"Translational models for acute asthma: critical evaluation of in vivo, in vitro, and emerging technologies in drug...

To critically evaluate conventional and emerging preclinical methodologies for screening novel asthma therapeutics; to compare their translational relevance; and to propose an integrated framework aimed at improving precision, safety, and phenotype-targeted efficacy in drug development.

A review of peer-reviewed literature was conducted using PubMed. Sources included studies on enzymatic and receptor-binding assays, in vitro cellular platforms, allergen-induced animal models, and recent innovations such as 3D airway organoids, lung-on-a-chip microfluidics, and omics-guided biomarker discovery.

Included studies focused on (i) molecular validation of drug targets, (ii) mechanistic and high-throughput screening in cellular systems, (iii) in vivo replication of asthma pathophysiology in animal models, or (iv) technologies enhancing preclinical predictability.

Conventional screening assays provide molecular validation but lack complexity. In vitro systems allow mechanistic insight and scalability, yet do not fully reproduce airway interactions. Allergen-induced animal models replicate inflammation and hyperresponsiveness but fail to capture human heterogeneity or acute exacerbations, a major contributor to morbidity and mortality. Acute asthma remains particularly difficult to model, limiting evaluation of therapies aimed at severe attacks. Emerging approaches, including organoids, lung-on-a-chip, and omics-based biomarkers, offer improved physiological relevance, dynamic assessment of inflammatory responses, and greater potential to model acute disease states.

Integrating conventional and innovative models may accelerate the development of safer, more effective, and phenotype-specific asthma therapies. Approaches that incorporate both chronic disease and acute exacerbations could reduce steroid resistance, improve emergency care, and enhance translational success across diverse populations.