Search

Background Appropriate indications for endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) are currently poorly defined. The lack of clear surgical indications for ESS likely contributes to the large geographic variation in surgical rates and contributes to reduced quality of care. The objective of this study was to define appropriateness criteria for ESS during management of adult patients with uncomplicated CRS. Methods The RAND/UCLA appropriateness methodology was performed. An international, multidisciplinary panel of 10 experts in CRS was formed and completed 2 rounds of a modified Delphi ranking process along with a face-to-face meeting. Results A total of 624 clinical scenarios were ranked, 312 scenarios each for CRS with and CRS without nasal polyps. For adult patients with uncomplicated CRS with nasal polyps, ESS can be appropriately offered when the CT Lund-Mackay score is ≥ 1 and there has been a minimum trial of a topical intranasal corticosteroid plus a short-course of systemic corticosteroid with a post-treatment total SNOT-22 score ≥ 20. For adult patients with uncomplicated CRS without nasal polyps, ESS can be appropriately offered when the CT Lund-Mackay score is ≥ 1 and there has been a minimum trial of a topical intranasal corticosteroid plus either a short-course of a broad spectrum/culture-directed systemic antibiotic or the use of a prolonged course of systemic low-dose anti-inflammatory antibiotic with a post-treatment total SNOT-22 score ≥ 20. Conclusion This study has developed and reported of list of appropriateness criteria to offer ESS as a treatment 'option' during management of uncomplicated adult CRS. The extent or technique of ESS was not addressed in this study and will depend on surgeon and patient factors. Furthermore, these criteria are the minimal threshold to make ESS a treatment 'option' and do not imply that all patients meeting these criteria require surgery. The decision to perform ESS should be made after an informed patient makes a preference-sensitive decision to proceed with surgery. Applying these appropriateness criteria for ESS may optimize patient selection, reduce the incidence of unwarranted surgery, and assist clinicians in providing high-quality, patient-centered care to patients with CRS [ABSTRACT FROM AUTHOR]

Background: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). Methods: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence‐based review, or evidence‐based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. Results: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. Conclusion: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further. [ABSTRACT FROM AUTHOR]

Background: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) Methods: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. Results: Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups. In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7–18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (rs = 0.182) and not significant (p = 0.12). Conclusions: In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to estimate the 1 year prevalence and recovery rate of self-reported chemosensory dysfunction in a series of subjects with previous mild-to-moderate symptomatic COVID-19. Methods: Prospective study based on the SNOT-22, item "sense of smell or taste" and additional outcomes. Results: 268/315 patients (85.1%) completing the survey at baseline also completed the follow-up interview. The 12 months prevalence of self-reported COVID-19 associated chemosensory dysfunction was 21.3% (95% CI 16.5–26.7%). Of the 187 patients who complained of COVID-19 associated chemosensory dysfunction at baseline, 130 (69.5%; 95% CI 62.4–76.0%) reported complete resolution of smell or taste impairment, 41 (21.9%) reported a decrease in the severity, and 16 (8.6%) reported the symptom was unchanged or worse 1 year after onset. The risk of persistence was higher for patients reporting a baseline SNOT-22 score ≥ 4 (OR = 3.32; 95% CI 1.32–8.36) as well as for those requiring ≥ 22 days for a negative swab (OR = 2.18; 95% CI 1.12–4.27). Conclusion: A substantial proportion of patients with previous mild-to-moderate symptomatic COVID-19 characterized by new onset of chemosensory dysfunction still complained on altered sense of smell or taste 1 year after the onset. [ABSTRACT FROM AUTHOR]

Keywords: anosmia; chest CT; coronavirus; COVID-19; hyposmia; olfactory; pneumonia; recovery; SARS-CoV-2; smell EN anosmia chest CT coronavirus COVID-19 hyposmia olfactory pneumonia recovery SARS-CoV-2 smell 103 107 5 12/31/21 20220101 NES 220101 INTRODUCTION The prognostic value of olfactory dysfunction (OD) in coronavirus disease 2019 (COVID-19) remains controversial, with conflicting reports of the association between OD and COVID-19 severity.1 Many of the prognostic studies published so far have important drawbacks that limit the reliability of the results; most are anamnestic studies that do not formally evaluate olfactory function with risk of recall bias, and use "need for hospitalization" alone to determine COVID-19 severity. Coronavirus, COVID-19, hyposmia, pneumonia, anosmia, chest CT, olfactory, recovery, SARS-CoV-2, smell At baseline, 35 patients (76.1%) had OD: 12 cases of anosmia (26.1%), severe hyposmia in 10 (21.7%), and moderate hyposmia in 13 cases (28.3%). [Extracted from the article]

