Longitudinal analysis of sinus microbiota post endoscopic surgery in patients with cystic fibrosis and chronic rhinosinusitis: a pilot study.

BACKGROUND: Cystic fibrosis is a debilitating, autosomal recessive disease which results in chronic upper and lower airway infection and inflammation. In this study, four adult patients presenting with cystic fibrosis and chronic rhinosinusitis were recruited. Culture and molecular techniques were employed to evaluate changes in microbial profiles, host gene expression and antimicrobial resistance (AMR) in the upper respiratory tract over time. METHODS: Swab samples from the sinonasal cavity were collected at the time of surgery and at follow-up clinics at regular time intervals for up to 18 months. Nucleic acids were extracted, and DNA amplicon sequencing was applied to describe bacterial and fungal composition. In parallel, RNA was used to evaluate the expression of 17 AMR genes and two inflammatory markers (interleukins 6 and 8) using custom qPCR array cards. Molecular results were compared with routine sinus and sputum culture reports within each patient. RESULTS: Bacterial amplicon sequencing and swab culture reports from the sinonasal cavity were mostly congruent and relatively stable for each patient across time. The predominant species detected in patients P02 and P04 were Pseudomonas aeruginosa, Staphylococcus aureus in patient P03, and a mixture of Enterobacter and S. aureus in patient P01. Fungal profiles were variable and less subject specific than bacterial communities. Increased expressions of interleukins 6 and 8 were observed in all patients throughout the sampling period compared with other measured genes. The most prevalent AMR gene detected was ampC. However, the prevalence of AMR gene expression was low in all patient samples across varying time-points. CONCLUSIONS: We observed a surprising degree of stability of sinonasal microbial composition, and inflammatory and AMR gene expression across all patients post sinus surgery.

The international sinonasal microbiome study: A multicentre, multinational characterization of sinonasal bacterial ecology.

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.

Oral microbial influences on oral mucositis during radiotherapy treatment of head and neck cancer.

PURPOSE: Oral mucositis (OM) remains a significant complication developed by many patients undergoing radiotherapy (RT) to the head and neck region. Emerging data suggest oral microbes may contribute to the onset and severity of this acute side effect. METHODS: In this study, saliva and oral swabs from head and neck cancer patients undergoing RT were collected. We employed molecular microbiological techniques to study the bacterial communities present in saliva, and both the bacterial and fungal communities present on the buccal mucosa and lateral tongue. Changes in microbiota composition with increasing radiation dose and the presence of mucositis were examined. RESULTS: The data suggest that the salivary microbiota remain stable during RT and are consistently dominated by Streptococcus, Prevotella, Fusobacterium and Granulicatella. Obligate and facultative anaerobic Gram-negative bacilli (GNB) Bacteroidales G2, Capnocytophaga, Eikenella, Mycoplasma and Sneathia, as well as anaerobic GNB in the periopathogenic genera Porphyromonas and Tannerella, were all positively correlated with ≥ grade 2 OM. Significant increases in the relative abundances of Bacteroidales G2, Fusobacterium and Sneathia were identified in buccal mucosa swabs at sites of ≥ grade 2 OM (p < 0.05). Furthermore, the abundance of several GNB (Fusobacterium, Haemophilus, Tannerella, Porphyromonas and Eikenella) on the buccal mucosa may influence patient susceptibility to developing OM. Candida was widely detected in buccal mucosa swabs, regardless of mucositis status. CONCLUSIONS: Our findings support previously hypothesized associations between oral health and the pathogenesis of OM, highlighting the importance of oral health interventions for head and neck cancer patients.

Chronic Rhinosinusitis and the Evolving Understanding of Microbial Ecology in Chronic Inflammatory Mucosal Disease.

