Low levels of miR-143-3p are associated with severe chronic rhinosinusitis with nasal polyps.

microRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules that regulate post-transcriptional gene expression. Accumulating evidence suggests their involvement in regulating various biological and pathological processes, including inflammation. Studies have revealed distinct expression patterns of miRNAs in Chronic Rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps (1). Specifically, miR-155 and miR-21 have been observed to be upregulated in CRSwNP, increasing and attenuating the expression of pro-inflammatory cytokines, respectively (2,3). Conversely, the downregulation of miR-34, miR-449, and members of the miR-200 family has been associated with impaired ciliogenesis and the regulation of epithelial-mesenchymal transition, respectively (4,5). Nonetheless, the direct role of miRNAs in CRSwNP is still being investigated.

EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

Mepolizumab improves sense of smell in severe chronic rhinosinusitis with nasal polyps: SYNAPSE.

BACKGROUND: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. RESULTS: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: −0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,−1.29 vs −0.23 vs −0.07; =3 years since last surgery, −0.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. CONCLUSIONS: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

Validation of Visual Analogue Scale for loss of smell as a quick test in chronic rhinosinusitis with nasal polyps.

BACKGROUND AND OBJECTIVE: Diagnostic criteria of chronic rhinosinusitis with nasal polyps (CRSwNP) include, among others, olfactory dysfunction (OD). We hypothesize that patients suffering with CRSwNP are good at self-assessing their sense of smell through visual analogue scale (VAS) compared to smell tests. METHODS: A controlled cross-sectional study was planned. Adults diagnosed with severe CRSwNP waiting for endoscopic sinus surgery were included. A cohort of healthy controls was also studied. All participants performed Barcelona smell test (BAST-24), sinonasal outcomes test 22 (SNOT-22), and VAS for loss of smell. CRSwNP underwent blood test (eosinophils count, total serum IgE), CT scan (Lund-Mackay Score), and nasal endoscopy. RESULTS: 138 severe CRSwNP and 40 controls subjects were included. The BAST-24 identification score was strongly correlated with the VAS score in the CRSwNP group (rho=-0.79, p<0.001) but not in the control group (rho=-0.14; p=0.39), this difference between groups being statistically significant (p<0.001). A significant correlation of SNOT-22 item 21 (loss of smell) was also found with BAST-24 identification (rho=-0.65, p<0.001), this difference being statistically significant (Z=-2.43; p=0.015). In the ROC curve, the area under the curve (AUC) was 0.85 with 72.5% sensitivity and 93.1% specificity. CONCLUSION: This study demonstrates a potential role of the VAS score for the screening of OD in severe CRSwNP in daily clinical practice.

EUFOREA summit in Brussels 2023: inspiring the future of allergy & respiratory care.

In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.

Position paper on olfactory dysfunction: 2023.

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Septoplasty and/or inferior turbinoplasty produce significant improvements of the sense of smell.

BACKGROUND: Patients with septal deviation and/or turbinal hypertrophy may experience olfactory disfunction (OD). The aim of this study was to analyse the effect of septoplasty and/or turbinoplasty on both lateralized and bilateral olfactory function. METHODOLOGY: Prospective study of 47 patients with nasal obstruction secondary to septal deviation and/or turbinal hypertrophy and 20 healthy controls. The Barcelona Olfactory test (BOT-8), a new supraliminal orthonasal subjective olfactometry, was applied 3 times in a row (in each nostril separately and in both simultaneously). The 8 items were applied randomly to minimize the possible risk of learning. The test has not established the minimal clinically important difference (MCID). Anterior rhinomanometry and acoustic rhinometry were performed. All participants self-assessed smell loss and nasal obstruction using a visual analogue scale (VAS) and completed questionnaires for nasal obstruction (Nasal Obstruction Symptom Evaluation, NOSE) and for quality of life (QoL), using disease-specific (SinoNasal Outcome Test-22, SNOT-22) and generic (Short Form-12 Health Survey, SF-12) questionnaires. Nasal measurements and questionnaires were performed preoperatively and 12 months after surgery. RESULTS: Before surgery, patients reported worse VAS on smell loss and on nasal obstruction compared to controls. Patients scored lower BOT-8 than controls. Lateralized preoperative olfactory function showed that all BOT-8 characteristics were lower at the narrow side than the wider one. Smell function and QoL improved significantly one year after surgery. CONCLUSIONS: Nasal septal deviation and turbinal hypertrophy lead to an olfactory impairment on the obstructed nostril. Nasal surgery provides a positive outcome on olfactory function, as well as on subjective and objective outcomes.