Background and purpose: The aim was to evaluate potential predictive factors of smell recovery in a clinical series of 288 patients presenting olfactory dysfunction (OD) related to coronavirus disease 2019 (COVID‐19). Potential correlations were sought between epidemiological, clinical and immunological characteristics of patients and the persistence of OD at 60 days. Methods: COVID‐19 positive patients presenting OD were prospectively recruited from three European hospitals. Baseline clinical and olfactory evaluations were performed within the first 2 weeks after OD onset and repeated at 30 and 60 days. In a subgroup of patients, anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies were measured in serum, saliva and nasal secretions at 60 days. Results: A total of 288 COVID‐19 patients with OD were included in the study. Two weeks after the onset of the loss of smell, 52.4% of patients had OD on psychophysical tests, including 113 cases (39.2%) of anosmia and 38 cases (13.2%) of hyposmia. At 60‐day follow‐up, 25.4% of the patients presented persistent OD. There was no significant correlation between sex, age, viral load on nasopharyngeal swab or COVID‐19 severity and poor olfactory outcome. In a subgroup of 63 patients, it was demonstrated that patients with poor olfactory outcomes at 60 days had lower levels of salivary and nasal immunoglobulin G (IgG) and IgG1, but similar levels of antibodies in the serum. Conclusions: No clinical markers predicted the evolution of OD at 60 days. Patients with poor olfactory outcome at 60 days had lower saliva and nasal antibodies, suggesting a role for local immune responses in the persistence of COVID‐19 related OD. [ABSTRACT FROM AUTHOR]

Making scents of loss of taste in COVID-19: Is self-reported loss of taste due to olfactory dysfunction? Three clinical presentations were accepted for patient eligibility: isolated sudden loss of smell, isolated sudden loss of taste, or concomitant sudden loss of smell and taste. These results support the idea that most patients with COVID-19 tend to unconsciously conflate taste loss and olfactory loss, even when taste function is clearly defined to them beforehand as only referring to the perception of sweet, salty, sour, and bitter tastes. [Extracted from the article]

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab‐2, omalizumab‐4, mepolizumab‐2, and reslizumab‐1) included 1236 adults, with follow‐up of 20–64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20–0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT‐22 (MD −19.14; 95% CI −22.80 to −15.47), with fewer treatment‐related adverse events (TAEs) (RR 0.95; 95% CI 0.89–1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78–0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10–1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD −15.65; 95% CI −16.16 to −15.13), with increased TAE (RR 1.73; 95% CI 0.60–5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64–0.94) and improving QoL (MD −13.3; 95% CI −23.93 to −2.67) and smell (MD +0.7; 95% CI −0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41–6.50). The evidence for reslizumab is very uncertain. [ABSTRACT FROM AUTHOR]

Reply to: It is necessary to assess olfactory and gustatory functions in post-COVID-19 patients due to the omicron variant infection We, therefore, agree with Machado et al. that a complete psychophysical evaluation is imperative to gauge the degree of chemosensory dysfunction during Omicron waves accurately, distinguish between smell and taste impairment, measure residual olfactory function, and identify individuals who may be unaware of a persistent olfactory impairment. Keywords: COVID-19; olfaction; olfactory loss; olfactory tests; omicron variant; smell EN COVID-19 olfaction olfactory loss olfactory tests omicron variant smell 1567 1568 2 07/26/23 20230801 NES 230801 We very much appreciated the letters from Machado et al. and are pleased to have inspired these interesting thoughts. [Extracted from the article]

Objectives: To report changes in practice brought about by COVID‐19 and the implementation of new guidelines, and to explore factors relating to unscheduled re‐presentations for patients discharged from the emergency department (ED). Design: Prospective multicentre national audit over 12 weeks from 6th April 2020. Setting: UK secondary care ENT departments. Participants: Adult patients with acute epistaxis. Main outcome measures: Re‐presentation within 10 days for patients discharged from the ED. Results: Eighty three centres from all four UK nations submitted 2631 valid cases. The majority of cases were ED referrals (89.7%, n = 2358/2631). 54.6% were discharged from the ED following ENT review (n = 1267/2322), of whom 19.5% re‐presented within 10 days (n = 245/1259) and 6.8% were ultimately admitted (n = 86/1259). 46.7% of patients had a non‐dissolvable pack inserted by ED prior to referral to ENT (n = 1099/2355). The discharge rates for ED patients and their subsequent re‐presentation rates were as follows: non‐dissolvable packs, 29.5% discharged (n = 332/1125), 18.2% re‐presented (n = 60/330); dissolvable products, 71.1% discharged (n = 488/686), 21.8% re‐presented (n = 106/486); cautery only, 89.2% discharged (n = 247/277), 20.0% re‐presented (n = 49/245); and no intranasal intervention, 85.5% discharged (n = 200/234), 15.2% re‐presented (n = 30/198). Univariable logistic regression showed that not being packed by ED, antiplatelet medications, failed cautery and recent epistaxis treatment were significant predictors of re‐presentation within 10 days. Conclusions: Management of acute epistaxis was notably affected during the initial peak of the pandemic, with a shift towards reduced admissions. This national audit highlights that many patients who may previously have been admitted to hospital may be safely discharged from the ED following acute epistaxis. [ABSTRACT FROM AUTHOR]