Chronic rhinosinusitis (CRS) encompasses a heterogeneous group of debilitating chronic inflammatory sinonasal diseases. Despite considerable research, the etiology of CRS remains poorly understood, and debate on potential roles of microbial communities is unresolved. Modern culture-independent (molecular) techniques have vastly improved our understanding of the microbiology of the human body. Recent studies that better capture the full complexity of the microbial communities associated with CRS reintroduce the possible importance of the microbiota either as a direct driver of disease or as being potentially involved in its exacerbation. This review presents a comprehensive discussion of the current understanding of bacterial, fungal, and viral associations with CRS, with a specific focus on the transition to the new perspective offered in recent years by modern technology in microbiological research. Clinical implications of this new perspective, including the role of antimicrobials, are discussed in depth. While principally framed within the context of CRS, this discussion also provides an analogue for reframing our understanding of many similarly complex and poorly understood chronic inflammatory diseases for which roles of microbes have been suggested but specific mechanisms of disease remain unclear. Finally, further technological advancements on the horizon, and current pressing questions for CRS microbiological research, are considered.

Bacterial community collapse: a meta-analysis of the sinonasal microbiota in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common, debilitating condition characterized by long-term inflammation of the nasal cavity and paranasal sinuses. The role of the sinonasal bacteria in CRS is unclear. We conducted a meta-analysis combining and reanalysing published bacterial 16S rRNA sequence data to explore differences in sinonasal bacterial community composition and predicted function between healthy and CRS affected subjects. The results identify the most abundant bacteria across all subjects as Staphylococcus, Propionibacterium, Corynebacterium, Streptococcus and an unclassified lineage of Actinobacteria. The meta-analysis results suggest that the bacterial community associated with CRS patients is dysbiotic and ecological networks fostering healthy communities are fragmented. Increased dispersion of bacterial communities, significantly lower bacterial diversity, and increased abundance of members of the genus Corynebacterium are associated with CRS. Increased relative abundance and diversity of other members belonging to the phylum Actinobacteria and members from the genera Propionibacterium differentiated healthy sinuses from those that were chronically inflamed. Removal of Burkholderia and Propionibacterium phylotypes from the healthy community dataset was correlated with a significant increase in network fragmentation. This meta-analysis highlights the potential importance of the genera Burkholderia and Propionibacterium as gatekeepers, whose presence may be important in maintaining a stable sinonasal bacterial community.

A potential role for staphylococcal and streptococcal superantigens in driving skewing of TCR Vß subsets in tonsillar hyperplasia.

The TCR Vß repertoire from patients with recurrent tonsillitis and/or tonsillar hyperplasia was examined to determine whether the TCR Vß composition is suggestive of local superantigen activity and if so, whether it is associated with the presence of superantigen producing bacteria. Tonsil specimens were cultured aerobically to allow identification and isolation of the bacterial pathogens Staphylococcus aureus and Group A Streptococcus. TCR Vß subset analysis of tonsil leucocytes was performed by flow cytometry. The superantigenic potential of tonsil S. aureus isolates was determined by multiplex PCR and a T-cell mitogenicity assay. Tonsils were collected from 40 patients who were predominantly pre-school-aged children undergoing surgery for either recurrent tonsillitis or tonsillar hyperplasia causing obstructive sleep apnoea. S. aureus was cultured from 23/40 and Group A Streptococcus from 5/40 patients. Both CD4+ and CD8+ TCR Vß populations were skewed in 17/40 patients. Twelve of these had recurrent tonsillitis of whom 9 also harboured S. aureus. Characterisation of tonsillar S. aureus isolates revealed that many contained genes for one or more potent superantigens and detection of these genes was associated with in vitro mitogenic activity. Skewing of the tonsillar TCR Vß repertoire was observed at high frequency and was most commonly associated with the presence of S. aureus. Many S. aureus isolates were mitogenic suggesting that they have a potential for local impact on the function of tonsil T cell populations. These results suggest the possibility that anti-staphylococcal antibiotics may be an effective treatment option for some patients.

Don't Just Stand There. Rethinking the Ideal Body Posture for Otorhinolaryngologists.

