Effect and mechanism of allergen-specific immunotherapy on small airway dysfunction in children with asthma.

IF 2.7 3区医学 Q1 PEDIATRICS Pediatric Pulmonology Pub Date : 2024-10-18 DOI:10.1002/ppul.27341

Wenwei Zhong, Xiaolan Ying, Lei Zhang, Wenfang Dong, Jie Lin, Lin Yang, Li Hong, Yong Yin, Jinhong Wu

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Abstract

Background: The purpose of this study was to investigate the effectiveness of allergen-specific immunotherapy (AIT) on small airway dysfunction (SAD) and the underlying mechanism with a special focus on basophils.

Methods: Sixty-five children with mild to moderate asthma who were under regular inhaled corticosteroid (ICS) treatment for more than 1 year but whose FEF₇₅ remained below 65% of the predicted value and had positive results for serum Der p or Der f were enrolled. Children with asthma underwent house dust mite (HDM) subcutaneous immunotherapy (SCIT) treatment for 1 year. Clinical symptoms and lung function were evaluated every 3 months during HDM SCIT treatment. Basophil activation test (BAT) was carried out before and after HDM SCIT treatment. RNA sequencing was performed in isolated basophils from peripheral blood after 6 months of HDM SCIT treatment, followed by GO term and KEGG pathway enrichment analysis between patients with and without HDM SCIT treatment.

Results: HDM AIT treatment ameliorated clinical symptoms while concurrently improved lung function parameters, such as FEV₁/FVC, FEF₇₅, FEF₅₀ and MMEF (p < .05). It is worth noting that FEF₇₅ values showed a highly significant, gradual and persistent increase (from 49.55 ± 1.27% at baseline to 71.89 ± 2.64% after 1 year of therapy) and 22 of 35 patients no longer had SAD after 1 year of treatment. BAT results revealed that AIT treatment significantly reduced basophil activity to the inhalant allergen mixtures containing HDM in vitro challenge from baseline. GO term and KEGG pathway enrichment analysis of basophils revealed that downregulated genes were mainly involved in immune cell activation, antigen presentation, and Th2 cell differentiation.

Conclusions: Our study demonstrated that HDM AIT not only improved SAD related lung function parameters, but also reduced basophil activity. RNA sequencing revealed the inhibition of phagocytosis and the phagosome pathway in basophils which may affect the polarization of Th2 cell differentiation after HDM AIT.

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背景：本研究的目的是探讨过敏原特异性免疫疗法（AIT）对小气道功能障碍（SAD）的疗效及其潜在机制，特别关注嗜碱性粒细胞：本研究旨在探讨过敏原特异性免疫疗法（AIT）对小气道功能障碍（SAD）的疗效及其机制，重点关注嗜碱性粒细胞：方法：研究人员招募了 65 名轻中度哮喘患儿，这些患儿接受常规吸入皮质类固醇（ICS）治疗 1 年以上，但 FEF75 仍低于预测值的 65%，且血清 Der p 或 Der f 检测结果呈阳性。哮喘患儿接受了为期一年的屋尘螨（HDM）皮下免疫疗法（SCIT）治疗。在 HDM 皮下免疫疗法（SCIT）治疗期间，每 3 个月对临床症状和肺功能进行一次评估。在 HDM SCIT 治疗前后进行了嗜碱性粒细胞活化试验（BAT）。在接受 HDM SCIT 治疗 6 个月后，对从外周血中分离的嗜碱性粒细胞进行 RNA 测序，然后对接受和未接受 HDM SCIT 治疗的患者进行 GO 项和 KEGG 通路富集分析：HDM AIT 治疗改善了临床症状，同时改善了肺功能参数，如 FEV1/FVC、FEF75、FEF50 和 MMEF（p 75 值显示了非常显著、渐进和持续的增加（从基线时的 49.55 ± 1.27% 增加到治疗 1 年后的 71.89 ± 2.64%），35 名患者中有 22 人在治疗 1 年后不再患有 SAD。BAT 结果表明，AIT 治疗可显著降低嗜碱性粒细胞对含有 HDM 的吸入性过敏原混合物的体外挑战活性。嗜碱性粒细胞的GO项和KEGG通路富集分析显示，下调的基因主要涉及免疫细胞活化、抗原递呈和Th2细胞分化：我们的研究表明，HDM AIT 不仅能改善与 SAD 相关的肺功能指标，还能降低嗜碱性粒细胞的活性。RNA 测序显示，嗜碱性粒细胞的吞噬作用和吞噬体通路受到抑制，这可能会影响 HDM AIT 后 Th2 细胞的极化分化。

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来源期刊

Pediatric Pulmonology 医学-呼吸系统

CiteScore

6.00

自引率

12.90%

发文量

468

审稿时长

3-8 weeks

期刊介绍： Pediatric Pulmonology (PPUL) is the foremost global journal studying the respiratory system in disease and in health as it develops from intrauterine life though adolescence to adulthood. Combining explicit and informative analysis of clinical as well as basic scientific research, PPUL provides a look at the many facets of respiratory system disorders in infants and children, ranging from pathological anatomy, developmental issues, and pathophysiology to infectious disease, asthma, cystic fibrosis, and airborne toxins. Focused attention is given to the reporting of diagnostic and therapeutic methods for neonates, preschool children, and adolescents, the enduring effects of childhood respiratory diseases, and newly described infectious diseases. PPUL concentrates on subject matters of crucial interest to specialists preparing for the Pediatric Subspecialty Examinations in the United States and other countries. With its attentive coverage and extensive clinical data, this journal is a principle source for pediatricians in practice and in training and a must have for all pediatric pulmonologists.