Osteitis is Associated with P-Glycoprotein Overexpression in Patients with Chronic Sinusitis without Nasal Polyps

Abstract

Background

P-glycoprotein (P-gp) is a membrane-bound efflux pump that is up-regulated in eosinophilic chronic rhinosinusitis and participates in epithelial cytokine secretion. Osteitis is associated with eosinophilic inflammation and may represent a method to predict patients with P-gp overexpression. The purpose of this article was to determine whether P-gp overexpression and increased osteitis scores are associated in patients with chronic rhinosinusitis (CRS).

Methods

An Institutional Review Board-approved study was performed using sinus tissue in 38 patients with CRS. P-gp expression was calculated using quantitative fluorescent immunohistochemistry to generate an epithelial-to-background staining ratio. Patients were stratified into low and high P-gp expression groups. Osteitis was scored radiologically using the Kennedy Osteitis Score (KOS) and Global Osteitis Score (GOS). Serum eosinophilia was assessed. KOS and GOS were compared using a Pearson's correlation coefficient. Osteitis scores and serum eosinophil concentrations between P-gp expression groups were compared using a nonparametric Mann-Whitney U test (two tailed).

Results

Among the 38 patients, 7(18.42%) had high P-gp expression (mean ± SD, 4.86 ± 1.33) whereas 31(81.57%) had low expression ratios (1.93 ± 0.45). No patients in the high P-gp expression group had undergone prior surgery. Median serum eosinophil values were significantly greater in the high versus low P-gp expression group (6.98 ± 2.17 versus 2.36 ± 1.38, p < 0.001). GOS and KOS values were significantly greater in the high versus low P-gp expression group (15.86 ± 4.91 versus 6.29 ± 1.25 and 4.55 ± 4.33 verus 2.23 ± 1.71; p < 0.001). KOS and GOS values were significantly correlated (r = 0.835; p < 0.001).

Conclusion

Increased osteitis burden as measured by either the KOS or the GOS is associated with creased P-gp membranous expression in CRS. Radiographic quantification of osteitis may therefore be used to identify patients with P-gp overexpression thereby providing a novel potential therapeutic target.