Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. OBJECTIVE: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. METHODS: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. RESULTS: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. CONCLUSIONS: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.

Olfactory and Gustatory Function 3 Years After Mild COVID-19-A Cohort Psychophysical Study.

This case-control study estimates the 3-year prevalence of measured olfactory dysfunction and gustatory dysfunction associated with SARS-CoV-2 infection.

Impact of Dupilumab on Sinonasal Symptoms and Outcomes in Severe Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVES: To assess the severity of the top 5 22-item Sino-Nasal Outcome Test (SNOT-22) items ranked most important by patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the effect of dupilumab on these items, and their association with objective disease measures. STUDY DESIGN: Post hoc analysis of the SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) clinical trials. SETTING: Multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies. METHODS: Patients ranked the SNOT-22 items most affecting their health at baseline. Item symptom severity (0-5 scale) was assessed at baseline, Week 24 (W24), and Week 52 (W52). Changes in nasal polyps score (NPS) and Lund-Mackay (LMK) scores were assessed in patients with/without SNOT-22 items improvements of at least 1 severity group point at W24 and W52. RESULTS: The SNOT-22 items ranked most important at baseline were "decreased sense of smell/taste" (87% of patients), followed by "nasal blockage" (82%), "postnasal discharge" (40%), "thick nasal discharge" (37%), and "wake up at night" (26%); 82%, 61%, 32%, 40%, and 26% of patients reported severe symptoms (score 4 or 5) for these items, respectively. Dupilumab improved score severity for all top 5 items versus placebo at W24 and W52. Improvements in NPS and LMK scores were numerically greater in patients with improvements in the SNOT-22 top 5 items. CONCLUSION: Loss of smell/taste was ranked as the most important symptom by patients with CRSwNP. Dupilumab reduced the severity of the top 5 most important SNOT-22 items versus placebo, in parallel with improvements in objective disease measures. CLINICAL TRIAL REGISTRATION: SINUS-24 and SINUS-52 clinical trials were registered with ClinicalTrials.gov, identifiers NCT02912468 and NCT02898454, respectively.

International clinical assessment of smell: An international, cross-sectional survey of current practice in the assessment of olfaction.

OBJECTIVES: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice. DESIGN: Anonymous online questionnaire with cross-sectional non-probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non-rhinologists') was performed, with geographical comparisons only made according to subgroup. PARTICIPANTS: ENT surgeons who assess olfaction. RESULTS: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country-specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios-though rhinologists did so more often than non-rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents. CONCLUSIONS: To our knowledge, this is the most comprehensive UK-based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems.

EUFOREA/EPOS2020 statement on the clinical considerations for CRSwNP care.

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.

Post-viral olfactory loss and parosmia.

The emergence of SARS-CoV-2 has brought olfactory dysfunction to the forefront of public awareness, because up to half of infected individuals could develop olfactory dysfunction. Loss of smell-which can be partial or total-in itself is debilitating, but the distortion of sense of smell (parosmia) that can occur as a consequence of a viral upper respiratory tract infection (either alongside a reduction in sense of smell or as a solo symptom) can be very distressing for patients. Incidence of olfactory loss after SARS-CoV-2 infection has been estimated by meta-analysis to be around 50%, with more than one in three who will subsequently report parosmia. While early loss of sense of smell is thought to be due to infection of the supporting cells of the olfactory epithelium, the underlying mechanisms of persistant loss and parosmia remain less clear. Depletion of olfactory sensory neurones, chronic inflammatory infiltrates, and downregulation of receptor expression are thought to contribute. There are few effective therapeutic options, so support and olfactory training are essential. Further research is required before strong recommendations can be made to support treatment with steroids, supplements, or interventions applied topically or injected into the olfactory epithelium in terms of improving recovery of quantitative olfactory function. It is not yet known whether these treatments will also achieve comparable improvements in parosmia. This article aims to contextualise parosmia in the setting of post-viral olfactory dysfunction, explore some of the putative molecular mechanisms, and review some of the treatment options available.

Evaluating long-term smell or taste dysfunction in mildly symptomatic COVID-19 patients: a 3-year follow-up study.

