Outcome measures for chronic rhinosinusitis with nasal polyps.

BACKGROUND: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus. METHODS: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses. RESULTS: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each. CONCLUSIONS: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Topical anaesthesia and decongestion in rhinology.

Topical anaesthesia and decongestion of the sinonasal mucosa are used commonly in rhinology practice to facilitate nasal endoscopy, as well as debridement and biopsies. Topical agents used for sinonasal anaesthesia include lignocaine, tetracaine and cocaine. Unlike lignocaine and tetracaine, cocaine also has a decongestant effect. Phenylephrine, oxymetazoline, xylometazoline or adrenaline are usually added to lignocaine and tetracaine to provide decongestion. Several studies have been performed seeking to identify the optimal nasal preparation for nasal endoscopy in the clinic setting. However, there remains no clear consensus in the literature resulting in ongoing wide variation between anaesthetic-decongestant preparations used in clinical practice. Indeed, some authors have argued that no anaesthetic is required at all for flexible nasendoscopy despite the apparent consensus that nasal instrumentation is generally uncomfortable, inferred by the persistence of ongoing research in this area. This review provides a practical summary of local anaesthetic and decongestant pharmacology as it relates to rhinologic practice and summarises the literature to date, with the goal of identifying current gaps in the literature and guiding future research efforts.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Fluorescence in situ hybridisation in Carnoy's fixed tonsil tissue.

Fluorescence in situ hybridisation (FISH) is a powerful molecular technique that enables direct visualisation of specific bacterial species. Few studies have established FISH protocols for tonsil tissue in Carnoy's fixative, accordingly limiting its application to investigate the pathogenesis of tonsillar hyperplasia. Tonsil tissue from 24 children undergoing tonsillectomy for either recurrent tonsillitis or sleep-disordered breathing were obtained during a previous study. The specificity of each of the five FISH probes (Fusobacterium spp., Bacteroides spp., Streptococcus spp., Haemophilus influenzae and Pseudomonas spp.) were successfully optimised using pure and mixed bacterial isolates, and in Carnoy's fixed tonsil tissue. Bacteroides spp. were present in 100% of patients with microcolonies. In comparison, the prevalence of Fusobacterium spp. was 93.8%, Streptococcus spp. 85.7%, H. influenzae 82.35% and Pseudomonas spp. 76.5%. Notable differences in the organisation of bacterial taxa within a single microcolony were also observed. This is the first study to establish a robust FISH protocol identifying multiple aerobic and anaerobic bacteria in Carnoy's fixed tonsil tissue. This protocol provides a strong foundation for combining histological and microbiological analyses of Carnoy's fixed tonsil samples. It may also have important implications on the analysis of microorganisms in other human tissues prepared using the same techniques.

The in vitro efficacy of neutral electrolysed water and povidone-iodine against CRS-associated biofilms.

BACKGROUND: Despite best medical and surgical practice, some cases of chronic rhinosinusitis (CRS) can remain recalcitrant. Bacterial biofilms have been associated with the recalcitrance of sinonasal inflammation. Biofilms are highly resistant to commonly prescribed antibiotics. Accordingly, more effective antimicrobial treatment options are needed to treat refractory CRS. The aim of this study was to determine the in vitro efficacy of neutral electrolysed water (NEW) and povidone-iodine (PVI) against CRS-associated Staphylococcus aureus biofilms. METHODS: Mature S. aureus biofilms were grown in a Centre for Disease Control (CDC) biofilm reactor. The antimicrobial activity of NEW, PVI and doxycycline was determined for both planktonic and biofilm cultures of a clinical S. aureus isolate using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum biofilm eradication concentration (MBEC) assays. RESULTS: MICs and MBCs were determined for all antimicrobials. MBC values were similar to MICs for both antiseptics, but doxycycline MBCs were significantly higher than the associated MICs. Biofilms were highly resistant to NEW and doxycycline. The MBEC for doxycycline was between 500 and 1000 Â#181;g/mL. NEW was ineffective against biofilms and no MBEC could be determined. In contrast, a concentration of 10% of the commercial PVI solution (10 mg/mL PVI) led to effective eradication of mature biofilms. CONCLUSION: In this study, only PVI showed promising antibiofilm activity at physiological concentrations. The in vivo efficacy of PVI warrants further investigation of its potential as a treatment for recalcitrant CRS.

