Severe Asthma Exacerbations: From Risk Factors to Precision Management Strategies

Background: Severe asthma exacerbations (SAEs) significantly contribute to asthma-related morbidity, mortality, and healthcare burden. Despite therapeutic advances, a subset of patients remains exacerbation-prone. This review aims to summarize current evidence on risk factors, phenotypes, and biomarkers associated with SAEs, and explore personalized strategies for their acute management. Methods: We conducted a comprehensive literature review focusing on clinical, inflammatory, and environmental drivers of SAE. Special attention was given to Type 2 (T2) biomarkers—blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO)—as tools for phenotyping and treatment guidance. Emerging evidence on the use of biologics during exacerbations was also analyzed. Results: SAEs are heterogeneous in etiology and inflammatory profile. Respiratory infections, allergen exposure, obesity, and comorbidities increase exacerbation risk. T2-high SAEs respond well to corticosteroids and biologics, whereas T2-low SAEs show limited treatment benefit. BEC and FeNO reliably predict exacerbation risk and corticosteroid responsiveness. Recent case reports suggest potential roles for anti-IL-5 and anti-thymic stromal lymphopoietin (TSLP) biologics in acute care. Conclusions: Biomarker-guided management of SAEs may enhance therapeutic precision and avoid overtreatment. Integrating phenotypic (observable characteristics) and endotypic (biological markers) assessment into acute care could improve patient outcomes and optimize resource use. Prospective trials are needed to confirm these approaches.