Sposato Bruno, Scalese Marco, Camiciottoli Gianna, Carpagnano Giovanna Elisiana, Pelaia Corrado, Santus Pierachille, Pelaia Girolamo, Cameli Paolo, Bargagli Elena, Lacerenza Leonardo Gianluca, Radovanovic Dejan, Rogliani Paola, Maniscalco Mauro, Masieri Simonetta, Cavaliere Carlo, Corsico Angelo Guido, Scichilone Nicola, Baglioni Stefano, Perrella Antonio, Paggiaro Pierluigi, Ricci Alberto
Pneumology Department, Azienda USL Toscana Sud-Est, "Misericordia" Hospital, Grosseto, Italy.
Clinic Physiology Institute, National Research Centre, Pisa, Italy.
J Asthma. 2025 Jun;62(6):1007-1012. doi: 10.1080/02770903.2025.2451691. Epub 2025 Jan 17.
It remains unclear whether baseline FeNO levels can predict response to anti-IL5/5R biologic treatment in patients with severe asthma.
We recruited 104 patients with severe eosinophilic asthma treated with anti-IL5/anti-IL5R for at least one year who had measured FeNO values before the beginning of anti-eosinophilic treatment. Population was divided into subjects with FeNO < 25 and ≥25 ppb. In each group we evaluated the changes in pulmonary function (FEV% and FEF%), clinical (ACT and exacerbations) and steroid-sparing effect, expressed as the modification of daily dosage of inhaled corticosteroids (ICS) and oral corticosteroids (OC), after anti-IL5/anti-IL5R.
FEV changes after treatment were 3.34 ± 15,97% in subjects with low baseline FeNO, whereas 11.2 ± 16.1% in individuals with FeNO ≥ 25 ppb ( = 0.012). Also, FEF% variations after treatment were different in the two groups: 2.1 ± 10.7% vs 9.6 ± 18% in individuals with FeNO < 25 and ≥25 respectively ( = 0.05). Conversely, ACT (4.4 ± 4.2 vs 5.9 ± 4.6; = 0.147), exacerbation changes (-2.46 ± 1.5 vs -2.9 ± 1.6; = 0.137) after treatment were similar in both groups where ICS dosages reduction was alike. On the contrary, the percentage of subjects that reduced/stopped OC treatment after anti-IL5/anti-IL5R was 71.7% in the group with FeNO < 25 ppb whereas 94.1% in individuals with FeNO ≥ 25 ( = 0.06). Multivariate analysis adjusted for all confounding factors also confirmed the relationship between FeNO ≥ 25 and improvement in FEV%/FEF% (β = 8.372, = 0.013 and β = 8.883; = 0.062 respectively) and the increased probability of discontinuing/reducing OC use (OR:17.838 [95%CI:3.159-100.730]; = 0.001) in the high FeNO group.
Pre-biologic FeNO might predict a greater response to treatment with anti-IL-5/5R especially in terms of lung function and OC sparing in subjects with severe eosinophilic/allergic asthma. This could likely be a biomarker that can better guide in choosing an anti-IL5/5R in severe overlapping asthma (eosinophilic/allergic) to maximize treatment effects.
目前尚不清楚基线呼出气一氧化氮（FeNO）水平能否预测重度哮喘患者对抗白细胞介素5（IL-5）/白细胞介素5受体（IL-5R）生物治疗的反应。
我们招募了104例接受抗IL-5/抗IL-5R治疗至少一年的重度嗜酸性粒细胞性哮喘患者，这些患者在抗嗜酸性粒细胞治疗开始前测量了FeNO值。将研究人群分为FeNO<25和≥25 ppb的两组。在每组中，我们评估了抗IL-5/抗IL-5R治疗后肺功能（第一秒用力呼气容积占预计值百分比[FEV%]和用力呼气流量占预计值百分比[FEF%]）、临床指标（哮喘控制测试[ACT]和急性加重情况）以及激素节省效果（以吸入性糖皮质激素[ICS]和口服糖皮质激素[OC]每日剂量的变化表示）的变化。
基线FeNO水平较低的患者治疗后FEV变化为3.34±15.97%，而FeNO≥25 ppb的患者为11.2±16.1%（P=0.012）。此外，两组治疗后FEF%的变化也不同：FeNO<25和≥25的患者分别为2.1±10.7%和9.6±18%（P=0.05）。相反，两组治疗后的ACT（4.4±4.2对5.9±4.6；P=0.147）和急性加重情况的变化（-2.46±1.5对-2.9±1.6；P=0.137）相似，ICS剂量减少情况也相似。相反，抗IL-5/抗IL-5R治疗后减少/停用OC治疗的患者百分比在FeNO<25 ppb组为71.7%，而在FeNO≥25组为94.1%（P=0.06）。对所有混杂因素进行校正的多变量分析也证实，FeNO≥25与FEV%/FEF%改善之间存在关联（β=8.372，P=0.013和β=8.883；P=分别为0.062），且高FeNO组停用/减少OC使用的概率增加（比值比：17.838[95%置信区间：3.159-100.730]；P=0.001）。
生物治疗前的FeNO可能预测对抗IL-5/IL-5R治疗有更大反应，尤其是在重度嗜酸性粒细胞性/过敏性哮喘患者的肺功能和OC节省方面。这可能是一种生物标志物，能够更好地指导在重度重叠性哮喘（嗜酸性粒细胞性/过敏性）中选择抗IL-5/IL-5R治疗，以最大化治疗效果。
