Cosío Borja G, Iglesias Amanda, Shafiek Hanaa, Mosteiro Mar, Escribano Inés, Toledo-Pons Nuria, Valera Jose Luis, Gómez Bellvert Cristina, Pérez de Llano Luis
Department of Respiratory Medicine, Hospital Universitario Son Espases-IdISBa-CIBERES, Palma de Mallorca, Spain.
CIBERES, Instituto de Salud Carlos III, Madrid, Spain; IdISBa, Palma de Mallorca, Spain.
Chest. 2025 Apr;167(4):945-955. doi: 10.1016/j.chest.2024.11.045. Epub 2024 Dec 30.
Up to two-thirds of patients with severe uncontrolled asthma (SUA) who received biologic therapy do not have a complete response.
Can bronchial biopsy (BB) play a role in the identification of patients with SUA who have a better response to biologic therapy?
This prospective multicenter study included consecutive patients with SUA who were candidates for biologic therapy. They underwent bronchoscopy and BB prior to biologic therapy, and clinical response was evaluated 6 months later. BB was evaluated according to a previously validated pathological score (PS) and was compared with a score of type 2 (T2) inflammation (T2 score) that includes blood eosinophil count and fractional exhaled nitric oxide in predicting response to biologic therapy. Response was graded as super-response, good response, and partial/no response according to a composite score that includes exacerbations, oral corticosteroid steroid (OCS) use, asthma control test, and improvement in FEV.
A total of 92 patients were recruited. Of the 92 patients recruited, 78 completed the study. Among them, 63 received an anti-IL-5 or IL-5 receptor (anti-IL5/5R) (mepolizumab, reslizumab, and benralizumab) while 15 received dupilumab. The proportion of super-responders was 36.5% in the anti-IL5/5R group and 26.6% in the dupilumab group (P = .126). The PS was the only variable independently associated with response; the T2 score was not. Super-responders had a statistically significantly higher PS. Response was better predicted by the PS compared with the T2 score in those receiving OCSs and especially in those taking anti-IL5/5Rs. Reduced eosinophil levels (< 10 eosinophils/field) were associated with poor response to biologic therapy.
Our findings indicate that BB is more precise in the prediction of response to biologic therapy than the T2 score, especially in those requiring OCSs or receiving anti-IL5/5Rs. Tissue eosinophilia is the main driver of this predictive capacity. However, other items in the PS related to bronchial remodeling might contribute to the identification of response to biologic therapy.
接受生物治疗的重度未控制哮喘（SUA）患者中，高达三分之二没有完全缓解。
支气管活检（BB）能否在识别对生物治疗反应较好的SUA患者中发挥作用？
这项前瞻性多中心研究纳入了连续的SUA患者，这些患者均为生物治疗的候选对象。他们在生物治疗前接受了支气管镜检查和BB，6个月后评估临床反应。根据先前验证的病理评分（PS）对BB进行评估，并将其与包括血液嗜酸性粒细胞计数和呼出一氧化氮分数在内的2型（T2）炎症评分（T2评分）进行比较，以预测对生物治疗的反应。根据包括病情加重、口服糖皮质激素（OCS）使用情况、哮喘控制测试和第一秒用力呼气容积（FEV）改善情况的综合评分，将反应分为超反应、良好反应和部分/无反应。
共招募了92例患者。在招募的92例患者中，78例完成了研究。其中，63例接受了抗IL-5或IL-5受体（抗IL5/5R）（美泊利单抗、瑞利珠单抗和贝那利珠单抗）治疗，15例接受了度普利尤单抗治疗。抗IL5/5R组的超反应者比例为36.5%，度普利尤单抗组为26.6%（P = 0.126）。PS是唯一与反应独立相关的变量；T2评分不是。超反应者的PS在统计学上显著更高。与T2评分相比，PS在接受OCS治疗的患者中，尤其是在接受抗IL5/5R治疗的患者中，对反应的预测更好。嗜酸性粒细胞水平降低（<10个嗜酸性粒细胞/视野）与生物治疗反应不佳相关。
我们的研究结果表明，BB在预测生物治疗反应方面比T2评分更精确，尤其是在那些需要OCS治疗或接受抗IL5/5R治疗的患者中。组织嗜酸性粒细胞增多是这种预测能力的主要驱动因素。然而，PS中与支气管重塑相关的其他项目可能有助于识别对生物治疗的反应。
