Eosinophilic Inflammation in Severe Asthma: Pathophysiology, Clinical Identification, and Therapeutic Implications.

OBJECTIVE: To provide a clinically grounded and pathobiological review of eosinophilic inflammation in severe asthma, addressing mechanisms, diagnostic interpretation, and implications for biologic therapy selection.Data Sources: Narrative review of guidelines, pivotal phase 2-3 randomized controlled trials, meta-analyses, registry data, and key translational studies evaluating eosinophils, type 2 (T2) inflammation, and targeted biologic therapies in severe asthma and eosinophilic chronic obstructive pulmonary disease.Study Selections: Publications were selected based on clinical relevance, methodological rigor, and impact on contemporary severe asthma management. Evidence was critically appraised and integrated with expert clinical perspective. No predefined systematic protocol or formal risk-of-bias assessment was undertaken. RESULTS: Eosinophils are central effector cells in T2-high severe asthma, contributing to airway inflammation, epithelial injury, mucus plugging, and remodelling. Interleukin (IL)-5 is the principal regulator of eosinophil maturation and survival, while IL-4, IL-13, and epithelial alarmins modulate tissue recruitment and amplification of inflammation. Blood eosinophil count (BEC) remains the most accessible biomarker in practice; however, its interpretation requires contextualization, considering corticosteroid exposure, biological variability, age at onset, and comorbidities. No single biomarker fully reflects airway eosinophilia, supporting a multidimensional assessment integrating clinical phenotype, longitudinal biomarkers, imaging, lung function, and therapeutic response. Biologics have transformed outcomes, with greater efficacy generally observed at higher BEC levels. CONCLUSION: Eosinophilia should be interpreted as a contextual biomarker within a comprehensive clinical framework. Precision phenotyping is essential to optimize biologic selection and advance toward sustained disease control and clinical remission in severe asthma.