Circadian Clock Disruption and Non-type 2 Asthma: A Hypothesis-Driven Perspective on Immune, Epithelial, and Steroid Response

Asthma is a major chronic non-communicable respiratory disease, affecting over 300 million individuals globally, with an adult prevalence of 4.3%. Despite advances in individualized treatment, a subset of patients, particularly those with non-type 2 (non-T2) asthma, fails to achieve optimal disease control. Non-T2 asthma, characterized by steroid resistance and heterogeneous immune responses, remains a therapeutic challenge. Emerging evidence suggests that circadian rhythm disruption may modulate key pathological processes relevant to non-T2 asthma, including immune imbalance, epithelial barrier dysfunction, and impaired glucocorticoid sensitivity. This review investigates evidence of an association between circadian clock dysfunction and non-type 2 asthma pathogenesis, and proposes a hypothesis-driven framework to guide future studies. Chronotherapeutic strategies and clock-targeted interventions may offer promising avenues for future research and individualized treatment.