Biologic therapies in type 2 asthma: mechanisms, clinical evidence, and impact in high-altitude populations

Abstract
Asthma is a common chronic airway disease, and type 2 asthma is typically characterised by eosinophilic airway inflammation and a suboptimal response to conventional therapies. The advent of biologic agents has driven a paradigm shift towards precision medicine in asthma management. However, environmental characteristics unique to high-altitude regions, including hypoxia, low temperatures, and intense ultraviolet radiation, may modify immune responses and asthma manifestations and thereby influence the efficacy of biologic treatments. This review summarises current evidence on biologic therapies for type 2 asthma, focusing on the mechanisms and clinical applications of anti-IgE, anti-IL-5, anti-IL-4Rα, and anti-TSLP agents. In addition, we discuss the potential impact of high-altitude environments on therapeutic outcomes with these biologics. Although existing evidence demonstrates that biologic therapies improve symptoms, enhance lung function, and reduce exacerbations in patients with type 2 asthma, we hypothesize that high-altitude environmental factors may amplify airway inflammation and thereby attenuate responses to these therapies. However, direct comparative clinical evidence evaluating treatment efficacy between high-altitude and sea-level cohorts remains lacking. The review also highlights the paucity of research on biologic therapies in high-altitude settings and underscores the need for studies specifically evaluating their safety, efficacy, and feasibility in such populations. Finally, we address practical challenges in asthma management at high altitude and advocate for personalised treatment strategies and innovative drug delivery models to improve access and adherence among high-altitude populations.