title: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Feldman
authors.forename: Allen C
authors.initials: AC
authors.lastname: Lam
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Bleier
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000328:Adult; D002908:Chronic Disease; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D010256:Paranasal Sinuses / Q000378:metabolism*; D011859:Radiography; D012220:Rhinitis / Q000000981:diagnostic imaging / Q000378:metabolism*; D012852:Sinusitis / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B
keywords: Lund-Mackay score; P-glycoprotein; Th1; Th2; active efflux pumps; chronic sinusitis; eosinophilia; eosinophilic chronic rhinosinusitis; inflammation; nasal polyposis