Domvri Kalliopi, Tsiouprou Ioanna, Bakakos Petros, Steiropoulos Paschalis, Katsoulis Konstantinos, Kostikas Konstantinos, Antoniou Katerina M, Papaioannou Andriana I, Rovina Nikoletta, Katsaounou Paraskevi, Papamitsou Theodora, Pastelli Nicoleta, Tryfon Stavros, Fouka Evangelia, Papakosta Despoina, Loukides Stelios, Porpodis Konstantinos
Pulmonary Department, George Papanikolaou Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; Laboratory of Histology-Embryology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Pathology, George Papanikolaou General Hospital of Thessaloniki, Thessaloniki, Greece.
Pulmonary Department, George Papanikolaou Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
J Allergy Clin Immunol. 2025 Feb;155(2):425-435. doi: 10.1016/j.jaci.2024.10.024. Epub 2024 Nov 7.
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.
We sought to investigate the effect of mepolizumab on airway structural remodeling in patients treated for severe asthma in routine clinical care.
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.
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 < .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 < .001). The extent of reduction in airway smooth muscle layer thickness positively correlated with the submucosal eosinophil reduction (r = 0.599; P < .001).
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.
临床试验和真实世界经验已为抗白细胞介素-5生物制剂美泊利珠单抗在重度哮喘中的临床益处提供了证据。然而，关于美泊利珠单抗对气道重塑影响的数据有限。
我们试图研究美泊利珠单抗对在常规临床治疗中接受重度哮喘治疗患者气道结构重塑的影响。
MESILICO（美泊利珠单抗在迟发性重度嗜酸性粒细胞性哮喘和固定性阻塞患者中的疗效）研究是一项多中心研究，涉及希腊的8个肺病科。本研究聚焦于因嗜酸性粒细胞性表型的重度哮喘而开始使用美泊利珠单抗且患有迟发性疾病并伴有阻塞模式（可逆性受损）的患者。招募了47名患者，其中41名纳入了支气管镜检查子研究。研究结果与临床结局相关。
12个月后，美泊利珠单抗治疗与肺功能和哮喘控制测试评分的显著改善相关，同时严重加重事件显著减少（P <.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。基底膜下厚度、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较基线均有显著降低（均P <.001）。气道平滑肌层厚度的降低程度与黏膜下嗜酸性粒细胞减少呈正相关（r = 0.599；P <.001）。
本研究表明，在具有嗜酸性粒细胞性和可逆性受损表型特征的迟发性重度哮喘患者中，12个月的美泊利珠单抗治疗不仅可带来临床改善，还可降低气道组织重塑指标，提示其具有疾病改善作用。
