The role of mepolizumab in atopic and nonatopic severe asthma with persistent eosinophilia.

Atopy is a common finding in asthma, but at least one third of severe asthmatics have no evidence of atopy (so-called ‘‘intrinsic’’ asthma) [1–4]. Despite the uncertainty of the mechanisms leading to nonatopic asthma, these patients have no history of allergic respiratory disease, no detectable specific IgE to common aeroallergens, and no positive skin-prick test. One hypothesis suggests that differences in the phenotypes might be driven by the local, and not by the systemic, production of IgE [5]. Eosinophils are involved in diverse inflammatory responses irrespective of atopy. Eosinophilic inflammation and IgE production are promoted by T-helper cell (Th)2 cytokines, such as interleukin (IL)-5, IL-4 and IL-13. IL-4/IL-13 are major factors involved in Th2 differentiation and IgE class switching [6], while IL-5 is involved primarily in eosinophil growth, survival, activation, and in mediating inflammation.