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1. Dupilumab improves outcomes in patients with chronic rhinosinusitis with nasal polyps irrespective of gender: results from the SINUS‐52 trial

Author: Wytske J Fokkens, Claus Bachert, Claire Hopkins, Osama Marglani, Amy Praestgaard, Scott Nash, Yamo Deniz, Paul J Rowe, Harry Sacks, and Juby A Jacob‐Nara
Subjects: chronic rhinosinusitis, health‐related quality of life, patient‐reported outcomes, post hoc analysis, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Objectives This post hoc analysis assessed disease characteristics and response to dupilumab treatment in male and female patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (SINUS‐52 study; NCT02898454). Methods Patients received dupilumab 300 mg or placebo every 2 weeks for 52 weeks on background intranasal corticosteroids. Efficacy was assessed through Week 52 using nasal polyp score (NPS), nasal congestion/obstruction score, loss of smell score and University of Pennsylvania Smell Identification Test score. Disease‐specific health‐related quality of life (HRQoL) was assessed using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22). Results The analysis included 192 male and 111 female patients. Female patients had higher mean SNOT‐22 total score (56.6 vs. 49.1, P
Published: 2024
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2. Alergijski rinitis in njegov vpliv na astmo (ARIA) – glavni povzetek 2016: Integrirane klinične poti za napovedno medicino v vseh življenjskih obdobjih

Author: Mihaela Zidarn, Nissera Bajrović, Klemen Jenko, Peter Kopač, Mitja Košnik, Natalija Edelbaher, Maja Jošt, Karmen Kramer Vrščaj, Anja Koren Jeverica, Samo Kreft, Nika Lalek, Bojan Madjar, Antonija Poplas-Susič, Irma Rozman Sinur, Tanja Soklič-Košak, Katja Triller, Nadja Triller, Jure Urbančič, Ioana Agache, Claus Bachert, Anna Bedbrook, Giorgio Walter Canonica, Thomas Casale, Alvaro A Cruz, Wytske J Fokkens, Peter W Hellings, Boleslaw Samolinski, and Jean Bousquet
Subjects: alergijski rinitis, astma, integrirana klinična pot, mobilna tehnologija, bolezni dihalnih poti, Medicine
Abstract: Pobudo »Alergijski rinitis in njegov vpliv na astmo« – (angl. Allergic Rhinitis and its Impact on Asthma, ARIA) – so leta 1999 ustanovili na delavnici Svetovne zdravstvene organizacije – World Health Organization (WHO). Njeni prvotni cilji so bili: 1. predlagati novo klasifikacijo alergijskega rinitisa, 2. spodbujati koncept večobolevnosti pri astmi in rinitisu ter 3. skupaj z vsemi deležniki razviti smernice, namenjene globalni uporabi v vseh državah in vsem skupinam bolnikov. Pobuda ARIA se uporablja v 70 državah, trenutno pa se osredinja na uporabo novih tehnologij za individualizirano in napovedno medicino. Mreža MASK – nadzorna mreža MACVIA (Proti kroničnim boleznim za aktivno staranje, franc. – Contre les Maladies Chroniques pour un Vieillissement Actif) in ARIA (angl. ARIA Sentinel NetworK) uporablja mobilno tehnologijo za razvoj klinične poti, ki bi bolnikom, multidisciplinarnim ekipam zdravnikov in raziskovalcem omogočila nadzor rinitisa in astme. Mobilna aplikacija (Android in iOS) je na voljo v 20 državah in 15 jezikih. Uporablja vizualno analogno lestvico za oceno nadzora nad simptomi in oceno delovne zmožnosti in ponuja sistem, ki pomaga pri kliničnem odločanju. Aplikacija omogoča povezovanje z zdravnikom ali drugimi zdravstvenimi delavci. Ta strategija upošteva priporočila Evropskega partnerstva za inovacije za aktivno in zdravo staranje (angl. European Innovation Partnership on Active and Healthy Ageing, EIP on AHA). Cilj novega pristopa pobude ARIA je zagotoviti aktivno in zdravo življenje bolnikov z rinitisom ne glede na njihovo starost, spol ali družbenogospodarski položaj zato, da bi se zmanjšali zdravstvena in družbena neenakost, ki sta posledici te bolezni.
Published: 2019
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3. ARIA‐EAACI care pathways for allergen immunotherapy in respiratory allergy

