BACKGROUND Clinical trials and real-world experience have provided evidence for the clinical benefit of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exists regarding the impact of mepolizumab on airway remodelling. OBJECTIVE We thus investigated the effect of mepolizumab on airway structural remodelling in patients treated for severe asthma in routine clinical care. METHODS MESILICO 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 sub-study. The findings were related to clinical outcome. RESULTS After 12 months, mepolizumab treatment was associated with significant improvements in lung function and ACT 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 and extent of epithelial damage, as well as a decrease in tissue eosinophil numbers (all p<0.001). The extent of ASMLT reduction positively correlated with the submucosal eosinophil reduction (r= 0.599, p<0.001). CONCLUSION This study identifies that 12 month of mepolizumab treatment in patients with late-onset severe asthma, who are also characterized by eosinophilic and impaired reversibility phenotypes, leads not only to clinical improvement but also reduces indices of airway tissue remodelling suggestive of a disease modifying effect.

中文翻译：

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美泊利单抗对嗜酸性粒细胞表型的晚发性严重哮喘患者气道重塑的影响。


背景 临床试验和真实世界经验为抗 IL-5 生物制剂美泊利单抗在严重哮喘中的临床益处提供了证据。然而，关于 mepolizumab 对气道重塑影响的数据有限。目的 因此，我们研究了美泊利单抗对常规临床护理中接受严重哮喘治疗的患者气道结构重塑的影响。方法 MESILICO 是一项涉及希腊 8 个肺病学科室的多中心研究。本研究的重点是开始使用美泊利单抗治疗嗜酸性粒细胞表型的严重哮喘，并患有阻塞性病变 （可逆性受损） 的晚发性疾病的患者。招募了 47 名患者，其中 41 名参加了支气管镜检查子研究。这些发现与临床结局有关。结果 12 个月后，美泊利单抗治疗与肺功能和 ACT 评分的显着改善相关，同时严重恶化事件显着减少 （p<0.001）。41 名参与者中有 34 名 （83%） 进行了配对活检以进行比较分析。基底下膜厚度、气道平滑肌面积、气道平滑肌层厚度和上皮损伤程度较基线显著减少，组织嗜酸性粒细胞数量减少 （均 p<0.001）。ASMLT 降低的程度与粘膜下嗜酸性粒细胞减少呈正相关 （r= 0.599，p<0.001）。结论 本研究确定，晚发性严重哮喘患者接受美泊利单抗治疗 12 个月，这些患者也以嗜酸性粒细胞和可逆性表型受损为特征，不仅导致临床改善，而且降低气道组织重塑指数，提示疾病缓解作用。