COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Department of Food Science, University of Copenhagen, Frederiksberg C, Denmark.
Allergy. 2021 Dec;76(12):3713-3722. doi: 10.1111/all.14862. Epub 2021 May 3.
The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood.
We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one-month-old healthy neonates from the COPSAC birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6 years. Principal component analyses were used to describe the airway cytokine and chemokine composition.
A neonatal airway immune profile particularly characterized by enhanced IL-1β and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune-associated markers, including IL-1β and CXCL8, showed trend of association with development of early asthma endpoints.
Development of early asthma endpoints and inhalant allergy during the first 6 years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre- and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy.
免疫系统在哮喘和过敏的发病机制中起着关键作用，但在症状出现之前的生命早期，气道细胞因子和趋化因子组成在体内的作用尚未被描述。在这里，我们旨在研究新生儿气道免疫组成是否与儿童期过敏和哮喘的发展有关。
我们测量了来自 COPSAC 出生队列的 620 名一个月大的健康新生儿的气道黏膜衬液中与 1 型、2 型、17 型或调节性免疫途径相关的 20 种免疫介质的未刺激水平。过敏和哮喘通过预先定义的算法和 6 岁时的客观评估在我们的研究诊所中诊断。主成分分析用于描述气道细胞因子和趋化因子组成。
新生儿气道免疫特征特别表现为 IL-1β 增强和 CCL26 减少，与以后发展为吸入过敏原特异性 IgE 升高、皮肤点刺试验阳性和过敏性鼻炎显著相关，但与食物过敏无关。相反，减少的 17 型免疫相关标志物，包括 IL-1β 和 CXCL8，与早期哮喘终点的发展呈趋势相关。
6 岁以下儿童早期哮喘终点和吸入性过敏的发展似乎与新生儿期明显失调的气道免疫特征有关，这表明儿童哮喘和过敏具有早期起源和不同的发病机制。这些探索性发现表明，产前和围产期是预防哮喘和吸入性过敏的重要机会窗口。
