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.