EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps 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.

Two-year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months.

BACKGROUND: Dupilumab is an anti-T2-inflammatory biological registered for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), indicated by integrated CRS-care pathways when optimal medico-surgical treatment yields insufficient CRS control. This study aims to evaluate long-term results with focus on established therapeutic efficacy while tapering dupilumab. METHODS: Real-life, prospective observational cohort study in single tertiary referral center with add-on dupilumab as primary biological treatment in adult (≥18 years) biological-naïve CRSwNP patients per the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)2020-indication with a 2-year follow-up. Tapering (increasing interdose interval) applied every 24 weeks, conditional to sufficient treatment response and CRS control. RESULTS: Mean scores (s.d.) of all co-primary outcomes improved significantly from baseline ( 228) to the 48 ( 214) and 96-weeks ( 99) timepoints: Nasal Polyp Score (0-8) improved from 5,3 (1,9) to 1,4 (1,8) and 1,3 (1,7); SinoNasal Outcome Test (SNOT)-22 (0-110) improved from 53,6 (19,6) to 20,2 (15,4) and 21,2 (15,6); Sniffin'Sticks-12 identification test (0-12; 0-6 anosmia, 7-10 hyposmia, 11-12 normosmia) improved from 3,7 (2,4) to 7,7 (2,9) and 7,3 (3,04); Asthma Control Test (5-25; >19 indicating well-controlled asthma) improved from 18,5 (4,8) to 21,8 (3,8) and 21,4 (3,9). Tapering was feasible in 79,5% of the patients at the 24-weeks timepoint, and in 93,7% and 95,8% at the 48- and 96-weeks timepoints, respectively. One-way repeated-measures ANOVA demonstrated no significant alterations of individual co-primary outcome mean-scores from 24 weeks onward. CONCLUSION: This first long-term real-life prospective observational cohort study shows high therapeutic efficacy of dupilumab for severe CRswNP in the first 2 years. Therapeutic efficacy is principally established within 24 weeks and endures while tapering dupilumab conditional to treatment response and CRS control.

The prevalence of non-allergic rhinitis phenotypes in the general population: A cross-sectional study.

BACKGROUND: Non-allergic rhinitis (NAR) can be subdivided into several phenotypes: rhinorrhea of the elderly, rhinitis medicamentosa, smokers', occupational, hormonal, drug-induced, gustatory, and idiopathic rhinitis. There are two pathophysiological endotypes of NAR: inflammatory and neurogenic. Phenotypes may serve as an indicator of an underlying endotype and, therefore, help to guide the treatment. The prevalence of each phenotype in the general population is currently unknown. METHODOLOGY/PRINCIPAL: Cross-sectional questionnaire-based study in the general population of the Netherlands. RESULTS: The prevalence of chronic rhinitis in the general population was 40% (N = 558, of those, 65% had NAR and 28% AR, in 7% allergy status is unknown). Individuals with NAR (N = 363) had significantly more complaints in October-February. Those with AR (N = 159) had significantly more complaints in April-August. The most common NAR phenotypes were idiopathic (39%) and rhinitis medicamentosa (14%), followed by occupational (8%), smokers' (6%), hormonal (4%), gustatory (4%), and rhinorrhea of the elderly (4%). The least prevalent phenotype was drug induced (1%). Nineteen percent of the NAR group could not be classified into any of the phenotypes. CONCLUSIONS: This is the first study to describe the prevalences of NAR phenotypes in the general population. AR and NAR have a distinct seasonality pattern with NAR being more prevalent in autumn/winter and AR in spring/summer. Our data on the prevalence of phenotypes may help clinicians to anticipate the type of patients at their clinic and help guide a tailored treatment approach. The high prevalence of rhinitis medicamentosa is alarming, since this is a potentially preventable phenotype.

Updates in biologic therapy for chronic rhinosinusitis with nasal polyps and NSAID-exacerbated respiratory disease.

Chronic rhinosinusitis with nasal polyps (CRSwNP) associated with type 2 inflammation and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) can be difficult to control with standard medical therapy and sinus surgery. In this group, biologicals are potentially promising treatment options. The phase III clinical trials for omalizumab, dupilumab, mepolizumab and benralizumab in CRSwNP have demonstrated favourable outcomes. Moving forward, direct comparisons among biologicals, refining patient selection criteria for specific biologicals, determining optimal treatment duration and monitoring long-term outcomes are areas of emerging interest. This review summarizes the clinical evidence from the recent 2 years on the role of biologicals in severe CRSwNP and N-ERD, and proposes an approach towards decision-making in their use.

Development and validation of combined symptom-medication scores for allergic rhinitis.

BACKGROUND: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. METHODS: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). RESULTS: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). CONCLUSION: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.

Highlights in the advances of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a complex upper airway inflammatory disease with a broad spectrum of clinical variants. As our understanding of the disease pathophysiology evolves, so too does our philosophy towards the approach and management of CRS. Endotyping is gaining favour over phenotype-based classifications, owing to its potential in prognosticating disease severity and delivering precision treatment. Endotyping is especially useful in challenging CRS with nasal polyposis cases, for whom novel treatment options such as biologicals are now available. The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) reflects these changes with updated rhinosinusitis classifications and new integrated care pathways. With the coronavirus disease 2019 (COVID-19) pandemic, physicians and rhinologists have to balance the responsibility of managing their patients' upper airway while adequately protecting themselves from droplet and aerosol transmission. This review summarises the key updates from EPOS2020, endotype-based classification and biomarkers. The role of biologicals in CRS and the lessons we can draw from their use in severe asthma will be examined. Finally, the principles of CRS management during COVID-19 will also be discussed.

