Severe refractory asthma is characterized by a higher risk of asthma-related symptoms, morbidities, and exacerbations. This disease also determines much greater healthcare costs and a deterioration in health-related quality of life. Another concern, which is currently much discussed, is the high percentage of patients needing regular use of oral corticosteroids, which can lead to several systemic side effects. Airway eosinophilia is present in the majority of asthmatic patients, and elevated levels of blood and sputum eosinophils are associated with worse control of asthma. Regarding severe refractory eosinophilic asthma, interleukin-5 plays a fundamental role in the inflammatory response, due to the profound effect on eosinophil biology. The advent of biological therapies provided an effective strategy, even if the increased number of molecules with different targets raised the challenge of choosing the right therapy and avoiding overlapping. For several years, the only available biologic therapy has been omalizumab. Recently, new drugs and nonpharmacologic options, such as anti-IL-5 mAbs, anti-IL-4/IL-13, and bronchial thermoplasty, are available as upcoming options, supported by encouraging results for patients not eligible or nonresponsive to omalizumab. Due to the number of available treatment alternatives, the identification of the right drug for the right patient represents a key aspect of treatment, which can be implemented by new biomarkers reflecting an underlying disease mechanism, in addition to the correct use of those already available. When considering severe refractory eosinophilic asthma and anti-IL-5 treatments, it is not easy to determine which drug to choose: mepolizumab, reslizumab, and benralizumab. It is important to address and clarify some of these aspects, which may further facilitate the clinical decision-making process to identify the most successful treatment option and obtain the best possible outcomes.

This special issue aims to help clinicians in the decision process of treatment choice, within the different available therapeutic options for severe refractory asthma. We welcome both original research and review articles.

Potential topics include but are not limited to the following:

• Severe asthma treatments: Th2 versus non-Th2
• The burden of systemic corticosteroids in severe asthma
• Anti-IL-5, anti-eosinophils, and the possible overlap with anti-IgE: clinical insights and positioning
• Anti-IL4/IL-13: advantages, safety profile, and positioning in the current context of targeted therapy of severe asthma
• Clinical efficacy and steroid-sparing effect of biologics: comparison between the available treatment options