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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.

Background: Nasal hyperreactivity (NHR) is prevalent in all chronic upper airway inflammatory phenotypes, including allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Although NHR in patients with non-allergic rhinitis is mediated by neuronal pathways, AR and CRSwNP are mainly characterized by type 2 inflammation., Methods: Eighteen healthy controls and 45 patients with symptomatic AR/CRSwNP underwent a cold, dry air (CDA) provocation test for objective diagnosis of NHR. Before and after, questionnaires were filled out and nasal secretions and biopsies were collected. Markers for neurogenic inflammation (substance P, calcitonin gene-related peptide, neurokinin A), epithelial activation (IL-33), and histamine were measured in secretions by ELISA; and expression of neuronal markers PGP9.5, TRPV1, and TRPM8 was studied in biopsies by RT-q-PCR. Effects of histamine on TRPV1/A1 were studied with Ca2+-imaging using murine trigeminal neurons., Results: CDA-provocation reduced peak nasal inspiratory flow (PNIF) of patients with subjective NHR but not of non-NHR controls/patients CDA-provocation reduced peak nasal inspiratory flow (PNIF) of patients with subjective NHR but not of non-NHR controls/patients. Subjective (subjectively reported effect of CDA) and objective (decrease in PNIF) effects of CDA were significantly correlated. Levels of neuropeptides and histamine in nasal secretions and mRNA expression of PGP9.5, TRPV1, and TRPM8 correlated with CDA-induced PNIF-reduction. CDA-provocation induced an increase in IL-33-levels. Both TRPV1 and TRPA1 expressed on afferent neurons were sensitized by exposure to histamine., Conclusion: NHR is not an on/off phenomenon but spans a continuous spectrum of reactivity. A neurogenic inflammatory background and increased histamine-levels are risk factors for NHR in AR/CRSwNP.

The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma., Competing Interests: DC: Serves as academic manager at the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) and as review editor at Frontiers in Allergy, rhinology section. MM: Honoraria for speaker and advisory boards: Sanofi, Glenmark, P&G, Immunotek, Cipla, Thermo-Scientific, Lancet laboratories. EUFOREA expert panel member. VB: Is recipient of consultancy/lecture fees or unrestricted research grants from Sanofi/Regeneron, Novartis, GSK, AZ, ALK Abello and BORK-npc. GS: has received speakers fees from ALK-Abello, Meda and Glenpharm, and received honoraria for participation in an advisory group from ALK-Abello. MB-S: Speaker honorarium from GSK Spain, Viatris Spain, Sanofi Spain, WIDEX Spain, Bionorica, Germany. ED: Received fee for consultation, speaker activity, advisory board by Sanofi, Regeneron, GSK, Novartis and AstraZeneca. ZD: In the past 3 years, received speaker or consultant honoraria and/or served on advisory boards at: Antabio, Arcede, Biosion, Foresee Pharmaceuticals, Galenushealth, GlaxoSmithKline, Hippo-Dx, QPS-Netherlands, Sanofi-Genzyme-Regeneron, and Springer Media all outside the submitted work. From 2012 to 2020 she acted as Director Respiratory & Allergy Research at QPS-Netherlands; in 2019-ongoing, QPS-Netherlands received a European grant from ERA4TB and funding Foresee Pharmaceuticals for early respiratory studies. CH: Ad boards—GSK, Sanofi Regeneron, Lilly. MJ: Has received consulting fees (ALK-Abello, Stallergenes-Greer, Takeda, Zentiva); honoraria for lectures, presentations (ALK-Abello, Stallergenes-Greer, Takeda, Zentiva, Mundipharma, AstraZeneca, SOBI, Chiesi, CSL Behring, Novartis, Benela, Pfizer, Viatris); support for attending meetings and/or travel (ALK-Abello, Stallergenes-Greer, Takeda, Novartis, Sanofi Pasteur) and honoraria for participation on Advisory Boards (ALK-Abello, Stallergenes-Greer, Chiesi, Novartis, SOBI, Pfizer, Sanofi Genzyme/Pasteur). JK: Jasper Kappen reports grants and/or personal fees from ALK, Chiesi, GSK, Novartis, AstraZeneca, Sanofi, Boerhinger, Teva, Viatris, Stallergen, Abbot, all outside the submitted work. JM: Joaquim Mullol is or has been member of national and international scientific advisory boards, consulting, received fees for lectures, and grants for research projects or clinical trials from AstraZeneca, Genentech-Roche, Glenmark, GSK, LETI, Lilly, Menarini, MSD, Mitsubishi-Tanabe, NOUCOR/Uriach Group, Novartis, OPTINOSE, Proctor & Gamble, Regeneron Pharmaceuticals Inc., Sanofi-Genzyme, UCB Pharma, and Viatris/MEDA Pharma. DP: David Price has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; consultancy agreements with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Chiesi, Viatris, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Viatris, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme, Teva Pharmaceuticals; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Novartis, Teva Pharmaceuticals; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. SQ: Speaking, lecture and consulting fees from Allergy Therapeutics, ALK, AstraZeneca, Chiesi, GSK, Mundipharma, Novartis, Sanofi-Genzyme, and Teva. SR: Has acted as a consultant and/or advisory board member for Sanofi, GSK, and Novartis. The department of Otorhinolaryngology and Head/Neck Surgery of the Amsterdam UMC has received research funding from Sanofi, GSK, and Novartis. ST-S: Reports consultancies for ALK-Abelló, AstraZeneca, ERT, GSK, Novartis, Sanofi, and Roche Products outside the submitted work, as well as grant of GSK outside the submitted work. BS: Lyra Therapeutics: consultant, Stryker: Consultant, Neurent: consultant, MCSP: consultant and American Rhinologic Society: VP of Development and Strategy. JT: Jacob Thyssen previously as an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, Pfizer, Regeneron, and Sanofi-Genzyme; a speaker for AbbVie, Almirall, Eli Lilly & Co, Pfizer, Regeneron, and Sanofi Genzyme; and received research grants from Pfizer, Regeneron, and Sanofi Genzyme. He currently holds a shared position between the university and LEO Pharma where he receives a salary and holds stock options. UW: Consulting for VIATRIS, lecture fees from ALK Germany. PH: Is recipient of consultancy/lecture fees or unrestricted research grants from Sanofi/Regeneron, Novartis, GSK, Medtronic and Viatris. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Scadding, Gray, Conti, McDonald, Backer, Scadding, Bernal-Sprekelsen, De Corso, Diamant, Hopkins, Jesenak, Johansen, Kappen, Mullol, Price, Quirce, Reitsma, Toppila-Salmi, Senior, Thyssen, Wahn and Hellings.)

