Table 1

Major endotypes of severe asthma in children

	Triggers	Major cellular drivers	Major molecular drivers	Related clinical features
Type 2 asthma
Allergic eosinophilic	Allergens	Airway epithelial cells, Th2 lymphocytes, eosinophils	IL-25, IL-33, TSLP, IL-4, IL-5, IL-13, IgE	More common in children Good response to corticosteroids Reversible airway obstruction Associated with upper airway comorbidities
Nonallergic eosinophilic	Pollutants, microbes, glycolipids	Airway epithelial cells, ILC2s, eosinophils	IL-25, IL-33, TSLP, PGD₂	Less common in children (late-onset) Significant AHR Relatively insensitive to corticosteroids No increased atopy
Non-type 2 asthma
Paucigranulocytic	Environmental factors (cigarette smoke, allergens, contractile agonists)	ASM dysfunction; no cellular inflammation	High level of oxidative stress (mechanisms not known)	High AHR Insensitivity to corticosteroids
Neutrophilic	Infections	Th17 lymphocytes, neutrophils	IL-17, IL-21, IL-22	Bacterial airway colonisation Poor response to corticosteroids Severe airway obstruction

Th: T-helper cell; IL: interleukin; TSLP: thymic stromal lymphopoietin; IgE: immunoglobulin E; ILC2s: innate lymphoid cells type 2; PGD₂: prostaglandin D₂; AHR: airway hyperresponsiveness; ASM: airway smooth muscle cells.