Author: Jean Bousquet, Oliver Pfaar, Ioana Agache, Anna Bedbrook, Cezmi A Akdis, G. Walter Canonica, Tomas Chivato, Mona Al‐Ahmad, Amir H Abdul Latiff, Ignacio J Ansotegui, Claus Bachert, Abdullah Baharuddin, Karl‐Christian Bergmann, Carsten Bindslev‐Jensen, Leif Bjermer, Matteo Bonini, Sinthia Bosnic‐Anticevich, Isabelle Bosse, Helen A. Brough, Luisa Brussino, Moises A Calderon, Luis Caraballo, Victoria Cardona, Pedro Carreiro‐Martins, Tomas Casale, Lorenzo Cecchi, Alfonso M Cepeda Sarabia, Ekaterine Chkhartishvili, Derek K Chu, Ieva Cirule, Alvaro A Cruz, Wienczyslawa Czarlewski, Stefano delGiacco, Pascal Demoly, Philippe Devillier, Dejan Dokic, Stephen L Durham, Motohiro Ebisawa, Yehia El‐Gamal✝, Regina Emuzyte, Amiran Gamkrelidze, Jean Luc Fauquert, Alessandro Fiocchi, Wytske J Fokkens, Joao A Fonseca, Jean‐François Fontaine, Radoslaw Gawlik, Asli Gelincik, Bilun Gemicioglu, Jose E Gereda, Roy Gerth van Wijk, R Maximiliano Gomez, Maia Gotua, Ineta Grisle, Maria‐Antonieta Guzmán, Tari Haahtela, Susanne Halken, Enrico Heffler, Karin Hoffmann‐Sommergruber, Elham Hossny, Martin Hrubiško, Carla Irani, Juan Carlos Ivancevich, Zhanat Ispayeva, Kaja Julge, Igor Kaidashev, Omer Kalayci, Musa Khaitov, Ludger Klimek, Edward Knol, Marek L Kowalski, Helga Kraxner, Inger Kull, Piotr Kuna, Violeta Kvedariene, Vicky Kritikos, Antti Lauerma, Susanne Lau, Daniel Laune, Michael Levin, Desiree E Larenas‐Linnemann, Karin C Lodrup Carlsen, Carlo Lombardi, Olga M Lourenço, Bassam Mahboub, Hans‐Jørgen Malling, Patrick Manning, Gailen D Marshall, Erik Melén, Eli O Meltzer, Neven Miculinic, Branislava Milenkovic, Mostafa Moin, Stephen Montefort, Mario Morais‐Almeida, Charlotte G Mortz, Ralph Mösges, Joaquim Mullol, Leyla Namazova Baranova, Hugo Neffen, Kristof Nekam, Marek Niedoszytko, Mikaëla Odemyr, Robyn E O'Hehir, Markus Ollert, Liam O'Mahony, Ken Ohta, Yoshitaka Okamoto, Kimi Okubo, Giovanni B Pajno, Oscar Palomares, Susanna Palkonen, Petr Panzner, Nikolaos GPapadopoulos, Hae‐Sim Park, Giovanni Passalacqua, Vincenzo Patella, Ruby Pawankar, Nhân Pham‐Thi, Davor Plavec, Todor A Popov, Marysia Recto, Frederico S Regateiro, Carmen Riggioni, Graham Roberts, Monica Rodriguez‐Gonzales, Nelson Rosario, Menachem Rottem, Philip W Rouadi, Dermot Ryan, Boleslaw Samolinski, Mario Sanchez‐Borges✝, Faradiba S Serpa, Joaquin Sastre, Glenis K. Scadding, Mohamed H Shamji, Peter Schmid‐Grendelmeier, Holger J Schünemann, Aziz Sheikh, Nicola Scichilone, Juan Carlos Sisul, Mikhail Sofiev, Dirceu Solé, Talant Sooronbaev, Manuel Soto‐Martinez, Manuel Soto‐Quiros, Milan Sova, Jürgen Schwarze, Isabel Skypala, Charlotte Suppli‐Ulrik, Luis Taborda‐Barata, Ana Todo‐Bom, Maria J Torres, Marylin Valentin‐Rostan, Peter‐Valentin Tomazic, Antonio Valero, Sanna Toppila‐Salmi, Ioanna Tsiligianni, Eva Untersmayr, Marilyn Urrutia‐Pereira, Arunas Valiulis, Erkka Valovirta, Olivier Vandenplas, Maria Teresa Ventura, Pakit Vichyanond, Martin Wagenmann, Dana Wallace, Jolanta Walusiak‐Skorupa, De Yun Wang, Susan Waserman, Gary WK Wong, Arzu Yorgancioglu, Osman M Yusuf, Mario Zernotti, Luo Zhang, Mihaela Zidarn, Torsten Zuberbier, and Marek Jutel
Subjects: allergic rhinitis, asthma, immunotherapy, precision medicine, Immunologic diseases. Allergy, RC581-607
Published: 2021
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4. Endotyping of non-allergic, allergic and mixed rhinitis patients using a broad panel of biomarkers in nasal secretions.

