Neutrophilic asthma: advances in experimental models from pathogenesis to therapeutic translation

Neutrophilic asthma (NA) is a severe and therapy-resistant asthma endotype marked by persistent airway inflammation, neutrophil infiltration, and limited response to glucocorticoids. The development of targeted therapies has been hampered by insufficient mechanistic insight and the lack of physiologically relevant experimental models.

This review comprehensively synthesizes current in vivo and in vitro models for NA, discussing their methodologies, mechanistic fidelity, and translational potential. Murine systems provide flexible genetic and induction platforms; rat models reliably replicate steroid resistance; and equine models spontaneously mimic chronic human disease. Advanced in vitro approaches including air-liquid interface cultures, patient-derived organoids and lung-on-a-chip devices, enable precise study of epithelial barrier dysfunction, immune crosstalk, and personalized drug responses.

By critically evaluating these tools, our review establishes a foundation for model standardization and underscores their collective role in elucidating NA pathogenesis and advancing precision medicine.