BackgroundChronic rhinosinusitis patients (CRS) suffer from chronic inflammation of the sinus mucosa associated with chronic relapsing infections. Mucosal biofilms, associated with Staphylococcus aureus, have been implicated as a cause. We compared the effect of exoproteins secreted from clinical isolates of S aureus from CRS patients in planktonic and biofilm form on the nasal epithelial barrier.MethodsClinical S aureus isolates from 39 CRS patients were grown in planktonic and biofilm forms and their exoproteins concentrated. These were applied to primary human nasal epithelial cells grown at the air‐liquid interface. Transepithelial electrical resistance, permeability of flourescein isothiocyanate‐dextrans, and cytotoxicity were measured. Structure and expression of tight junctions zona occludens‐1, and claudin‐1 proteins were assessed by electron microscopy and immunofluorescence. The Wilcoxon signed rank test was used for statistical analyses.ResultsS aureus biofilm exoproteins showed dose‐ and time‐dependent reduction of transepithelial electrical resistance, increased cell toxicity, and increased permeability (p < 0.001) compared with equal concentrations of planktonic cultures. Discontinuity in zona occludens‐1 and claudin‐1 immunofluorescence was confirmed as disrupted tight junctions on electron microscopy.ConclusionS aureus biofilm exoproteins disrupt the mucosal barrier structure in a time‐ and dose‐dependent manner and are toxic. Damage to the mucosal barrier by S aureus biofilm exoproteins may play a major role in CRS etiopathogenesis.
Objectives: This study aimed to determine the safety and efficacy of Chitogel, with and without Deferiprone (Def) and Gallium Protoporphyrin (GaPP), as a promoter of wound healing to improve surgical outcomes after endoscopic sinus susgery. Design: A double-blinded, randomised control human clinical trial was conducted in patients undergoing ESS as a treatment for chronic rhinosinusitis. Participants underwent functional ESS or FESS with drill out as required and were randomised to receive test product Chitogel, Chitogel in combination with Def or Def-GaPP versus no packing (control). Setting: Ostial stenosis and persistent inflammation are the main reasons for revision endoscopic sinus surgery (ESS). Post-operative (PO) dressings can improve PO wound healing and patient outcomes after ESS. Participants: Eighty two patients were included in this study with 79 patients completing the study with 40 undergoing full house FESS and 39 FESS plus frontal drillout.Main Outcome Measures: Patients were followed up at 2, 6 and 12 weeks PO, and outcome scores such as SNOT-22, VAS and LKS, pre and post-surgery (12 weeks) were compared.Results: Seventy nine patients completed the study, there was a significant reduction in SNOT-22 score and improvement of VAS at 12 weeks in patients treated with Chitogel compared to control (p < .05). In those patients, the mean ostium area for the Chitogel and the Chitogel + Def + GaPP groups was higher across all three sinuses compared to the no-treatment control group, without statistical significance.Sphenoid sinus ostium was significantly more patent in patients treated with Chitogel compared to the control at the 12-week time point (p < .05). Conclusion:Chitogel as a PO dressing after ESS results in the best patient-reported symptom scores and objective measurements. The combination of Def and GaPP to Chitogel though proving safe, had no effect on the ostium patency or mucosal healing.
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