Department of Otolaryngology, Tucson, Ariz; College of Medicine, Tucson, Ariz; Asthma/Airway Disease Research Center, Tucson, Ariz; University of Arizona BIO5 Institute, University of Arizona, Tucson, Ariz.
Department of Biomedical Informatics, the University of Utah School of Medicine, Salt Lake City, Utah.
J Allergy Clin Immunol. 2022 Sep;150(3):604-611. doi: 10.1016/j.jaci.2022.03.020. Epub 2022 Mar 31.
The study of pathogenic mechanisms in adult asthma is often marred by a lack of precise information about the natural history of the disease. Children who have persistent wheezing (PW) during the first 6 years of life and whose symptoms start before age 3 years (PW) are much more likely to have wheezing illnesses due to rhinovirus (RV) in infancy and to have asthma into adult life than are those who do not have PW (PW).
Our aim was to determine whether nasal epithelial cells from PW asthmatic adults as compared with cells from PW asthmatic adults show distinct biomechanistic processes activated by RV exposure.
Air-liquid interface cultures derived from nasal epithelial cells of 36-year old participants with active asthma with and without a history of PW in childhood (10 PW participants and 20 PW participants) from the Tucson Children's Respiratory Study were challenged with a human RV-A strain (RV-A16) or control, and their RNA was sequenced.
A total of 35 differentially expressed genes involved in extracellular remodeling and angiogenesis distinguished the PW group from the PW group at baseline and after RV-A stimulation. Notably, 22 transcriptomic pathways showed PW-by-RV interactions; the pathways were invariably overactivated in PW patients, and were involved in Toll-like receptor- and cytokine-mediated responses, remodeling, and angiogenic processes.
Asthmatic adults with a history of persistent wheeze in the first 6 years of life have specific biomolecular alterations in response 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.
成人哮喘发病机制的研究常常因缺乏对疾病自然史的准确信息而受到阻碍。在生命的头 6 年中持续喘息（PW）且症状在 3 岁之前开始的儿童，比没有 PW 的儿童（PW）更有可能在婴儿期因鼻病毒（RV）引起喘息性疾病，并在成年后患有哮喘。
我们的目的是确定与 PW 非哮喘成年患者相比，PW 哮喘成年患者的鼻上皮细胞在暴露于 RV 后是否表现出不同的生物力学过程。
来自图森儿童呼吸研究的 36 岁患有活跃性哮喘且有或无儿童期 PW 史（10 名 PW 参与者和 20 名 PW 参与者）的参与者的鼻上皮细胞衍生的气液界面培养物，用人类 RV-A 株（RV-A16）或对照物进行刺激，并对其 RNA 进行测序。
在基线和 RV-A 刺激后，共有 35 个涉及细胞外重塑和血管生成的差异表达基因将 PW 组与 PW 组区分开来。值得注意的是，22 个转录组途径显示 PW 与 RV 相互作用；这些途径在 PW 患者中始终过度激活，并且与 Toll 样受体和细胞因子介导的反应、重塑和血管生成过程有关。
在生命的头 6 年中持续喘息的有 PW 史的哮喘成年患者对 RV-A 有特定的生物分子改变，而没有这种病史的患者则没有这些改变。针对这些机制可能会减缓这些患者哮喘的进展。