Author: Christine L Segboer, Wytske J Fokkens, Ingrid Terreehorst, and Cornelis M van Drunen
Subjects: Medicine, Science
Abstract: BACKGROUND:Endotyping chronic rhinitis has proven hardest for the subgroup of non-allergic rhinitis (NAR) patients. While IgE-related inflammation is typical for allergic rhinitis (AR), no markers have been found that can be seen to positively identify NAR. A further complication is that AR and NAR might co-exist in patients with mixed rhinitis. As previous studies have considered only a limited number of inflammatory mediators, we wanted to explore whether a wider panel of mediators could help us refine the endotyping in chronic rhinitis patients. OBJECTIVE:To endotype chronic rhinitis, and non-allergic rhinitis in particular, with help of molecular or cellular markers. METHOD:In this study we included 23 NAR patients without allergen sensitizations and with persistent rhinitis symptoms, 22 pollen sensitized rhinitis patients with seasonal symptoms, 21 mixed rhinitis patients with pollen-related symptoms and persistent symptoms outside of the pollen season, and 23 healthy controls without any symptoms. Nasal secretions were collected outside of pollen season and differences between the endotypes were assessed for a broad range of inflammatory mediators and growths factors using a multiplex ELISA. RESULTS:Although we were able to identify two new nasal secretion makers (IL-12 and HGF) that were low in mixed and AR patients versus NAR and healthy controls, the most intriguing outcome is that despite investigating 29 general inflammatory mediators and growth factors no clear profile of non-allergic or mixed rhinitis could be found. CONCLUSION:Classical inflammatory markers are not able to differentiate between non-allergic or mixed rhinitis patients and healthy controls.
Published: 2018
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5. Specific Induction of TSLP by the Viral RNA Analogue Poly(I:C) in Primary Epithelial Cells Derived from Nasal Polyps.

Author: Korneliusz Golebski, Joost van Tongeren, Danielle van Egmond, Esther J de Groot, Wytske J Fokkens, and Cornelis M van Drunen
Subjects: Medicine, Science
Abstract: INTRODUCTION:Chronic rhinosinusitis with nasal polyposis is an inflammatory disease that, although not directly linked to allergy, often displays a Th2-skewed inflammation characterized by elevated local IgE and IL-5 levels. The nasal cavity is constantly exposed to bacteria and viruses that may trigger epithelial inflammatory responses. To gain more insight into mechanisms by which such a biased inflammation might arise, we have investigated the epithelial expression of the Th2 skewing mediators (TSLP, IL-25, and IL-33) in relationship to disease and microbial triggers. METHODS:Epithelial cells were obtained from polyp tissues of nasal polyposis patients and from inferior turbinates of non-diseased controls. Cells were exposed to various TLR-specific triggers to study the effect on mRNA and protein expression level of TSLP, IL-25, and IL-33 and the potential regulatory mechanisms through the expression profile the transcription factors ATF-3, DUSP-1, EGR-1, and NFKB-1. RESULTS:The TLR3 agonist and viral analogue poly(I:C) induced TSLP mRNA 13.0 ± 3.1 fold (p < 0.05) and protein expression by 12.1 ± 2.3-fold (p < 0.05) higher in epithelium isolated from nasal polyposis patients than in epithelium form healthy controls. This enhanced induction of TSLP may be a consequence of a down-regulated expression of DUSP-1 in polyp epithelium. CONCLUSION:The TLR3 induced expression of TSLP introduces a mechanism by which the Th2-skewed tissue environment might arise in nasal polyps and invites a further evaluation of the potential contribution of current or past viral infections to polyposis pathogenesis.
Published: 2016
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6. Dendritic Cell Subsets in Oral Mucosa of Allergic and Healthy Subjects.

Author: Susanne M Reinartz, Joost van Tongeren, Danielle van Egmond, Esther J J de Groot, Wytske J Fokkens, and Cornelis M van Drunen
Subjects: Medicine, Science
Abstract: Immunohistochemistry was used to identify, enumerate, and describe the tissue distribution of Langerhans type (CD1a and CD207), myeloid (CD1c and CD141), and plasmacytoid (CD303 and CD304) dendritic cell subsets in oral mucosa of allergic and non-allergic individuals. Allergic individuals have more CD141+ myeloid cells in epithelium and more CD1a+ Langerhans cells in the lamina propria compared to healthy controls, but similar numbers for the other DC subtypes. Our data are the first to describe the presence of CD303+ plasmacytoid DCs in human oral mucosa and a dense intraepithelial network of CD141+ DCs. The number of Langerhans type DCs (CD1a and CD207) and myeloid DCs (CD1c), was higher in the oral mucosa than in the nasal mucosa of the same individual independent of the atopic status.
Published: 2016
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7. ICON: chronic rhinosinusitis