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., (© 2023 The Authors. Otolaryngology‐Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology‐Head and Neck Surgery Foundation.)

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic inflammatory disease of the nose and paranasal sinus cavities that significantly affects well-being and social function, particularly in young adults and middle-aged populations. CRSwNP is a common health condition in the Western world, with an estimated prevalence of 3%. Despite worldwide evidence-based treatment guidelines such as the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) chronic rhinosinusitis (CRS) pocket guide, a significant number of patients remain undiagnosed and/or uncontrolled with repeated oral corticosteroids (OCS) treatments and/or (multiple) endoscopic sinus surgeries (ESS)., Competing Interests: DMC: Serves as academic manager at the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) and as review editor at Frontiers in Allergy, rhinology section. GKS: Honoraria for articles, speaker and advisory boards: ALK, Bayer, GlaxoSmithKline, Haleon, Noucor, Sanofi-Regeneron, and Viatris. Chair of BSACI rhinitis guidelines, Scientific Chief Editor, Rhinology Section of Frontiers in Allergy, Board member and AR lead for EUFOREA, and Chair/member Data Monitoring Committees on SLIT for ALK. MM: Honoraria for speaker and advisory boards: Sanofi, Glenmark, P&G, Immunotek, Cipla, Thermo-Scientific, Lancet laboratories. EUFOREA expert panel member. PWH: Is recipient of consultancy/lecture fees or unrestricted research grants from Sanofi/Regeneron, Novartis, GSK, Medtronic and Viatris. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Teeling, Djouder, Laurens, Preyra, Shire, Van Staeyen, Conti, Scadding and Hellings.)

Background: To date, research on preoperative patient selection has mainly focused on patient personality, with body dysmorphic disorder (BDD) being the most studied. Despite the many reasons for not planning a rhinoplasty, no data are available on the nature of these reasons. Our aim is to conduct a multicentre international observational study on the reasons for rejection of patients seeking rhinoplasty in 5 tertiary rhinoplasty care centres., Methods: Surgeons documented the reasons for not scheduling a rhinoplasty in consecutive patients who consulted them between January 2021 and March 2022 using a predefined list of reasons for rejection. Surgeons were also asked to report on the patient attitudes after rejection, and about the advice given to patients in the event of refusal., Results: 186 patients seeking rhinoplasty were included. Multiple reasons for rejection were present in 76% of patients, with a mean of 2.9 reasons for rejection per patient. Overall, patient-related factors were most frequently associated with rejection (64.3%), followed by nose-related factors (28.4%), surgeon-related factors (6.0 %) and surgery-related factors (1.3%). The presence of severe BDD symptoms was reported in only 11.3% of the rejected patients. Patients rejected for rhinoplasty were advised to reconsider the surgery (32.8 %) and/or were referred to another surgeon (32.8%). No further action was taken in 39.8% of the patients. Of the patients who were rejected, most had a neutral (39.2 %) or positive (37.1 %) attitude in relation to the lack of rhinoplasty planning., Conclusion: This study highlights the variety of reasons for which patients seeking rhinoplasty are not considered good candidates for a rhinoplasty, with patient-related factors being more prevalent than nose-related and other factors. Increasing awareness on the impact of adequate patient selection for rhinoplasty may contribute to better outcomes in rhinoplasty.

Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma., Competing Interests: GKS: Honoraria for articles, speaker and advisory boards: ALK, Bayer, GlaxoSmithKline, Haleon, Noucor, Sanofi- Regeneron, and Viatris. Chair of BSACI rhinitis guidelines, Scientific Chief Editor, Rhinology Section of Frontiers in Allergy, Board member and AR lead for EUFOREA, and Chair/ member Data Monitoring Committees on SLIT for ALK. MM: Honoraria for speaker and advisory boards: Sanofi, Glenmark, P&G, Immunotek, Cipla, Thermo-Scientific, Lancet laboratories. EUFOREA expert panel member. VB: Is recipient of consultancy/llecture fees or unrestricted research grants from Sanofi/Regeneron, Novartis, GSK, AZ, ALK Abello and BORK-npc. GS: GWS has received speakers fees from ALK-Abello, Meda and Glenpharm, and received honoraria for participation in an advisory group from ALK-Abello. MB-S: Speaker honorarium from GSK Spain, Olympus Europe, Viatris Spain, Sanofi Spain. Editor-in-Chief Eur.Arch.ORL-HNS. ED: Received fee for consultation, speaker activity, advisory board by Sanofi, Regeneron, GSK, Novartis and Astrazeneca. ZD: In the past 3 years, ZD received speaker or consultant honoraria and/or served on advisory boards at: Antabio, Foresee Pharmaceuticals, GlaxoSmithKline, Hippo-Dx, QPS-Netherlands, Sanofi-Genzyme-Regeneron, and Springer Media all outside the submitted work. From 2012 to 2020 she acted as Director Respiratory & Allergy Research at QPS-Netherlands; in 2019-ongoing, QPS-Netherlands received a European grant from ERA4TB and funding Foresee Pharmaceuticals for early respiratory studies. CH: Ad boards - GSK, Sanofi Regeneron, Lilly. MJ: Has received consulting fees (ALK-Abello, Stallergenes-Greer, Takeda, Zentiva); honoraria for lectures, presentations (ALK-Abello, Stallergenes-Greer, Takeda, Zentiva, Mundipharma, AstraZeneca, SOBI, Chiesi, CSL Behring, Novartis, Benela, Pfizer, Viatris); support for attending meetings and/or travel (ALK-Abello, Stallergenes-Greer, Takeda, Novartis, Sanofi Pasteur) and honoraria for participation on Advisory Boards (ALK-Abello, Stallergenes-Greer, Chiesi, Novartis, SOBI, Pfizer, Sanofi Genzyme/Pasteur). JK: Jasper Kappen reports grants and/or personal fees from ALK, Chiesi, GSK, Novartis, AstraZeneca, Sanofi, Boerhinger, Teva, Viatris, Stallergen, Abbot, all outside the submitted work. JM: Joaquim Mullol is or has been member of national and international scientific advisory boards, consulting, received fees for lectures, and grants for research projects or clinical trials from AstraZeneca, Genentech-Roche, GSK, LETI, Lilly, Menarini, MSD, Mitsubishi-Tanabe, NOUCOR/Uriach Group, Novartis, OPTINOSE, Proctor & Gamble, Regeneron Pharmaceuticals Inc., Sanofi-Genzyme, UCB Pharma, and Viatris/MEDA Pharma. DP: David Price has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; consultancy agreements with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Chiesi, Viatris, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Viatris, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme, Teva Pharmaceuticals; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Novartis, Teva Pharmaceuticals; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. SQ: Speaking, lecture and consulting fees from Allergy Therapeutics, ALK, AstraZeneca, Chiesi, GSK, Mundipharma, Novartis, Sanofi-Genzyme, and Teva. SR: Has acted as a consultant and/or advisory board member for Sanofi, GSK, and Novartis. The department of Otorhinolaryngology and Head/Neck Surgery of the Amsterdam UMC has received research funding from Sanofi, GSK, and Novartis. SS: Reports consultancies for ALK-Abelló, AstraZeneca, ERT, GSK, Novartis, Sanofi, and Roche Products outside the submitted work, as well as grant of GSK outside the submitted work. BS: Lyra Therapeutics: consultant, Stryker: Consultant, Neurent: consultant, MCSP: consultant and American Rhinologic Society: VP of Development and Strategy. JT: Jacob Thyssen previously as an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, Pfizer, Regeneron, and Sanofi-Genzyme; a speaker for AbbVie, Almirall, Eli Lilly & Co, Pfizer, Regeneron, and Sanofi Genzyme; and received research grants from Pfizer, Regeneron, and Sanofi Genzyme. He currently holds a shared position between the university and LEO Pharma where he receives a salary and holds stock options. UW: Consulting for VIATRIS, lecture fees from ALK Germany. PH: Is recipient of consultancy/llecture fees or unrestricted research grants from Sanofi/Regeneron, Novartis, GSK, Medtronic and Viatris. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Scadding, McDonald, Backer, Scadding, Bernal-Sprekelsen, Conti, De Corso, Diamant, Gray, Hopkins, Jesenak, Johansen, Kappen, Mullol, Price, Quirce, Reitsma, Salmi, Senior, Thyssen, Wahn and Hellings.)

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.

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., Competing Interests: HPW: Is recipient of consultancy/lecture fees or unrestricted research grants from Sanofi/Regeneron, Novartis, GSK, Medtronic and Viatris. LS: Honoraria by Allergopharma, DBV Technologies, Sanofi-Aventis, Leti, Nutricia. AD-Boards: Leo-Pharma, GSK, Sanofi-Aventis. SGK: Honoraria for articles, speaker and advisory boards: ALK, Bayer, GlaxoSmithKline, Haleon, Noucor, Sanofi- Regeneron, and Viatris. Chair of BSACI rhinitis guidelines, Scientific Chief Editor, Rhinology Section of Frontiers in Allergy, Board member and AR lead for EUFOREA, and Chair/ member Data Monitoring Committees on SLIT for ALK. BV: Is recipient of consultancy/lecture fees or unrestricted research grants from Sanofi/Regeneron, Novartis, GSK, AZ, ALK Abello and BORK-npc. CAM: Grants, speaker honoraria, consultancy or advisory fees and/or research support all via Technical University of Munich from Allergopharma, ALK Abello, AstraZeneca, Bencard/Allergen Therapeutics, Immunetek, GSK, Novartis, LETI, Roche, Zeller, Sanofi Genzyme, Regeneron, European Institute of Technology, Federal German Ministery of Research and Education. Travel support by EUFOREA, EAACI and DGAKI. DCE: Lecture fees and participations in experts board meeting of GSK, Novartis, Sanofi, Regeneron, Astrazeneca. DR: No conflict of interest to declare related to this work, but declares a general COI arising out of consulting pharmaceutical companies (GlaxoSmithKline, Sanofi, Kymab and Synairgen) and honoraria for speaking (GlaxoSmithKline). FW: The department of Otorhinolaryngology of the Amsterdam University Medical centre, location AMC received grants for research in Rhinology from ALK, AllergyTherapeutics, Novartis, EU, GSK, MYLAN, Sanofi-Aventis, and Zon-MW. WF: Received consultation and/or speaker fees from Dianosic, GSK, Novartis and Sanofi-Aventis/Regeneron. GP: Has participated in advisory boards and received speaker fees from ALK-Abelló, Argenx, AstraZeneca, Genentech, GSK, Novartis, Regeneron, Roche, Sanofi Genzyme, and Stallergenes- Greer. HJK: Research consultant for Sanofi, Regeneron, GlaxoSmithKline, and AstraZeneca. HLG: Has received grant funding, participated in advisory boards and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Hoffmann la Roche, GlaxoSmithKline, Novartis, Theravance, Evelo Biosciences, Sanofi, and Teva; he has received grants from MedImmune, Novartis UK, Roche/ Genentech Inc, and Glaxo Smith Kline, Amgen, Genentech/Hoffman la Roche, Astra Zeneca, MedImmune, Glaxo Smith Kline, Aerocrine and Vitalograph; he has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Napp Pharmaceuticals; he has also taken part in asthma clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Hoffmann la Roche, and GlaxoSmithKline for which his institution received remuneration; he is the Academic Lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma which involves industrial partnerships with a number of pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffmann la Roche, and Janssen. JM: Declares a general COI arising out of consulting pharmaceutical companies (BerlinChemie Menarini, AstraZeneca, Chiesi, Stallergenes-Greer, ALK, Novartis) and honoraria for speaking (BerlinChemie Menarini, Chiesi, Stallergenes-Greer, Sanofi, Takeda, Novartis). ME: Has received lecture and/or advisory board fees from Airsonett, ALK, AstraZeneca, Chiesi, Novartis and Sanofi outside the submitted work. MJ: Grants from Mylan Pharma, Noucor/Uriach Group, and GSK. Personal and advisory board fees from Sanofi-Genzyme & Regeneron, Novartis, Mylan Pharma, Noucor/Uriach Group, Mitsubishi-Tanabe, Menarini, UCB, AstraZeneca, GSK, and MSD. RS: Declares a general COI arising out of consulting pharmaceutical companies and/or advisory boards (GlaxoSmithKline, Sanofi, Novartis). SG: Have received speaker fees from ALK-Abello, Meda, Glenmark and funding to attend a conference from GSK and Mylan/Meda. WU: Has received honoraria for advising and lecturing from Viatris, Stallergenes, and ALK. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Hellings, Lau, Scadding, Bjermer, Backer, Chaker, Conti, De Corso, Diamant, Djukanovic, Fokkens, Gevaert, Gray, Han, Heaney, Hoffmann, Jesenak, Johansen, Kumaran, McDonald, Melén, Mullol, Reitsma, Ryan, Scadding, Schmid-Grendelmeier, Teeling, Odemyr and Wahn.)