Background: Randomised controlled trials (RCTs) are considered the 'gold standard' of medical evidence; however, recruitment can be challenging. The MACRO trial is a NIHR-funded RCT for chronic rhinosinusitis (CRS) addressing the challenge of comparing surgery, antibiotics and placebo. The embedded MACRO conversation study (MCS) used qualitative research techniques pioneered by the University of Bristol QuinteT team to explore recruitment issues during the pilot phase, to maximise recruitment in the main trial.Methods: Setting: Five outpatient Ear Nose and Throat (ENT) departments recruiting for the pilot phase of the MACRO trial (ISRCTN Number: 36962030, prospectively registered 17 October 2018). We conducted a thematic analysis of telephone interviews with 18 recruiters and 19 patients and 61 audio-recordings of recruitment conversations. We reviewed screening and recruitment data and mapped patient pathways at participating sites. We presented preliminary findings to individual site teams. Group discussions enabled further exploration of issues, evolving strategies and potential solutions. Findings were reported back to the funder and used together with recruitment data to justify progression to the main trial.Results: Recruitment in the MACRO pilot trial began slowly but accelerated in time to progress successfully to the main trial. Research nurse involvement was pivotal to successful recruitment. Engaging the wider network of clinical colleagues emerged as an important factor, ensuring the patient pathway through primary and secondary care did not inadvertently affect trial eligibility. The most common reason for patients declining participation was treatment preference. Good patient-clinician relationships engendered trust and supported patient decision-making. Overall, trial involvement appeared clearly presented by recruiters, possibly influenced by pre-trial training. The weakest area of understanding for patients appeared to be trial medications. A clear presentation of medical and surgical treatment options, together with checking patient understanding, had the potential to allay patient concerns.Conclusion: The MACRO conversation study contributed to the learning process of optimising recruitment by helping to identify and address recruitment issues. Although some issues were trial-specific, others have applicability to many clinical trial situations. Using qualitative research techniques to identify/explore barriers and facilitators to recruitment may be valuable during the pilot phase of many RCTs including those with complex designs. [ABSTRACT FROM AUTHOR]

This study prospectively assessed the 6-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and seven being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of the sense of smell or taste and olfactory test scores (Spearman's r = −0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had a self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of syndrome coronavirus 2 (SARS-CoV-2) infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection. [ABSTRACT FROM AUTHOR]

Objective: To investigate the coronavirus disease 2019 (COVID-19) status of patients with initial sudden olfactory anosmia (ISOA) through nasopharyngeal swabs for reverse transcription–polymerase chain reaction (RT-PCR) analysis and to explore their olfactory dysfunctions with psychophysical olfactory evaluation. Methods: A total of 78 ISOA patients were recruited from April 6, 2020, to April 10, 2020, through a public call of University of Mons (Mons, Belgium). Patients benefited from nasopharyngeal swabs and fulfilled the patient-reported outcome questionnaire. Among them, 46 patients performed psychophysical olfactory evaluation using olfactory identification testing. Based on the duration of the ISOA, 2 groups of patients were compared: patients with olfactory dysfunction duration ≤12 days (group 1) and those with duration >12 days (group 2). Results: In group 1, 42 patients (87.5%) had a positive viral load determined by RT-PCR and 6 patients (12.5%) were negative. In group 2, 7 patients (23%) had a positive viral load and 23 patients (77%) were negative. The psychophysical olfactory evaluation reported that anosmia and hyposmia occurred in 24 (52%) and 11 (24%) patients, respectively. Eleven patients were normosmic. The viral load was significantly higher in patients of group 1 compared with those of group 2. Conclusions: Coronavirus disease 2019 was detected in a high proportion of ISOA patients, especially over the first 12 days of olfactory dysfunction. Anosmia is an important symptom to consider in the detection of COVID-19 infection. [ABSTRACT FROM AUTHOR]

Objectives: Conebeam computed tomography (CBCT) imaging is commonly requested by dental implant surgeons, preoperatively, for patients being considered for dental implants. Incidental maxillary sinus findings often result in otolaryngology (ENT) referral for further assessment. CBCT findings include transient and benign mucosal changes that may not require any intervention and therefore unnecessarily delay implant surgery. We aim to define appropriateness criteria for ESS in the management of adult dental implant patients with incidental maxillary sinus findings on CBCT and provide guidance to both dental implant and ENT surgeons. Design: The RAND/UCLA appropriateness methodology was used to develop and define the appropriateness criteria. Setting: A virtual panel of 13 international experts in ESS. Participants: The expert panel completed two rounds of a modified Delphi ranking process for nine clinical scenarios, considering various factors affecting decision‐making processes. Main outcome measures: To define appropriateness criteria for ESS in adult dental implant patients who have incidental maxillary sinus findings on CBCT. Results: Patients with clinical symptoms and endoscopic findings of chronic rhinosinusitis together with an obstructed ostiomeatal complex (OMC) and concentric mucosal thickening of the ipsilateral maxillary sinus or pansinusitis were deemed appropriate candidates for ESS prior to their dental implant. ESS was not appropriate in asymptomatic patients with a patent OMC and mucosal thickening isolated to floor of the ipsilateral maxillary sinus. For uncertain scenarios, further discussion between dental implant and ENT surgeon should be considered. Conclusions: This study has developed and reported a list of appropriateness criteria to offer ESS in adult dental implant patients with incidental maxillary sinus findings on CBCT. [ABSTRACT FROM AUTHOR]

