Unmet Needs in Severe Asthma Subtyping and Precision Medicine Trials: Bridging Clinical and Patient Perspectives

Severe asthma affects a small proportion of asthma patients (~ 3-5%) and reflects a failure of conventional asthma medications to provide adequate control. Severe asthma is a disease of significant clinical heterogeneity, likely caused by different pathobiological mechanisms, frequently referred to as endotypes. In the last decade, multiple monoclonal therapies have been developed to target airway type-2 eosinophilic and/or allergic severe asthma. However, the underlying mechanisms of both type 2 immunity and eosinophilia (blood and airway) remain incompletely understood and offer a potential for novel therapies that target eosinophil maturation in the bone marrow and specific kinases expressed in type 2 cells, such as JAK-STAT inhibitors. Furthermore, some patients do not consistently demonstrate a type 2 disease clinical profile and display other inflammatory phenotypes at a given point in time. Targeting airway smooth muscle dysfunction, airway mucous, type-17 immunity and airway dysbiosis, may represent novel therapeutic approaches for severe asthma in the future. Unfortunately, the biomarkers for these subtypes of severe asthma are underdeveloped, rendering it difficult to conduct effective clinical trials. There are also barriers regarding the efficiency of standard clinical trials. Moving beyond these barriers will require innovation in trial design, effective partnerships with patient groups and effective multi-national trials consortia. There are current transatlantic opportunities to conduct clinical trials that could facilitate the development of common trial platforms to maximize overall efficiency and move the field of severe asthma forward.