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

1. Rachel E. Feldman BA¹, 
2. Allen C. Lam MD¹, 
3. Peter M. Sadow MD, PhD², 
4. Benjamin S. Bleier MD^1,*

Article first published online: 15 MAY 2013

DOI: 10.1002/alr.21176

© 2013 The Authors. International Forum of Allergy & Rhinology, published by Wiley Periodicals, Inc., on behalf of ARS-AAOA, LLC.

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International Forum of Allergy & Rhinology

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How to CiteAuthor InformationPublication History

1. Potential conflict of interest: B.S.B. is an inventor on a provisional patent regarding modulation of P-glycoprotein in the treatment of chronic rhinosinusitis.

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Keywords:

• chronic sinusitis;
• nasal polyposis;
• P-glycoprotein;
• active efflux pumps;
• inflammation;
• Th1;
• Th2;
• eosinophilia;
• eosinophilic chronic rhinosinusitis;
• Lund-Mackay score

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 2-tailed="" a="" and="" average="" calculated="" compared="" em="" eosinophils="" field="" high="" hpf="" lund-mackay="" nbsp="" p-gp="" per="" powered="" ratios="" respectively="" scores="" staining="" student="" style="background-color: transparent; border: 0px; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" using="" were="" with="">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.

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