Background: The clinical presentation of European patients with mild-to-moderate COVID-19 infection is still unknown.Objective: To study the clinical presentation of COVID-19 in Europe.Methods: Patients with positive diagnosis of COVID-19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analysing the relationship between outcomes.Results: A total of 1,420 patients completed the study (962 females, 30.7% of healthcare workers). The mean age of patients was 39.17 ± 12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by 45.4%. The mean duration of COVID-19 symptoms of mild-to-moderate cured patients was 11.5 ± 5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate COVID-19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients.Conclusion: The clinical presentation of mild-to-moderate COVID-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate COVID-19 that needs to be recognized as such by the WHO. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. Methods: Cross-sectional study based on ad hoc questions. Results: Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (p < 0.001). Conclusion: Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection. [ABSTRACT FROM AUTHOR]

The skull base and nasopharynx are distinct anatomical sites that may benefit from robotic surgical techniques. This study intends to assess a combined transorbital and transnasal approach to anterior skull base and nasopharynx for robotic surgery utilising a novel robotic platform. A cadaver study was performed using the Versius robotic system (CMR Surgical, Cambridge UK) to assess the feasibility of transorbital and transnasal approaches to the nasopharynx and anterior skull base. [Extracted from the article]

Background: Periorbital cellulitis is a potential sight‐threatening complication of sinusitis. The majority of patients improve with medical management. Previous studies have suggested significant variations in practice and lack of evidence regarding the optimal management of this condition. Methods: A prospective study was conducted over a 12‐month period at 8 centers in the United Kingdom assessing the management of patients requiring inpatient treatment for periorbital cellulitis secondary to sinonasal infections. Results: A total of 143 patients were recruited, of whom 40 were excluded. Of the remaining 103 patients, 5 (4.9%) were diagnosed with neurosurgical complications. This resulted in 98 patients admitted with periorbital cellulitis secondary to an upper respiratory tract infection/sinusitis. A total of 72 were children, of whom 12 (16.7%) required surgical intervention; and of 26 adults, 5 (19.2%) required surgery: the most common antimicrobial regimes administered were intravenous ceftriaxone (with or without metronidazole), and co‐amoxiclav. The use of both ceftriaxone and metronidazole from admission was associated with the shortest duration of inpatient stay (3.8 days) in comparison to ceftriaxone alone (5.8 days) or co‐amoxiclav (4.5 days) and a reduction in number of patients requiring surgical intervention. There was also an association between the early use of intranasal decongestants and steroids and reduction in requirement for surgical intervention. Conclusion: For a condition where swab and blood cultures are often negative, this study supports the use of ceftriaxone in combination with metronidazole. The administration of intranasal decongestants and corticosteroids correlated with a smaller percentage of those progressing to surgery in those with and without periorbital abscesses. [ABSTRACT FROM AUTHOR]

Keywords: DP1; DP2 (CRTH2); mast cells; nasal polyps; prostaglandin D2 EN DP1 DP2 (CRTH2) mast cells nasal polyps prostaglandin D2 1477 1480 4 06/01/20 20200601 NES 200601 To the Editor, Mast cells are important effector cells playing a critical role in regulation of immune responses in allergic diseases. Altogether, neither LAD2 nor LUVA human mast cell lines were activated by PGD SB 2 sb despite high expression of DP2 detected in LUVA cells. Expression of DP2 (CRTH2) was measured on peripheral blood basophils (CD123+, FceRIa+) (A), mast cells from nasal polyps (c-kit+, Fc RIa+) (B), and mast cells from nasal turbinates (C) by flow cytometry. [Extracted from the article]

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that—potentially severe—side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease. [ABSTRACT FROM AUTHOR]

Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy. Type 2‐targeting biologics such as anti‐IgE, anti‐IL4Rα, anti‐IL5, and anti‐IL5Rα have entered the market for selected pheno/endotypes of asthma patients and may soon also become available for CRSwNP patients. Given the high prevalence of chronic respiratory diseases and the high cost associated with biologics, patient selection is crucial in order to implement such therapies into chronic respiratory disease care pathways. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized a multidisciplinary Expert Board Meeting to discuss the positioning of biologics into the care pathways for CRSwNP patients with and without comorbid asthma. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both.Methods: LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 were two multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies assessing dupilumab added to standard of care in adults with severe CRSwNP. SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries. Eligible patients were 18 years or older with bilateral CRSwNP and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had sinonasal surgery. Patients in SINUS-24 were randomly assigned (1:1) to subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned (1:1:1) to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks. All patients were randomly assigned centrally with a permuted block randomisation schedule. Randomisation was stratified by asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery at screening, and country. Patients with or without comorbid asthma were included. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores (a coprimary endpoint in Japan), done in an intention-to-treat population. Safety was assessed in a pooled population of both dupilumab groups in SINUS-52 up to week 24 and the dupilumab group in SINUS-24 and the placebo groups in both studies until week 24. The trials are complete and registered at ClinicalTrials.gov, NCT02912468 and NCT02898454.Findings: Between Dec 5, 2016, and Aug 3, 2017, 276 patients were enrolled in SINUS-24, with 143 in the dupilumab group and 133 in the placebo group receiving at least one study drug dose. Between Nov 28, 2016, and Aug 28, 2017, 448 patients were enrolled in SINUS-52, with 150 receiving at least one dose of dupilumab every 2 weeks, 145 receiving at least one dose of dupilumab every 2 weeks for 24 weeks and every 4 weeks until week 52, and 153 receiving at least one dose of placebo. Dupilumab significantly improved the coprimary endpoints in both studies. At 24 weeks, least squares mean difference in NPS of dupilumab treatment versus placebo was -2·06 (95% CI -2·43 to -1·69; p<0·0001) in SINUS-24 and -1·80 (-2·10 to -1·51; p<0·0001) in SINUS-52; difference in nasal congestion or obstruction score was -0·89 (-1·07 to -0·71; p<0·0001) in SINUS-24 and -0·87 (-1·03 to -0·71; p<0·0001) in SINUS-52; and difference in Lund-Mackay CT scores was -7·44 (-8·35 to -6·53; p<0·0001) in SINUS-24 and -5·13 (-5·80 to -4·46; p<0·0001) in SINUS-52. The most common adverse events (nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema) were more frequent with placebo.Interpretation: In adult patients with severe CRSwNP, dupilumab reduced polyp size, sinus opacification, and severity of symptoms and was well tolerated. These results support the benefits of adding dupilumab to daily standard of care for patients with severe CRSwNP who otherwise have few therapeutic options.Funding: Sanofi and Regeneron Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Objective (s): To estimate the prevalence and associations among rhinosinusitis symptoms, smoking and chronic obstructive pulmonary disease (COPD). Design: Cross‐sectional study. Setting: Population‐based. Participants: All adults aged 40 years or more living in the selected households in the city of Florianópolis (Florianópolis, Santa Catarina, Brazil). Main outcome measures: Assessment instruments comprised household interviews, anthropometric measurements and spirometry. Rhinosinusitis symptoms were based on the responses to the 22‐item Sinonasal Outcome Test (SNOT‐22) questionnaire; smoking status was defined by the criteria of the CDC, and the functional diagnosis of COPD was done by spirometry. Results: The prevalence (n = 1056) of rhinosinusitis symptoms, smoking and COPD was 14.7%, 17.9% and 8.7%, respectively. Multivariate analysis showed that, with the exception of COPD, all other clinical variables (smoking, previous diagnosis of rhinitis, previous diagnosis of gastritis/ulcer/gastroesophageal reflux, and symptoms of depression) remained associated with higher prevalence of rhinosinusitis symptoms. Conclusions: Rhinosinusitis symptoms were common both in smokers and in patients with COPD. However, only tobacco was significantly associated with rhinosinusitis symptoms and can act as a cofounder in the association between COPD and rhinosinusitis symptoms. [ABSTRACT FROM AUTHOR]

Keywords: cocaine; cocaine rhinitis; drug screening; drug-induced rhinitis; rhinitis; substance abuse; toxicology EN cocaine cocaine rhinitis drug screening drug-induced rhinitis rhinitis substance abuse toxicology 608 610 3 06/24/20 20200701 NES 200701 Key Points There is a paucity of literature on the epidemiology of cocaine-induced rhinitis. Although it is widely recognised in medicine that patients are oftentimes unwilling to be forthcoming in their medical history, these results highlight a growing concern and reality that leads to misdiagnosis and mistreatment of cocaine-induced rhinitis. Cocaine, cocaine rhinitis, drug screening, drug-induced rhinitis, rhinitis, substance abuse, toxicology. [Extracted from the article]

Background: Chronic rhinosinusitis (CRS) is one of common health conditions that affects patients' health-related quality of life. Our purpose is to assess the reliability and validity of Thai-version of Sino-Nasal Outcome Test 22 in chronic rhinosinusitis. Methods: Permission for translation of SNOT-22 from English language to Thai language was obtained from the developer. The translation process was done based on the international standard of translation method. A total of 80 subjects were recruited into the study and divided into two groups comprising of 50 patients with chronic rhinosinusitis and 30 healthy volunteers. Cronbach's a and Intraclass correlation coefficient were evaluated for its reliability. Validity test was evaluated against VAS score, SF-36 (Thai version) questionnaire and CT scan (based on Lund-Mackay score). Responsiveness was assessed between pre-operative and post-operative scores in 34 patients. Results: The Thai version of SNOT-22 showed good reliability according to high value of Cronbach's a coefficient (r =0.929) and intraclass correlation coefficient (r = 0.935). It also showed good validity by its ability to differential the patients with chronic rhinosinusitis from normal (p < 0.001), and different severity of symptoms (p < 0.05). In addition, the SNOT-22 Thai version also showed good responsiveness when compared between pre-operative and post-operative scores (p < 0.001) and also well-performed in effect size calculation (1.37). Conclusion: We demonstrated that Thai -version of SNOT-22 has good reliability and validity, suitable for evaluation of chronic rhinosinusitis symptoms together with severity of the disease and response to treatment. Trial registration: Thai clinical trials registry TCTR20170320003. Date of registration 20/03/2017 (retrospectively registered). [ABSTRACT FROM AUTHOR]