Aerodynamic impact of total inferior turbinectomy versus inferior turbinoplasty - a computational fluid dynamics study.

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.

Quantification of airflow in the sinuses following functional endoscopic sinus surgery.

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.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Measuring antibiotic levels and their relationship with the microbiome in chronic rhinosinusitis.

BACKGROUND: The evidence supporting the efficacy of antibiotic therapy in the treatment of chronic rhinosinusitis is not compelling. A limited number of studies show that the changes in the nasal microbiome in patients following drug therapy are unpredictable and variable. The evidence for the impact of oral antibiotics on the gut microbiota is stronger, possibly as a result of differences in drug distribution to various sites around the body. There are few studies on sinus mucosal and mucus levels of oral antibiotics used in the treatment of chronic rhinosinusitis. The distribution dependent effects of antibiotics on the sinonasal microbiome is unclear. CONCLUSION: This review highlights that relative drug concentrations and their efficacy on microbiota at different sites is an important subject for future studies investigating chronic rhinosinusitis.

The sinonasal mycobiota in chronic rhinosinusitis and control patients.

BACKGROUND: While bacterial associations with chronic rhinosinusitis (CRS) are increasingly well described, fewer studies have examined the fungal component of the sinonasal microbiota. Here we present a study of the sinonasal mycobiota in a cohort of 144 patients (106 patients with CRS and 38 controls). METHODOLOGY: Fungal communities were characterised by analysis of mucosal swab samples of the left and right middle meatuses via ITS2 marker amplicon sequencing on the Illumina MiSeq platform. Fungal associations with previously published bacterial community and inflammatory cytokine and cell data for this cohort (collected at the same intra-operative time point) were also investigated. RESULTS: Malassezia spp. were ubiquitous and often highly predominant. Season of sampling explained more of the variability in the data than any of the clinical parameters. The predominant Malassezia sp. was distinct in patients with cystic fibrosis compared to those without. However, distinctions in the mycobiota were not evident between any other patient groupings assessed, and few fungal-bacterial or fungal-inflammatory associations were observed. CONCLUSIONS: This study confirms the prominent place of Malassezia spp. within the upper respiratory tract. Overall, few distinctions between patient groups were evident, and these data lend further support to the hypothesis that fungal community types may have no direct causative association with idiopathic CRS. Additional studies incorporating a broader array of inflammatory markers are required to assess whether these ubiquitous fungi nonetheless play an exacerbating role in some sensitive individuals.

The clinical implications of computerised fluid dynamic modelling in rhinology.

BACKGROUND: The nose is a dynamic organ and is the first point of contact between inhaled air and mucosal surfaces. Within the nasal cavity, there are changes of air flow and pressure occurring during the respiratory cycle, as well as exchanges of heat and humidity, and important immune responses to inhaled antigens and allergens. METHODOLOGY: This review is a summary for rhinologists covering what is known about airflow within the nose and sinuses and the impact of pathology and treatments on the physical environment of the nasal cavity. The review will concentrate largely on the significant contribution that computational fluid dynamics has had on this field. RESULTS: The complex anatomical structure of the nasal cavity provides an aerodynamic environment that guides the airflow throughout the nasal cavities. However, anatomical or inflammatory changes can modify the air flow, heat and humidity exchanges, with negative consequences on nasal physiology. Restoration of normal airflow is a key goal to achieve success in the treatment of nasal diseases. CONCLUSIONS: Computational fluid dynamics is a method of analysis originating from engineering which has been adapted for rhinology. Although still an expensive and laborious technique, it may become a viable diagnostic tool in the future for studying nasal physiology.

