visit would occur when volunteers were asymptomatic and serve as a prospective baseline (BL) for the study.

急性呼吸道感染（Acute respiratory illness, ARI）是引发哮喘急性加重的首要诱因，但其二者间关联的分子机制仍未阐明。为弥补我们在ARI诱导哮喘急性加重的分子机制认知上的不足，本研究针对有哮喘病史、过敏性鼻炎病史及无基础呼吸系统疾病的人群，在ARI发病进程中对其鼻黏膜开展了转录谱分析研究。研究发现，ARI以动态、时间特异性的转录谱为特征，其基因表达幅度受基础呼吸系统疾病及ARI诱发的黏膜修复特征影响。最引人注目的是，本研究证实，经历ARI诱导哮喘急性加重的患者，其特征表现为炎症性免疫应答减弱但持续时间延长、黏膜修复激活不足，以及一种新报道的加重特异性特征的表达。本研究结果为阐明ARI诱导哮喘急性加重的典型复杂分子相互作用机制做出了重要贡献。在出现“普通感冒”症状后，受试者需前往研究诊所参与三次规定访视中的首次访视。首次与第二次访视分别用于采集有症状疾病早期及晚期阶段的样本与临床数据，而第三次访视则在受试者无症状时开展，作为本研究的前瞻性基线（BL）。