On March 29, 2017, a European Summit on the Prevention and Self-Management of Chronic Respiratory Diseases (CRD) was organized by the European Forum for Research and Education in Allergy and Airway Diseases. The event took place in the European Parliament of Brussels and was hosted by MEP David Borrelli and MEP Sirpa Pietikainen. The aim of the Summit was to correspond to the needs of the European Commission and of patients suffering from CRD to join forces in Europe for the prevention and self-management. Delegates of the European Rhinologic Society, European Respiratory Society, European Academy of Allergy and Clinical Immunology, European Academy of Paediatrics, and European Patients Organization EFA all lectured on their vision and action plan to join forces in achieving adequate prevention and self-management of CRD in the context of Precision Medicine. Recent data highlight the preventive capacity of education on optimal care pathways for CRD. Self-management and patient empowerment can be achieved by novel educational on-line materials and by novel mobile health tools enabling patients and doctors to monitor and optimally treat CRDs based on the level of control. This report summarizes the contributions of the representatives of different European academic stakeholders in the field of CRD. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a common disorder associated with other respiratory tract diseases such as asthma and inhalant allergy. However, the prevalence of these co-morbidities varies considerably in the existing medical literature and by phenotype of CRS studied. The study objective was to identify the prevalence of asthma, inhalant allergy and aspirin sensitivity in CRS patients referred to secondary care and establish any differences between CRS phenotypes.Methods: All participants were diagnosed in secondary care according to international guidelines and invited to complete a questionnaire including details of co-morbidities and allergies. Data were analysed for differences between controls and CRS participants and between phenotypes using chi-squared tests.Results: The final analysis included 1470 study participants: 221 controls, 553 CRS without nasal polyps (CRSsNPs), 651 CRS with nasal polyps (CRSwNPs) and 45 allergic fungal rhinosinusitis (AFRS). The prevalence of asthma was 9.95, 21.16, 46.9 and 73.3% respectively. The prevalence of self-reported confirmed inhalant allergy was 13.1, 20.3, 31.0 and 33.3% respectively; house dust mite allergy was significantly higher in CRSwNPs (16%) compared to CRSsNPs (9%, p < 0.001). The prevalence of self- reported aspirin sensitivity was 2.26, 3.25, 9.61 and 40% respectively. The odds ratio for aspirin sensitivity amongst those with AFRS was 28.8 (CIs 9.9, 83.8) p < 0.001.Conclusions: The prevalence of asthma and allergy in CRS varies by phenoytype, with CRSwNPs and AFRS having a stronger association with both. Aspirin sensitivity has a highly significant association with AFRS. All of these comorbidities are significantly more prevalent than in non-CRS controls and strengthen the need for a more individualised approach to the combined airway. [ABSTRACT FROM AUTHOR]

References 1 Vaira LA, De Vito A, Deiana G, Pes C, Giovanditto F, Fiore V. Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: a preliminary study. The results of the correlation analysis are confirmed by the analysis of the interleukin-6 (IL-6) median concentration differences between clinical groups of olfactory function, determined on the basis of the olfactory scores (Kruskal-Wallis test I p i = 0.369). The choice of the statistical test for the study of correlations between variables that is burdened by the lowest rate of bias has always been at the centre of a heated debate among biostatisticians. [Extracted from the article]

Phenology is a key aspect of plant success. Recent research has demonstrated that herbarium specimens can provide important information on plant phenology. Massive digitization efforts have the potential to greatly expand herbarium-based phenological research, but also pose a serious challenge regarding efficient data collection., Here, we introduce CrowdCurio, a crowdsourcing tool for the collection of phenological data from herbarium specimens. We test its utility by having workers collect phenological data (number of flower buds, open flowers and fruits) from specimens of two common New England ( USA) species: Chelidonium majus and Vaccinium angustifolium. We assess the reliability of using nonexpert workers (i.e. Amazon Mechanical Turk) against expert workers. We also use these data to estimate the phenological sensitivity to temperature for both species across multiple phenophases., We found no difference in the data quality of nonexperts and experts. Nonexperts, however, were a more efficient way of collecting more data at lower cost. We also found that phenological sensitivity varied across both species and phenophases., Our study demonstrates the utility of CrowdCurio as a crowdsourcing tool for the collection of phenological data from herbarium specimens. Furthermore, our results highlight the insight gained from collecting large amounts of phenological data to estimate multiple phenophases. [ABSTRACT FROM AUTHOR]

Objectives To assess SNOT-22 and its subscales in a non-rhinosinusitis UK-wide population. Design Self-reported questionnaire. Setting Based from 30 ENT departments around the UK. Participants 250 Non-rhinosinusitis adults - no self-reported nasal problems in the past, no chronic conditions undergoing active treatment and no hospital admissions in the preceding 12 months. Main outcome measures SNOT-22, SF-36. Results The mean SNOT-22 total score overall was 12.0. The mean was 10.2 for males with a median of 6.5 and a mean of 13.2 for females with a median of 9. Females scored significantly more highly than males on the sleep/fatigue and facial domains. Conclusions Our data demonstrate differences in SNOT-22 amongst males and females. These data can be used in future studies for comparison with different disease populations with rhinosinusitis. [ABSTRACT FROM AUTHOR]

A response from the author of the article, about the Registry of the American Rhinologic Society Clinical Endpoints (RACE) Database in the October 2016 issue is presented.

