Investigation of novel topical therapeutics for chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a common condition that arises from interactions between anatomical factors, perturbations of the local microbial community including the formation of bacterial biofilms, and dysfunction of the host immune responses. First-line treatments are saline nasal irrigation and topical corticosteroids, with the addition of courses of systemic antibiotics and corticosteroids when indicated. If these therapies do not yield a satisfactory improvement in symptoms, functional endoscopic sinus surgery (FESS) may be performed, with subsequent postoperative debridement using topical anaesthesia, and ongoing irrigation and topical corticosteroids. Despite appropriate therapy, CRS may be recalcitrant and further surgery and/or systemic treatment may be necessary. The sinonasal cavity is well suited to topical treatments delivered by a nasal spray or added to an irrigation solution, especially following FESS. All currently available topical therapies have either limited efficacy or significant side effects. The studies described in this thesis sought to identify potential new topical treatments for use in CRS: antimicrobial agents with activity against biofilms of the CRS-relevant pathogens Staphylococcus aureus and Pseudomonas aeruginosa, including Maxitrol, polymyxin B, ethylenediaminetetraacetic acid, Zoono GermFree24 and Nasodine; tofacitinib, a Janus kinase inhibitor, for management of the dysregulated immune response; and tetracaine with oxymetazoline to facilitate postoperative debridement and optimise surgical outcomes. All antimicrobials tested had varying degrees of efficacy against biofilms of S. aureus and P. aeruginosa, with Nasodine being the most likely to offer the best balance between antibiofilm efficacy and sinonasal toxicity. Tofacitinib suppresses the transcription of target genes of cytokine receptor activation relevant to CRS. Tetracaine 2% with oxymetazoline 0.05% produced more rapidly acting and potent anaesthesia than the current standard Co-phenylcaine. The findings of this thesis may encourage and inform future clinical trials to improve CRS care.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Surgery

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2025

Author dc:creator

• Hale, Samuel James Mitchell

Advisors dc:contributor.advisor

• Douglas, Richard
• Kim, Raymond
• Biswas, Kristi
• Mackenzie, Brett Wagner

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/72241

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/72241