Author: Claus Bachert, Ruby Pawankar, Luo Zhang, Chaweewan Bunnag, Wytske J Fokkens, Daniel L Hamilos, Orathai Jirapongsananuruk, Robert Kern, Eli O Meltzer, Joaquim Mullol, Robert Naclerio, Renata Pilan, Chae-Seo Rhee, Harumi Suzaki, Richard Voegels, and Michael Blaiss
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: Chronic rhinosinusitis (CRS) is a public health problem that has a significant socio-economic impact. Moreover, the complexity of this disease due to its heterogeneous nature based on the underlying pathophysiology - leading to different disease variants - further complicates our understanding and directions for the most appropriate targeted treatment strategies. Several International/national guidelines/position papers and/or consensus documents are available that present the current knowledge and treatment strategies for CRS. Yet there are many challenges to the management of CRS especially in the case of the more severe and refractory forms of disease. Therefore, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), a collaboration between EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus (ICON) on Chronic Rhinosinusitis. The purpose of this ICON on CRS is to highlight the key common messages from the existing guidelines, the differences in recommendations as well as the gaps in our current knowledge of CRS, thus providing a concise reference. In this document we discuss the definition of the disease, its relevance, pharmacoeconomics, pathophysiology, phenotypes and endotypes, genetics and risk factors, natural history and co-morbidities as well as clinical manifestations and treatment options in both adults and children comprising pharmacotherapy, surgical interventions and more recent biological approaches. Finally, we have also highlighted the unmet needs that wait to be addressed through future research. Keywords: Chronic rhinosinusitis, Pharmacoeconomics, Pathophysiology, Phenotypes, Genetics, Co-morbidities, Treatment, Biologicals, Unmet needs
Published: 2014
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8. The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.

Author: Ariane H Wagener, Aeilko H Zwinderman, Silvia Luiten, Wytske J Fokkens, Elisabeth H Bel, Peter J Sterk, and Cornelis M van Drunen
Subjects: Medicine, Science
Abstract: BACKGROUND: The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. OBJECTIVE: Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. METHODS: This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls). The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used. RESULTS: The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions. CONCLUSIONS: Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be potential targets for future drug development.
Published: 2013
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9. European Academy of Allergy and Clinical Immunology position paper on endoscopic scoring of nasal polyposis

Author: Philippe Gevaert, Jarno De Craemer, Claus Bachert, Manon Blauwblomme, Adam Chaker, Cemal Cingi, Peter W. Hellings, Claire Hopkins, Valérie Hox, Wytske J. Fokkens, Ludger Klimek, Valerie Lund, Ralph Mösges, Joaquim Mullol, Oliver Pfaar, Glenis Scadding, Peter Valentin Tomazic, Thibaut Van Zele, Stephan Vlaminck, Martin Wagenmann, Sanna Toppila‐Salmi, Isam Alobid, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (SLuc) Service d'oto-rhino-laryngologie
Subjects: Immunology, Immunology and Allergy
Published: 2023
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10. Migration and allergic diseases

Author: Abena S. Amoah, Maria Prins, Elisabeth H. D. Bel, Wytske J. Fokkens, Aeilko H. Zwinderman, Maria Yazdanbakhsh, Anke H. Maitland‐van der Zee, Ronald van Ree, Pulmonary medicine, Infectious diseases, AII - Infectious diseases, AII - Inflammatory diseases, APH - Global Health, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, Pulmonology, Paediatric Pulmonology, APH - Personalized Medicine, and Experimental Immunology
Subjects: Adult, Immune System Diseases, Immunology, Immunology and Allergy, Humans, Netherlands
Published: 2022
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11. Updates in biologic therapy for chronic rhinosinusitis with nasal polyps and <scp>NSAID</scp> ‐exacerbated respiratory disease

Author: Xinni Xu, Sietze Reitsma, De Yun Wang, and Wytske J. Fokkens
Subjects: Biological Products, NSAID-exacerbated respiratory disease, chronic rhinosinusitis, Anti-Inflammatory Agents, Non-Steroidal, Immunology, Respiration Disorders, Biological Therapy, Nasal Polyps, biologicals, Chronic Disease, Humans, Immunology and Allergy, Sinusitis, Rhinitis
Abstract: Chronic rhinosinusitis with nasal polyps (CRSwNP) associated with type 2 inflammation and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) can be difficult to control with standard medical therapy and sinus surgery. In this group, biologicals are potentially promising treatment options. The phase III clinical trials for omalizumab, dupilumab, mepolizumab and benralizumab in CRSwNP have demonstrated favourable outcomes. Moving forward, direct comparisons among biologicals, refining patient selection criteria for specific biologicals, determining optimal treatment duration and monitoring long-term outcomes are areas of emerging interest. This review summarizes the clinical evidence from the recent 2 years on the role of biologicals in severe CRSwNP and N-ERD, and proposes an approach towards decision-making in their use.
Published: 2022
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12. Patient-centred digital biomarkers for allergic respiratory diseases and asthma:the ARIA-EAACI approach