INTRODUCTION: No studies have reported data on 3-year prevalence and recovery rates of self-reported COVID-19-related olfactory and gustatory dysfunction. The aim of the present study was to estimate the 3-year prevalence and recovery rate of self-reported COVID-19-related chemosensory dysfunction in a cohort of patients with antecedent mild COVID-19. METHODS: This is a prospective observational study, measuring the prevalence of altered sense of smell or taste at follow-up and their variation from baseline, on adult patients consecutively assessed at Treviso and Trieste University Hospitals, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction during March 2020. RESULTS: Overall, out of 403 respondents, 267 patients (66.3%) reported an altered sense of smell or taste (SNOT-22 > 0) at baseline, while 56 (13.9%), 29 (7.2%), and 21 (5.2%) reported such alterations at 6-24 months, 2 years, and 3 years, respectively. Among the 267 patients with COVID-19-associated smell or taste dysfunction at baseline, 246 (92.1%) reported complete resolution at 3 years. Of the patients who still experienced smell or taste dysfunction 2 years after COVID-19, 27.6% and 37.9% recovered completely and partially, respectively, at the 3-year follow-up. CONCLUSION: Among subjects with antecedent mildly symptomatic SARS-CoV-2 infection, the 3-year prevalence and recovery rate of COVID-19-related alteration in sense of smell or taste was 5% and 92%, respectively. In approximately two-thirds of patients experiencing chemosensory dysfunction still 2 years after COVID-19, it is still possible to observe a delayed complete or partial recovery after a period of 3 years, while the remaining one-third of individuals continues to have unchanged persistent chemosensory alteration.

Exploring Endotypes in Chronic Rhinosinusitis (ExpRess): Protocol for a cohort study.

BACKGROUND: Chronic Rhinosinusitis (CRS) affects approximately 1 in 10 UK adults and impacts quality of life quality of life significantly. Response to treatment may be driven by individual CRS endotypes and therefore work to delineate biomarker clusters that may separate responders from non-responders is needed. The ongoing MACRO three-arm parallel-group trial randomises adult CRS patients to endoscopic sinus surgery, macrolide therapy or placebo. AIM: This study aims to correlate CRS endotypes with clinical parameters from the ongoing MACRO trial, including olfactory function and outcomes in terms of response to treatment using core biomarkers sets. METHODS: Adult CRS patients enrolled into the MACRO trial will be recruited from participating UK otorhinolaryngology departments. Nasal tissue samples and swabs will be obtained in theatre or clinic from patients randomised to all three trial arms. Nasal tissue will be analysed with multiplex electrochemiluminescence for 32 cytokines including IL-5, IL-13, IgE and periostin. Bacterial swabs will be analysed using illumina miSeq 16S amplicon sequencing. Mean expression for each biomarker will be reported for treatment responder and non-responder groups. Correlation of biomarkers with MACRO trial outcome data such as endoscopic evaluation scores and quality-of-life improvement scores will be reported. DISCUSSION: Defining clear endotypes in CRS will contribute to refining patient pathways for the efficient use of clinical resources. This work may lay the groundwork for future studies to predict which patients might respond to medical or surgical therapy.

Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials: SINUS-24 and SINUS-52.

BACKGROUND: This post hoc analysis of the international SINUS-24/-52 trials (NCT02912468/NCT02898454) aimed to assess dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) according to different definitions of type 2 inflammatory signature. METHODS: Six definitions of type 2 inflammation were used: ≥150 eosinophils/µL or total immunoglobulin E (IgE) ≥100 IU/mL with a coexisting type 2 condition; ≥150 eosinophils/µL or total IgE ≥100 IU/mL; ≥150 eosinophils/µL; ≥250 eosinophils/µL or total IgE ≥100 IU/mL; coexisting asthma or ≥300 eosinophils/µL; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (≥1 point) from baseline to week 24 (pooled SINUS-24/-52) and week 52 (SINUS-52) were calculated for nasal polyp score (NPS; range 0-8), nasal congestion/obstruction score (NC; 0-3), and loss of smell score (LoS; 0-3). RESULTS: At baseline (n = 724), most patients displayed a type 2 inflammatory signature across definitions (64.2%-95.3%). At week 24, ORs for clinically meaningful improvement ranged from 11.9 to 14.9 for NPS across type 2 definitions, 6.5-9.6 for NC, and 12.2-17.8 for LoS (all p < 0.0001). OR ranges were similar or greater at week 52: 19.0-36.6, 7.6-12.1, and 9.2-33.5, respectively (all p < 0.0001). CONCLUSION: Most patients with CRSwNP in the SINUS study had type 2 inflammation. Dupilumab demonstrated robust efficacy across definitions of type 2 inflammation, consistent with its profile as an inhibitor of Interleukin-4 and Interleukin-13 signaling, key and central drivers of type 2 inflammation in CRSwNP. KEY POINTS: This study assessed type 2 inflammation prevalence and dupilumab efficacy in chronic rhinosinusitis with nasal polyps according to algorithm-defined type 2 inflammation Dupilumab efficacy was similar across all type 2 definitions.

