哮喘联盟

    摘要
    背景：临床试验和真实世界证实重度哮喘患者可以从美泊利单抗（抗 IL-5单抗）治疗中获益。然而，美泊利单抗对气道重塑的确切作用尚不明确。

    目的：探究美泊利单抗对临床中接受常规治疗的重度哮喘患者气道重塑的影响。

    方法：MESILICO研究（探索美泊利单抗对迟发性嗜酸性粒细胞表型且合并气流受限重度哮喘患者的疗效）是一项涉及希腊 8个肺科的多中心研究。共纳入了47例接受美泊利单抗治疗的重度哮喘患者，其中 41 名参加了支气管镜检查的子研究。观察接受美泊利单抗治疗与临床结局的关系。

    结果：接受美泊利单抗治疗12个月后，哮喘患者的肺功能和哮喘控制测试（ACT）评分显著改善，且重度急性加重事件显著减少 （P < 0.001）。34/41（83%）进行了活检分析。结果发现较基线，接受美泊利单抗治疗后基底膜厚度、气道平滑肌面积、气道平滑肌层厚度、上皮损伤程度和组织嗜酸性粒细胞数量均显著降低 （均 P < 0.001），且气道平滑肌层厚度减少的程度与黏膜下嗜酸性粒细胞减少呈正相关（r = 0.599; P < 0.001）。

    结论：美泊利单抗治疗12月可以显著改善迟发性嗜酸性粒细胞且存在持续气流受限的重度哮喘患者临床症状和气道重塑，提示其具有疾病修饰的作用。

    关键词：严重哮喘; 气道重塑; 支气管镜; 嗜酸性; 固定阻塞; 美泊利单抗

     文献来源：（Domvri K, Tsiouprou I, Bakakos P, Steiropoulos P, Katsoulis K, Kostikas K, Antoniou KM, Papaioannou AI, Rovina N, Katsaounou P, Papamitsou T, Pastelli N, Tryfon S, Fouka E, Papakosta D, Loukides S, Porpodis K. Effect of mepolizumab in airway remodeling in patients with late-onset severe asthma with an eosinophilic phenotype. J Allergy Clin Immunol. 2025 Feb;155(2):425-435. doi: 10.1016/j.jaci.2024.10.024）

（南方医科大学南方医院 欧阳文珊 龚钊乾 赵海金）

Abstract

Background: Clinical trials and real-world experience have provided evidence for the clinical benefits of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exist regarding the impact of mepolizumab on airway remodeling.

Objective: We sought to investigate the effect of mepolizumab on airway structural remodeling in patients treated for severe asthma in routine clinical care.

Methods: The MESILICO (Efficacy of Mepolizumab in patients with latE-onset Severe eosInophiLic asthma and fIxed obstruCtiOn) study is a multicenter study involving 8 pulmonology departments in Greece. This study focused on patients who initiated mepolizumab for severe asthma with an eosinophilic phenotype and had late-onset disease with obstructive patterns (impaired reversibility). Forty-seven patients were recruited, of whom 41 were enrolled in the bronchoscopy substudy. The findings were related to clinical outcome.

Results: After 12 months, mepolizumab treatment was associated with significant improvements in lung function and Asthma Control Test score, along with a significant decrease in severe exacerbation events (P < 0.001). Thirty-four of the 41 participants (83%) had paired biopsies for comparative analysis. There was a significant reduction from baseline in sub-basement membrane thickness, airway smooth muscle area, airway smooth muscle layer thickness, extent of epithelial damage, and number of tissue eosinophils (all P < 0.001). The extent of reduction in airway smooth muscle layer thickness positively correlated with the submucosal eosinophil reduction (r = 0.599; P <0 .001).

Conclusions: This study identified that 12 months of mepolizumab treatment in patients with late-onset severe asthma, who are also characterized by eosinophilic and impaired reversibility phenotypes, not only leads to clinical improvement but also reduces indices of airway tissue remodeling suggestive of a disease-modifying effect. 

Keywords: Severe asthma; airway remodeling; bronchoscopy; eosinophilic; fixed obstruction; mepolizumab.