Developing a core outcome set for clinical trials in olfactory disorders: a COMET initiative.

STATEMENT OF PROBLEM: Evaluating the effectiveness of the management of Olfactory Dysfunction (OD) has been limited by a paucity of high-quality randomised and/or controlled trials. A major barrier is heterogeneity of outcomes in such studies. Core outcome sets (COS) - standardized sets of outcomes that should be measured/reported as determined by consensus-would help overcome this problem and facilitate future meta-analyses and/or systematic reviews (SRs). We set out to develop a COS for interventions for patients with OD. METHODS: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed patients and healthcare practitioners to individually rate the outcomes in terms of importance on a 9-point Likert scale. RESULTS: After 2 rounds of the iterative eDelphi process, the initial outcomes were distilled down to a final COS including subjective questions (visual analogue scores, quantitative and qualitative), quality of life measures, psychophysical testing of smell, baseline psychophysical testing of taste, and presence of side effects along with the investigational medicine/device and patient's symptom log. CONCLUSIONS: Inclusion of these core outcomes in future trials will increase the value of research on clinical interventions for OD. We include recommendations regarding the outcomes that should be measured, although future work will be required to further develop and revalidate existing outcome measures.

Spanish Consensus on the Management of Chronic Rhinosinusitis With Nasal Polyps (POLIposis NAsal/POLINA 2.0).

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent and burdensome disease for both individuals and health systems. Its management involves many specialties, including otorhinolaryngology, allergology, pulmonology, primary care, pharmacy, and pediatrics. A multidisciplinary approach and the participation of the patient in decision-making are essential, both for diagnosis and for therapy. The authors of the consensus aim to translate current knowledge into an easy-to-read practical guide and emphasize those aspects requiring further discussion or with unmet needs owing to the lack of appropriate scientific evidence. An iterative approach for the development of an evidence-based systematic review with recommendations was followed using a standard quality assessment approach (Scottish Intercollegiate Guidelines Network [SIGN] and National Institute for Health and Care Excellence [NICE]). The guideline was critically evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) and Recommendation Excellence (AGREE REX) instruments. Consequently, POLINA has been considered a high-quality guideline by an independent agency. The POLINA consensus provides new definitions of control, therapeutic management (including surgery and evaluation of severity), indications for use of biologics, and response. Finally, this guideline focuses on unmet research needs in CRSwNP.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

Prevalence of asthma in Catalonia (Spain): a retrospective, large-scale population-based study.

BACKGROUND AND OBJECTIVE: Asthma epidemiology reports an estimated global prevalence of about 4.3-8.6% in adults, with last differences among geographical regions. This study analyses a more significant population of asthma patients (473,737 individuals).To study the prevalence of medical diagnosis of asthma, overall and by age, gender, and disease severity, as well as comorbidities and type 2 biomarkers, and undergo medical treatments of a retrospective population-based asthma cohort from Catalonia (Spain). METHODS: Individuals with a diagnosis of asthma established by medical records at different healthcare levels (primary, hospital, and emergency) from the Catalan Health System (CHS) were included. Socio-demographic characteristics, prevalence, overall and by age and gender, disease severity, comorbidities, and biomarkers of type-2 inflammation were evaluated, together with appropriate medical treatment. RESULTS: The overall diagnosed asthma prevalence in the population of Catalonia was 6.3%, where patients mainly had mild asthma (5.3%) and were significantly higher in females (6.8%) than males (5.7%). By age groups, asthma was more prevalent in boys and young men adults; however, being more prevalent in females above the age of 30y. The prevalence of severe asthma was 0.4%, 42.6% had uncontrolled asthma, and a high proportion (84.2%) were under systemic corticosteroid prescription. As expected, SABAs were the most prescribed drug (62.6%), followed by systemic corticosteroids (43.3%). More than half (53.8%) of patients showed type 2 inflammation. CONCLUSION: Asthma prevalence in Catalonia is similar to other areas studied in Spain, with a high prevalence in women and of T2 asthma.

Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Prevalence of Atopic Dermatitis in the adult population of Catalonia (Spain): a retrospective, large-scale population-based study.