Background The long-term impact of chronic rhinosinusitis (CRS) with or without allergic rhinitis (AR) on asthma is poorly documented. This study analyzed potential associations of ongoing CRS and AR on asthma. Methods Using the MarketScan™ claims database, patients with CRS and endoscopic sinus surgery (ESS) in 2010 were identified. The date of first sinusitis was determined for all. Patients with asthma at time of first sinusitis diagnosis were excluded. The remaining patients were grouped based on duration of sinusitis, from first diagnosis to surgery-group 1: 1 to <2 years (n = 181); group 2: 2 to <3 years (n = 195); group 3: 3 to <4 years (n = 292); and group 4: 4 to <5 years (n = 536). Yearly incidence and prevalence of newly diagnosed asthmatics was analyzed for all groups. A secondary analysis evaluated the association between AR and asthma. Results Preoperatively, yearly incidence of patients with new asthma diagnoses averaged 4.48% (95% confidence interval [CI], 3.93% to 5.11%) and was significantly greater for patients with AR (5.93%; 95% CI, 4.56% to 7.66%) vs non-AR (4.15%; 95% CI, 3.56% to 4.82%); p = 0.03. Postoperatively, yearly incidence of asthma was 0.42% (95% CI, 0.18% to 0.88%). No patient had asthma at time of first diagnosis; however, by time of surgery, 9.4%, 12.8%, 18.2%, and 22.40% of patients had been diagnosed with asthma, in groups 1 through 4, respectively. Conclusion AR was a significant risk factor for asthma in patients with CRS. Medically recalcitrant CRS was associated with high incidence rates of asthma, which declined post-operatively. Patients operated earlier in the disease continuum were therefore at decreased risk of developing asthma. [ABSTRACT FROM AUTHOR]

Introduction: SYNAPSE, a Phase III, randomised, doubleblind trial, assessed the efficacy of mepolizumab in severe chronic rhinosinusitis with nasal polyps (CRSwNP) (Han JK, et al. Lancet Respir Med 2021; S2213-2600(21)00097-7). Aim: To assess the clinical response to mepolizumab in severe CRSwNP. Method: In SYNAPSE, patients received standard of care plus mepolizumab (100 mg subcutaneous) or placebo for 52 weeks. This post hoc, descriptive analysis, classified patients in the intent-totreat (ITT) population without sinus surgery during the study period as responders, using 5 modified European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) criteria (Bachert C, et al. JACI, 2021;147:29). Results: In the ITT population (n=407), 381 and 343 patients had not had sinus surgery by Weeks 24 and 52, respectively. For each EUFOREA criterion (reduced nasal polyp size and nasal obstruction, improved sense of smell, improved quality of life, improved overall symptoms) proportion of patients classified as responders was higher with mepolizumab than placebo at Weeks 24 and 52. The proportion of patients who met =3 criteria was 55% with mepolizumab vs 35% with placebo at Week 24, and 67% vs 49% at Week 52. Conclusion: Clinical response, as defined by the modified EUFOREA criteria, was greater with mepolizumab than placebo and increased from Week 24 to Week 52, suggesting a sustained, progressive response in patients with severe CRSwNP without sinus surgery during the study. [ABSTRACT FROM AUTHOR]

(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up. [ABSTRACT FROM AUTHOR]

The article reviews the present literature on allergic rhinitis with respect to Allergic Rhinitis and its Impact on Asthma guidelines produced by the World Health Organization (WHO). Topics covered include the definition of allergic rhinitis as an IgE mediated disorder triggered by exposure of nasal mucosa to allergens, the increased prevalence of allergic rhinitis in children and the classifications of allergic rhinitis into intermittent or persistent depending on the frequency of symptoms.

A letter to the editor is presented in response to an article related to the risk of cardiovascular and acute coronary syndromes in the chronic obstructive pulmonary disease patients, being treated with clarithromycin, in the March 22, 2013 issue.

This study reports on the prevalence, intensity, and timing of an altered sense of smell or taste in patients with SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

The article discusses the impact and safety of nasal lavages (NL) during viral infections like coronavirus disease 2019 (COVID-19). Topics include the possible benefits of NL in upper viral respiratory infectious diseases, the effectiveness of saline solutions in improving mucociliary clearance in chronic rhinosinusitis, and the possible advantages and hars of NL to personal contacts/healthcare workers (HCW) caring for COVID-19 patients.

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

The coronavirus pandemic raging worldwide since December 2019 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which invades human cells via the angiotensin-converting enzyme 2 (ACE2) receptor. Although it has already been identified in many organs, ACE2 expression remains largely unknown in the head and neck (HN) sphere. Thus, this study aims to investigate its protein expression in several sites of the upper aerodigestive tract in order to highlight potential routes of infection. We compared ACE2 immunohistochemical expression between 70 paraffin-embedded specimens with two different antibodies and reported the quantified expression in each histological location. Surprisingly, we obtained different results depending on the antibody, an absence of labeling having been observed with a monoclonal antibody raised against the extracellular domain, whereas the polyclonal, against the cytoplasmic part of the protein, revealed enriched ACE2 expression, particularly in sinuses, vocal cords, salivary glands and oral cavity epithelial cells. The interpretation of these discordant results has brought several exciting lines of reflection. In conclusion, this study provides possible routes of entry for the SARS-CoV-2 in HN region and, above all, has led us to encourage caution when studying the ACE2 expression which is currently at the center of all attention. [ABSTRACT FROM AUTHOR]

