Eosinophils in the pathogenesis of paediatric severe asthma.
OBJECTIVE
The importance and functional contribution of eosinophils to the pathogenesis of severe asthma was questioned when adult studies reported neutrophilic inflammation and Th17 cells were central to disease.


RESULTS
Eosinophilic inflammation, atopic sensitization and airway remodelling are the hallmark features of severe asthma in children. Contrary to adult reports, neutrophils, Th17 and Th2 cytokines are rarely detected in children with severe disease who are prescribed high-dose steroids. Type 2 innate lymphoid cells (ILCs), which are induced by the epithelial cytokine interleukin (IL)-33, and also release the Th2 cytokines IL-5 and IL-13, have been shown to be important in mediating asthma, and specifically, ILCs have a role in mediating eosinophil homeostasis. A direct link between IL-33, airway remodelling and steroid resistance in paediatric severe asthma suggests the steroid-resistant eosinophilia may be mediated by ILCs rather than classical Th2 lymphocytes.


CONCLUSIONS
Data from children with severe asthma have shown that findings from adults cannot be translated to children, and that steroid-resistant eosinophilic inflammation appears central to the pathogenesis of paediatric disease. Age-appropriate experimental models and use of airway samples from children are critical to understanding the underlying mechanisms and identifying novel therapeutic targets.
aLeukocyte Biology Section, National Heart & Lung Institute, Imperial College London bDepartment of Respiratory Paediatrics, Royal Brompton Hospital, London, UK.
Sejal
S
Saglani
Clare M
CM
Lloyd
D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D002648:Child; D004351:Drug Resistance; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology