Targeting neutrophil extracellular traps: an emerging strategy for improving the management of refractory asthma

Treatment-refractory asthma, particularly the neutrophilic-predominant phenotype, poses a significant clinical challenge. Current therapies, especially corticosteroids, have limited efficacy in controlling inflammation in these patients, highlighting the need for novel targets against non-eosinophilic inflammation. This review examines the central role of neutrophil extracellular traps (NETs) in driving persistent airway inflammation, tissue damage, and remodeling in refractory asthma. It also evaluates preclinical and translational evidence for therapeutic strategies targeting NETs-such as inhibiting their formation, promoting degradation, neutralizing toxic components, and enhancing clearance. Despite challenges in target specificity, patient heterogeneity, and delivery, integrating these strategies with precision medicine could open new disease-modifying avenues to improve outcomes in treatment-refractory asthma, especially the neutrophilic phenotype.