BackgroundViral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting.ObjectivesTo investigate in situ virus‐specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma.MethodsWe included 493 episodes of acute respiratory illnesses in 277 children aged 0–3 years from the COPSAC2010 mother–child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high‐sensitivity MesoScale Discovery kits and compared between children with and without viral PCR‐identification in nasopharyngeal samples. Finally, we investigated whether the virus‐specific immune response was associated with asthma by age 6 years.ResultsViral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN‐ɣ, TNF‐α, CCL4, CXCL10 and IL‐10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL‐10 (FDR <0.05) during viral episodes compared to children not developing asthma.ConclusionWe described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL‐10) immune mediator level. This provides insight into the interplay between early‐life viral infections, airway immunity and asthma development.

中文翻译：

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哮喘的发展与生命早期病毒感染期间的低粘膜 IL-10 有关


背景病毒感染是早期严重呼吸系统疾病的常见诱因，也是以后哮喘发展的危险因素。导致哮喘的机制可能涉及对病毒感染的异常气道免疫反应，但这很少在人类环境中进行研究。目的探讨呼吸系统疾病病毒发作期间上气道免疫介质水平的原位病毒特异性差异以及与后期哮喘的相关性。方法我们纳入了 493 例急性呼吸系统疾病发作，涉及 277 名 0-3 岁儿童COPSAC2010母子队列。使用高灵敏度 MesoScale Discovery 试剂盒评估鼻上皮衬里液中 18 种不同免疫介质的水平，并在鼻咽样本中有和没有病毒 PCR 鉴定的儿童之间进行比较。最后，我们调查了病毒特异性免疫反应是否与 6 岁时的哮喘相关。结果病毒检测与几种 1 型和调节免疫介质的上调有关，包括 IFN-ɣ、TNF-α、CCL4、CXCL10 和 IL-10，以及 2 型和 17 型免疫介质的下调，包括 CCL13 和 CXCL8 （FDR <0.05）。与未发生哮喘的儿童相比，患哮喘的儿童在病毒发作期间 IL-10 （FDR <0.05） 水平降低。结论我们描述了生命早期病毒性呼吸系统疾病期间的气道免疫介质概况，并表明 6 岁时发生哮喘的儿童调节 （IL-10） 免疫介质水平降低。这提供了对早期病毒感染、气道免疫和哮喘发展之间相互作用的见解。