Introduction
Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition of the upper airways that often has a profound negative impact on sufferers’ quality of life and exacts a major societal economic burden.CRS is a complex disease consisting of several disease variants, divided by endotype dominance into type-2 or non type-2. The type-2 CRS endotype generally translates to an eosinophilic CRS (eCRS) phenotype and is diagnosed by marked infiltration of eosinophils in sinonasal mucosa [eosinophil count >10/high power field (HPF 400x) on histopathological analysis].1 eCRS is associated with high rates of treatment resistance and post-treatment recurrence,2accentuating the need to develop targeted therapies for eCRS.
Type-2 inflammation in CRS is driven by an accumulation of type-2 innate lymphoid (ILC2) cells, type-2 T helper (Th2) cells, and cytokines, including interleukin (IL)-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-13, that work in concert to generate eosinophilic infiltration in sinonasal tissue.3,4, 5  
On the basis of IL-5’s actions as an upstream cytokine that stimulates eosinophils,blocking this cytokine is a promising treatment approach in eCRS. Mepolizumab, a humanised IgG1 monoclonal antibody (mAb) drug, binds with and neutralises IL-5.6, 7  Mepolizumab has shown efficacy in refractory eosinophilic asthma,6, 8-10 which commonly co-occurs with eCRS in a ‘united airway disease’.11 However, only two asthma trials have studied the effect of mepolizumab in bronchial mucosa,12, 13 and there are no data regarding the effect of the drug on cytokines.14 Mepolizumab has been shown to reduce the total eosinophil count in bronchial mucosa in asthma.12 Mepolizumab reduces nasal polyp size and need for surgery in CRS.15-17 The effect of mepolizumab in sinonasal tissue and in the eCRS phenotye have not yet been reported. By examining the effects of mepolizumab on local tissue, more knowledge may be gained about the drug’s mechanism of action and underlying disease processes. The study aim was to assess tissue outcomes following treatment of severe eCRS with mepolizumab.