Surgeons have a high rate of work-related musculoskeletal injuries; an area that has received little attention. These injuries result in surgeons performing less efficiently, needing to take time off work, suffering higher rates of burnout, and may ultimately lead surgeons to retire earlier than planned. Otorhinolaryngologists are at particular risk for work-related musculoskeletal injuries. Beyond the clinician, sustaining such injuries can negatively impact patient safety. Ergonomic interventions have been used effectively to reduce work-related musculoskeletal injuries in other professions, yet not in surgery. With traditional teachings of ideal body postures to avoid injury and manual handling training being re-evaluated, it is important to explore evidence based interventions for reducing work-related musculoskeletal injuries in otorhinolaryngologists. New research encourages us to shift the focus away from the traditional one-size-fits-all approach to ergonomics and toward postural recommendations and education that promote a dynamic, individualized approach to avoiding sustained, static and awkward postures.

Work-Related Musculoskeletal Disorders in Endoscopic Sinus and Skull Base Surgery: A Systematic Review With Meta-analysis.

OBJECTIVE: Endoscopic sinus and skull base surgery has led to significant improvements in patient outcomes, yet may have come at a cost to surgeons' musculoskeletal (MSK) health. We aimed to determine the prevalence and characteristics of work-related MSK disorders (WRMDs) in endoscopic sinus and skull base surgeons; to investigate contributing factors for WRMD in this population; and to evaluate the effectiveness of ergonomic interventions on the severity or prevalence of WRMD in this population. DATA SOURCES: Medline, Embase, CINAHL, Web of Science, and Scopus from inception to April 2, 2024. A bibliographic examination was performed for further papers. REVIEW METHODS: Inclusion criteria included original peer-reviewed papers with work-related MSK outcomes (prevalence, contributing factors, and interventions) relating to endoscopic sinus and/or skull base surgeons in any language. RESULTS: Of 25,772 unique citations, 37 studies met the inclusion criteria. The pooled lifetime, point, and 12-month prevalences of WRMD were 75.9% (95% confidence interval; I2, 67.2%-83.6%, I2 95.6%), 80.8% (77.0%-84.3%, I2 98.0%), and 82.0% (71.8%-90.3%, I2 60.96%) respectively. The neck, lumbar spine, and thoracic spine were the most commonly involved areas. One of 9 studies on contributing factors investigated discomfort as an outcome. The remainder focussed on surrogate outcomes (eg, posture, hand dysfunction). Two of the 13 intervention studies investigated pain or fatigue as an outcome. The remainder targeted posture, muscle activity, or workload. CONCLUSION: WRMDs are highly prevalent in endoscopic sinus and skull base surgeons. Further studies focusing on the direct outcomes of WRMD such as pain are needed.

A methodological pipeline for the preclinical evaluation of novel topical agents for the treatment of CRS.

KEY POINTS: Novel topical therapeutics require extensive pre-clinical testing to assess efficacy and safety. Antibiofilm or immunosuppressant agents can utilize ex vivo models to measure ciliotoxicity. Agents that are found to be effective and non-toxic ex vivo warrant further investigation in vivo.

Polymyxin B and ethylenediaminetetraacetic acid act synergistically against Pseudomonas aeruginosa and Staphylococcus aureus.