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.

Background: Disruption of the nasal epithelial barrier is believed to play a role in Coronavirus Disease-2019 (COVID-19) outcomes. Fluticasone propionate has been shown to restore the nasal epithelial barrier in allergic rhinitis to the level of healthy controls. The therapeutic potential of nasal steroid sprays in COVID-19 has recently been reported. However, further insight into the mode of action is warranted., Objectives: To explore the in vitro mechanisms of the preventive potential of fluticasone propionate in SARS-CoV-2 infection., Methods: Human air liquid interface cultures of Calu-3 cells and primary nasal epithelial cells isolated from healthy donors were used to investigate the preventive effect of fluticasone propionate on SARS-CoV-2 induced barrier disruption, virus replication and ACE2 expression., Results: 48 hours pre-treatment with fluticasone propionate prevented the SARS-CoV-2 induced increase in fluorescein isothiocyanate-dextran 4 kDa permeability and reduced infection with SARS-CoV-2. Pre-treatment with fluticasone propionate also decreased ACE2 expression in SARS-CoV-2 infected Calu-3 cells., Conclusion: Fluticasone propionate pre-treatment prevented SARS-CoV-2 increased epithelial permeability, reduced ACE2 expression and SARS-CoV-2 infection, underscoring the therapeutic potential of fluticasone propionate in the context of COVID-19.

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

Background: The aetiology of chronic rhinosinusitis (CRS) is multifactorial with a complex interplay between environmental, microbial endogenous and genetic factors. The impact of outdoor air pollution on prevalence or severity of CRS remains largely unknown., Methods: Real-life geolocation data (2017-2018, Belgium) from 278 CRS patients (2576 health records) using the mySinusitisCoach mobile application were analysed to calculate the patients' individual exposure to outdoor air pollutants (ozone (O 3 ), black carbon (BC), nitrogen dioxide (NO 2 ) and particulate matter with diameter < 2.5 μm (PM 2.5 )) and to associate these pollutants with the patients' sinus related symptoms measured at multiple occasions by visual analogue scale (VAS)., Results: The adjusted seasonal model for the spring-summer (n = 1000 health entries, N = 83 patients) population revealed an increase of 6.07 (p < 0.0001) in overall CRS symptom scoring for an interquartile range (IQR) increase in exposure to O 3 (26.9 μg/m 3 ). An increase of 1.69 (p = 0.05) in total CRS symptom scoring was observed for an IQR increase of PM 2.5 (7.1 µg/m 3 ) exposure. Sex-stratified analysis in the spring-summer population showed significant interaction between air pollution and sex with male patients having higher total CRS symptom scores for an IQR increase in exposure to PM 2.5 (3.52, p = 0.001), and O 3 (8.33, p < 0.0001), while no significant association with symptom severity was seen in the female patients. In the analysis stratified by comorbid asthma, CRS patients with comorbid asthma had higher total CRS symptoms for an IQR increase in exposure to PM 2.5 (2.58, p = 0.04) and O 3 (7.72, p < 0.0001) while the patients without comorbid asthma had no significant symptom increases., Conclusion: Exposure to outdoor air pollution is associated with increased symptom severity in CRS patients. The extent to which CRS patients are sensitive to outdoor air pollution exposure varies per season and depends on their sex and comorbid asthma status. mHealth technology has the potential to reveal novel insights on the patients' exposome and disease severity in the real-life situation., (© 2022. The Author(s).)

The aim of this paper is to review intranasal trigeminal system and associated reflexes. The literature survey was performed on PubMed, ProQuest Central database of Kirikkale University and Google Scholar. The intranasal trigeminal system and associated reflexes play an important role in humans in both health and disease, including in rhinitis of non-allergic and mixed type. The intranasal trigeminal nerve provides sensory perception to the lining of the nose, supplying information on how patent the nasal airway is and responding to various chemical signals. The reflexes known to exist within the intranasal trigeminal system are nasobronchial reflex, trigemino-cardiac reflex, nasogastric reflex, and nasal cycle. The intranasal trigeminal system and its reflexes play a vital role in normal human physiology. Alterations in how this system operates may underlie multiple forms of rhinitis and more research is needed to fully understand the mechanisms involved.

Mepolizumab improves quality of life and reduces activity impairments in patients with CRSwNP.