The Role of Biologics in the Treatment of Chronic Rhinosinusitis.

The last decade has seen significant developments in the field of biologics for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). Translational research borne from knowledge of the pathophysiology of type 2 inflammatory disease of the lower airways and the strong association with CRSwNP, has led to major therapeutic breakthroughs, with phase 3 trials of four biologics completed at the time of writing, and more underway. This article explores the evidence behind biologics for CRSwNP, the guidance on their use and the health economic factors influencing their position amongst the established therapeutic options for this common chronic condition.

Recovery from olfactory and gustatory dysfunction following COVID-19 acquired during Omicron BA.1 wave in Italy.

BACKGROUND: Despite alterations in the sense of smell and taste have dominated the symptoms of SARS-CoV-2 infection, the prevalence and the severity of self-reporting COVID-19 associated olfactory and gustatory dysfunction has dropped significantly with the advent of the Omicron BA.1 subvariant. However, data on the evolution of Omicron-related chemosensory impairment are still lacking. OBJECTIVE: The aim of the present study was to estimate the prevalence and the recovery rate of self-reported chemosensory dysfunction 6-month after SARS-CoV-2 infection acquired during the predominance of the Omicron BA.1 subvariant in Italy. METHODS: Prospective observational study based on the sino-nasal outcome tool 22 (SNOT-22), item "sense of smell or taste" and additional outcomes conducted in University hospitals and tertiary referral centers in Italy. RESULTS: Of 338 patients with mild-to-moderate COVID-19 completing the baseline survey, 294 (87.0 %) responded to the 6-month follow-up interview. Among them, 101 (34.4 %) and 4 (1.4 %) reported an altered sense of smell or taste at baseline and at 6 months, respectively. Among the 101 patients with COVID-19-associated smell or taste dysfunction during the acute phase of the disease, 97 (96.0 %) reported complete resolution at 6 months. The duration of smell or taste impairment was significantly shorter in vaccinated patients (p = 0.007). CONCLUSIONS: Compared with that observed in subjects infected during the first wave of the pandemic, the recovery rate from chemosensory dysfunctions reported in the present series of patients infected during the predominance of the Omicron BA.1 subvariant was more favorable with a shorter duration being positively influenced by vaccination.

Real-world characterisation of patients with chronic rhinosinusitis with nasal polyps with and without surgery in England.

OBJECTIVES: To characterise the real-world burden of chronic rhinosinusitis with nasal polyps (CRSwNP) in the UK, stratified by number of surgeries. DESIGN: Retrospective cohort study. SETTING: UK Clinical Practice Research Datalink Aurum database with Hospital Episodes Statistics linkage (2007-2019). PARTICIPANTS: Adults ≥18 years of age with a first NP diagnosis (index) and 365 days of baseline and ≥180 days of follow-up data. Follow-up continued until disenrollment, death or end of data collection. MAIN OUTCOME MEASURES: Primary: primary care physician prescribed CRSwNP-related treatments, and all-cause healthcare resource utilisation (HCRU) in 90 days post-index, stratified by surgeries during follow-up. Secondary: rate of surgery and CRSwNP point prevalence. Baseline patient demographics, clinical characteristics and comorbidities were also assessed. RESULTS: Of the 33 107 patients included, 23.5% and 2.2% had ≥1 and ≥2 surgeries during follow-up, respectively (mean follow-up: 5.3 years). Patients with more surgeries (≥2/≥1/0) during follow-up were more likely to be male (67.3%/69.0%/58.0%), have asthma (37.8%/28.2%/20.2%) and have baseline blood eosinophil counts ≥300 cells/µL (68.5%/66.0%/51.5%). During the first 90-days post-index as surgery number increased, the proportion of patients using oral corticosteroids (25.8%/20.7%/14.2%) and mean (SD) number of all-cause healthcare visits (5.9 [4.2]/5.4 [4.0]/4.9 [4.2]) increased. Time between surgeries was shorter among patients with more surgeries. CRSwNP prevalence on 31 December 2018 was 476 cases per 100 000 persons. CONCLUSION: A small proportion of patients in the UK required multiple surgeries for CRSwNP and this was associated with increasing comorbidity burden, baseline blood eosinophil counts, CRSwNP-related treatment and HCRU use.