Polymyxin B and ethylenediaminetetraacetic acid are antimicrobials possessing antibiofilm activity. They act by displacement and chelation, respectively, of divalent cations in bacterial membranes and may therefore act synergistically when applied in combination. If so, this combination of agents may be useful for the treatment of diseases like cystic fibrosis (CF), in which biofilms are present on the respiratory epithelium. We used checkerboard assays to investigate the synergy between these agents using reference strains Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 6538 in planktonic form. We then determined the efficacy of each agent against biofilms of both species grown on 96-pin lids and proceeded to combination testing against the P. aeruginosa reference strain and 10 clinical isolates from patients with CF. Synergism was observed for planktonic forms of both species and for biofilms of P. aeruginosa. The susceptibility of biofilms of P. aeruginosa clinical isolates to these agents was variable compared to the laboratory reference strain. This combination of agents may be useful in the management of biofilm-associated conditions, particularly those amenable to topical therapies. These results provide a basis upon which the antimicrobial and antibiofilm efficacy of preparations containing these agents may be enhanced.IMPORTANCEBacteria living in biofilms produce a protective matrix which makes them difficult to kill. Patients with severe respiratory disease often have biofilms. Polymyxin B is an antibiotic commonly used in topical medications, such as eye drops and nasal sprays. Ethylenediaminetetraacetic acid (EDTA) is used widely as a preservative in medication but also has antimicrobial properties. It has been hypothesized that Polymyxin B and EDTA could have a synergistic relationship: when used in combination their antimicrobial effect is enhanced. Here, we evaluated the levels at which Polymyxin B and EDTA work together to kill common pathogens Pseudomonas aeruginosa and Staphylococcus aureus. We found that Polymyxin B and EDTA were synergistic. This synergy may be useful in the management of planktonic infection with P. aeruginosa and S. aureus, or biofilm infection with P. aeruginosa. This synergy may be beneficial in the treatment of respiratory biofilms, in which P. aeruginosa biofilms are common.

Bacterial communities in the nasal passage of postviral olfactory dysfunction patients.

KEY POINTS: Bacterial composition is uniform in the sinuses of postviral olfactory dysfunction patients. Significant reduction of genus Corynebacterium in PVOD patients compared to controls.

In vitro Nasodine Can be an Effective Antibiofilm Agent for Biofilms that May Cause CRS.

OBJECTIVES: Bacterial biofilms on the sinonasal mucosa, especially biofilms of Staphylococcus aureus, are associated with greater severity and recalcitrance of chronic rhinosinusitis (CRS). There are few, if any, antibiofilm agents suitable for sinonasal application available for the management of this problem. Nasodine® Nasal Spray (Nasodine) is a 0.5% povidone-iodine-based formulation that has been developed for sinonasal application. We investigated the antibiofilm efficacy of Nasodine to determine whether it may be a candidate for the treatment of biofilm-associated CRS. METHODS: Biofilms of S. aureus ATCC 6538 were grown in vitro using the Centers for Disease Control biofilm reactor. Intact biofilms were treated by immersion in 0.9% saline (control), half concentration Nasodine, or full concentration Nasodine for between 5 min and 6 h. Further biofilm cells were dispersed into suspension then treated for between 30 s and 5 min. Surviving bacteria were then enumerated by culture and counting colonies, and the log10 reduction in viable bacteria was compared with control. RESULTS: Nasodine demonstrated time and concentration-dependent bacterial killing against intact biofilm. Statistically significant reductions in viable bacteria from intact biofilms were seen with exposures as brief as 5 min. Nasodine consistently eradicated dispersed biofilm within 1 min. CONCLUSION: Nasodine is highly active against biofilms of S. aureus ATCC 6538 in vitro. Biofilm killing is impeded by the presence of the intact biofilm structure. LAY SUMMARY: In chronic rhinosinusitis (CRS), bacterial communities called biofilms are associated with more severe inflammation. An iodine-based nasal spray called Nasodine almost completely eradicates bacterial biofilms after 6 h of exposure. Nasodine may be useful for treating CRS. Laryngoscope, 133:2490-2495, 2023.

Topical Antibiofilm Agents With Potential Utility in the Treatment of Chronic Rhinosinusitis: A Narrative Review.