Using microwave cooking to evaluate tenderness and its relationship to sensory analysis.

This study evaluated a microwave (Mw) cooking method for determining beef toughness using the Warner-Bratzler slice shear force (WBsSF) protocol. Longissimus thoracis muscles were aged for 1, 10, 19, and 28 days at 4C. They were then either cooked on a clam-shell grill until reaching an internal temperature of 72C, in a Mw for 100 s at maximum power (Mw100) or for 140 s at 60% of maximum power (Mw60). Cooking loss and shear force (SF) values were higher in Mw samples than in grilled ones. SF assessment by grill and Mw100 were able to discriminate tenderness by aging times in the same way as the sensory panel. The SF measured in a grilled sample had higher repeatability (R = .74) and correlation with sensory scores (r = -.79) than Mw100 (R = .61; r = -.62) and Mw60 (R = .51; r = -.53). Mw100 can be considered as an appropriate alternative for the WBsSF protocol. PRACTICAL APPLICATIONS: Tenderness is the most important attribute for consumers. Many studies have evaluated tenderness in meat and different protocols for cooking. This work was intended to optimize and evaluate the use of the microwave as a cooking method for shear force determination, against a standard protocol and establish the correlation to sensory tenderness.

Effect of homogenisation speed and centrifugation on particle size analysis of beef and the relationship with shear force.

This study aimed to investigate the effect of homogenisation speed and centrifugation on particle size (PS) evaluation, and examine its relationship with shear force. Beef Longissimus lumborum (LL) muscle portions were randomly assigned to different ageing periods (0, 3 or 5 weeks), and tested for PS and shear force. The PS analysis was conducted at different homogenisation speeds (11,000, 16,000 and 19,000 rpm) with and without a centrifugation step prior to measurement. Samples homogenised at 11,000 rpm and not centrifuged gave PS results significantly different at each ageing time as did samples homogenised at 19,000 rpm and centrifuged. Overall samples homogenised at 11,000 rpm produced the lowest coefficient of variation for PS results. There was a significant correlation between PS and shear force across the different homogeniser speeds and centrifugation statuses. It is concluded that best practice when measuring PS in beef includes a homogeniser speed of 11,000 rpm with no centrifugation prior to measurement.

Microwave as a rapid cooking method for beef tenderness evaluation.

Semitendinosus (ST) muscle steaks were grouped according to three locations (proximal, middle, and distal end), grilled to endpoint temperature of 71C or cooked for 20, 30, 40, 50, or 60 s in a microwave oven (Mw). The location did not affect (p > .05) the cooking loss (CL) or shear force (SF) values. The CL increased (p < .05) with longer microwave cooking times, but only the Mw40 samples did not differ (p > .05) from the grill samples. None of the microwaves' SF values were different (p > .05) from the grill values, with treatments Mw30 to Mw50 showing moderate repeatability (R = 0.51-0.60) and Mw30 and Mw60 showing higher correlations (r > .71) with grill values. Cooking beef strips with a microwave is a potential method for tenderness evaluation, but requires additional study to evaluate and optimize this application in different muscles and for comparison to sensorial data. PRACTICAL APPLICATIONS: The work was intended to evaluate the possibility of using a microwave oven for cooking meat to be used in objective measurement protocols for meat tenderness and to optimize the conditions for this purpose. The use of a standardized microwave procedure allows a dramatic reduction in analysis time and may reduce error variance due to nonuniform cooking procedures.

