J Asthma. 2025 Jan 17:1-6. doi: 10.1080/02770903.2025.2451691. Online ahead of print.
Bruno Sposato 1, Marco Scalese 2, Gianna Camiciottoli 3, Giovanna Elisiana Carpagnano 4, Corrado Pelaia 5, Pierachille Santus 6, Girolamo Pelaia 7, Paolo Cameli 8, Elena Bargagli 8, Leonardo Gianluca Lacerenza 9, Dejan Radovanovic 6 10, Paola Rogliani 11, Mauro Maniscalco 12 13, Simonetta Masieri 14, Carlo Cavaliere 15, Angelo Guido Corsico 16, Nicola Scichilone 17, Stefano Baglioni 18, Antonio Perrella 1, Pierluigi Paggiaro 19, Alberto Ricci 20
Abstract
Objective: It remains unclear whether baseline FeNO levels can predict response to anti-IL5/5R biologic treatment in patients with severe asthma.
Methods: 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 (FEV1% and FEF25-75%), 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.
Results: FEV1 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 (p = 0.012). Also, FEF25-75% 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 (p = 0.05). Conversely, ACT (4.4 ± 4.2 vs 5.9 ± 4.6; p = 0.147), exacerbation changes (-2.46 ± 1.5 vs -2.9 ± 1.6; p = 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 (p = 0.06). Multivariate analysis adjusted for all confounding factors also confirmed the relationship between FeNO ≥ 25 and improvement in FEV1%/FEF25-75% (β = 8.372, p = 0.013 and β = 8.883; p = 0.062 respectively) and the increased probability of discontinuing/reducing OC use (OR:17.838 [95%CI:3.159-100.730]; p = 0.001) in the high FeNO group.
Conclusion: 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.