Introduction
Asthma is a heterogeneous chronic inflammatory disease of the respiratory system that affects approximately 10% of adults1. A typical feature of asthma is a variable airflow limitation associated with symptoms such as dyspnoea, cough, wheezing and chest tightness2. The heterogenicity of the immunologic disorder is reflected in different phenotypes that differ in etiology, pathogenic mechanisms, symptoms, and severity3. Based on airway inflammation, asthma has been subdivided into type 2-high (T2-high) and -low (T2-low), although the latter form is rare in clinical practice3-5. A similar distinction is made between eosinophilic and non-eosinophilic asthma (GINA 2021) 6. Severe asthma is defined as asthma that is not well controlled despite the administration of high-dose drug therapy7. Up to 10% of asthma patients have severe asthma, with a reduced quality of life, and increased risk of exacerbations, hospitalizations, and death8, 9.
In T2-high asthma, immunologic stimuli (e.g., allergens, viral and bacterial superantigens) activate primary effector cells of allergic disorders (i.e., mast cells, basophils) through the engagement of specific IgE to release a plethora of interleukins (ILs) (e.g., IL-3, IL-4, IL-5, IL-13) 10, 11. Eosinophils and their mediators contribute to the pathogenesis of allergic asthma and play pivotal roles in eosinophilic asthma. T2-low asthma is heterogeneous, incompletely defined and understood and presumably includes different phenotypes characterized by the involvement of mast cells, macrophages, neutrophils and/or a mixture of these immune cells 3,5. Bronchial epithelial cell-derived alarmins (e.g., TSLP, IL-33 and IL-25) are upstream cytokines that initiate immunologic events culminating in airway remodeling 12-14. The latter is a complex process requiring a timely expression of fibrogenic15 and angiogenic factors causing profound structural alterations of the bronchial walls and blood vessels16, 17. These alterations contribute to the reduction of airway caliber and stiffening, resulting clinically in airflow limitations and respiratory symptoms18.