Abstract / Summary
Bronchiectasis is increasingly recognized as biologically heterogeneous, yet the clinical meaning of eosinophilic and type 2 (T2)-associated signals remains uncertain. This review reassesses whether the field has progressed from recognition of an eosinophilic phenotype to a bronchiectasis-specific, therapeutically actionable T2 endotype. Blood eosinophil count (BEC), airway eosinophilia, fractional exhaled nitric oxide, total immunoglobulin E, and pathway-level signatures capture overlapping but non-equivalent features. Current evidence supports an eosinophilic phenotype more strongly than a unified bronchiectasis-specific T2 endotype. Airway studies confirm eosinophil activation in selected patients, but direct evidence for a complete and reproducible epithelial alarmin–T2-cell–IL-4/IL-5/IL-13 pathway is limited, and asthma, allergic bronchopulmonary aspergillosis, fungal sensitization, chronic rhinosinusitis, and chronic obstructive pulmonary disease can confound biomarker interpretation. Prognostic associations are non-linear and context dependent: persistent or high eosinophilia and very low BEC have each been associated with adverse outcomes in different settings. Inhaled corticosteroids show biological effects and exploratory eosinophil-associated response signals, but these do not validate BEC as a predictive biomarker or support treatment solely for elevated BEC. In MAHALE, benralizumab produced profound eosinophil depletion without demonstrated clinical efficacy in the population studied; severe under-recruitment and limited eosinophilic enrichment restrict inference for persistently eosinophilic disease. Evidence from biologic-treated severe asthma with coexisting bronchiectasis remains indirect for bronchiectasis efficacy. The review therefore defines the validation pathway required before phenotype recognition can inform treatment selection: repeated stable-state phenotyping, airway biological validation, separation from T2 comorbidities, prespecified treatment-by-biomarker interaction analyses, and adequately powered biomarker-enriched trials.