Impact of sputum neutrophilia on the efficacy of biologics in severe asthma

Introduction Patients with severe asthma have new therapeutic opportunities with biologic agents, reducing exacerbation rates, symptom scores, and oral corticosteroid use; however, their effects on lung function appear to be variable. The aim of this study is to evaluate the clinical and inflammatory outcomes of biologic therapy in patients with severe asthma, stratified according to baseline bronchial inflammation. Methods This was a retrospective observational study in patients with severe asthma at 6 and 12 months after initiation of biologic therapy. Patients were categorized according to their baseline airway inflammatory profile. The inflammatory biomarkers evaluated included induced sputum, fractional exhaled nitric oxide (FeNO), and peripheral blood leukocyte counts. Lung function, comorbidities, exacerbation rate, and asthma control (assessed by ACQ-6 and ACT) were also recorded. Results A total of 113 patients with severe asthma were analyzed. Patients with a paucigranulocytic pattern were excluded from further analyses due to their small number ( n = 10). Among the remaining subjects ( n = 103), 62.8% exhibited an eosinophilic pattern, 13.3% a mixed granulocytic pattern, and 15.0% a neutrophilic pattern. Most neutrophilic patients (82.7%) presented elevated type 2 (T2) biomarkers (FeNO and/or blood eosinophils). Differences in baseline biomarkers and comorbidities reflected the underlying airway inflammatory patterns; forced vital capacity (FVC, L) was lower in neutrophilic patients compared with the other groups. Neutrophilic patients had higher frequencies of obstructive sleep apnea and lower chronic rhinosinusitis with nasal polyps than eosinophilic subjects. During follow-up, all patients showed a significant reduction in their ability to produce sputum ( p 0.001), as well as significant decreases in exacerbation rate and symptom burden. Eosinophilic and mixed granulocytic patients exhibited significant improvements in lung function, whereas neutrophilic patients did not. Only eosinophilic patients showed a significant reduction in airway inflammation. Oral corticosteroid doses decreased across all groups, but significantly only in eosinophilic patients. Clinical and inflammatory improvements were observed after 6 months of biologic therapy, with no further significant changes at 12 months. Conclusions After 12 months of biologic therapy, patients showed phenotype-dependent responses, with neutrophilic patients demonstrating smaller clinical and inflammatory improvements compared with those with eosinophilic or mixed granulocytic phenotypes.