What should we be aware when eosinophils are elevated in severe asthma?

Abstract

Severe asthma with an eosinophilic phenotype is a well-recognized presentation, associated with type 2 (T2) inflammation, and is typically responsive to targeted biologic therapies. However, the presence of persistent eosinophilia greater than 1,000 cells/μL necessitates diagnostic investigation, as various systemic diseases can mimic or coexist with asthma. This chapter reviews the mechanisms of eosinophilic activation through T2 and non-T2 pathways, highlights the impact of corticosteroids on the interpretation of eosinophilia, and describes a systematic approach for diagnostic evaluation. Key differential diagnoses discussed include eosinophilic granulomatosis with polyangiitis (EGPA), allergic bronchopulmonary aspergillosis (ABPA), and hypereosinophilic syndrome, among others. Integrating medical history, thorough physical examination, and complementary laboratory and imaging studies is critical for the early identification of these conditions. Proper recognition of eosinophilia in the context of severe asthma directly influences clinical management and therapeutic decision-making.