BACKGROUND AND OBJECTIVES: Studies on the prevalence of Atopic Dermatitis (AD) for the adult cohort in general-based populations are scarce worldwide. We performed a retrospective population-based observational cohort study of 537,098 adult patients diagnosed with AD in Catalonia (Spain), a larger population than in previous studies. To study the prevalence of AD generally by age, gender, disease severity, multi-morbidities, and serum total Immunoglobin E (tIgE) and undergo appropriate medical treatment (AMT) for the Catalan population. METHODS: Adult individuals (≥18 years old) diagnosed with AD by medical records at different health care levels (primary, hospital, emergency) from the Catalan Health System (CHS) were included. Statistical analyses were conducted to evaluate socio-demographic characteristics, prevalence, multi-morbidities, serum tIgE and AMT. RESULTS: The overall diagnosed AD prevalence in the adult Catalan population was 8.7%, being higher for the non-severe (8.5%) than for the severe (0.2%) populations and females (10.1%) than males (7.3%). Topical corticosteroids were the most prescribed drug (66.5%), and the use of all prescribed treatments was higher in severe AD patients, especially systemic corticosteroids (63.8%) and immunosuppressant agents (60.7%). More than half (52.2%) of severe AD patients reported serum tIgE ≥ 100 KU/L, and higher values were observed for those with multi-morbidities. Acute bronchitis (13.7%), allergic rhinitis (12.1%), and asthma (8.6%) were the most frequent comorbid respiratory diseases. CONCLUSIONS: Our study provides new and robust evidence of AD´s prevalence and related characteristics in adults using a large-scale population-based study and a more significant cohort of individuals.

Evaluating treatment response to mepolizumab in patients with severe CRSwNP.

BACKGROUND: The SYNAPSE study (NCT03085797) demonstrated that mepolizumab decreased nasal polyp (NP) size and nasal obstruction in patients with chronic rhinosinusitis with NP (CRSwNP). METHODS: SYNAPSE, a randomized, double-blind study, included patients with recurrent, refractory, severe CRSwNP, eligible for repeated surgery despite receiving standard of care (SoC). Patients received 4-weekly mepolizumab 100 mg or placebo subcutaneously plus SoC for 52 weeks. This post hoc analysis further characterized treatment responses and association with patient characteristics. The proportion of patients meeting any and each of five response criteria indicating improvement in disease-specific quality of life, NP size, nasal obstruction, loss of smell, and overall symptoms at Weeks 24 and 52, were assessed in subgroups: 1) no surgery; 2) neither surgery nor systemic corticosteroids (SCS). RESULTS: Of 407 patients in the intention-to-treat population, 381 and 343 patients had no sinus surgery by Weeks 24 and 52, respectively. More mepolizumab- versus placebo-treated patients without surgery by Weeks 24 and 52 met each response criteria. Of the mepolizumab-treated patients without surgery by Week 24, 109 (55%) responded across >=3 criteria, increasing to 126 (67%) by Week 52. Similar response trends were seen for patients with neither surgery nor SCS by Weeks 24 and 52. At either timepoint, there were no major differences in baseline characteristics between mepolizumab-treated full- (5/5 categories) and non-responders (0/5 categories). CONCLUSIONS: Most patients who completed SYNAPSE required neither surgery nor SCS use and in addition achieved a progressive and sustained clinical response to mepolizumab underscoring the therapeutic benefits of mepolizumab in severe CRSwNP.

Weight Loss and Vitamin D Improve Hyporesponsiveness to Corticosteroids in Obese Asthma.

BACKGROUND AND OBJECTIVES: Obesity negatively impacts on the response of asthma patients to inhaled corticosteroids. The mechanisms underlying this impact are unknown. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma patients is associated with impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both of which are improved by weight loss. METHODS: The study population comprised 23 obese asthma patients (OA) (18 females; median (IQR) age 56 [51-59] years), 14 nonobese asthma patients (NOA) (11 females; 53 [43-60] years), 15 obese patients (OP) (13 females; 47 [45-60] years), and 19 healthy controls (HC) (14 females; 43 [34-56] years). Ten OA and 11 OP were evaluated at baseline (V1) and 6 months after bariatric surgery (V2). Corticosteroid response was measured using dexamethasone-induced inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function and serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2. RESULTS: We found a reduced response to dexamethasone in PBMCs of OP and OA with respect to NOA and HC; this inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in OP and OA and normalized the adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP1 expression in OP and OA. CONCLUSION: The efficacy of weight loss to improve symptoms and lung function in OA may be due, at least in part, to the recovered anti-inflammatory effects of corticosteroids. Vitamin D deficiency may contribute to corticosteroid hyporesponsiveness in OA.