Orbital and intracranial complications of pediatric acute rhinosinusitis (ARS) are uncommon. With a risk of significant morbidity, hospital utilization and the financial burden of these entities are often high. We sought to assess utilization trends for complicated ARS and elucidate which factors influence cost. Analysis of Kids' Inpatient Database (2006, 2009 and 2012). Children were selected based on diagnosis codes for ARS and grouped as: uncomplicated ARS, orbital complications (OC), or intracranial complications (IC). Patients with IC were subdivided into abscess (ICa), meningitis, or sinus thrombosis. Length of stay (LOS), cost and management information were analysed. Data presented as median [IQR]. A weighted total of 20,775 children were included. OC and IC were observed in 10.9% and 2.7% of these patients. LOS was longer for IC compared to OC (9 [8] v 4 [3]days, p < 0.001). Daily cost for IC was greater than OC ($2861 [4044] v $1683 [1187], p < 0.001), likely due to differences in need for surgery (IC 66.3% v OC 37.1%, p < 0.001). Within the ICa group, patients who received both otolaryngologic (ENT) and neurosurgery, compared to neurosurgery alone, had higher total cost ($41,474 [41,976] v $32,299 [18,235], p < 0.001) but similar LOS (12 [10] v 11 [9] days, p = 0.783). Children with IC required more surgery than their OC counterparts, resulting in a longer LOS and increased cost. Within the ICa group, the addition of ENT surgery to neurosurgery resulted in higher costs, but with a similar LOS. Considering the increased costs, the additional benefit of ENT surgery to those with children with IC should be investigated further. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a common source of ill health; 11% of UK adults reported CRS symptoms in a worldwide population study. Guidelines are conflicting regarding whether antibiotics should be included in primary medical management, reflecting the lack of evidence in systematic reviews. Insufficient evidence to inform the role of surgery contributes to a fivefold variation in UK intervention rates. The objective of this trial is to establish the comparative effectiveness of endoscopic sinus surgery (ESS) or a prolonged course of antibiotics (clarithromycin) in adult patients with CRS in terms of symptomatic improvement and costs to the National Health Service compared with standard medical care (intranasal medication) at 6 months.Methods/design: A three-arm parallel-group trial will be conducted with patients who remain symptomatic after receiving appropriate medical therapy (either in primary or secondary care). They will be randomised to receive: (1) intranasal medication plus ESS, (2) intranasal medication plus clarithromycin (250 mg) or (3) intranasal medication plus a placebo. Intranasal medication (current standard medical care) is defined as a spray or drops of intranasal corticosteroids and saline irrigations. The primary outcome measure is the SNOT-22 questionnaire, which assesses disease-specific health-related quality of life. The study sample size is 600. Principal analyses will be according to the randomised groups irrespective of compliance. The trial will be conducted in at least 16 secondary or tertiary care centres with an internal pilot at six sites for 6 months.Discussion: The potential cardiovascular side effects of macrolide antibiotics have been recently highlighted. The effectiveness of antibiotics will be established through this trial, which may help to reduce unnecessary usage and potential morbidity. If ESS is shown to be clinically effective and cost-effective, the trial may encourage earlier intervention. In contrast, if it is shown to be ineffective, then there should be a significant reduction in surgery rates. The trial results will feed into the other components of the MACRO research programme to establish best practice for the management of adults with CRS and design the ideal patient pathway across primary and secondary care.Trial Registration: ISRCTN36962030 . Registered on 17 October 2018. [ABSTRACT FROM AUTHOR]

Background: MACRO (Defining best Management for Adults with Chronic RhinOsinusitis) is an NIHR-funded programme of work designed to establish best practice for adults with chronic rhinosinusitis (CRS). The 7-year programme comprises three consecutive workstreams, designed to explore NHS care pathways through analysis of primary and secondary data sources, and to undertake a randomised controlled trial to evaluate a longer-term course of macrolide antibiotics and endoscopic sinus surgery for patients with CRS. A number of outstanding elements still required clarification at the funding stage. This paper reports an expert panel review process designed to agree and finalise the MACRO trial design, ensuring relevance to patients and clinicians whilst maximising trial recruitment and retention.Methods: An expert panel, consisting of the MACRO Programme Management Group, independent advisors, and patient contributors, was convened to review current evidence and the mixed-method data collected as part of the programme, and reach agreement on MACRO trial design. Specifically, agreement was sought for selection of macrolide antibiotic, use of orally administered steroids, inclusion of CRS phenotypes (with/without nasal polyps), and overall trial design.Results: A 12-week course of clarithromycin was agreed as the main trial comparator due to its increasing use as a first- and second-line treatment for patients with CRS, and the perceived need to establish its role in CRS management. Orally administered steroids will be used as a rescue medication during the trial, rather than routinely either pre or post trial randomisation, to limit any potential effects on surgical outcomes and better reflect current UK prescribing habits. Both CRS phenotypes will be included in a single trial to ensure that the MACRO trial is both pragmatic and generalisable to primary care. A modified, three-arm trial design was agreed after intense discussions and further exploratory work. Inclusion criteria were amended to ensure that the patients recruited would be considered eligible for the treatment offered in the trial due to having already received appropriate medical therapy as deemed suitable by their ENT surgeon. A proposed 6-week run-in period prior to randomisation was removed due to the new criteria prior to randomisation.Conclusion: The expert panel review process resulted in agreement on key elements and an optimal design for the MACRO trial, considered most likely to be successful in terms of both recruitment potential and ability to establish best management of patients with CRS. [ABSTRACT FROM AUTHOR]