The role of bacterial biofilms in chronic and recalcitrant diseases is widely appreciated, and the treatment of biofilm infection is an increasingly important area of research. Chronic rhinosinusitis (CRS) is a complex disease associated with sinonasal dysbiosis and the presence of bacterial biofilms. While most biofilm-related diseases are associated with highly persistent but relatively less severe inflammation, the presence of biofilms in CRS is associated with greater severity of inflammation and recalcitrance despite appropriate treatment. Oral antibiotics are commonly used to treat CRS but they are often ineffective, due to poor penetration of the sinonasal mucosa and the inherently antibiotic resistant nature of bacteria in biofilms. Topical non-antibiotic antibiofilm agents may prove more effective, but few such agents are available for sinonasal application. We review compounds with antibiofilm activity that may be useful for treating biofilm-associated CRS, including halogen-based compounds, quaternary ammonium compounds and derivatives, biguanides, antimicrobial peptides, chelating agents and natural products. These include preparations that are currently available and those still in development. For each compound, antibiofilm efficacy, mechanism of action, and toxicity as it relates to sinonasal application are summarised. We highlight the antibiofilm agents that we believe hold the greatest promise for the treatment of biofilm-associated CRS in order to inform future research on the management of this difficult condition.

The Effect of Amoxicillin with Clavulanate on the Microbiota of Tonsillar Tissue in Disease: a Randomized Control Trial.

Despite antibiotics being the primary medical treatment for recurrent tonsillitis, the impact of antibiotics on the tonsillar microbiome is not well understood. This study aimed to determine the effect of amoxicillin with clavulanate on the composition and quantity of bacteria in the tonsils of children with recurrent tonsillitis. A multicenter randomized clinical trial in Auckland, New Zealand was undertaken between August 1, 2017, and June 30, 2018. Sixty children undergoing tonsillectomy for the indication of recurrent tonsillitis were recruited for this study. Following random allocation, 30 participants were prescribed amoxicillin with clavulanate for the week before surgery. The remaining 30 received no antibiotics. Immediately following surgery, the crypts of the right and left tonsils were swabbed. Bacterial 16S rRNA gene-targeted amplicon sequencing and histological techniques were utilized. In the control group, there were significantly higher relative abundances of Haemophilus, Streptococcus, Neisseria, and Porphyromonas. Members from the genera Fusobacterium and Treponema were found to be significantly more abundant in the antibiotic group. There were no significant differences in the absolute quantities of bacteria between the groups. Microscopic examination found fewer bacterial microcolonies present in the tonsillar crypts of participants in the antibiotic group. Streptococcus pyogenes was not present in these bacterial microcolonies. These results suggest that a single course of antibiotics has a significant impact on the tonsil microbiota composition. The duration of this effect and the effect that the altered microbiome has on the course of the condition need to be determined. IMPORTANCE Several studies have identified the presence of multiple pathogenic bacteria in hyperplastic adenoids and palatine tonsils. However, there are currently no studies that utilize this technology to investigate the effect of oral antibiotics in children with recurrent tonsillitis on the tonsillar microbiome. This is the first study to investigate the effect of antibiotics on the microbiome of tonsillar tissue in children with recurrent tonsillitis using molecular techniques. This study has shown that participants who received amoxicillin with clavulanate immediately before tonsillectomy had a significantly reduced number of bacterial taxa commonly associated with recurrent tonsillitis, as well as the number of bacterial microcolonies observed in the tonsillar crypts. This novel finding suggests that either the effect of antibiotics is not sustained or that they are not an effective treatment for recurrent tonsillitis.

Sinonasal Tissue Remodelling during Chronic Rhinosinusitis.

The purpose of this review is to summarise contemporary knowledge of sinonasal tissue remodelling during chronic rhinosinusitis (CRS), a chronic disease involving long-term inflammation of the paranasal sinuses and nasal passage. The concept of tissue remodelling has significant clinical relevance because of its potential to cause irreversibility in chronic airway tissues. Recent studies have indicated that early surgical treatment of CRS may improve clinical outcome. Tissue remodelling has been described in the literature extensively with no consensus on how remodelling is defined. This review describes various factors implicated in establishing remodelling in sinonasal tissues with a special mention of asthma as a comorbid condition. Some of the main histological features of remodelling include basement membrane thickening and collagen modulation. This may be an avenue of research with regard to targeted therapy against remodelling in CRS.

A scoping review of longitudinal airway microbiota studies.

