Variability of Type 2 inflammatory markers guiding biologic therapy of severe asthma: A 5-year retrospective study from a single tertiary hospital()

BACKGROUND: Currently, biotherapy is mainly administered to treat patients with severe asthma with the Type 2 (T2) inflammation phenotype. The variability of T2 inflammatory markers remains poorly understood. OBJECTIVE: We aimed to describe the individual distributions of different biomarkers at varying thresholds and their variation patterns in participants with severe asthma. METHODS: We retrospectively reviewed the data of participants who had completed 2 or more fraction of exhaled nitric oxide (FeNO) and peripheral blood eosinophil counts in our centre within 5 years. The individual distribution of biomarkers (blood or sputum eosinophils, FeNO, and serum total IgE) with repeated measurements at different thresholds was analysed. The varied patterns of biomarkers were analysed by cluster analysis. RESULTS: A total of 241 eligible participants were screened. Through long-term longitudinal multiple measurements, we found that approximately 50% of severe asthmatics had blood eosinophil levels fluctuating around the threshold defined by biological agents. FeNO persisted at levels >19.5 ppb or 25 ppb in more than half of patients; about 30% of participants crossed this threshold. In our centre, 47.4% of participants consistently exceeded sputum eosinophils >3%, and 47.4% of patients crossed this threshold. Approximately 66.7% of participants had more than 50% alterations of serum total IgE, and 98.1% of participants continued to have IgE levels greater than 30 IU/mL. We used cluster analysis to classify variability and levels of FeNO and blood eosinophils and identified 4 patient clusters. Cluster 1 can be summarised as T2 severe asthma with low blood eosinophil levels and stability. Cluster 2 can be summarised as asthma with continuous increase and small fluctuations in various T2 inflammatory markers. Cluster 3 can be summarised as a non/low-T2 inflammatory phenotype. Cluster 4 can be summarised as a stable, moderate T2 inflammatory phenotype. CONCLUSION: We identified the distributions and variable patterns of the T2 inflammatory markers currently used to guide asthma biotherapy in clinical practice. The longitudinal comprehensive multiple assessments of T2 inflammatory markers provide support for initiating biologic therapy patients with severe asthma whose biomarker levels vary.