Histone deacetylase activity is a novel target for epithelial barrier defects in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Studies have independently indicated that eosinophils and histone deacetylases (HDACs) may compromise the integrity of the epithelial barrier in nasal polyps; however, the underlying mechanisms are not clear. In this study, we aimed to investigate the role of eosinophilia and HDACs in regulation of tight junctions (TJs) and nasal epithelial barrier integrity in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. METHODS: Expression of mRNAs and proteins of TJs and HDACs of biopsy specimens and air-liquid interface (ALI) human nasal epithelial cell cultures (HNECs) from eosinophilic and noneosinophilic CRSwNP patients and healthy controls was assessed. The ALI HNECs were also assessed for changes in transepithelial electrical resistance (TER) and paracellular flux of fluorescein isothiocyanate (FITC)-labelled dextran. Meanwhile, the assessments for the effect of HDAC inhibitor in eosinophilic nasal polyps were also conducted. RESULTS: Decreased TER and increased paracellular flux of FITC-labelled dextran in the ALI cultures were found in both eosinophilic and noneosinophilic CRSwNP, along with irregular, patchy and reduced expression of claudin-1, 4, 7, occludin, zonula occludens (ZO)-1 and ZO-2 and increased expression of HDAC1, 9 and SIRT7 for both ALI culture cells and biopsy specimens, especially for the eosinophilic CRSwNP group. Treatment of eosinophilic CRSwNP ALI-HNECs with an HDAC inhibitor improved the TJs expression and epithelial barrier integrity. CONCLUSIONS: Our data suggest that eosinophilia and HDACs influence epithelial barrier function in CRSwNP patients by regulating TJ protein expression. Targeting HDACs with specific inhibitors may be a potential treatment option for patients with eosinophilic CRSwNP.

Efficacy of buffered hypertonic seawater in different phenotypes of chronic rhinosinusitis with nasal polyps after endoscopic sinus surgery: a randomized double-blind study.

PURPOSE: Nasal douching is commonly used as a postoperative management strategy for chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies to date have compared the effectiveness of nasal douching in CRSwNP phenotypes after endoscopic sinus surgery (ESS). We evaluated the efficacy of seawater types in eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (nonECRSwNP) after ESS. METHODS: Patients with bilateral CRSwNP who had undergone ESS were blindly randomized to receive buffered hypertonic seawater (BHS) (n = 48) or physiological seawater (PS) (n = 45). CRSwNP patients were stratified by phenotypes (ECRSwNP and nonECRSwNP) retrospectively according to whether tissue eosinophils exceeded 10%. Follow-up evaluations were conducted at 2, 8, 16, and 24 weeks after surgery. Evaluations included the 22-item Sino-Nasal Outcome Test (SNOT-22), visual analog scale (VAS), Lund-Kennedy endoscopic score (LKES), saccharine clearance time (SCT), and adverse events. RESULTS: All of the patients experienced significant improvements in SNOT-22 scores, VAS scores, and LKES over time. BHS resulted in better improvement of LEKS and SCT relative to PS at 8 weeks postoperatively. Mucosal edema formation was significantly reduced with less crusting among HBS recipients at 8 weeks. After stratification, only patients in the nonECRSwNP + BHS subgroup showed a significant improvement in LEKS and SCT at 8 weeks postoperatively. Side effect profiles were not significantly different among the groups. CONCLUSIONS: BHS has a better inhibitory effect on mucosal edema and crusting during the early postoperative care period of CRSwNP. Among all of the patients, nonECRSwNP patients showed a significant improvement in LEKS and SCT at 8 weeks.

Integrated miRNA and mRNA expression profiling reveals dysregulated miRNA-mRNA regulatory networks in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: The precise mechanisms underlying pathogenesis of different subtypes of chronic rhinosinusitis with nasal polyps (CRSwNP) are still unclear. Emerging evidence indicates that microRNAs may play a role in the pathogenesis of CRSwNP. This study aimed to identify the dysregulated microRNA-messenger RNA (miRNA-mRNA) regulatory networks in eosinophilic (E) and non-eosinophilic (non-E) CRSwNP. METHODS: Whole-transcriptome sequencing was performed on nasal tissues of patients with ECRSwNP and non-ECRSwNP, and control subjects. An integrated analysis of miRNA and mRNA expression was conducted to identify key mRNAs and miRNAs involved in the pathogenesis of ECRSwNP and non-ECRSwNP. The miRNAs of interest and their target genes were validated using quantitative real-time polymerase chain reaction (PCR). RESULTS: A group of differentially expressed mRNAs (DE-mRNAs) and miRNAs (DE-miRs) were identified in ECRSwNP patients vs control subjects, non-ECRSwNP patients vs control subjects, and non-ECRSwNP vs ECRSwNP patients, respectively. Pathway enrichment analysis showed distinct immune and inflammatory functions associated with DE-mRNAs and target genes of DE-miRs in ECRSwNP vs control and non-ECRSwNP vs control groups. The miRNA-mRNA regulatory networks constructed with Cytoscape highlighted the roles of miR-154, miR-221, and miR-223 family miRNAs relating to both ECRSwNP and non-ECRSwNP, and the roles of the let-7 and miR-34/449 families in the development of non-ECRSwNP. Assessment using real-time PCR for the expression of miRNAs and target genes demonstrated highly consistent data with the RNA sequencing data. CONCLUSION: ECRSwNP and non-ECRSwNP patients express distinct miRNA-mRNA regulatory networks compared with control subjects, thus providing potential targets for future development of novel therapeutic approaches for the management of CRSwNP.