美妥珠单抗对晚发重症嗜酸性粒细胞表型哮喘患者气道重塑的影响
2025/03/03
摘要
研究背景：临床试验和实际经验证明了抗IL-5生物制剂美泊利珠单抗对重症哮喘的临床疗效。然而，有关mepolizumab对气道重塑影响的数据却很有限。
研究目的：我们试图研究在常规临床治疗中美泊利珠单抗对重症哮喘患者气道结构重塑的影响。
研究方法：MESILICO（美泊利珠单抗对晚发严重嗜酸性粒细胞性哮喘患者的疗效）研究是一项多中心研究，涉及希腊的8个肺病科部门。这项研究的重点是因嗜酸性粒细胞表型的重症哮喘而开始使用美泊利珠单抗治疗的患者，这些患者发病较晚，并伴有阻塞模式（可逆性受损）。共招募了47名患者，其中41人参加了支气管镜研究。研究结果与临床预后有关。
研究结果：12个月后，甲泼尼单抗治疗可显著改善肺功能和哮喘控制测试评分，并显著减少严重恶化事件（P<0.001）。41名参与者中有34人（83%）进行了配对活检以进行比较分析。与基线相比，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均有明显减少（P<0.001）。气道平滑肌层厚度的减少程度与粘膜下嗜酸性粒细胞的减少呈正相关（r=0.599；P<0.001）。
研究结论：本研究发现，对同时具有嗜酸性粒细胞和可逆性受损表型的晚发性重症哮喘患者进行12 个月的美泊利珠单抗治疗，不仅能改善临床症状，还能降低气道组织重塑指数，这表明它具有改善疾病的作用。
研究背景：临床试验和实际经验证明了抗IL-5生物制剂美泊利珠单抗对重症哮喘的临床疗效。然而，有关mepolizumab对气道重塑影响的数据却很有限。
研究目的：我们试图研究在常规临床治疗中美泊利珠单抗对重症哮喘患者气道结构重塑的影响。
研究方法：MESILICO（美泊利珠单抗对晚发严重嗜酸性粒细胞性哮喘患者的疗效）研究是一项多中心研究，涉及希腊的8个肺病科部门。这项研究的重点是因嗜酸性粒细胞表型的重症哮喘而开始使用美泊利珠单抗治疗的患者，这些患者发病较晚，并伴有阻塞模式（可逆性受损）。共招募了47名患者，其中41人参加了支气管镜研究。研究结果与临床预后有关。
研究结果：12个月后，甲泼尼单抗治疗可显著改善肺功能和哮喘控制测试评分，并显著减少严重恶化事件（P<0.001）。41名参与者中有34人（83%）进行了配对活检以进行比较分析。与基线相比，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均有明显减少（P<0.001）。气道平滑肌层厚度的减少程度与粘膜下嗜酸性粒细胞的减少呈正相关（r=0.599；P<0.001）。
研究结论：本研究发现，对同时具有嗜酸性粒细胞和可逆性受损表型的晚发性重症哮喘患者进行12 个月的美泊利珠单抗治疗，不仅能改善临床症状，还能降低气道组织重塑指数，这表明它具有改善疾病的作用。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2025 Feb;155(2):425-435. DOI: 10.1016/j.jaci.2024.10.024.）
（J Allergy Clin Immunol. 2025 Feb;155(2):425-435. DOI: 10.1016/j.jaci.2024.10.024.）
Effect of mepolizumab in airway remodeling in patients with late-onset severe asthma with an eosinophilic phenotype
Kalliopi Domvri, Ioanna Tsiouprou, Petros Bakakos, et.al
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).
CONCLUSION: 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.
Kalliopi Domvri, Ioanna Tsiouprou, Petros Bakakos, et.al
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).
CONCLUSION: 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.
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嗜酸性粒细胞增多性多血管炎重症哮喘门诊患者的特征
