Academic literature on the topic 'Recalcitrant Chronic Rhinosinusitis'

INTRODUCTION: There is increasing interest in the underlying bone of the paranasal sinuses as an important player in recalcitrant Chronic Rhinosinusitis. Close inspection of CT scans often reveals areas of increased bone density and irregular thickening of the sinus walls. This osteitic bone could at least partly explain, why inflammation of the mucosa persists. METHODS: We searched PubMed for all relevant studies, using the following text words: chronic rhinosinusitis, sinusitis, bone, osteitis, osteomyelitis, histology, and treatment. Cited references of retrieved articles were also examined. RESULTS: Background, available data, potential diagnostic options, treatment implications, and suggestions for future research are discussed. CONCLUSION: Osteitis is associated with CRS, however its role in the pathogenic process is not well defined. More research is needed.

Chronic rhinosinusitis is a common condition affecting 5–12% of the general population worldwide. In a limited number of cases, the disease is recalcitrant to medical and surgical interventions, causing a major impact on physical, social and emotional well-being and increasing pressure on healthcare systems. Biofilm formation and dysbiosis caused by Staphylococcus aureus and Pseudomonas aeruginosa play a role in the pathogenesis of recalcitrant chronic rhinosinusitis. In these cases, a promising treatment alternative is the application of bacteriophages, which are viruses that infect and lyse bacteria. In this review, we appraise the evidence for the use of bacteriophages in the treatment of recalcitrant chronic rhinosinusitis. Additionally, (dis)advantages of bacteriophages and considerations for implementation of phage therapy in otorhinolaryngology practice will be discussed.

AbstractBackground:Chronic rhinosinusitis is a common, heterogeneous condition. An effective means of mitigating disease in chronic rhinosinusitis patients remains elusive. A variety of causes have been implicated, with the biofilm theory gaining increasing prominence.Objective:This article reviews the literature on the role of biofilms in chronic rhinosinusitis, in terms of pathophysiology and with regard to avenues for future treatment.Methods:A systematic review of case series was performed using databases with independently developed search strategies, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane library, and Zetoc, in addition to conference proceedings and a manual search of literature, with the last search conducted on 18 January 2014. The search terms included the following, used in various combinations to maximise the yield of articles identified: ‘biofilms’, ‘chronic rhinosinusitis’, ‘DNase’, ‘extracellular DNA’ and ‘biofilm dispersal’.Results:The existing evidence lends further support for the role of biofilms (particularly the Staphylococcus aureus phenotype) in more severe, recalcitrant disease and poorer surgical outcomes.Conclusion:Multimodality treatment, with a shift in paradigm to incorporate anti-biofilm strategies, is likely to form the mainstay of future recalcitrant chronic rhinosinusitis management.

Background Chronic rhinosinusitis with nasal polyposis is a complex inflammatory disorder, which is often recalcitrant to medical and surgical management. Recently, biologic agents have been studied as an adjunct treatment for this patient population. Objective The purpose of this study is to examine the role of biologic agents for chronic rhinosinusitis patients by reviewing literature and clinical trials. Methods A comprehensive review of literature and clinical trials—both recently completed and ongoing—was undertaken to examine up-to-date evidence of current biologic therapy and its role in chronic rhinosinusitis patients—including anti-IgE, anti-IL-4, anti-IL-5, anti-IL-13, and GATA-3 DNAzyme. Results Specific biologic agents discussed include omalizumab, reslizumab, mepolizumab, benralizumab, dupilumab, and Hgd40/SB010. Risks, side effects, and administration information are also reviewed. An algorithm for the use of biologics in patients with chronic rhinosinusitis with nasal polyposis is proposed. Conclusion These treatments have promising results and may prove to be an important adjunct for patients with recalcitrant sinus disease.

Corticosteroids are the mainstay of treatment for refractory chronic rhinosinusitis. The off-label use of steroid-eluting stents has increasingly gained popularity in functional endoscopic sinus surgery for decreasing postoperative inflammation and synechiae formation. However, there is a paucity of data outlining the safety profile of this device despite its widespread use. This study was designed to report a newly described complication of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. This report highlights a potential risk of the drug-eluting stent in the treatment of recalcitrant rhinosinusitis and the need for further clinical investigations whenever a novel medical device becomes available on the market.