Author: Jean Bousquet, Mohamed H. Shamji, Josep M. Anto, Holger J. Schünemann, G. Walter Canonica, Marek Jutel, Stefano Del Giacco, Torsten Zuberbier, Oliver Pfaar, Joao A. Fonseca, Bernardo Sousa‐Pinto, Ludger Klimek, Wienczyslawa Czarlewski, Anna Bedbrook, Rita Amaral, Ignacio J. Ansotegui, Sinthia Bosnic‐Anticevich, Fulvio Braido, Claudia Chaves Loureiro, Bilun Gemicioglu, Tari Haahtela, Marek Kulus, Piotr Kuna, Maciej Kupczyk, Paolo M. Matricardi, Frederico S. Regateiro, Boleslaw Samolinski, Mikhail Sofiev, Sanna Toppila‐Salmi, Arunas Valiulis, Maria Teresa Ventura, Cristina Barbara, Karl C. Bergmann, Michael Bewick, Hubert Blain, Matteo Bonini, Louis‐Philippe Boulet, Rodolphe Bourret, Guy Brusselle, Luisa Brussino, Roland Buhl, Victoria Cardona, Thomas Casale, Lorenzo Cecchi, Denis Charpin, Ivan Cherrez‐Ojeda, Derek K. Chu, Cemal Cingi, Elisio M. Costa, Alvaro A. Cruz, Philippe Devillier, Stephanie Dramburg, Wytske J. Fokkens, Maia Gotua, Enrico Heffler, Zhanat Ispayeva, Juan Carlos Ivancevich, Guy Joos, Igor Kaidashev, Helga Kraxner, Violeta Kvedariene, Désirée E. Larenas‐Linnemann, Daniel Laune, Olga Lourenço, Renaud Louis, Mika Makela, Michael Makris, Marcus Maurer, Erik Melén, Yann Micheli, Mario Morais‐Almeida, Joaquim Mullol, Marek Niedoszytko, Robyn O’Hehir, Yoshitaka Okamoto, Heidi Olze, Nikolaos G. Papadopoulos, Alberto Papi, Vincenzo Patella, Benoit Pétré, Nhân Pham‐Thi, Francesca Puggioni, Santiago Quirce, Nicolas Roche, Philip W. Rouadi, Ana Sá‐Sousa, Hironori Sagara, Joaquin Sastre, Nicola Scichilone, Aziz Sheikh, Milan Sova, Charlotte Suppli Ulrik, Luis Taborda‐Barata, Ana Todo‐Bom, Maria J. Torres, Ioanna Tsiligianni, Omar S. Usmani, Erkka Valovirta, Tuula Vasankari, Rafael José Vieira, Dana Wallace, Susan Waserman, Mihaela Zidarn, Arzu Yorgancioglu, Luo Zhang, Tomas Chivato, and Markus Ollert
Subjects: Immunology, Immunology and Allergy
Abstract: Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.
Published: 2023
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13. A Comparison of International Guidelines for Rhinosinusitis

Author: Wytske J. Fokkens, Valerie Lund, Amber U. Luong, Richard R. Orlandi, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: Nasal Polyps, Rhinosinusitis, Chronic Disease, International guidelines, Humans, Immunology and Allergy, Iron-Dextran Complex, Sinusitis, Rhinitis, Allergic, Rhinitis
Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), latest version EPOS2020, and the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS), latest version ICAR-RS-2021, assimilate thousands of articles on the topic of rhinosinusitis. Encompassing scores of subtopics and relying on the perspectives of many international experts, EPOS2020 and ICAR-RS-2021 reduce the existing data into consumable formats and create evidence-based recommendations. The approaches and findings are similar in many respects but have significant differences. This clinical commentary, authored by some of the principal authors of these documents, compares and contrasts EPOS2020 and ICAR-RS-2021, examining methodology, diagnostic and treatment recommendations, and each document's emphases. This commentary demonstrates that, through somewhat differing methodologies, the 2 documents arrive at largely similar conclusions. Those who care for patients suffering from rhinosinusitis will find the documents complementary and valuable in their differences as much as in their similarities.
Published: 2022
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14. International consensus statement on allergy and rhinology:Allergic rhinitis - 2023

