Table 2

Summary of available biomarkers of childhood severe asthma

Biomarker	Sampling method	Strengths	Limitations
Type 2 asthma endotype
Eosinophils	Bronchoscopy Bronchial biopsy BAL	Gold standard to measure airway inflammation	Invasive and not feasible in routine clinical practice Contraindicated in cases of severe airway obstruction No consensus on clear cut-off values
	Induced sputum	Feasible in advanced clinical settings Sampling of central airway inflammation Cut-off of ≥3% to indicate sputum eosinophilia May indicate steroid responsiveness	Semi-invasive Time-consuming Requires specialised laboratory facilities and personnel Contraindicated in cases of severe airway obstruction
	Peripheral blood	Easily obtained, even in younger children Correlation with sputum eosinophil counts (except during systemic corticosteroid treatment) Cut-off of ∼300 cells·μL⁻¹ to indicate eosinophilic inflammation	Daily variations in number Affected by secondary causes of eosinophilia (i.e. parasitosis, common in children) No demonstrated correlation with airway eosinophilia
IgE	Peripheral blood	Easily obtained, even in younger children	Affected by secondary causes (i.e. parasitosis, common in children)
Periostin	Peripheral blood	Easily obtained, even in younger children	Baseline levels are higher in children, probably due to growth Conflicting results in children Not available in most laboratories
F_ENO	Exhaled breath	Noninvasive Fast measurement Repeatable and reproducible	May be affected by several factors
VOCs	Exhaled breath	Noninvasive	No standardised methods for collection and analysis
pH, markers of oxidative stress, leukotrienes, cytokines and chemokines	Exhaled breath condensate	Noninvasive	Requires specialised laboratories Expensive To be validated in children with severe asthma
Non-type 2 asthma endotype
Neutrophils	Bronchoscopy Bronchial biopsy BAL	Gold standard to measure airway inflammation Correlation with better lung function in younger children with severe asthma	Invasive and not feasible in routine clinical practice Contraindicated in cases of severe airway obstruction No consensus on clear cut-off values
	Induced sputum	Cut-off of ≥61% to indicate sputum neutrophilia	Semi-invasive Time-consuming Requires specialised laboratory facilities and personnel Contraindicated in cases of severe airway obstruction
	Peripheral blood	Easily obtained, even in younger children	No correlation with sputum or airway neutrophil counts

F_ENO: exhaled nitric oxide fraction; VOCs: volatile organic compounds.