Background: The extracellular matrix (ECM) is a potentially important component of mucosal immunity. ECM dysregulation in chronic rhinosinusitis (CRS) is suggested by genomewide association studies identifying ECM genes as top candidates. Further support is afforded by the demonstration of increased expression of periostin (POSTN) in CRS biopsy samples compared to controls, and by reported roles in eosinophilic inflammation and steroid responsiveness. We wished to evaluate the potential utility of POSTN as a biomarker for disease activity by determining whether POSTN levels were modified in disease and whether they were modulated by endoscopic sinus surgery (ESS). Methods: Twelve patients undergoing ESS for CRS and 10 controls undergoing ESS for skull-base access were recruited. An epithelial sample from the frontal recess was collected using a cytology brush at time of and 3 months after surgery. Microarray analysis of gene expression was performed using the Illumina HumanHT-12 Beadchip v3. POSTN protein level in biopsy samples taken from the same place of brushings at surgery was analyzed by immunohistochemistry (IHC) staining. Results: All patients resolved CRS with ESS. At surgery, a higher expression of POSTN was seen in the CRS group compared to controls (fold change [FC] = 4.89, positive false discovery rate (pFDR) = 0.0006), which was also verified by IHC. After ESS, POSTN expression in CRS group decreased (FC = -3.074, pFDR = 0.0044), and was no longer different from controls (FC = 1.56, pFDR = 0.3). Conclusion: Demonstration of reduced levels in the expression of POSTN, an ECM gene, following resolution of disease, implicates POSTN, a potential pathogenesis indicator or biomarker of CRS disease activity and responsiveness to treatment. (c) 2012 ARS-AAOA, LLC.