Olfactory recovery following omicron variant infection: a psychophysical prospective case-control study with six-month follow up.

OBJECTIVE: This study aimed to evaluate the recovery of olfactory function at six months in individuals infected with the coronavirus disease 2019 omicron variant, using psychophysical tests. METHODS: A prospective case-control study that included severe acute respiratory syndrome coronavirus-2 patients infected in February and March 2022 was conducted. Patients underwent the Sniffin' Sticks test within 10 days of infection and again after at least 6 months. The olfactory scores were compared with those of a control group. RESULTS: In all, 102 patients and 120 controls were enrolled in the study. At baseline, 26 patients (25.5 per cent) self-reported smell loss. The median threshold, discrimination and identification score was 33.6 (interquartile range, 12.5) for the cases and 36.5 (interquartile range, 4.38) for the controls (p < 0.001). Based on the threshold, discrimination and identification scores, 12 controls and 34 patients reported olfactory dysfunction (p < 0.001). Eighty cases underwent re-evaluation at six months; the median threshold, discrimination and identification score was 37.1 (interquartile range, 4.75) with no significant differences compared with the controls. CONCLUSION: Six months after infection, the prevalence of olfactory dysfunction in patients did not differ significantly from the control population.

Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. METHODS: This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0-35, moderate 36-48, or severe 49-70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. FINDINGS: Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19-30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11-46] vs 30 days [14-65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65; <0·0001). 191 adverse events in 90 (39%) of 231 participants were deemed related to tonsillectomy. The most common adverse event was bleeding (54 events in 44 [19%] participants). No deaths occurred during the study. INTERPRETATION: Compared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. FUNDING: National Institute for Health Research.

Determinants of physician assessment of chronic rhinosinusitis disease control using EPOS 2020 criteria and the importance of incorporating patient perspectives of disease control.

BACKGROUND: We identify chronic rhinosinusitis (CRS) manifestations associated with how rhinologists assess CRS control, with a focus on patient perspectives (patient-reported CRS control). METHODS: Fifteen rhinologists were provided with real-world data from 200 CRS patients. Participating rhinologists first classified patients' CRS control as "controlled," "partly controlled," and "uncontrolled" using seven CRS manifestations reflecting European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) CRS control criteria (nasal obstruction, drainage, impaired smell, facial pain/pressure, sleep disturbance, use of systemic antibiotics/corticosteroids in past 6 months, and nasal endoscopy findings) and patient-reported CRS control. They then classified patients' CRS control without knowledge of patient-reported CRS control. Interrater reliability and agreement of rhinologist-assessed CRS control with patient-reported CRS control and EPOS guidelines were determined. RESULTS: CRS control classification with and without knowledge of patient-reported CRS control was highly consistent across rhinologists (κw  = 0.758). Rhinologist-assessed CRS control agreed with patient-reported CRS control significantly better when rhinologists had knowledge of patient-reported CRS control (κw  = 0.736 vs. κw  = 0.554, p < 0.001). Patient-reported CRS control, nasal obstruction, drainage, and endoscopy findings were most strongly associated with rhinologists' assessment of CRS control. Rhinologists' CRS control assessments weakly agreed with EPOS CRS control guidelines with (κw  = 0.529) and without (κw  = 0.538) patient-reported CRS control. Rhinologists classified CRS as more controlled than EPOS guidelines in almost 50% of cases. CONCLUSIONS: This study directly demonstrates the importance of patient-reported CRS control as a dominant influence on rhinologists' CRS control assessment. Knowledge of patient-reported CRS control may better align rhinologists' CRS control assessments and treatment decisions with patients' perspectives.

Health-Related Quality of Life Impairment Among Patients with Severe Chronic Rhinosinusitis with Nasal Polyps in the SINUS-24 Trial.