The allergen provocation test is an established model of allergic airway diseases, including asthma and allergic rhinitis, allowing the study of allergen-induced changes in respiratory physiology and inflammatory mechanisms in sensitised individuals as well as their associations. In the upper airways, allergen challenge is focused on the clinical and pathophysiological sequelae of the early allergic response, and is applied both as a diagnostic tool and in research settings. In contrast, bronchial allergen challenge has almost exclusively served as a research tool in specialised research settings with a focus on the late asthmatic response and the underlying type 2 inflammation. The allergen-induced late asthmatic response is also characterised by prolonged airway narrowing, increased nonspecific airway hyperresponsiveness and features of airway remodelling including the small airways, and hence allows the study of several key mechanisms and features of asthma. In line with these characteristics, allergen challenge has served as a valued tool to study the cross-talk of the upper and lower airways and in proof-of-mechanism studies of drug development. In recent years, several new insights into respiratory phenotypes and endotypes including the involvement of the upper and small airways, innovative biomarker sampling methods and detection techniques, refined lung function testing as well as targeted treatment options further shaped the applicability of the allergen provocation test in precision medicine. These topics, along with descriptions of subject populations and safety, in line with the updated Global Initiative for Asthma 2021 document, will be addressed in this review., Competing Interests: G.M. Gauvreau declares grants from AstraZeneca, Biohaven, Novartis and Genentech; consulting fees from AstraZeneca, Biohaven, Novartis, Sterna Biologicals and Certior Consulting; and payment or honoraria from AstraZeneca, Genzyme and Genentech, all in the 36 months prior to manuscript submission. B.E. Davis declares no competing interests. G. Scadding declares support from ALK-Abelló (provision of active and placebo medication for the GRASS clinical trial referenced in the article) and the Immune Tolerance Network (NIAID, NIH, USA; sponsor of the GRASS clinical trial) related to the present manuscript; as well as payment for lectures from ALK-Abelló in 2020 and 2021; and support from GlaxoSmithKline for attendance at the 2021 European Academy of Allergy and Clinical Immunology meeting. L-P. Boulet declares research grants for participation in multicentre studies or research projects proposed by the investigator from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi-Regeneron; royalties from UptoDate and Taylor & Francis; lecture fees from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck and Sanofi, all in the 36 months prior to manuscript submission; and the following unpaid contributions: Chair of the Global Initiative for Asthma (GINA) Board of Directors; President of the Global Asthma Organisation (Interasma); Member of the Canadian Thoracic Society Respiratory Guidelines Committee; and Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. L. Bjermer declares no competing interests. A. Chaker declares grants or contracts, via Technical University Munich, from EIT Health (European Institute of Technology), BMBF (German Federal Ministry of Education and Research), AstraZeneca, Sanofi-Genzyme, Roche, GlaxoSmithKline and ALK-Abelló; payments or honoraria, via Technical University Munich, from ALK-Abelló, Allergopharma, AstraZeneca, GlaxoSmithKline, Immunotek, Novartis, Regeneron, Sanofi-Genzyme, Leti, Zeller and Bencard; travel reimbursement to attend European Academy of Allergy and Clinical Immunology meetings (2018 and 2021 from the European Academy of Allergy and Clinical Immunology; 2019 from ALK-Abelló); patents, via Technical University Munich, relating to allergen-specific immunotherapy and treatment of SARS-CoV-2 infection; participation, via Technical University Munich, on a data safety monitoring board or advisory board for ALK-Abelló, Allergopharma, AstraZeneca, GlaxoSmithKline, Immunotek, Novartis, Regeneron and Sanofi-Genzyme; and the following unpaid roles: Past Chair of the Allergy, Clinical Immunology and Environmental Medicine Section of the German ENT Society; board member at large of the German Allergy Society (DGAKI); scientific advisor/board member to the German Society for Applied Allergy (AeDA); board member of the Allergen Immuntherapy Interest Group, European Academy of Allergy and Clinical Immunology. D.W. Cockcroft reports the following research grants in the 36 months prior to manuscript submission: research grant Dept of Medicine University of Saskatchewan (Effect of tiotropium on airway response to allergen); Canadian Society of Allergy and Clinical Immunology (The effect of deep inhalation on mannitol responsiveness); AstraZeneca (A phase 2a double blind randomised parallel group placebo controlled multicentre study to evaluate the effect of AZD8154 administered via nebuliser once daily on allergen-induced inflammation in subjects with mild allergic asthma challenged with inhaled allergen); AllerGen NCE (Methacholine challenge comparison of a jet nebuliser and vibrating mesh nebuliser); Novartis (Inhaled CSJ117 in adult asthmatics with mild atopic asthma). B. Dahlén declares payment to their institution in 2004 for a clinical trial by AstraZeneca, related to the present work; and grants to support the Karolinska Severe Asthma Centre from GlaxoSmithKline and Novartis; consulting fees from Teva, AstraZeneca and Sanofi; and payment for lectures from AstraZeneca and Sanofi, all in the 36 months prior to manuscript submission. W. Fokkens declares grants to their institution from ALK, Mylan, Allergy Therapeutics, GlaxoSmithKline, Sanofi, Novartis and Chordate; consulting fees from Sanofi and Bioinspire; payment or honoraria from Sanofi, GlaxoSmithKline and Novartis; and participation on a data safety monitoring board or advisory board for Lyra, Sanofi and GlaxoSmithKline, all in the 36 months prior to manuscript submission; and that they are Secretary General of the European Rhinologic Society. P. Hellings declares no competing interests. N. Lazarinis declares no competing interests. P.M. O'Byrne reports grants from AstraZeneca, GlaxoSmithKline, Biohaven, Merck, Bayer and Novartis; consulting fees from AstraZeneca, Covis, GlaxoSmithKline, Amgen and Novartis; and payment or honoraria from AstraZeneca, Covis and Novartis, all in the 36 months prior to manuscript submission; and that they are a Section Editor of the European Respiratory Journal. E. Tufvesson declares no competing interests. S. Quirce declares consulting fees and payment or honoraria from GlaxoSmithKline, Sanofi and AstraZeneca; and payment or honoraria from Novartis, Chiesi, Mundipharma and Teva, all in the 36 months prior to manuscript submission. M. Van Maaren declares payment or honoraria from ALK-Abelló, Takeda and CSL Behring, in the 36 months prior to manuscript submission; and an unpaid role as Chairman of the Dutch Society of Allergology and Clinical Immunology since 2020. F. H. de Jongh declares an unpaid role as European Respiratory Society Assessment Director. Z. Diamant reports that until May 2020 they worked as Research Director Respiratory & Allergy at a CRO (QPS-NL), which received funding from biotech and several pharma companies for conduct of phase I–II clinical studies (drug development); and declares consulting fees from ALK-Abelló, AstraZeneca, Antabio, GlaxoSmithKline, HAL Allergy, QPS-NL and Sanofi-Genzyme; and payment or honoraria from BMR, Boehringer Ingelheim, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Merck Sharp & Dohme and Sanofi-Genzyme, all in the 36 months prior to manuscript submission; and unpaid roles as the European Academy of Allergy and Clinical Immunology Asthma Section Chair (2017–2019) and EUFOREA Asthma Expert Panel Chair (since 2020)., (Copyright ©The authors 2022.)

