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.1 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,3 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.