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease with a high symptom burden. Data are lacking on the comparative health status of patients with CRSwNP. This analysis compared baseline physical and mental health-related quality of life (HRQoL) and overall health status of patients with severe CRSwNP enrolled in a Phase 3 clinical trial with general population norms and with other chronic diseases. Methods: In this post hoc cross-sectional analysis of baseline data from the SINUS-24 study (NCT02912468), HRQoL was measured using the 36-item Short Form (SF-36) questionnaire and general health status was measured using the EuroQol-5 Dimension visual analog scale (EQ-VAS). Analyses included the intention-to-treat (ITT) population and subgroups defined by prior sinonasal surgery, systemic corticosteroid use, and coexisting asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Scores were compared with published values for population norms (50 for SF-36 physical component summary (PCS) and mental component summary (MCS), 70.4-83.3 for EQ-VAS) and for rheumatoid arthritis, type 2 diabetes, and asthma. Results: In the ITT population (n=276), mean SF-36 physical component summary (PCS), SF-36 mental component summary (MCS), and EQ-VAS scores were below general population norms (46.4, 48.6, and 66.0, respectively). Mean SF-36 PCS and EQ-VAS scores were below population norms across all subgroups; mean SF-36 MCS scores were below the population norm in all subgroups except no prior surgery. SF-36 PCS and MCS scores from SINUS-24 were generally similar to other chronic diseases, except SF-36 PCS which was lower in rheumatoid arthritis. EQ-VAS scores in SINUS-24 were lower than in other chronic diseases. HRQoL scores weakly correlated with objective measures of disease severity. Conclusion: In patients with severe CRSwNP, including those with coexisting asthma/NSAID-ERD, HRQoL was worse than population norms and as burdensome as diseases such as type 2 diabetes, asthma, and rheumatoid arthritis.

Association between laryngopharyngeal reflux, gastroesophageal reflux and recalcitrant chronic rhinosinusitis: A systematic review.

OBJECTIVE: To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS). DATA SOURCES: PubMed, Cochrane Library and Scopus. REVIEW METHODS: Three investigators searched the specified databases for studies investigating the relationship between LPR, GERD and recalcitrant CRS with or without polyposis. The following outcomes were investigated with PRISMA criteria: age; gender; reflux and CRS diagnosis; association outcomes and potential treatment outcomes. The authors performed a bias analysis of papers and provided recommendations for future studies. RESULTS: A total of 17 studies investigated the association between reflux and recalcitrant CRS. According to pharyngeal pH monitoring, 54% of patients with recalcitrant CRS reported hypo or nasopharyngeal acid reflux events. The number of hypo- and nasopharyngeal acid reflux events was significantly higher in patients compared to healthy individuals in 4 and 2 studies, respectively. Only one study did not report intergroup differences. The proportion of GERD was significantly higher in CRS patients compared to controls, with a prevalence ranging from 32% to 91% of cases. No author considered nonacid reflux events. There was significant heterogeneity in the inclusion criteria; definition of reflux and association outcomes, limiting the ability to draw clear conclusions. Pepsin was found in sinonasal secretions more frequently in CRS patients than controls. CONCLUSION: Laryngopharyngeal reflux and GERD may be contributing factors of CRS therapeutic resistance, but future studies are needed to confirm the association considering nonacid reflux events.

SARS-CoV-2 Effects on Psychophysical Olfactory Scores: Prospective Study With Evaluation Before and 60-Days After Infection.

The aim of this study was to prospectively evaluate the olfactory function in a series of individuals infected with SARS-CoV-2 and who had undergone psychophysical olfactory assessment prior to infection. Individuals unexposed to SARS-CoV-2 infection underwent a psychophysical evaluation of smell with the Sniffin' Sticks test. The subjects were followed prospectively and included in the study if they developed SARS-CoV-2 infection with a second test 60 days after recovery. At the 60-day follow-up of the 41 included subjects, 2 (4.9%) self-reported persistent olfactory dysfunction (OD). The differences between TDI scores before and after infection were statistically significant (37 [interquartile range (IQR), 34.25-39.25] vs 34.75 [IQR, 32.25-38]; p = .021). Analyzing the individual olfactory domains, the differences were significant for threshold (T) (9.75 [IQR, 9-11.25] vs 8.25 [IQR, 7.25-10.25]; p = .009) but not for odor discrimination (D) (p = .443) and identification (I) (p = .159). SARS-CoV-2 causes a significant reduction in the olfactory function, in particular affecting the olfactory threshold, even in subjects who do not self-report an OD.