Background: Type 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and differences in experiences and perspectives of the current management of patients with comorbid Type 2 inflammatory diseases., Aims: To improve insight into the common and organ-specific needs of patients with Type 2 inflammation and comorbidities, allowing the formulation of recommendations to better address these needs in the future., Methodology: This qualitative study was conducted between July 2021 and December 2021 using semi-structured face-to-face or telephone interviews with patients suffering from year-long severe chronic Type 2 inflammation and at least one co-morbid inflammatory condition. Seven participating academic centers in Europe interviewed asthma (Copenhagen and Leuven), CRSwNP (London, Amsterdam and Crete) and/or AD (Oldenburg and Zurich) patients on patient characteristics, disease severity, shortcomings of current care pathways and suggestions for improvement of care. Transcripts were analyzed using an inductive thematic analysis approach., Results: Eighty-one patients with severe Type 2 inflammation and comorbidities were interviewed. Similar needs were recognized by patients with Type 2 inflammation, with both a lack of coordination in care and a lack of a real cure reported as being most frustrating. However, several needs are specific to asthma, CRSwNP and AD. Suggestions for improvement of care were generic across diseases, such as the implementation of a multidisciplinary approach, the improved facilitation of access to better treatments, the increase of general awareness on disease burden, and better educational programs for healthcare providers and patients. Of note, patients with CRSwNP also stated the need for alternatives to sinus surgery, whereas patients with asthma requested better medical care to prevent exacerbations and patients with AD would warmly welcome the reimbursement of emollients., Conclusion: Patients with asthma, CRSwNP and AD have shared unmet needs that need to be addressed by physicians, the academic community and health policy makers. This survey provides unique recommendations made by patients for the implementation of better care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 De Prins, Raap, Mueller, Schmid-Grendelmeier, Haase, Backer, Fokkens, Benoist, Prokopakis, Hopkins, Claeys, Teeling, Cypers, Cools, Bjermer, Diamant, Wahn, Scadding, Bachert, Patel, Van Staeyen and Hellings.)

Background: European patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have had only limited occasions to unite to have their voices heard, hence missing the opportunity to contribute to the improvement of CRSwNP care. Aims: To identify unmet needs in CRSwNP from the perspective of CRSwNP patients from the Patient Advisory Board (PAB) of the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA). Methodology: Semi-structured interviews were conducted individually with 15 European patients with CRSwNP and with a disease history of more than 2 years. Patients shared their burden of the disease and frustrations related to CRSwNP care, experiences with key pillars of current treatment options, shortcomings of the current care pathways and recommendations for improvement of care. A panel of 30 members of the Patient Advisory Board reviewed the interview report and provided further input during 2 virtual meetings. Results: CRSwNP patients indicated the need for greater awareness from society and physicians of the disease burden with impact on social function and well-being. Along with a loss of ability to smell and the continuous presence of secretions in the nose, most patients reported poor sleep quality and psychological impact as the most bothersome symptoms. Patients' frustrations relate primarily to the underestimation of the disease burden, the lack of coordination of care and the limited treatment options available to them. Treatment options with oral corticosteroids and/or sinus surgery both have positive and negative aspects, including the lack of long-lasting efficacy. Better coordination of care, more patient-centered care, greater public awareness, increases in research on the disease mechanisms and better therapeutic options would be warmly welcomed by CRSwNP patients. Conclusions: This statement of the EUFOREA Patient Advisory Board on CRSwNP provides novel insights on the underestimation of the burden of CRSwNP and shortcomings of current care. Multiple recommendations made by the patients can underpin action plans for implementation of better care for CRSwNP among all physicians treating patients with this disabling disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Claeys, Teeling, Legrand, Poppe, Verschueren, De Prins, Cools, Cypers, Fokkens, Hopkins and Hellings.)

Background: Chronic rhinosinusitis (CRS) is a frequent condition that is treated by endoscopic sinus surgery (ESS) when medical treatment fails. Irritating or sensitizing airborne agents can contribute to uncontrolled CRS. A prior study showed a linear correlation between occupational exposure and the number of ESS., Methods: In this cross-sectional study we tested the hypothesis that occupational exposure is a risk for undergoing ESS. We sent questionnaires enquiring occupational exposure in patients with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). An expert assessed blindly the reported work exposures to inhaled agents. The relationship between occupational exposure on undergoing ESS was analysed., Results: Among all patients who underwent ESS (n=343), 30% reported a relevant occupational exposure, which is significantly higher than the 4.8% found among CRS patients that underwent no prior sinus surgery (n=21). Besides occupational exposure, self-reported doctor-diagnosed asthma were independent variables contributing to the chance of undergoing ESS., Conclusion: In our study we confirm occupational exposure as a risk factor for uncontrolled CRS, if defined by undergoing ESS. In CRS patients with uncontrolled symptoms, despite maximal conservative therapy, the clinician should explore the possible contribution of occupational exposure.

Background: Among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), randomized clinical trials (RCTs) of biologics, such as anti-interleukin-4/interleukin-13 (dupilumab) and anti-immunoglobulin E (omalizumab), have demonstrated efficacy compared with intranasal corticosteroids (INCS). However, no head-to-head RCTs exist between biologics., Objective: To perform an indirect treatment comparison (ITC) of the efficacy of biologics plus INCS versus placebo (INCS) as a common comparator., Methods: Embase, MEDLINE, and Cochrane were searched for RCTs of biologics in CRSwNP. Bucher ITCs were performed for outcomes at week 24: nasal polyp score (NPS) (range, 0-8), nasal congestion (NC) (range, 0-3), loss of smell (range, 0-3), University of Pennsylvania Smell Identification Test (range, 0-40), total symptom score (range, 0-12), 22-item sinonasal outcome test (range, 0-110), and responder analyses based on NPS or NC improvement of 1 point or greater., Results: Assessment of trial design, baseline characteristics, and outcome measures suggested that ITC was feasible with four phase 3 RCTs: dupilumab SINUS-24 and SINUS-52 (NCT02912468/NCT02898454) and omalizumab POLYP 1 and POLYP 2 (NCT03280550/NCT03280537). In the intent-to-treat population, dupilumab had significantly greater improvements from baseline to week 24 versus omalizumab across key outcomes: NPS (least squares mean difference [95% confidence interval], -1.04 [-1.63 to -0.44]), NC (-0.35 [-0.60 to -0.11]), loss of smell (-0.66 [-0.90 to -0.42]), University of Pennsylvania Smell Identification Test (6.70 [4.67-8.73]), and total symptom score (-1.18 [-1.95 to -0.41]). Improvement in the 22-item sinonasal outcome test was greater in dupilumab versus omalizumab but was not statistically significant. Dupilumab patients were significantly more likely to achieve ≥1-point improvement in NPS (odds ratio [95% CI] = 3.58 [1.82-7.04]) and NC (2.13 [1.12-4.04]) versus omalizumab., Conclusions: Although ITCs have limitations, these results demonstrated that dupilumab had consistently greater improvements in key CRSwNP outcomes versus omalizumab at week 24., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery., Methodology: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153)., Results: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test., Conclusions: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.