Prevalence of chronic rhinosinusitis in the general population based on sinus radiology and symptomatology.

BACKGROUND: The prevalence of chronic rhinosinusitis (CRS) measured in epidemiologic studies is 5% to 12%. This might be an overestimation because of overlap with other diseases, such as allergic rhinitis. OBJECTIVE: We aimed to calculate the prevalence of CRS using a combination of epidemiologically based CRS according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) together with sinonasal opacification on imaging. METHODS: Subjects who underwent a computed tomographic or magnetic resonance imaging scan of the head for any nonrhinologic indication were asked to fill in the Global Allergy and Asthma European Network survey containing EPOS symptom criteria. The scans were evaluated according to the Lund-Mackay (LM) scoring system. Epidemiologically based CRS is based on nasal symptoms according to EPOS; clinically based CRS also encompasses endoscopy and/or CT scanning. RESULTS: Eight hundred thirty-four subjects were included. One hundred seven (12.8%) had epidemiologically based CRS according to EPOS. Of these subjects, 50% had an LM score of 0, 26% had an LM score of 1 to 3, and 23% had an LM score of 4 or greater. Twenty-five (3.0%) subjects had clinically based CRS (based on LM score ≥4), and 53 (6.4%) subjects had clinically based CRS (based on LM score >0). Allergic rhinitis was reported by 167 (20%) subjects. In subjects who did not report upper airway symptoms, 57% had an LM score of 0, 30% had an LM score of 1 to 3, and 12% had an LM score of 4 or greater. CONCLUSION: We found a prevalence of 3.0% to 6.4% of clinically based CRS (depending on an LM cutoff point; ie, LM ≥ 4 or LM > 0, respectively) in a relatively randomly selected group of subjects.

Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.

BACKGROUND: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. OBJECTIVES: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. METHODS: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H1-antihistamines were studied. RESULTS: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H1-antihistamines were found. CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study.

BACKGROUND: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. OBJECTIVES: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. METHODS: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. RESULTS: A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. CONCLUSION AND CLINICAL RELEVANCE: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.

Recent developments and highlights in rhinitis and allergen immunotherapy.

This review paper aims to provide an overview of recent developments in the field of allergic and non-allergic rhinitis, as well as allergen immunotherapy. Recent advances in phenotyping and endotyping various forms of rhinitis have brought us one step closer towards tailoring treatment more appropriately for a given patient. Updates on local allergic rhinitis are also covered. Allergen immunotherapy (AIT) is an area of significant interest, with multiple original papers and recent position papers and guidelines published. Evidence related to the application of AIT in seasonal and perennial allergic rhinitis (AR), local allergic rhinitis and novel and expanded applications is discussed in the publication.

Pediatric Idiopathic Intracranial Hypertension Presenting With Sensorineural Hearing Loss.

OBJECTIVE: To present the rare case of a young boy with idiopathic intracranial hypertension presenting with bilateral sensorineural hearing loss developing over several months. This was accompanied by headaches, otalgia, tinnitus, and vertigo. Furthermore, we aim to provide a concise review on this matter, as this report represents the second case in literature of pediatric idiopathic intracranial hypertension presenting with hearing loss. METHODS: Workup of a 9-year-old boy with bilateral sensorineural hearing loss, including (among others) physical examination, audiometry, diagnostic imaging, and lumbar puncture. RESULTS: Physical examination including fundoscopy as well as imaging showed no abnormalities. At presentation, pure tone audiometry revealed bone conduction thresholds of about 30 dB HL in both ears. Two months later, this declined to about 35 dB HL in both ears. Lumbar puncture revealed an increased intracranial pressure. The boy was thus diagnosed with idiopathic intracranial hypertension. After the lumbar puncture, the otological complaints gradually resolved, and the hearing normalized (bone conduction thresholds of 0-5 dB HL). CONCLUSION: Although rare, sensorineural hearing loss in the pediatric population together with otalgia, tinnitus, and vertigo can be due to idiopathic intracranial hypertension and as such can be reversible.

Human CD127 negative ILC2s show immunological memory.

ILC2s are key players in type 2 immunity and contribute to maintaining homeostasis. ILC2s are also implicated in the development of type 2 inflammation-mediated chronic disorders like asthma. While memory ILC2s have been identified in mouse, it is unknown whether human ILC2s can acquire immunological memory. Here, we demonstrate the persistence of CD45RO, a marker previously linked to inflammatory ILC2s, in resting ILC2s that have undergone prior activation. A high proportion of these cells concurrently reduce the expression of the canonical ILC marker CD127 in a tissue-specific manner. Upon isolation and in vitro stimulation of CD127-CD45RO+ ILC2s, we observed an augmented ability to proliferate and produce cytokines. CD127-CD45RO+ ILC2s are found in both healthy and inflamed tissues and display a gene signature of cell activation. Similarly, mouse memory ILC2s show reduced expression of CD127. Our findings suggest that human ILC2s can acquire innate immune memory and warrant a revision of the current strategies to identify human ILC2s.

Unified Airway Disease: A Contemporary Review and Introduction.

Upper and lower airways diseases are very common, with population prevalence of 10% to 40%. The conditions are usually interlinked and referred to as "unified airway disease" or "the united airways." Especially in phenotypes with more severe disease, type 2 immunologic endotype is often noted. Comorbid upper and lower airway diseases are usually caused by similar underlying immunologic response. Any patient with rhinitis or rhinosinusitis should have their lower respiratory tract evaluated. A multidisciplinary approach in the diagnosis and treatment of airway disease is advised, especially, for more severe phenotypes.