ASTHMA PHENOTYPES AND ENDOTYPES
An analysis by Dr SK Kapoor
Asthma is complex biological network of distinct and interrelating inflammatory pathways.
Based on underlying mechanisms, asthma has heterogeneity in terms of
1. severity,
2. natural history
3. treatment responsiveness
All variants have
a. Wheezing
b. shortness of breath
c. cough
d. chest tightness
e. variable airflow obstruction.
The traditional dogma of asthma is that of
i. excessive T-helper cell type 2 (Th2) cell responses
ii. specific IgE driving airway hyper responsiveness.
The term asthma is encompasses several diseases with different
1) ENDOTYPES encompass distinct mechanistic pathways which present a granular approach to inflammatory component by delineation of molecular pathways driving the disease.
It based on CD4+ T-cell responses that are heterogeneous, comprising multiple subsets that promote a particular asthma subtype.
CD4+ T-cell has subsets viz. Th1 and Th2 subpopulations.
Th2 cells are the principal driver of eosinophilic airway inflammation by generating abundant quantities of IL-4, IL-5, and IL-13.
There are two major asthma endotypes:
I. Th2-(T2) high -eosinophilic
II. Th2-(T2) low -non-eosinophilic
Understanding endotypes helps in management and has therapeutic and prognostic implications.
Several biologic agents have been approved for T2-high asthma, with numerous other therapeutics that are targeted at specific molecular mechanisms leading to tailor made therapies.
2) PHENOTYPES variable clinical presentations. They are observable combinations of clinical, biological, and physiological factors and result from hereditary and environmental influences. (young atopic, obese middle aged, and elderly)
The two major phenotypes are:
a) non-atopic or “intrinsic” asthma; mainly seen in older age groups.
b) atopic or “extrinsic” asthma: Early-onset atopic asthma is most prevalent during childhood and into young adulthood
Patients with severe disease have refractory symptoms despite high-intensity therapy leading to morbidity and mortality.
Biologic agents are selected on a basis of a classification system and biomarkers.
T2-high phenotypes have been classified into three groups:
i. early-onset allergic asthma,
ii. late-onset eosinophilic asthma, and
iii. aspirin-exacerbated respiratory disease (AERD).
T2-low phenotypes have been classified according to clinical characteristics that include
i. Non atopic
ii. Obesity
iii. Smoking
iv. Age