INTRODUCTION: The role of the microbiota in inflammatory airway diseases is unclear. Antimicrobial therapies have predominantly been guided by culture results. However, molecular sequencing has shown that the airway microbiota is much more complex and accurate modeling requires longitudinal analysis. AREAS COVERED: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses scoping review was performed by searching Medline, Scopus, and Web of Science databases for all longitudinal airway microbiota studies that utilized molecular techniques. 38 studies with 1,993 participants were included in this review. Healthy microbial communities were more diverse, individualized and stable over time. Acute infections resulted in changes in the microbiota that were detected earlier and more sensitively by molecular sequencing than culture. Distinct microbiota profiles have been demonstrated in chronic obstructive pulmonary disease patients associated with exacerbation frequency and severity. EXPERT OPINION: Longitudinal studies provide essential data on the stability of the microbiota over time and valuable information about the dynamic interactions between host, disease and microbes. We believe that molecular sequencing will be increasingly incorporated into research and clinical practice in the future. These advances can lead to improved diagnosis, enhanced prescribing guidance and reduce unnecessary antibiotic usage.

Multiomic analysis identifies natural intrapatient temporal variability and changes in response to systemic corticosteroid therapy in chronic rhinosinusitis.

INTRODUCTION: The pathophysiology and temporal dynamics of affected tissues in chronic rhinosinusitis (CRS) remain poorly understood. Here, we present a multiomics-based time-series assessment of nasal polyp biopsies from three patients with CRS, assessing natural variability over time and local response to systemic corticosteroid therapy. METHODS: Polyp tissue biopsies were collected at three time points over two consecutive weeks. Patients were prescribed prednisone (30 mg daily) for 1 week between Collections 2 and 3. Polyp transcriptome, proteome, and microbiota were assessed via RNAseq, SWATH mass spectrometry, and 16S ribosomal RNA and ITS2 amplicon sequencing. Baseline interpatient variability, natural intrapatient variability over time, and local response to systemic corticosteroids, were investigated. RESULTS: Overall, the highly abundant transcripts and proteins were associated with pathways involved in inflammation, FAS, cadherin, integrin, Wnt, apoptosis, and cytoskeletal signaling, as well as coagulation and B- and T-cell activation. Transcripts and proteins that naturally varied over time included those involved with inflammation- and epithelial-mesenchymal transition-related pathways, and a number of common candidate target biomarkers of CRS. Ten transcripts responded significantly to corticosteroid therapy, including downregulation of TNF, CCL20, and GSDMA, and upregulation of OVGP1, and PCDHGB1. Members of the bacterial genus Streptococcus positively correlated with immunoglobulin proteins IGKC and IGHG1. CONCLUSIONS: Understanding natural dynamics of CRS-associated tissues is essential to provide baseline context for all studies on putative biomarkers, mechanisms, and subtypes of CRS. These data further our understanding of the natural dynamics within nasal polypoid tissue, as well as local changes in response to systemic corticosteroid therapy.

Characterising clinical Staphylococcus aureus isolates from the sinuses of patients with chronic rhinosinusitis.

The role of Staphylococcus aureus in the pathogenesis of the chronic sinonasal disease chronic rhinosinusitis (CRS), has not been definitively established. Comparative analyses of S. aureus isolates from CRS with those from control participants may offer insight into a possible pathogenic link between this organism and CRS. The intra- and inter-subject S. aureus strain-level diversity in the sinuses of patients with and without CRS were compared in this cross-sectional study. In total, 100 patients (CRS = 64, control = 36) were screened for S. aureus carriage. The overall carriage prevalence of S. aureus in this cohort was 24% (CRS n = 13, control n = 11). Cultured S. aureus isolates from 18 participants were strain-typed using spa gene sequencing. The bacterial community composition of the middle meatus was assessed using amplicon sequencing targeting the V3V4 hypervariable region of the bacterial 16S rRNA gene. S. aureus isolates cultured from patients were grown in co-culture with the commensal bacterium Dolosigranulum pigrum and characterised. All participants harboured a single S. aureus strain and no trend in disease-specific strain-level diversity was observed. Bacterial community analyses revealed a significant negative correlation in the relative abundances of S. aureus and D. pigrum sequences, suggesting an antagonistic interaction between these organisms. Co-cultivation experiments with these bacteria, however, did not confirm this interaction in vitro. We saw no significant associations of CRS disease with S. aureus strain types. The functional role that S. aureus occupies in CRS likely depends on other factors such as variations in gene expression and interactions with other members of the sinus bacterial community.

