Corticosteroid nasal irrigations after endoscopic sinus surgery for recalcitrant chronic rhinosinusitis

"A thesis submitted to fulfil the requirements for the degree of Doctor of Philosophy".Thesis by publication."May 2013"Includes bibliographical references.1. Background -- 2. Structured histopathology profiling of chronic rhinosinusitis in routine practice -- 3. Eosinophilic rhinosinusitis is not a disease of ostiomeatal occlusion -- 4. Osteitic bone: a surrogate marker of eosinophilia in chronic rhinosinusitis -- 5. Correlation of the Kennedy Osteitis Score to clinico-histologic features of chronic rhinosinusitis -- 6. Topical steroid for chronic rhinosinusitis without polyps -- 7. Topical steroid for nasal polyps -- 8. Sinus surgery and delivery method influence the effectiveness of topical corticosteroid for chronic rhinosinusitis; systematic review and meta-analysis -- 9. Corticosteroid nasal irrigations after endoscopic sinus surgery in the management of chronic rhinosinusitis -- 10. Thesis discussion and conclusion -- Appendix.Chronic rhinosinusitis (CRS) is a heterogeneous disease with multiple pathogenic factors and various inflammatory mechanisms. Although high eosinophil content in the sinus tissue has been acknowledged as a marker of recalcitrant CRS, eosinophilic chronic rhinosinusitis (ECRS) is traditionally diagnosed by its phenotypes other than structured histopathology profiling. Osteitis is another marker associated with recalcitrant inflammation. However, the pathogenesis of osteitis in patients without previous sinus surgery is poorly understood. Patients with ECRS and patients with osteitis have higher disease severity and poorer treatment outcomes. Both observed changes are thought to be features of disordered inflammation. Currently, topical steroid is the first line drug recommended for treating CRS. Although having strong anti-inflammatory effects, topical steroid sprays provide poor sinus delivery. Published randomized controlled trials on the efficacy of topical steroids in CRS use either nasal delivery (nasal drop, nasal spray) or sinus delivery (sinus catheter, sinus irrigation) in patients with or without sinus surgery. This heterogeneity influences topical drug delivery and distribution. This thesis examines the basis of diagnosis, characterisation of the inflammatory process, influence of surgery and device in drug delivery and proposes a revised treatment of CRS with postoperative corticosteroid nasal irrigation which combines the therapeutic effects of sinus surgery and sinus delivery of corticosteroid for an inflammatory condition. In this treatment paradigm, the purpose of sinus surgery is to create access for topical therapies rather than a fundamental concept of relieving ostiomeatal obstruction. Even for the challenging subgroups of ECRS and patients with osteitis, had favourable outcomes and even greater improvement than the non ECRS subgroup. When CRS is managed as an inflammatory condition with local mucosal inflammation controlled with effectively delivered pharmaceutical solutions, therapy is greatly optimized compared to traditional regimes.Mode of access: World wide web1 online resource (507 pages) illustration