P-glycoprotein is a marker of tissue eosinophilia and radiographic inflammation in chronic rhinosinusitis without nasal polyps

Abstract

Background: P-glycoprotein (P-gp) is a membrane-bound efflux pump that is upregulated in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and participates in epithelial cytokine secretion. Eosinophilic CRS (ECRS) shares a similar cytokine profile with CRSwNP and is associated with significant inflammation and poor surgical outcomes. The goal of this study is to determine if P-gp expression is associated with degree of eosinophilia and severity of radiographic inflammation in patients with CRS without polyps (CRSsNP). Methods: An institutional review board (IRB)-approved study using sinus tissue in 39 steroid-naive patients with CRS. P-gp expression was calculated using quantitative fluorescent immunohistochemistry (Q-FIHC) to generate an epithelial to background staining ratio. Patients were stratified into low and high epithelial expression groups (<3 and ≥3, respectively). Average eosinophils per high powered field (hpf) and Lund-Mackay scores were calculated and compared with P-gp staining ratios using a 2-tailed Student t test. Results: Among the 39 patients, 7 (17.95%) had high P-gp expression ratios (mean ± SD, 4.86 ± 1.33) while 32 (82.05%) had low expression ratios (1.91 ± 0.45). The number of eosinophils/hpf were significantly greater in the high P-gp expression group as compared to the low expression group (62.38 ± 83.69 vs 5.11 ± 10.12, p = 0.0003). The Lund-Mackay scores were significantly greater in the high P-gp expression group as compared to the low expression group (11.86 ± 2.79 vs 6.84 ± 4.19, p = 0.005). Conclusion: P-gp is known to be overexpressed in CRSwNP. This study suggests that among patients with CRSsNP, P-gp is similarly overexpressed in those with high tissue eosinophilia and correlates with severity of radiographic inflammation. © 2013 The Authors. International Forum of Allergy & Rhinology, published by Wiley Periodicals, Inc., on behalf of ARS-AAOA, LLC.