Unilateral Intervention in the Sinuses of Rabbits Induces Bilateral Inflammatory and Microbial Changes.

Background: Chronic rhinosinusitis (CRS) is a globally prevalent inflammatory condition of the paranasal sinuses which severely impairs patients' quality of life. An animal model of unilateral sinusitis by transient sinus occlusion has been described previously in rabbits. The aim of this study was to characterise the sinusitis rabbit model by investigating temporal and bilateral changes in the bacterial community and mucosal inflammation. Methods: Development of sinusitis was achieved by endoscopically placing Merocel ® , a sterile nasal packing material, in the left middle meatus of six New Zealand white rabbits for four weeks. After a total period of 14 weeks, rabbits were assessed for sinusitis by endoscopic examination, magnetic resonance imaging (MRI) and histology. Swabs from the left and right middle meatus were obtained for bacterial community analysis at three time points (week 0, week 4, week 14) during the study. Results: Endoscopic evaluation showed unilateral inflammation in all animals examined after the 4-week blocking period and at week 14. Notably, inflammatory changes were also seen in the contralateral sinus of all animals at week 4. MRI images demonstrated unilateral sinus opacification at week 4 in two rabbits, and partial unilateral sinus opacification at week 14 in one rabbit only. Histological analyses revealed substantial spatial heterogeneity of mucosal inflammation with inconsistent findings across all animals. No significant differences in mucosal inflammatory markers (such as goblet cell hyperplasia, epithelial denudation and oedema) could be identified between nostrils at week 14. The bacterial community in the rabbit sinuses was heavily dominated by Helicobacter at week 0 (baseline). At the end of the blocking period (week 4), bacterial alpha and beta diversity were significantly increased in both nostrils. The bacterial community composition at week 14 had primarily returned to baseline, reflecting the endoscopic and radiological results. Conclusion: This study reaffirmed the ability for development of sinusitis without inoculation of any pathogens in a rabbit model. We were able to demonstrate bilateral sinonasal mucosal inflammation, by inducing unilateral sinus blockage, which resulted in significant changes to the sinonasal bacterial community. These findings may explain some of the clinical observations seen in CRS and warrant further research to reveal potential implications for its therapeutic management.

Pathogenesis and treatment of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is one of the most common diseases in western societies, causing significant morbidity and resulting in great financial cost. Some patients suffer persistent or recurrent symptoms despite receiving optimal medical and surgical treatment. The recent publication of revised diagnostic criteria and management guidelines will assist both clinical research and practice. Multiple theories have been advanced regarding the underlying pathogenesis including allergy, bacterial or fungal infection, genetic predisposition and structural anomalies, but at present the majority of cases are still considered idiopathic. Recent studies have shown that traditional laboratory culture techniques may fail to detect microorganisms growing within biofilms or within host mucosal cells. Both bacteria and fungi possess a number of mechanisms for both the evasion and modulation of host immune responses, including the formation of biofilms and the production of superantigens. Historically, treatments such as antibiotics that had been directed at putative causative agents have often been disappointing. There are, however, a broad range of medical and surgical therapies with proven efficacy available to the treating physician. Endoscopic surgical management is evolving rapidly, and there have been pronounced improvements in outcome and reduction in the risk of complications. Recent advances in the understanding of the pathogenesis of this condition have led to some promising therapeutic developments, particularly in respect to topical treatments. Despite improvements in therapy, CRS remains a challenging condition to manage.