Background: The majority of patients with uncontrolled severe CRSwNP, asthma and atopic dermatitis share a similar T helper 2 type inflammation linked to their underlying phenotype. This discovery has triggered new research around treatments targeting specific cytokines driving inflammation in CRSwNP like IL-4, IL-13, IL-5 and IgE. Biologicals are increasingly tested as additional tre- atment for patients suffering from severe chronic rhinosinusitis with nasal polyps (CRSwNP). Their efficacy has been demonstrated in multiple studies. All studies differ in terms of baseline characteristics of included patients and outcome parameters analysed., Aims: A comparative analysis of the efficacy of reported biologicals for CRSwNP based on the published data for phase 2 and 3 studies. The aim was to provide a comprehensive overview across the different biologicals and outcome parameters., Methods: In a first step we critically selected out of all available phase 2 and 3 clinical trials the ones containing the most rigorous and compatible study designs. Meaning studies that comply with a need for a clear definition of CRSwNP, at least two administra- tion doses, comparable timeframes and the same outcome parameters studied. This assessment was performed using a PRISMA search. We retained 7 studies with significant data for dupilumab, mepolizumab and omalizumab. In a second step the effect-sizes of treatment with those biologicals were compared for the most important outcome parameters both patient relevant (nasal con- gestion, smell loss and SNOT-22 scores) and patient irrelevant (CT scan Lund-Mackay, smell test and nasal polyp scores). Therapy duration of 16 to 25 weeks was chosen for evaluation of efficacy., Results: A direct comparison of efficacy between dupilumab, mepolizumab and omalizumab is challenging given differences in inclusion criteria, outcome parameters and time-points of analyses. We have been able to conclude that effect sizes of dupilumab, mepolizumab and omalizumab seem large enough to reflect a major reduction in symptom burden as experienced by patients suffering from refractory CRSwNP. The effect size of dupilumab on both patient relevant and patient irrelevant parameters of smell loss are clearly significant and reflect the clinical experience of major reduction of smell impairment in treated patients., Conclusion: Despite the heterogeneity of protocols, dosages and time-points of analyses of biological trials in CRSwNP, this over- view highlights outcomes of biological treatment in CRSwNP in a comprehensive way. Real-life registries, comparative trials and/ or endotype-driven treatment plans are needed to provide the answers to the multiple questions that are still open today.

Purpose of Review: A multidisciplinary approach is regarded as the best practice for many chronic diseases, such as cancer and asthma, with well-documented value. There is also evidence that it may be beneficial to patients with chronic rhinosinusitis (CRS) and/or allergic airway disease presenting to tertiary referral centres. We discuss here whether and how organizing this kind of healthcare transition into a more integrated care pathway would benefit severe chronic upper airways disease (SCUAD) management., Recent Findings: Based on a recent related EUFOREA panel discussion, literature search, and review of the best overseas practices, an appropriate implementation strategy of multidisciplinary care and its potential results are presented. Organizational principles, hurdles, and challenges of the process, as well as envisaged solutions and results, are being reported. The efficiency of care and the quality control assessment are concepts that are currently gaining importance. At the same time, novel treatment options based on molecular and precision medicine advancements, such as biologics, are being increasingly prescribed. Appropriately organized multidisciplinary care teams can adapt to new demands, data, and discoveries to assure maximum benefit for both patients and healthcare professionals.

I., Executive Summary: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document., Methods: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary., Results: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided., Conclusion: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS., (© 2021 ARS-AAOA, LLC.)

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Allergic rhinitis induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies., Objective: We sought to assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus:Dermatophagoides farinae 1:1 extract in adolescents (aged ≥12) and adults with moderate to severe HDM-induced allergic rhinitis., Methods: In a phase III, international, double-blind, placebo-controlled, randomized clinical trial, participants received approximately 12 months of treatment with placebo or the 300 IR tablet. The primary end point was the average total combined score during 4 weeks at the end of the treatment period., Results: A total of 1607 participants were randomized, and 1476 (including 555 [37.6%] with concomitant mild controlled asthma at inclusion) comprised the full analysis set. Over the primary evaluation period, the least squares mean average total combined score in the 300 IR group (3.62) was significantly lower (P < .0001) than in the placebo group (4.35), with a relative least squares mean difference of -16.9% (95% CI, -24.0% to -9.2%). All prespecified secondary end points were consistently improved in the 300 IR group, relative to placebo. The 300 IR tablet was generally well tolerated. Treatment-related adverse events (mainly mild or moderate local reactions) were reported for 51.0% of the patients in the 300 IR group and 14.9% in the placebo group., Conclusions: The 300 IR sublingual HDM tablet is an effective, safe treatment for HDM-induced allergic rhinitis., (Copyright © 2020. Published by Elsevier Inc.)

Not available.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis; it is typically characterized by a type 2 inflammatory reaction and by comorbidities, including asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, and allergies. Here, the European Forum for Research and Education in Allergy and Airway Diseases proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinical practice. A rational approach for the treatment of uncontrolled severe CRSwNP is discussed; it consists of evaluating the perspective and risks of surgery and efficacy and adverse events of biologics on the basis of currently available data. Further, possible combinations of surgery and biologics are discussed, and a rationale is provided. Here, it is of importance to adequately counsel the patient about both approaches to enable a decision-making process with an informed patient. Criteria for the selection of a biologic drug are provided, as several biologics for uncontrolled severe CRSwNP will be available in many countries within a short time. Further, suggestions for monitoring of the drug effects that support recognition of responders to the therapy and, subsequently, the decision regarding continuation or discontinuation of the biologic are proposed., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To review the current literature regarding the role of biologics in the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP)., Data Sources: PubMed/MEDLINE, EMBASE, Cochrane Review, ClinicalTrials.gov., Review Methods: We conducted a comprehensive review of the literature on clinical studies investigating the efficacy of emerging biologics in CRSwNP, with a focus on randomized controlled trials., Conclusions: There appears to be promising evidence to support the safety and efficacy of biologics in CRSwNP with and without asthma for select patients. However, additional large-scale randomized studies with longer follow-up are necessary to determine which patients would benefit the most from these novel systemic treatments., Implications for Practice: Chronic rhinosinusitis with nasal polyposis refractory to medical and surgical therapy remains a challenging clinical problem for otolaryngologists. However, emerging biologic therapies may offer a new therapeutic option for such patients with recalcitrant disease.

