title: Secreted P-glycoprotein is a noninvasive biomarker of chronic rhinosinusitis.
abstract: The discovery of noninvasive biomarkers of chronic rhinosinusitis (CRS) is critical to enable our ability to provide prognostic information and targeted medical therapy. Epithelial P-glycoprotein (P-gp) is overexpressed in CRS and exists in an extracellular, secreted form. The objective of this study was to determine whether secreted P-gp concentrations are elevated in CRS and can be used to predict disease severity.
  
  
  
  Institutional review board-approved study examining mucus concentrations of P-gp in 36 patients (10 control, 16 CRS without nasal polyps [CRSsNP], and 10 CRS with nasal polyps [CRSwNP]). P-gp concentrations were determined by enzyme-linked immunosorbent assay and normalized to total protein (TP). Clinical indices of disease severity, including the Sino-Nasal Outcomes Test (SNOT-22) and Lund-Mackay score, were collected for all patients.
  
  
  
  Secreted P-gp concentration was significantly higher in CRS versus control patients (mean ± standard deviation; 247.8 ± 224.8 vs. 102.4 ± 81.7 pcg P-gp/μg TP, P = 0.022). A threshold value of 250 pcg/μg TP was used to differentiate low versus high secretors. High P-gp secretors with CRS (sNP and wNP, n = 9) demonstrated significantly higher SNOT-22 and Lund-Mackay scores (57.1 ± 7.9 and 13.9 ± 7.3) versus low secretors (38.3 ± 23.9 and 6.8 ± 7.3; P = 0.030 and P = 0.013, respectively) and had a significantly higher proportion of CRSwNP (66.7%) versus the low secretors (23.5%, n = 17, P = 0.046).
  
  
  
  P-gp secretion levels are significantly elevated in patients with CRS. High P-gp secretion is associated with a higher incidence of CRSwNP and confers worse subjective and objective measures of disease severity. The presence of elevated P-gp secretion may therefore represent a novel noninvasive biomarker of CRS and could be used to predict patients who may benefit from P-gp inhibitory therapeutic strategies.
  
  
  
  NA Laryngoscope, 127:E1-E4, 2017.
authors: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors: Angela L
authors: AL
authors: Nocera
authors: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors: Ana T
authors: AT
authors: Meurer
authors: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors: Marcel M
authors: MM
authors: Miyake
authors: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors: Peter M
authors: PM
authors: Sadow
authors: Department of Biomedical Engineering, Boston University, Boston, Massachusetts, U.S.A.
authors: Xue
authors: X
authors: Han
authors: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors: Benjamin S
authors: BS
authors: Bleier
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D012220:Rhinitis / Q000378:metabolism*; D012720:Severity of Illness Index; D012852:Sinusitis / Q000378:metabolism*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D015415:Biomarkers
keywords: P-glycoprotein; biomarker; chronic rhinosinusitis; chronic rhinosinusitis with nasal polyps; secreted P-gp