In many patients with asthma, chronic airway inflammation is driven by Th2 cells, or ILC2, which produce IL-4, IL-5-, and IL-13.
Type 2 cytokines promote the hallmarks of the disease, such as eosinophilia, mucus hypersecretion, bronchial hyperresponsiveness (BHR), IgE production, and susceptibility to exacerbation.
The review, entitled “The Basic Immunology of Asthma,” was published online March 11, 2021 in Cell. This review reviews The potential immunological basis for various endotypes of asthma by discussing results obtained from animal studies and results generated from clinical studies targeting specific immune pathways.
Asthma is a chronic inflammatory respiratory disease that causes coughing, wheezing, shortness of breath and chest tightness.
Asthma symptoms are driven by inflammation in the airways, which triggers processes such as mucus production, airway wall remodeling, and bronchial hyperresponsiveness (BHR, the tendency of smooth muscle cells to respond to nonspecific stimuli such as cold air).
Asthma usually begins at a young age (childhood asthma), but some patients can develop asthma later in life (late asthma). Childhood and late asthma are different in many ways, with late asthma having a higher incidence.
In children, atopic, lower lung function, and respiratory tract infections (especially rhinoviruses) are severe and less associated with allergic reactions, and are major risk factors for persistent asthma.
The pathogenicity of respiratory viruses or the frequency of viral infections early in life still sets the stage for the development of asthma. Because inflammation is so important in the pathogenesis of asthma, the main goal of asthma treatment has been to control symptoms and underlying inflammation to avoid future disease progression.
Unsupervised clustering of the course and clinical features of asthma has shown that it is a heterogeneous disease, reflected in age at onset, associated risk factors and severity, comorbidities, and response to treatment, which vary largely from patient to patient.
Historically, only two main forms of asthma have been found: allergic asthma and non-allergic asthma, but this has proved too simplistic.
Allergic asthma tends to begin in childhood and is associated with T-helper 2 (Th2) cell response, which is also seen in other allergic diseases such as atopic dermatitis or allergic rhinitis.
This form of asthma is triggered by early life encounters with environmental allergens (such as house dust mites (HDM), pollen, cockroaches or animal dander), but can also be triggered later in life by encounters with new allergens such as occupational allergens.
After identifying the allergen, allergen specific Th2 cells produce cytokines type 2 (interleukin (IL) – 4, 5, IL – IL – 9 and IL – 13), resulting in a large number of eosinophils in the airway wall accumulation, overproduction, mucus and allergen specific B cell synthesis of immunoglobulin E (IgE), can be in the serum or detected by positive skin prick test.
Although the mechanisms of sensitization, environmental risks, and protective factors of childhood allergies are well understood and extensively modeled in mice, it is not clear why the disease is confined to the respiratory tract and persists into adulthood.
However, the onset of the disease coincides with a critical period in early childhood when the immune system and lung structure are developing.
Lifelong homeostasis and susceptibility to immune-mediated diseases such as asthma develop during the neonatal period.
Thus, changes in the lung environment during this “window of opportunity” may lead to changes in the behaviour of immune cells and organs that persist long after the initial trigger has disappeared.
Compared with allergic asthma, non-allergic asthma usually starts later, is more common in women and obese people, and can sometimes be difficult to treat.
The phenotypes of advanced asthma are divided into Th2 and non-Th2 advanced asthma.
Non-Th2 forms are commonly associated with obesity, aging and smoking.
Th2-associated forms are often associated with nasal polyps (CRSWNP) and aspirin-sensitive recurrent and chronic rhino-sinusitis, and may be associated with increased eosinophils in the airway.
As with many chronic inflammatory diseases, clinicians now realize that dividing asthma into two clinical forms is too simplistic.
In recent years, the classification of asthma phenotypes has evolved into endoasthmatic, such as 2-high or -ultra-high (basically eosinophilic) and 2-low (non-eosinophilic, sometimes neutrophilic and metabolic).
Endotypes are defined by underlying pathophysiological mechanisms that may lead to direct differences in response to common therapies such as inhaled corticosteroids or specific organisms.
In this review, we will focus on the potential immunological basis of various endotypes of asthma.
The review will discuss results obtained from animal studies where molecular pathways have been elaborated, as well as the use of molecular-specific biologics to target specific pathways in clinical studies.