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了解实验性鼻病毒感染引起的哮喘反应:探索阻断 IgE 的影响。

Understanding the asthmatic response to an experimental rhinovirus infection: Exploring the effects of blocking IgE.

机构信息

Asthma and Allergic Diseases Center, University of Virginia, Charlottsville, Va; Division of Pediatric Respiratory Medicine, University of Virginia, Charlottsville, Va.

Asthma and Allergic Diseases Center, University of Virginia, Charlottsville, Va.

出版信息

J Allergy Clin Immunol. 2020 Sep;146(3):545-554. doi: 10.1016/j.jaci.2020.01.035. Epub 2020 Feb 1.

Abstract

BACKGROUND

Rhinovirus frequently causes asthma exacerbations among children and young adults who are allergic. The interaction between allergen and rhinovirus-induced symptoms and inflammation over time is unclear.

OBJECTIVE

Our aim was to compare the response to an experimental inoculation with rhinovirus-16 in allergic asthmatics with the response in healthy controls and to evaluate the effects of administrating omalizumab before and during the infection.

METHODS

Two clinical trials were run in parallel. In one of these trials, the response to an experimental inoculation with rhinovirus-16 among asthmatics with high levels of total IgE was compared to the response in healthy controls. The other trial compared the effects of administering omalizumab versus placebo to asthmatics in a randomized, double-blind placebo-controlled investigation. The primary outcome for both trials compared lower respiratory tract symptoms (LRTSs) between study groups over the first 4 days of infection.

RESULTS

Frequent comparisons of symptoms, lung function, and blood eosinophil counts revealed differences that were more pronounced among allergic asthmatics than among controls by days 2 and 3 after virus inoculation. Additionally, an augmentation of upper respiratory tract symptom scores and LRTS scores occurred among the atopic asthmatics versus the controls during the resolution of symptoms (P < .01 for upper respiratory symptom tract scores and P < .001 for LRTS scores). The beneficial effects of administering omalizumab on reducing LRTSs and improving lung function were strongest over the first 4 days.

CONCLUSIONS

LRTSs and blood eosinophil counts were augmented and lung function was reduced among allergic asthmatics early after rhinovirus inoculation but increased late in the infection during symptom resolution. The effect of administering omalizumab on the response to rhinovirus was most pronounced during the early/innate phase of the infection.

摘要

背景

鼻病毒常引起过敏的儿童和青年哮喘加重。过敏原与鼻病毒诱导的症状和炎症随时间的相互作用尚不清楚。

目的

我们的目的是比较过敏哮喘患者对鼻病毒-16 实验接种的反应与健康对照者的反应,并评估在感染前和感染期间给予奥马珠单抗的效果。

方法

平行进行了两项临床试验。其中一项试验比较了高水平总 IgE 的哮喘患者对鼻病毒-16 实验接种的反应与健康对照者的反应。另一项试验比较了奥马珠单抗与安慰剂对随机、双盲、安慰剂对照研究中哮喘患者的影响。两项试验的主要结局均为比较感染后前 4 天研究组下呼吸道症状(LRTS)。

结果

频繁比较症状、肺功能和血嗜酸性粒细胞计数,结果显示在病毒接种后第 2 和第 3 天,过敏哮喘患者与对照组之间的差异更为明显。此外,在症状缓解期间(上呼吸道症状评分 P <.01,LRTS 评分 P <.001),特应性哮喘患者的上呼吸道症状评分和 LRTS 评分均增加。给予奥马珠单抗可减轻 LRTSs 和改善肺功能,在前 4 天内效果最强。

结论

在鼻病毒接种后早期,过敏哮喘患者的 LRTSs 和血嗜酸性粒细胞计数增加,肺功能降低,但在感染后期症状缓解时增加。奥马珠单抗对鼻病毒反应的影响在感染的早期/先天阶段最为明显。

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