Table 1

Major endotypes of severe asthma in children

TriggersMajor cellular driversMajor molecular driversRelated clinical features
Type 2 asthma
 Allergic eosinophilicAllergensAirway epithelial cells, Th2 lymphocytes, eosinophilsIL-25, IL-33, TSLP, IL-4, IL-5, IL-13, IgEMore common in children
Good response to corticosteroids
Reversible airway obstruction
Associated with upper airway comorbidities
Nonallergic eosinophilicPollutants, microbes, glycolipidsAirway epithelial cells, ILC2s, eosinophilsIL-25, IL-33, TSLP, PGD2Less common in children (late-onset)
Significant AHR
Relatively insensitive to corticosteroids
No increased atopy
Non-type 2 asthma
 PaucigranulocyticEnvironmental factors (cigarette smoke, allergens, contractile agonists)ASM dysfunction; no cellular inflammationHigh level of oxidative stress (mechanisms not known)High AHR
Insensitivity to corticosteroids
 NeutrophilicInfectionsTh17 lymphocytes, neutrophilsIL-17, IL-21, IL-22Bacterial 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.