Table 1.

 Overview on asthma biomarkers.

BIOMARKER	ENDOTYPE	ACTIVATED CYTOKINES	ROLE IN INFLAMMATION PATHWAY	BIOLOGICAL AGENTS
IgE (serum)	T2 high: Allergic	IL-4, IL-13 through activated Th2 cells	Binds FcεRI expressed on the surface of mast cells, eosinophils, basophils and B lymphocytes  Leads to subsequent degranulation and release of mediators	Omalizumab
Eosinophils (serum and sputum)	T2 high: Eosinophilic	IL-5	Involved in production of reactive oxygen species, desquamation and lysis of airway epithelial cells  Promote airway remodelling	Mepolizumab, Reslizumab, Benralizumab
Surrogate periostin (serum, sputum)	T2 High: Eosinophilic-Allergic	IL-4, IL-13	Induce an amplification and persistence of chronic inflammation of allergic diseases  Involved in the process of subepithelial fibrosis in asthma patient and in airway remodelling	Lebrikizumab, Tralokizumab, Omalizumab
Exhaled nitric oxide (FeNO)	T2 high: Allergic	IL-4, IL-13	Useful surrogate of airways inflammation  Due to increased nitric oxide production by activated bronchial epithelial cells	No biological agents, but guideline recommended therapies
Dipeptidyl peptidase 4 (DPP-4 serum)	T2 High: Eosinophilic	IL-13	Induces the proliferation of airway smooth muscle cells, lung fibroblasts and fibronectin production	Tralokinumab
Galectin-3 (bronchial tissue)	T2 high: Allergic	No target identified	Involved in eosinophil recruitment, airway remodelling and development of Th2 phenotype  Early predictive biomarker of modulation of airway remodelling in severe asthma patients treated with omalizumab.	Omalizumab
Neutrophils (sputum)	T2 low: Neutrophilic/Paucigranulocytic	IL-8	Induce the release of O2, matrix metalloproteinase-9 (MMP-9), leukotrienes-4 (LTB-4), and platelet-activating factor (PAF)	No biological agents still available