Author: Sarah K. Wise, Cecelia Damask, Lauren T. Roland, Charles Ebert, Joshua M. Levy, Sandra Lin, Amber Luong, Kenneth Rodriguez, Ahmad R. Sedaghat, Elina Toskala, Jennifer Villwock, Baharudin Abdullah, Cezmi Akdis, Jeremiah A. Alt, Ignacio J. Ansotegui, Antoine Azar, Fuad Baroody, Michael S. Benninger, Jonathan Bernstein, Christopher Brook, Raewyn Campbell, Thomas Casale, Mohamad Chaaban, Fook Tim Chew, Jeffrey Chambliss, Antonella Cianferoni, Adnan Custovic, Elizabeth Mahoney Davis, John M. DelGaudio, Anne K. Ellis, Carrie Flanagan, Wytske J. Fokkens, Christine Franzese, Matthew Greenhawt, Amarbir Gill, Ashleigh Halderman, Jens M. Hohlfeld, Cristoforo Incorvaia, Stephanie A. Joe, Shyam Joshi, Merin Elizabeth Kuruvilla, Jean Kim, Adam M. Klein, Helene J. Krouse, Edward C. Kuan, David Lang, Desiree Larenas‐Linnemann, Adrienne M. Laury, Matt Lechner, Stella E. Lee, Victoria S. Lee, Patricia Loftus, Sonya Marcus, Haidy Marzouk, Jose Mattos, Edward McCoul, Erik Melen, James W. Mims, Joaquim Mullol, Jayakar V. Nayak, John Oppenheimer, Richard R. Orlandi, Katie Phillips, Michael Platt, Murugappan Ramanathan, Mallory Raymond, Chae‐Seo Rhee, Sietze Reitsma, Matthew Ryan, Joaquin Sastre, Rodney J. Schlosser, Theodore A. Schuman, Marcus S. Shaker, Aziz Sheikh, Kristine A. Smith, Michael B. Soyka, Masayoshi Takashima, Monica Tang, Pongsakorn Tantilipikorn, Malcolm B. Taw, Jody Tversky, Matthew A. Tyler, Maria C. Veling, Dana Wallace, De Yun Wang, Andrew White, Luo Zhang, Omar G. Ahmed, Khashayar Arianpour, Emily Barrow, Carlo Cavaliere, Juan Carlos Ceballos Cantu, Mark B. Chaskes, Andy Jian Kai Chua, Srihari Daggumati, Luke Daines, Paul Daraei, Thomas Edwards, Deanna Gigliotti, Mitchell Gore, Khodayar Goshtasbi, Doo Hee Han, Lubnaa Hossenbaccus, Megan Jolicoeur, Dichapong Kanjanawasee, Suat Kilic, Sophia Linton, David Liu, Christoper Low, Chengetai Mahomva, Jordan A. Malenke, Amar Miglani, Peter Nagy, Jin‐A Park, Marianella Paz‐Lansberg, Paul Pfeffer, Marisa Ryan, Anirudh Saraswathula, Cameron Sheehan, Nadja Struss, Kevin Tie, Sina Torabi, Esmond F. Tsai, Nathalia Velasquez, Jackson Vuncannon, Duncan Watley, and Xinni Xu
Subjects: microbiome, IgE, allergen extract, allergen immunotherapy, allergic rhinitis, allergy, antihistamine, asthma, atopic dermatitis, avoidance, biologic, cockroach, conjunctivitis, consensus, corticosteroid, cough, cromolyn, decongestant, environment, eosinophilic esophagitis, epicutaneous, epidemiology, evidence-based medicine, food allergy, house dust mite, immunoglobulin E, immunotherapy, inhalant allergy, leukotriene, occupational rhinitis, omalizumab, pediatric, perennial, pet dander, pollen, probiotic, rhinitis, rhinosinusitis, saline, seasonal, sensitization, sinusitis, socioeconomic, specific IgE, subcutaneous immunotherapy, sublingual immunotherapy, systematic review, total IgE, transcutaneous immunotherapy, validated survey, Immunology and Allergy, Otorhinolaryngology
Abstract: BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document.METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work.RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost.CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.
Published: 2023
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15. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): in-depth sinus surgery analysis

Author: Wytske J. Fokkens, Joaquim Mullol, David Kennedy, Carl Philpott, Veronica Seccia, Robert C. Kern, André Coste, Ana R. Sousa, Peter H. Howarth, Victoria S. Benson, Bhabita Mayer, Steve W. Yancey, Robert Chan, Simon B. Gane, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: refractory, recurrence, Immunology, Immunology and Allergy, mepolizumab, chronic rhinosinusitis with nasal polyps, sinonasal surgery
Abstract: Background: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in-depth assessment of surgery endpoints in SYNAPSE. Methods: SYNAPSE was a double-blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. Results: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan–Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (
Published: 2023

