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Objectives/hypothesis: To investigate the effect of oral plus intranasal corticosteroid (CS) treatment on nasal polyp (NP) mucosa remodeling from patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP)., Study Design: Case series, retrospective study., Methods: Patients (n = 18) with severe CRSwNP were treated with oral prednisone for 2 weeks and intranasal budesonide for 12 weeks. NP biopsies were obtained from patients biopsies before (w0) and after 2 weeks (w2) and 12 weeks (w12) of CS treatment. Matrix metalloprotease 1 (MMP-1), MMP-2, MMP-7, MMP-9, and tissue inhibitor of metalloprotease type 1 (TIMP-1) expression was evaluated by immunohistochemistry in cell and tissue structures. Epithelial damage, eosinophil infiltration, and collagen content were also examined in NP tissues before and after CS treatment., Results: Compared to w0: 1) oral plus intranasal CS significantly (P < .01) increased presence of submucosal glands at w2, decreased epithelial cell hyperplasia at w12, and decreased tissue eosinophilia at w2 and w12; 2) CS treatment significantly (P < .05) increased immunoreactivity for MMP-1 and MMP-2 in the epithelium at w2, but decreased immunoreactivity for MMP-9 in the epithelium at w2 and w12; 3) at w12, CS significantly (P < .05) reduced MMP-9 immunoreactive positivity and intensity in the extracellular matrix, while increasing total collagen amount in the extracellular matrix; and 4) CS treatment significantly (P < .01) reduced the number of eosinophils and their MMP and TIMP-1 immunoreactive expression., Conclusions: CS treatment modulates NP mucosa remodeling, particularly by promoting epithelial repair, regulating tissue remodeling markers, increasing total collagen content, and reducing tissue eosinophil infiltration., Level of Evidence: 4, (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Human adult basal stem/progenitor cells (BSCs) obtained from chronic rhinosinusitis with nasal polyps (CRSwNP) when differentiated in an air‐liquid interface (ALI) usually provide a pseudostratified airway epithelium with similar abnormalities than original in vivo phenotype. However, the intrinsic mechanisms regulating this complex process are not well defined and their understanding could offer potential new therapies for CRSwNP (incurable disease). Methods: We performed a transcriptome‐wide analysis during in vitro mucociliary differentiation of human adult BSCs from CRSwNP, compared to those isolated from control nasal mucosa (control‐NM), in order to identify which key mRNA and microRNAs are regulating this complex process in pathological and healthy conditions. Results: A number of genes, miRs, biological processes, and pathways were identified during mucociliary differentiation of both CRSwNP and control‐NM epithelia, and notably, we have demonstrated for the first time that genetic transcriptional program responsible of ciliogenesis and cilia function is significantly impaired in CRSwNP epithelium, presumably produced by an altered expression of microRNAs, particularly of those miRs belonging to mir‐34 and mi‐449 families. Conclusions: This study provides for the first time a novel insight into the molecular basis of sinonasal mucociliary differentiation, demonstrating that transcriptome related to ciliogenesis and cilia function is significantly impaired during differentiation of CRSwNP epithelium due to an altered expression of microRNAs. [ABSTRACT FROM AUTHOR]

Background and objective Anomalies in the regulation of cyclooxygenase ( COX)-1 and -2 have been described in nasal polyps of aspirin-induced asthma ( AIA). Whether these anomalies are specific to nasal polyps or affect all the nasal mucosa ( NM) of upper airways is still unclear. The objective of this study was to compare the COX pathway in NM of AIA patients with the NM of control subjects. Methods Fibroblasts were isolated from NM of five AIA patients ( AIA-NM) and five control subjects (control- NM). Cells were treated with 10 ng/mL interleukin ( IL)-1β for up to 72 h. Prostaglandin E2 ( PGE2) production was measured by enzyme-linked immunosorbent assay ( ELISA), expression of COX-1 protein by Western blot and COX-2 protein by ELISA, Western blot and immunofluorescence techniques. Results IL-1β increased PGE2 production and COX-1 protein expression in control- NM fibroblasts, but no changes were found in AIA-NM. IL-1β provoked a significant time-dependent increase in COX-2 protein expression in control- NM fibroblasts but had a very mild effect on COX-2 protein expression in AIA-NM. Conclusions Our data suggest that abnormalities in the COX pathway are not a phenomenon exclusive to nasal-polyp mucosa as they are also present in all the NM of AIA patients. These anomalies may be involved in the pathogenesis of airway inflammation and non-steroidal anti-inflammatory drug intolerance in asthma patients with chronic rhinosinusitis and nasal polyposis. [ABSTRACT FROM AUTHOR]