Secreted P-Glycoprotein Is a Noninvasive Biomarker of Chronic Rhinosinusitis

Objective: 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. Methods: 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. Results: 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/mu g TP, P = 0.022). A threshold value of 250 pcg/mu g 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). Conclusion: 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.