16. Digitally-enabled, patient-centred care in rhinitis and asthma multimorbidity: The ARIA-MASK-air® approach

Author: Jean Bousquet, Josep M. Anto, Bernardo Sousa‐Pinto, Wienczyslawa Czarlewski, Anna Bedbrook, Tari Haahtela, Ludger Klimek, Oliver Pfaar, Piotr Kuna, Maciej Kupczyk, Frederico S. Regateiro, Boleslaw Samolinski, Arunas Valiulis, Arzu Yorgancioglu, Sylvie Arnavielhe, Xavier Basagaña, Karl C. Bergmann, Sinthia Bosnic‐Anticevich, Luisa Brussino, G. Walter Canonica, Victoria Cardona, Lorenzo Cecchi, Claudia Chaves‐Loureiro, Elisio Costa, Alvaro A. Cruz, Bilun Gemicioglu, Wytske J. Fokkens, Juan Carlos Ivancevich, Helga Kraxner, Violeta Kvedariene, Désirée E. Larenas‐Linnemann, Daniel Laune, Renaud Louis, Michael Makris, Marcus Maurer, Erik Melén, Yann Micheli, Mario Morais‐Almeida, Joaquim Mullol, Marek Niedoszytko, Yoshitaka Okamoto, Nikolaos G. Papadopoulos, Vincenzo Patella, Nhân Pham‐Thi, Philip W. Rouadi, Joaquin Sastre, Nicola Scichilone, Aziz Sheikh, Mikhail Sofiev, Luis Taborda‐Barata, Sanna Toppila‐Salmi, Ioanna Tsiligianni, Erkka Valovirta, Maria Teresa Ventura, Rafael José Vieira, Mihaela Zidarn, Rita Amaral, Ignacio J. Ansotegui, Annabelle Bédard, Samuel Benveniste, Michael Bewick, Carsten Bindslev‐Jensen, Hubert Blain, Matteo Bonini, Rodolphe Bourret, Fulvio Braido, Pedro Carreiro‐Martins, Denis Charpin, Ivan Cherrez‐Ojeda, Tomas Chivato, Derek K. Chu, Cemal Cingi, Stefano Del Giacco, Frédéric de Blay, Philippe Devillier, Govert De Vries, Maria Doulaptsi, Virginie Doyen, Gérard Dray, Jean‐François Fontaine, R. Maximiliano Gomez, Jan Hagemann, Enrico Heffler, Maja Hofmann, Ewa Jassem, Marek Jutel, Thomas Keil, Vicky Kritikos, Inger Kull, Marek Kulus, Olga Lourenço, Eve Mathieu‐Dupas, Enrica Menditto, Ralph Mösges, Ruth Murray, Rachel Nadif, Hugo Neffen, Stefania Nicola, Robyn O’Hehir, Heidi Olze, Yuliia Palamarchuk, Jean‐Louis Pépin, Benoit Pétré, Robert Picard, Constantinos Pitsios, Francesca Puggioni, Santiago Quirce, Filip Raciborski, Sietze Reitsma, Nicolas Roche, Monica Rodriguez‐Gonzalez, Jan Romantowski, Ana Sá‐Sousa, Faradiba S. Serpa, Marine Savouré, Mohamed H. Shamji, Milan Sova, Annette Sperl, Cristiana Stellato, Ana Todo‐Bom, Peter Valentin Tomazic, Olivier Vandenplas, Michiel Van Eerd, Tuula Vasankari, Frédéric Viart, Susan Waserman, Joao A. Fonseca, Torsten Zuberbier, uBibliorum, Ilmatieteen laitos, Finnish Meteorological Institute, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (MGD) Service de pneumologie
Subjects: Pulmonary and Respiratory Medicine, Immunology, MASK-air, nuha, patients, allergia, medical devices, hoito, pharmacotherapy, potilaat, rhinitis, HDE ALER, astma, Immunology and Allergy, care, asthma, digital, MASK‐air, mHealth, MASK.-air, ennusteet, allergy, respiratory tract diseases, lääkintälaitteet, lääkkeet, forecasts, lääkehoito, hengityselinten taudit, medicines
Abstract: MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma. info:eu-repo/semantics/publishedVersion
Published: 2023
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17. Cut-off values of MASK-air® Patient-Reported Outcome Measures (PROMs)

Author: Bernardo, Sousa-Pinto, Ana, Sá-Sousa, Rafael José, Vieira, Rita, Amaral, Ana Margarida, Pereira, Josep M, Anto, Ludger, Klimek, Wienczyslawa, Czarlewski, Joaquim, Mullol, Oliver, Pfaar, Anna, Bedbrook, Luisa, Brussino, Violeta, Kvedariene, Desirée E, Larenas-Linnemann, Yoshitaka, Okamoto, Maria Teresa, Ventura, Ignacio J, Ansotegui, Sinthia, Bosnic-Anticevich, G Walter, Canonica, Victoria, Cardona, Lorenzo, Cecchi, Tomas, Chivato, Cemal, Cingi, Elísio M, Costa, Alvaro A, Cruz, Stefano, Del Giacco, Philippe, Devillier, Wytske J, Fokkens, Bilun, Gemicioglu, Tari, Haahtela, Juan Carlos, Ivancevich, Piotr, Kuna, Igor, Kaidashev, Helga, Kraxner, Daniel, Laune, Renaud, Louis, Michael, Makris, Riccardo, Monti, Mario, Morais-Almeida, Ralph, Mösges, Marek, Niedoszytko, Nikolaos G, Papadopoulos, Vincenzo, Patella, Nhân, Pham-Thi, Frederico S, Regateiro, Sietze, Reitsma, Philip W, Rouadi, Boleslaw, Samolinski, Aziz, Sheikh, Milan, Sova, Luis, Taborda-Barata, Sanna, Toppila-Salmi, Joaquin, Sastre, Ioanna, Tsiligianni, Arunas, Valiulis, Arzu, Yorgancioglu, Mihaela, Zidarn, Torsten, Zuberbier, Joao A, Fonseca, and Jean, Bousquet
Abstract: In clinical and epidemiological studies, cut-offs of Patient-Reported Outcome Measures (PROMs) can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cut-offs in MASK-air® have not been tested.To calculate cut-offs for VAS global, nasal, ocular, and asthma symptoms.In a cross-sectional study design of all MASK-air® participants, we compared (i) approaches based on the percentiles (tertiles or quartiles) of VAS distributions, and (ii) data-driven approaches based on clusters of data from two comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air® real-world cross-sectional and longitudinal data to assess the most relevant cut-offs.We assessed 395,223 days from 23,201 MASK-air® users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cut-off values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cut-off differentiating "controlled" and "partly-controlled" patients was similar to the cut-off value which had been arbitrarily used (20/100). However, a lower cut-off was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 versus the arbitrarily-used value of 50/100).Using a data-driven approach, we were able to define cut-off values for MASK-air® VASs on allergy and asthma symptoms. This may allow for a better classification of rhinitis and asthma patients according to different levels of control, supporting improved disease management.
Published: 2022