Background: Many different etiologies have been proposed to be responsible for the pathogenesis of chronic rhinosinusitis, including dysbiosis of the sinus microbiome. Attempts have recently been made to identify a pathogenic organism via advanced culture mechanisms. The purpose of this study is to use culture-dependent and culture-independent means of microtyping to determine whether any association exists between the quantity and quality of bacteria identified in patients with recalcitrant chronic rhinosinusitis. Methods: Medical records were retrospectively reviewed for patients with a history of revision sinus surgery and persistent symptoms who underwent endoscopically directed culture and underwent quantitative polymerase chain reaction analysis of the 16S ribosomal RNA of bacteria and fungi from February 1, 2014, to January 1, 2017. A total of 21 patients met the inclusion criteria. Medical records were reviewed to determine the number of bacterial isolates and relative abundance of bacteria and fungi on culture and polymerase chain reaction. Results: Using culture-independent techniques of examining purulent secretions in patients with recalcitrant chronic rhinosinusitis, an average of 3.61 isolates were identified per specimen, compared with culture-dependent methods that revealed 2.10 isolates per specimen ( P < .05). The dominant species identified on each culture was rarely the most abundant species identified using polymerase chain reaction techniques. Conclusions: Traditional culture methodologies may fail to identify potential pathogens or the dominant pathogen in patients with recalcitrant chronic rhinosinusitis with acute exacerbations.

Chapter 1 of this thesis reviews the current literature on Chronic Rhinosinusitis (CRS) including its aetiology and the role of bacterial biofilms in CRS. It also presents an updated review on all current and emerging topical anti-biofilm options in the management of CRS. Chapter 2 describes the optimisation of an in vivo model using Chitogel (CG) as a drug delivery vehicle for anti-biofilm agents to treat Staphylococcus aureus biofilms. Budesonide and Mupirocin were incorporated as they have some efficacy in the management of recalcitrant CRS in the form of topical irrigations. This study showed that Chitogel- Budesonide-Mupirocin gel significantly reduces S. aureus biofilms in vivo and is the first study to suggest an alternative mode of topical drug delivery to the sinuses. Chapter 3 furthers the study of topical anti-biofilm gel by incorporating novel antimicrobial agents Deferiprone and Gallium Protoporphyrin (DG) into Chitogel. DG has a synergistic anti-biofilm effect against S. aureus and Methicillin Resistant S. aureus (MRSA) biofilms by targeting the iron metabolism pathway that is crucial for bacterial growth and survival. This study has shown that Chitogel- Deferiprone- Gallium Protoporphyrin is safe and effective in eradicating S. aureus biofilms in vivo. Chapter 4 explores the potential wound healing properties of Deferiprone in vitro. In this study Deferiprone was shown to delay primary nasal fibroblast migration without affecting epithelial migration, decrease collagen and reactive oxygen species (ROS) production and reduce interleukin 6 (IL-6) production. This anti-inflammatory potential and ability to limit scar tissue formation has wide prospective applications in the field of sinus surgery. Chapter 5 explores the long-term safety of S. aureus bacteriophage (NOV012) in vivo as a novel treatment option in CRS. Bacteriophage (Phage) therapy was first proposed as an antibacterial treatment in the 1910s and has been recently revived in the face of a global antibiotic resistance crisis. In this study we have shown that S. aureus phage are safe as a topical sinus irrigation in vivo for up to 3 weeks. Chapter 6 furthers the study of Pseudomonas aeruginosa phage (CT-PA) in vivo. Topical sinus irrigation of CT-PA was safe and effective in reducing P. aeruginosa biofilms in vivo over 3 weeks. Chapter 7 explores the translation of our in vivo studies into the first phase-1 clinical trial investigating the safety and preliminary efficacy of phage in S. aureus CRS. It was safe and well tolerated up to 3×109 PFU twice daily for 14 days with no dose-limiting side effects. Preliminary efficacy indicated favourable outcomes across all cohorts with 2 out of 9 patients achieving eradication of infection. Chapter 8 presents a pilot study investigating the evidence behind alternative treatments like colloidal silver (CS) in recalcitrant CRS. This is the first clinical study looking at the safety and efficacy of CS as a topical sinus irrigation in the management of CRS despite it being widely available for purchase over-the-counter. Twice daily CS sinonasal rinses for 10 days is safe but not superior to culture-directed oral antibiotics. We believe that a larger study and further optimisation of treatment duration could further the potential of this therapy. Chapter 9 investigates the role of manuka honey (MH) sinus irrigations with augmented methylglyoxal (MGO) in recalcitrant CRS. Twice daily MH rinses for 14 days have not been shown to be superior to culture-directed oral antibiotics and saline rinses in bacterial eradication but have shown significant improvement in endoscopic scores comparable to control. In the face of a global antibiotic resistance crisis, now more than ever, clinicians are practising more judicious use of systemic oral antibiotics. With an eye to the future, we hope that this thesis on novel topical anti-biofilm therapies would spur further research and someday offer clinicians viable alternatives to systemic oral antibiotics in the management of recalcitrant CRS.
Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2020