Predictors and characteristics of asthma exacerbations on biologic therapy

Asthma affects millions globally, with severe asthma posing significant healthcare challenges. Biologic therapy targets specific aspects of the immune cascade, notably the T2 immune response, and has emerged as an effective therapy for severe asthma, particularly in terms of reducing exacerbations and improving asthma symptoms. Despite the effectiveness of this therapy, exacerbations can persist. This project aims to investigate the inflammatory patterns that define breakthrough asthma exacerbations on biologic therapy. We demonstrated the heterogeneity of asthma exacerbations in this cohort, and specifically that exacerbations defined by either elevated markers of T2 inflammation or suppressed markers of T2 inflammation were present in the cohort. Sputum eosinophils during a period of control were predictive of exacerbation risk, as well as the presence of acute T2 inflammation. Exacerbations that were not characterised by acute T2 inflammation were often associated with neutrophilic inflammation and the presence of acute viral infection. This research underscores the complexity of asthma exacerbations among participants established on biologic therapy for severe asthma, and the importance of tailored management strategies.