Evidence-based answers to clinical controversies in the management of severe asthma

Asthma is a chronic inflammatory airway disorder characterized by recurrent symptoms, airflow obstruction, and bronchial hyperresponsiveness. Approximately 5–10% of asthma cases are classified as severe, requiring high-dose inhaled corticosteroids (ICS) plus additional controllers, often including systemic corticosteroids. Severe asthma imposes a substantial burden on patients due to frequent exacerbations and reduced quality of life. The pathophysiology of severe asthma involves distinct phenotypic and endotypic variations, primarily classified into high-type 2 (T2) and low-T2 inflammatory profiles. While high-T2 asthma, encompassing eosinophilic and allergic subtypes, benefits from targeted biologic therapies such as monoclonal antibodies against interleukin-5 (IL-5), IL-4/IL-13, thymic stromal lymphopoietin (TSLP), and IgE, treatment options for low-T2 asthma remain limited. The advent of precision medicine has facilitated the identification of novel biomarkers for severe asthma, guiding therapeutic decisions and enabling disease stratification. However, key clinical challenges remain, including selecting the most effective biologic therapy, optimal treatment duration, and safe de-escalation strategies upon achieving remission. This review explores the latest evidence on biological therapies, their immunomodulatory effects, and their potential role in reversing bronchial remodelling. Additionally, it discusses emerging biomarkers that may predict treatment response and remission, ultimately contributing to a more personalized approach to asthma management.