Abstract: The role of bacterial biofilms in patients with persistent CRS is of growing concern. The limited efficacy of some medical and surgical treatments for CRS illustrates the need for further progress in this area. The current treatments of chronic rhinosinusitis are concentrated on medical +/- surgical therapy. In this thesis, we consider two methods performed in chronic rhinosinusitis, endoscopic sinus surgery and long term low-dose macrolide therapy, and consider how they can affect bacterial biofilms. The effect of endoscopic sinus surgery on bacterial biofilms and the clinical impact of this condition on CRS patients may be far more profound than we can currently understand. To understand the impact of ESS on bacterial biofilms, we have performed the first prospective study to evaluate the effect of ESS on bacterial biofilms in patients with CRS and patients’ clinical outcomes after 3 months follow-up. We have shown that ESS results in a statistically significant improvement in QoL, subjective and objective outcome measures. In terms of bacterial biofilms, the mean OD630nm of isolates was significantly reduced after 3 months follow-up (p=0.043). No correlations between the reduction of bacterial biofilms with any of the objective, subjective and QoL outcomes were seen in our study. Macrolides have demonstrated their anti-inflamatory effects in the treatment of diffuse panbronchiolitis, asthma, cystis fibrosis and chronic rhinosinusitis. In recent years, there are a number of in vitro studies supporting the anti-biofilm effects of macrolide antibiotics, especially at sub-MICs level. These have shown that macrolides alter the outer membrane, lipopolysaccharide of biomass and inhibit the expression of other bacterial virulence factors which may disrupt the adherence of bacteria to form biofilms. Long term low dose macrolide therapy, therefore, may transform bacterial biofilms from the protected organized form into the plantonic form. In this thesis, we also report the first in vivo efficacy of long term low dose macrolides on bacterial biofilms in patients with CRS. Patients receiving oral macrolide showed significant improvements in subjective, objective and QoL scores following a 12 week course. Nasal swabs were taken from CRS patients at the first visit and 3 months after macrolide therapy. Using the microtiter biofilm assay, these swabs showed a reduction in the mean OD630nm of isolates in 8/12 patients. While it is well-known that bacterial biofilms are established in CRS patients, the relationship between the improvement of clinical symptoms and the severity of bacterial biofilm is less clear.

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