Moving beyond descriptions of diversity: clinical and research implications of bacterial imbalance in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a debilitating disease which affects 5-16% of the general population and involves long-term inflammation of the sinonasal cavity. While microbial involvement in the pathogenesis of CRS has long been suspected, the exact role of microbes remains unclear. Recent application of cultivation-independent, molecular methods has provided much new information, taking advantage of developments in both laboratory- and bioinformatics-based analyses. The aim of this mini-review is to present a variety of available bioinformatics approaches, such as data classification techniques and network analyses, with proven applications in other aspects of human microbiome health and disease research. The uses of molecular techniques in the clinical setting are still in its infancy, but these tools can further our understanding of microbial imbalance during chronic disease and help guide effective patient treatment. The mini-review emphasises ways in which CRS bacterial gene-targeted sequencing data can progress beyond descriptive summaries and toward unlocking the mechanisms by which bacterial communities can be markers for sinus health.

Effectiveness of extensive sinus surgery with post-operative medical management for chronic rhinosinusitis.

OBJECTIVE: To prospectively assess treatment outcomes of chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery and post-operative medical treatment over a prolonged follow-up period. METHODS: Patients undergoing functional endoscopic sinus surgery in the tertiary referral practice of a single surgeon were studied prospectively. Symptoms were scored by patients pre-operatively and over a minimum follow-up period of 12 months. RESULTS: The study comprised 200 non-consecutive patients. The median pre-operative symptom score was 16 (out of a maximum of 25) (95 per cent confidence interval = 15 to 17). Symptom scores reduced to a median of 7 (95 per cent confidence interval = 6 to 8) after 12 months of follow up (p < 0.0001). The median symptom score improved for all symptoms and across all patient subgroups. CONCLUSION: Extensive functional endoscopic sinus surgery offers significant and durable symptom improvement in patients with chronic rhinosinusitis refractory to medical treatment. This improvement extends to all patient subgroups. Prolonged medical therapy is recommended after functional endoscopic sinus surgery.

Comparison of Warner-Bratzler shear force values between round and square cross-section cores for assessment of beef Longissimus tenderness.

The objective of this experiment was to determine whether there is a difference between Warner-Blatzler shear force values of round (WBSF) and square (WBsSF) cross-section cores for assessment of beef tenderness. To compare the effect of core sampling, Longissimus thoracis muscles were obtained from 43 beef carcasses at 1, 14, and 28days postmortem. For each sample, tenderness was assessed by a trained sensory panel and by WBSF and WBsSF techniques. There was a strong and linear relationship (R2=0.77) between WBSF and WBsSF, but the average shear force of square cores were (P<0.05) greater than those of round cores. The WBsSF had greater repeatability (R=0.85 vs 0.81) and explained slightly more of the variation in sensory panel perception of beef tenderness (76% vs 74%) than WBSF. The results indicate that WBsSF seems to be a more precise method of measuring shear force, being little more sensitive for detecting tenderness differences than WBSF.

Toll-like receptor activation by sino-nasal mucus in chronic rhinosinusitis.

BACKGROUND: The sino-nasal disease chronic rhinosinusitis (CRS) is primarily an inflammatory condition that manifests in several ways. However, the aetiology of this complex disease is poorly understood. The aim of this study was to explore the association between toll-like receptor (TLR) activation, host immune response and sino-nasal mucus in healthy and diseased patients. METHODS: The activation of TLR2/1 and TLR4 by sino-nasal mucus from 26 CRS patients and 10 healthy controls was measured. In addition, 7 inflammatory cytokines, bacterial community composition and bacterial abundance within the sino-nasal mucus were measured using molecular and diagnostic tools. RESULTS: TLR activity was observed in 9/36 samples, including 2 healthy controls. There was a strong, positive correlation between members of the Gammaproteobacteria (Haemophilus, Enterobacter, Pseudomonas) and TLR2/1 and TLR4 activity. Bacterial abundance and cytokine (tumour necrosis factor) abundance were also positively correlated with TLR activity. CONCLUSIONS: These findings suggest that a small proportion (20-30%) of individuals in each sub-group are more predisposed to TLR activity, which may be related to bacterial composition, diversity and abundance in the sinuses.