Precision identification and targeted therapy for neutrophilic asthma: from molecular mechanisms to clinical translation.

Neutrophilic asthma represents a distinct inflammatory phenotype characterized by sputum neutrophilia (≥61% neutrophils), glucocorticoid resistance, and more severe disease course compared to eosinophilic asthma. This review comprehensively examines the molecular mechanisms underlying neutrophilic asthma pathogenesis, focusing on the Th17/IL-17 axis, neutrophil extracellular traps (NETs), and NLRP3 inflammasome activation. We present a precision identification framework integrating molecular endotypes with clinical phenotypes and biomarker profiles to guide therapeutic decisions. Unlike eosinophilic asthma, neutrophilic asthma demonstrates intrinsic resistance to glucocorticoids due to impaired neutrophil apoptosis and persistent activation of pro-inflammatory pathways. Emerging therapeutic approaches targeting IL-17, NET formation, and inflammasome components show promise, with several agents in clinical development. The microbiome-neutrophil axis represents a novel therapeutic target, with evidence suggesting that airway dysbiosis perpetuates neutrophilic inflammation through pattern recognition receptor activation. This review provides a comprehensive framework for understanding neutrophilic asthma pathogenesis and outlines precision medicine approaches for this difficult-to-treat asthma phenotype.