Background: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users., Methods: The Allergy Diary-MASK-air-mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis., Results: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines., Conclusions: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.

The October 2020 issue of Rhinology is a very interesting edition as it illustrates how world-wide colleagues pave the way for a better future of patients affected by nose and sinus diseases. After the successful launch of EPOS2020 in Spring 2020, the editorial team of Rhinology is proud to present to you the latest and most exciting data in Rhinology research. Getting insight into the complexity and relevance of proteomics in CRS, epithelial-mesenchymal contribution to CRS, zinc levels in nasal and systemic compartment of CRS, nasal biomarkers of CRSwNP that predict recurrence of disease after sinus surgery, and the odor identification test for children, called "U-Sniff", and FID scores (Frequency, Intensity and Duration) scores for epistaxis are all in the 2020 October issue and highly relevant for Rhinology practice. These studies build further on the solid grounds of previous Rhinology research meeting the unmets needs in the field.

The third Rhinology Future Debates was organized by the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) in 2018 in Brussels. Experts from different specialties and countries, alongside patients, health policy makers and industry representatives discussed relevant topics in Rhinology, in an attempt to improve current clinical practices, through implementation of precision medicine, by empowering patients' participation and the use of eHealth tools. The debates which are available on-line (www.rhinology-future.com) dealt with 5 topics in Rhinology: the adoption of allergen-specific immunotherapy (AIT) by implementing change management strategies, the needs and obstacles in care delivery in respiratory diseases, 3D technology in nose and sinus surgery, ambulatory nasal surgery, and clinical evidence for efficacy of biologicals in CRSwNP and asthma. This report summarizes the outcomes of the brainstorming sessions highlighting novel approaches and unmet needs in the field of respiratory diseases by focusing on integrated care pathways.

On March 11th 2020, the World Health Organization (WHO) declared COVID-19 pandemic, with subsequent profound impact on the entire health care system. During the COVID-19 outbreak, activities in the rhinology outpatient clinic and operation rooms are limited to emergency care only. Health care practitioners are faced with the need to perform rhinological and skull base emergency procedures in patients with a positive or unknown COVID-19 status. This article aims to provide recommendations and relevant information for rhinologists, based on the limited amount of (anecdotal) data, to guarantee high-quality patient care and adequate levels of infection prevention in the rhinology clinic.

The April issue of Rhinology includes the Executive Summary of EPOS2020, highlighting the most important up-dates on disease definitions, treatment algorithms and integrated care pathway approaches of CRS. EPOS2020 (1) is the result of major efforts by a team of passionate rhinologists and associate health care providers coming from all corners of the world coordinated by Professors Wytske Fokkens and Valerie Lund. The Executive Summary presented here illustrates the most important graphs for use in daily practice and teaching purposes. In addition, the April issue of Rhinology also brings relevant CRS-related aspects to the attention of the readers of Rhinology.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012(1-3). The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings.

Gerçek yaşamda, çevresel maruziyetlerin de etkilediği rinit ve astım mültimorbidite durumlarında, dijitalleşmiş ve kişiye odaklanan tedaviler için bütünleştirilmiş tedavi yollarının değerlendirilmesi önerilmektedir. Gerçek yaşamdaki bu durum mültisipliner bir yaklaşımla basamaklandırılıp, rehberilerinde ülkelerdeki gereksinimlere göre değiştilmesini gerektirebilir. Allerjik rinitte hem farmakoterapi hem immünoterapi açısından acil yeni yaklaşımlara ihtiyaç olduğu görülmüştür. 3. Aralık 2018'de Paris'te bir toplantı yapılmış ve iki ayrı belge hazırlanmıştır. Bu yayında bunlara ait bir özet sunulup, ülkeye ve sağlık sistemine uygun kullanımın çerçevesi oluşturulmak istenmiştir.

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

Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

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., Competing Interests: Competing interestsGS: Honoraria for articles, speaker and advisory boards: ALK, Astra Zeneca, Brittania Pharmaceuticals, Capnia, Church & Dwight, Circassia, Groupo Uriach, GSK, Meda/Mylan, Merck, MSD, Ono Pharmaceuticals, Oxford Therapeutics, Sanofi-Aventis, UCB. Travel funding: ALK, Bayer, GSK, Meda. Chair of BSACI Rhinitis guidelines, EAACI Ethics Committee, Rhinology & Laryngology Research Fund. Chair of Data Monitoring Board for Acarizax paediatric AR trial. CH: Reimbursed for Advisory Board work for sanofi, Smith and Nephew and speakers bureau for Medtronic. CB: Advisory board of Sanofi, GSK, Novartis, Astra-Zeneca, Mylan and reimbursed for presentations and travel. TVZ: Consultant for Medtronic and 3NT. STS: has acted as paid consultant for ERT and Roche Products. All these are outside the submitted work. All other authors declare that they have no competing interests., (© The Author(s) 2020.)

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients' organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Chronic rhinosinusitis (CRS) significantly affects health-related quality of life (HRQoL). Few multinational observational studies have evaluated the impact of CRS with nasal polyps (CRSwNP) on patients’ HRQoL. This study aimed to assess HRQoL outcomes (including analyses by disease severity and impact of comorbidities and refractory disease) in CRSwNP patients from a large European database., Methodology: Data were analysed from the Global Allergy and Asthma European Network (GALEN) Rhinosinusitis Cohort, including sociodemographic data, patient-reported disease severity (visual analogue scale), and scores on the 36-Item ShortForm Health Survey (SF-36) questionnaire. Differences in mean SF-36 scores were evaluated between patients with CRSwNP and population norms and between subgroups of interest (disease severity, comorbidity, and refractory disease, defined by a history of sinonasal surgery)., Results: Patients with CRSwNP (N = 445) had significantly lower mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores vs population norms, demonstrating that CRSwNP negatively affects HRQoL. The presence of comorbidities affected HRQoL, as shown by significant differences in PCS scores in patients with asthma or non-steroidal antiinflammatory drug-exacerbated respiratory disease, compared with patients without asthma. Patients with moderate-to-severe disease had significantly lower PCS scores than patients with mild disease. Severe disease had a significant impact on MCS score. History of surgery had a clinically meaningful negative effect on HRQoL compared with no history of surgery., Conclusions: CRSwNP patients have significantly lower HRQoL compared with population norms. The impact is greater in patients with greater disease severity, comorbidities, or refractory disease.

The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs.