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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.

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.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.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.

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., The pathophysiology and temporal dynamics of affected tissues in chronic rhinosinusitis (CRS) remain poorly understood. This study comprised a comprehensive multiomics analysis of polyp biopsies from three patients with chronic rhinosinusitis with nasal polyps, assessing natural variability over time as well as local response to systemic corticosteroids. Overall, these data provide further support for current hypotheses of CRS and polyposis pathogenesis, provide essential temporal context to studies on biomarkers and mechanisms of polyposis, and highlight areas of focus for future targeted therapeutic options.

I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

BackgroundNasal lavage is an ancient practice that still has a fundamental role in the management of sinonasal conditions. The history related to these devices is extensive and remarkable. By reviewing it, it is hoped that a broader view can be achieved on what is currently possible with nasal lavage and how advances may be made in the future.MethodsA careful review of different sources, such as ancient manuscripts, registered patents and scientific papers, was conducted to achieve a thorough examination of the history related to nasal rinsing devices.ConclusionNasal lavage has evolved significantly since first considered for medical use and has always played a central role in the treatment of patients with sinonasal conditions. Further innovation is still necessary to surmount the shortcomings of current nasal lavage systems.

BACKGROUND: Preoperative screening for coronavirus disease 2019 (COVID-19) aims to preserve surgical safety for both patients and surgical teams. This rapid review provides an evaluation of current evidence with input from clinical experts to produce guidance for screening for active COVID-19 in a low prevalence setting. METHODS: An initial search of PubMed (until 6 May 2020) was combined with targeted searches of both PubMed and Google Scholar until 1 July 2020. Findings were streamlined for clinical relevance through the advice of an expert working group that included seven senior surgeons and a senior medical virologist. RESULTS: Patient history should be examined for potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hyposmia and hypogeusia may present as early symptoms of COVID-19, and can potentially discriminate from other influenza-like illnesses. Reverse transcription-polymerase chain reaction is the gold standard diagnostic test to confirm SARS-CoV-2 infection, and although sensitivity can be improved with repeated testing, the decision to retest should incorporate clinical history and the local supply of diagnostic resources. At present, routine serological testing has little utility for diagnosing acute infection. To appropriately conduct preoperative testing, the temporal dynamics of SARS-CoV-2 must be considered. Relative to other thoracic imaging modalities, computed tomography has the greatest utility for characterizing pulmonary involvement in COVID-19 patients who have been diagnosed by reverse transcription-polymerase chain reaction. CONCLUSION: Through a rapid review of the literature and advice from a clinical expert working group, evidence-based recommendations have been produced for the preoperative screening of surgical patients with suspected COVID-19.

Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa occurs remains largely undefined.Twenty subjects undergoing functional endoscopic sinus surgery (FESS) for CRS were randomized to one of two groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal mucus, sinonasal tissues and serum at steady state.Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, p p p = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, p Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complexity of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS. Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa occurs remains largely undefined. Twenty subjects undergoing functional endoscopic sinus surgery (FESS) for CRS were randomized to one of two groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal mucus, sinonasal tissues and serum at steady state. Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, p p p = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, p Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complexity of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.

Xerostomia detrimentally affects the oral health of many head and neck cancer patients who undergo radiotherapy. Its sequelae become an ongoing burden for patients that often manifest as periodontal disease and dental decay. Bacteria play a major role in the pathogenesis of these conditions and here we explore the use of an oral probiotic to beneficially modulate the oral bacterial community post-radiotherapy. In this pilot study, a four-week intervention with oral probiotic lozenges containing Streptococcus salivarius M18 was trialled in seven patients. Post-intervention changes in oral health and in the composition of the plaque and saliva bacterial communities were compared with six patients in a placebo group. An improvement in periodontal screening and plaque index scores was observed in both groups after the intervention period. The oral probiotic lozenges did not significantly impact bacterial community composition or diversity, nor did the probiotic lozenges increase the relative sequence abundance of ZOTU_1 (the probiotic-associated sequence assigned to S. salivarius) detected in the samples. Network analyses suggest negative interactions occurred between ZOTU_1 and species from the periopathogenic genera Campylobacter, Fretibacterium, Selenomonas and Treponema but further investigation is required to more fully understand the beneficial properties of this oral probiotic.

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.

Children who undergo adenotonsillectomy have a range of symptoms. Some present with infective symptoms, others with obstructive symptoms, and many with a combination of both. The most common surgical indication has changed over the past several decades from infective symptoms to obstructive symptoms. However, there are few data available to differentiate these groups of children in terms of their clinical characteristics. This study aimed to determine the clinical characteristics of children with obstructive sleep apnea versus infectious adenotonsillar hyperplasia.Data were obtained from the medical records of two district health boards in Auckland, New Zealand. Extraction of clinical information was performed following the identification of all patients under the age of 16 years undergoing adenotonsillectomy between December 2015 and December 2017.A total of 1538 children were included in this study. There were 112 (7.3%) with recurrent tonsillitis (RT) symptoms only, 624 (40.6%) with RT and sleep-disordered breathing symptoms (SDB), and 802 (52.1%) with symptoms suggestive of obstructive sleep apnea (OSA). Children with OSA were more likely to be male (p 0.001), younger (p 0.001), and have lower body mass indexes at time of surgery (p 0.001). There was no difference between groups in the number of antibiotic courses prescribed in the year before surgery (p = 0.7). There was no significant difference in tonsil or adenoid grade between groups (p = 0.2). Children with OSA were more likely to have a diagnosis of asthma (p 0.001) and allergic rhinitis (p 0.001), but less likely than those with RT to have a diagnosis of eczema (p 0.001). Children with OSA were more likely to have otitis media with effusion requiring ventilation tube insertion (p 0.001) and a documented history of speech delay (p 0.001). Thirty-day readmission rates were higher in the OSA (8.5%) and SDB/RT (9.3%) groups when compared to those with RT (1.8%) (p = 0.03).Children with OSA have different perioperative characteristics than those with recurrent tonsillitis, including increased risk of postoperative bleeding and need for post op readmission. Therefore, management strategy may vary according to the indications for tonsillectomy and adenoidectomy.

Olfactory impairment affects ~ 20% of the population and has been linked to various serious disorders. Microbes in the nasal cavity play a key role in priming the physiology of the olfactory epithelium and maintaining a normal sense of smell by the host. The aim of this study was to explore the link between olfactory dysfunction and nasal bacterial communities. A total of 162 subjects were recruited for this study from a specialized olfactory dysfunction clinic and placed into one of three groups: anosmia, hyposmia or normosmia. Swabs from the nasal middle meatus were collected from each subject then processed for bacterial 16S rRNA gene sequencing. No overall differences in bacterial diversity or composition were observed between the three cohorts in this study. However, the relative abundances of Corynebacterium spp. and Streptococcus spp. were significantly (p p

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.

PURPOSE OF REVIEW A significant complication of the frontal sinus drill-out procedure is restenosis of the frontal neo-ostium. To improve postoperative healing in this region, various mucosal grafts and pedicled flaps have been designed to reconstruct the mucosal lining of the frontal neo-ostium. We provide an overview of the types of grafts described for reconstruction and discuss the latest evidence on their efficacy. RECENT FINDINGS Frontal neo-ostium mucosal reconstruction may be performed using free, pedicled, or a combination of grafts. There are several case series that report good outcomes and low revision rates following the use of grafts in frontal sinus drill-outs, and one randomized controlled study demonstrating increased ostial patency. However, the use of grafts did not alter the rate of revision surgery and only one study reported an improvement in Sino-Nasal Outcome Test-22 scores after one year. SUMMARY Studies have suggested that frontal sinus drill-out grafts result in favorable restenosis and graft success rates. However, larger randomized control trials will be required to determine whether frontal sinus drill-out grafts contribute to a tangible clinical benefit for patients.

This chapter is the first of two chapters demonstrating the wide variety of CFD studies in clinical applications presented from leading researchers in their respective fields. This chapter covers the latest research techniques and outcomes in airflow and conditioning in the nasal cavity; fluid and particle dynamics from sniffing; nasal obstruction and empty nose syndrome; nasal nitric oxide (nNO) dynamics and the ostiomeatal complex.

There is an enormous range of anatomical variants of the nasal cavity and paranasal sinuses, and these can be influenced by gender, age and ethnic adaptations to local climate. A further factor is pneumatization of the paranasal sinuses which is highly variable between individuals. When significant deviations occur from typical airway geometries, this can lead to nasal airway obstruction having the potential to significantly reduce quality of life in patients. This chapter presents the main factors affecting anatomy geometry, and common disorders, diseases, and its management.

A good understanding of the normal human nose anatomy and function is critical to perform human respiratory system computer modelling and computational fluid dynamic (CFD) analysis. This chapter provides a broad overview of the function and organisation of the human respiratory system, including essential anatomical definitions, anatomy and naming conventions, as well as particular areas of surgical interest. The topics include Functions and Organisation of the Respiratory System, and the nasal cavity anatomy, function, physiology, and histology.

Human microbiome studies remain focused on bacteria, as they comprise the dominant component of the microbiota. Recent advances in sequencing technology and optimization of amplicon sequencing protocols have allowed the description of other members of the microbiome, including eukaryotes (fungi) and, most recently, archaea. There are no known human-associated archaeal pathogens. Their diversity and contribution to health and chronic respiratory diseases, such as chronic rhinosinusitis (CRS), are unknown. Patients with CRS suffer from long-term sinus infections, and while the microbiota is hypothesized to play a role in its pathogenesis, the exact mechanism is poorly understood. In this cross-sectional study, we applied a recently optimized protocol to describe the prevalence, diversity and abundance of archaea in swab samples from the middle meatus of 60 individuals with and without CRS. A nested PCR approach was used to amplify the archaeal 16S rRNA gene for sequencing, and bacterial and archaeal load (also based on 16S rRNA genes) were estimated using Droplet Digital™ PCR (ddPCR). A total of 16 archaeal amplicon sequence variants (ASVs) from the phyla Euryarchaeota and Thaumarchaeota were identified. Archaeal ASVs were detected in 7/60 individuals, independent of disease state, whereas bacterial ASVs were detected in 60/60. Bacteria were also significantly more abundant than archaea. The ddPCR method was more sensitive than amplicon sequencing at detecting archaeal DNA in samples. Phylogenetic trees were constructed to visualize the evolutionary relationships between archaeal ASVs, isolates and clones. ASVs were placed into phylogenetic clades containing an apparent paucity of human-associated reference sequences, revealing how little studied the human archaeome is. This is the largest study to date to examine the human respiratory-associated archaeome, and provides the first insights into the prevalence, diversity and abundance of archaea in the human sinuses.

BackgroundDespite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa influences their efficacy remains largely undefined.MethodsThirty subjects undergoing functional endoscopic sinus surgery (FESS) for bilateral CRS were randomized to one of three groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days) and 3) control (no antibiotics given). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal secretions, sinonasal tissues and serum at steady state. Nasal endoscopy (Modified Lund-Kennedy) and Gastrointestinal Symptom Rating Scale (GSRS) scores were recorded.ResultsAntibiotic concentrations in the nasal secretions were significantly lower compared to those in the serum and tissue (mean mucus/serum ratio at steady state = 0.16 and 0.37 for doxycycline and roxithromycin respectively; pp=0.04).ConclusionsAlthough the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complication of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.

Background The aim of this study was to use computational fluid dynamics (CFD) to investigate the effects on nasal heat exchange and humidification of two different surgical techniques for reducing the inferior turbinate under different environmental conditions. Methods Virtual surgery using two techniques of turbinate reduction was performed in eight nasal airway obstruction patients. Bilateral nasal airway models for each patient were compared: 1) Pre-operative 2) Post inferior turbinoplasty 3) Post total inferior turbinate resection (ITR). Two representative healthy models were included. Three different environmental conditions were investigated 1) ambient air 2) cold, dry air 3) hot, humid air. CFD modelling of airflow and conditioning was performed under steady-state, laminar, inspiratory conditions. Findings Nasal conditioning is significantly altered following inferior turbinate reduction surgery, particularly with ITR under cold, dry inspired air (CDA). The degree of impairment is minor under the simulated range of environmental conditions (temperature = 12–40 °C; relative humidity = 13–80%). Streams of significantly colder air are found in the nasopharynx and more prevalent under CDA in ITR. These are related to high velocity flow streams, which remain cool in their centre throughout the widened inferior nasal cavity. Interpretation Reduced air-mucosal heat exchange and moisture carrying capacity occurs under cooler temperatures in patients following inferior turbinate surgery. The clinical impact in extremely cold and dry conditions in groups with poor baseline respiratory function, respiratory illness, or endurance athletes is of special interest.

Tonsillectomy is the second most common surgical procedure performed in pediatric otolaryngology. Multiple courses of antibiotics are usually prescribed prior to surgical intervention. Surgery is indicated when patients reach a certain number of infective episodes, or their obstructive symptoms warrant intervention. Little is known about the role of tonsillectomy on long term postoperative antibiotic use. Recently, our group published a retrospective case series that described the clinical characteristics and outcomes of children under the age of 16 years who underwent tonsillectomy. This study is a follow-up on this previous case series and its purpose is to determine whether tonsillectomy in this group of children led to a reduction in the number of antibiotics prescribed in the year following surgery.Data were collected from the clinical records departments of two district health boards in Auckland, New Zealand. Hospital morbidity records were reviewed for all children younger than 16 years old, who underwent a tonsillectomy between December 2015 and December 2017 in the Auckland region. All antibiotics prescribed following surgery were obtained from New Zealand's national community prescribing database.A total of 1538 children underwent tonsillectomy during the study period. Following surgery, antibiotics were prescribed to 828 (54%) patients at the time of discharge, with an average of 1.2 ± 0.1 courses in the year following surgery. This was significantly reduced compared to preoperative antibiotic intake (3.4 ± 0.1 courses) in the year preceding surgery (p 0.001). Readmission within 30 days of discharge was not associated with increased antibiotic usage postoperatively. In the two weeks following surgery, 25% of patients were prescribed a course of antibiotics for a presumed postoperative infection.These findings support the benefit of tonsillectomy in reducing antibiotic consumption in the year following surgery. Furthermore, it has highlighted areas of practice, such as perioperative antibiotic prescription, which can be improved to further reduce the prescription of antibiotics for children with tonsillar hyperplasia.

BACKGROUND The aim of this study was to investigate using computational fluid dynamics (CFD) the effects on nasal aerodynamics of two different techniques for reducing the inferior turbinate. This may assist in surgical planning to select the optimal procedure. METHODS Virtual surgery using two techniques of turbinate reduction was performed in eight nasal airway obstruction patients. Three bilateral nasal airway models for each patient were compared: 1) Pre-operative 2) Bilateral inferior turbinoplasty 3) Bilateral total inferior turbinate resection (ITR). Two representative healthy models were included. CFD modeling of airflow was performed under steady-state, laminar, inspiratory conditions. RESULTS Nasal airway resistance was slightly more reduced following ITR compared to turbinoplasty due to loss of the pressure gradient at the head of the IT. Turbinoplasty resulted in ventilation, pressure and wall shear stress profiles closer to those of healthy models. A more prominent jet-like course of the main flow stream was observed inferiorly in the ITR group. CONCLUSIONS Nasal air conditioning was significantly altered following IT surgery. Overall differences between the groups were small and are unlikely to bear influence on nasal function in normal environments. Further studies using a larger number of patients and healthy subjects are required, attempting to establish a clinical correlation with long-term outcomes such as the perception of nasal patency, mucosal crusting and drying, and air conditioning in different environments. Since a large proportion of IT mucosa remains following turbinoplasty, future dependence on topical therapy should also be considered.

Background Chronic rhinosinusitis (CRS) is a spectrum of complex inflammatory conditions of the sinonasal mucosa. Identification of biomarkers that enable classification and improved delineation among CRS endotypes is of increasing interest. However, the extent to which less invasive sampling methods identify genuine tissue inflammatory patterns is not well understood. The aim of this study was to investigate mucosal swab and cytobrush sampling as less invasive proxies for tissue transcription levels of putative biomarkers of CRS. Methods Expression levels of 21 biomarkers of interest were assessed via custom TaqMan array cards from mucosal biopsy, cytobrush, and swab samples, in 32 patients with CRS. Reported expression levels were compared between each of the 3 sample types within each patient. Results Reported transcription levels from swab samples for IL33, MUC5AC, IL1RN, CXCL8 (IL-8), TNF, IFNG, IL5, OSM, IL1A, and IL17C, and cytobrush levels for IL33, MUC5AC, IL5RA, IL1RN, CXCL8 (IL-8), and IL5 were significantly different to tissue levels from matched biopsy samples. Conclusion Reported expression via swab and cytobrush sampling differed from patterns observed in matched tissue for 10 of 21 and 6 of 21 markers, respectively. Non-biopsy-based studies for these particular markers may therefore not adequately represent tissue inflammatory processes and should be interpreted with caution. Cytobrush samples largely tracked tissue patterns for the remaining target biomarkers. In these cases, cytobrush sampling appears to adequately reflect tissue patterns for several putative biomarkers of CRS, supporting their use in clinical and research settings as a less-invasive proxy for the assessment of mucosal tissue inflammatory transcription patterns.

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus, suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future.

Background Despite functional endoscopic sinus surgery (FESS) being the standard of care in medically recalcitrant chronic rhinosinusitis (CRS), its effect on sinus ventilation has not been fully characterized. Airflow simulations can help improve our understanding of how surgical strategies affect post-surgical sinus ventilation. Methods Eight postoperative sinonasal cavity models were reconstructed from a wide spectrum of CRS patients who had undergone FESS. Computational fluid dynamics modeling of steady-state, laminar, inspiratory airflow was performed. Ventilation was quantified and observed for all the sinuses in each model. Results Sinus aeration was enhanced following FESS, particularly in the maxillary and ethmoid sinuses. The degree of improvement was related to the extent of surgery performed. This finding was accentuated at a higher inhalational flow rate of 15L/min. The relationship between ostium size and corresponding sinus inflow was stronger for the maxillary and sphenoid sinuses. Maxillary inflow reached 50% in a mega-antrostomy patient, while negligible flow occurred in the frontal sinuses for except one whom had undergone a modified Lothrop procedure. Conclusions This study has quantified sinus airflow in the largest set of post-FESS patients to date, to show that with increasing extensive surgery, the sinus and nasal cavity become more interconnected and functionally interdependent. Accordingly, sinus ventilation is improved. This may have important consequences for pre- and post-surgical assessment and planning, and on predicting how drug delivery treatments and devices can be designed to target the postoperative sinuses.

Culture-independent methods, based on bacterial 16 S rRNA gene sequencing, have been used previously to investigate the adenotonsillar microbiota. However, these studies have focused on a single sampling site (usually a surface swab). We aimed to investigate potential differences in adenotonsillar microbiota according to sampling location, both on and within the adenoids and palatine tonsils.Pediatric patients (n = 28, mean age five years) undergoing adenotonsillectomy were recruited for this study. At the time of surgery, a mucosal adenoid surface swab and an adenoid tissue biopsy was collected. Immediately following surgery, the crypts of the right and left tonsils were swabbed, and a surface and core tissue sample from the right tonsil were also collected. Bacterial 16 S rRNA gene-targeted amplicon sequencing was used to determine the bacterial composition of the collected samples.There was no significant difference in diversity or composition of the adenoid microbiota based on sampling site. However, the Shannon-Wiener and Inverse-Simpson diversity indices differed significantly (p 0.05) between the microbial communities of the three different tonsil sampling sites. There was a higher average relative abundance of members from the genera Streptococcus, Actinobacillus, and Neisseria in the tonsil crypts when compared with surface and core tonsil tissue samples.Our results indicate that there is variation in bacterial diversity and composition based on sampling sites in the tonsils but not the adenoids. The difference in microbiota between the surface and the tissue may have implications for our understanding of the pathogenesis of recurrent tonsillitis and have treatment implications.

Introduction Obstructive sleep apnea (OSA) is now a more common indication for tonsillectomy than recurrent tonsillitis (RT) [1,2]. Few studies have addressed possible differences in pathogenesis between these two conditions. Children with RT and OSA are often being treated in the community with multiple courses of antibiotics before surgery. Current understanding of the role of bacteria in disorders of the tonsils is mainly based on the culture of tonsil swabs. Swab cultures reflect only a very small fraction of the bacteria present on the mucosal surface and may not represent the bacterial communities within the tonsil crypts [3,4]. This study aimed to evaluate the local lymphocyte response and associations with bacterial community composition using molecular techniques of the tonsils removed from children for RT or OSA. Method The palatine tonsils were removed by extracapsular dissection from 24 patients with age range one to ten years, 14 of whom had RT and 10 had OSA. The fixed tonsil tissues were evaluated for bacteria by Gram-staining and presence of connective tissue by safranin staining. B lymphocytes and T lymphocytes were also measured immunohistochemically. Finally, previously published bacterial community data for this cohort were reassessed for associations with RT and OSA, and with the observed lymphocyte patterns. Results In tonsils from patients with RT, large micro-colonies of bacteria were observed in the tonsil crypts, and a large number of B and T lymphocytes were noted immediately adjacent to the tonsil crypt itself. In marked contrast, the tonsils from patients with OSA had no bacteria identified, and no significant skewing of lymphocytes based on site (such as follicles or crypts). We observed that the majority of lymphocytes surrounding the bacterial micro-colonies were B lymphocytes with a mean ratio of 109:55 (B lymphocytes: T lymphocytes). Bacterial community diversity was not different between the two cohorts; however, there were significant differences in bacterial community composition. Children with RT had a higher relative abundance of members from the genera Parvimonas, Prevotella, and Treponema. While children with OSA had a higher relative abundance of Haemophilus, and Capnocytophaga. Conclusion These results demonstrate significant differences in the local lymphocyte response and bacterial community composition in tonsil tissue between RT and OSA patients. It suggests that the response to antibiotics used in the treatment of these two conditions may be different. Furthermore, the presence of lymphocytes in RT within the tonsil crypt outside the tonsil epithelium is a unique observation of the location of these cells.

Background This study aimed to compare the incidence and outcomes of Maori and non-Maori children with otitis media with effusion who underwent myringotomy plus ventilation tube insertion (MVTI). Methods De-identified extraction of Auckland District Health Board (ADHB) morbidity records belonging to all children who underwent an MVTI procedure between January 1996 and June 2016 at Starship Children's Hospital was performed. Demographic, procedural and outcome data were analysed. Results A total of 11 941 children aged less than 10 years underwent at least one MVTI procedure in the Auckland region from January 1996 to June 2016. Of those, 2387 (20%) were Maori and 9554 (80%) were non-Maori. There was no difference in gender, age, length of stay, 30-day readmissions or complications between Maori and non-Maori at index or subsequent surgeries. Maori were not more likely than non-Maori to require subsequent MVTI (P = 0.13). There was no difference between Maori and non-Maori rates of having MVTI alone (P = 0.11) or MVTI with adenoidectomy ± tonsillectomy (P = 0.61). Conclusions Some epidemiological evidence suggests that Maori have a higher incidence of middle ear disease in the community. However, this study indicates that there is no difference in the post-operative course between Maori and non-Maori children.