18. CHronic RhINOSinusitis Outcome Registry (CHRINOSOR): establishment of an international outcome registry driven by mHealth technology

Author: Sven F. Seys, Peter W. Hellings, Isam Alobid, Vibeke Backer, Emilie Bequignon, Christian von Buchwald, Carlo Cavaliere, André Coste, Lauren Deneyer, Zuzana Diamant, Julia Eckl-Dorna, Wytske J. Fokkens, Simon Gane, Philippe Gevaert, Christiane Holbaek-Haase, Clemens Holzmeister, Claire Hopkins, Valérie Hox, Caroline Huart, Roger Jankowski, Mark Jorissen, Anette Kjeldsen, Lisa Knipps, Bibi Lange, Rik van der Lans, Anu Laulajainen-Hongisto, Kenneth Larsen, David T. Liu, Valerie Lund, Gert Mariën, Simonetta Masieri, Geoffrey Mortuaire, Joaquim Mullol, Sietze Reitsma, Philippe Rombaux, Sven Schneider, Andreas Steinsvik, Peter-Valentin Tomazic, Sanna K. Toppila-Salmi, Laura Van Gerven, Thibaut Van Zele, Paula Virkkula, Martin Wagenmann, Claus Bachert, UCL - (SLuc) Service d'oto-rhino-laryngologie, and UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie
Subjects: biologic therapy, chronic rhinosinusitis, mobile health technology, nasal polyps, real-world evidence, Immunology and Allergy
Abstract: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on prevalence of uncontrolled CRS and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery or biologics.To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology.A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes as well as a set of relevant clinical outcomes. Adult patients with a diagnosis of chronic rhinosinusitis are eligible for inclusion.A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy and data security aspects. Up to 300 patients have already been included.CHRINOSOR is a collaborative effort that aims at improving our understanding of chronic rhinosinusitis, its comorbidities and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by real-world evidence.
Published: 2022

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

Author: Klementina S. Avdeeva, Wytske J. Fokkens, Christine L. Segboer, Sietze Reitsma, Ear, Nose and Throat, Graduate School, Other Research, and AII - Inflammatory diseases
Subjects: Cross-Sectional Studies, Rhinorrhea, phenotype, Immunology, prevalence, Immunology and Allergy, Humans, epidemiology, non-allergic rhinitis, endotype, Rhinitis, Allergic, Aged, Rhinitis
Abstract: Background: Non-allergic rhinitis (NAR) can be subdivided into several phenotypes: rhinorrhea of the elderly, rhinitis medicamentosa, smokers', occupational, hormonal, drug-induced, gustatory, and idiopathic rhinitis. There are two pathophysiological endotypes of NAR: inflammatory and neurogenic. Phenotypes may serve as an indicator of an underlying endotype and, therefore, help to guide the treatment. The prevalence of each phenotype in the general population is currently unknown. Methodology/Principal: Cross-sectional questionnaire-based study in the general population of the Netherlands. Results: The prevalence of chronic rhinitis in the general population was 40% (N = 558, of those, 65% had NAR and 28% AR, in 7% allergy status is unknown). Individuals with NAR (N = 363) had significantly more complaints in October–February. Those with AR (N = 159) had significantly more complaints in April–August. The most common NAR phenotypes were idiopathic (39%) and rhinitis medicamentosa (14%), followed by occupational (8%), smokers' (6%), hormonal (4%), gustatory (4%), and rhinorrhea of the elderly (4%). The least prevalent phenotype was drug induced (1%). Nineteen percent of the NAR group could not be classified into any of the phenotypes. Conclusions: This is the first study to describe the prevalences of NAR phenotypes in the general population. AR and NAR have a distinct seasonality pattern with NAR being more prevalent in autumn/winter and AR in spring/summer. Our data on the prevalence of phenotypes may help clinicians to anticipate the type of patients at their clinic and help guide a tailored treatment approach. The high prevalence of rhinitis medicamentosa is alarming, since this is a potentially preventable phenotype.
Published: 2022

20. Endoscopic sinus surgery with medical therapy versus medical therapy for chronic rhinosinusitis with nasal polyps: a multicentre, randomised, controlled trial

Author: Evelijn S Lourijsen, Sietze Reitsma, Marleen Vleming, Gerjon Hannink, Gwijde F J P M Adriaensen, Marjolein E Cornet, D Rienk Hoven, Ward J M Videler, Jochen H Bretschneider, Susanne M Reinartz, Maroeska M Rovers, Wytske J Fokkens, Otolaryngology / Head & Neck Surgery, Ear, Nose and Throat, Graduate School, and AII - Inflammatory diseases
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Adolescent, Endoscopy, Middle Aged, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Nasal Polyps, Treatment Outcome, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Quality of Life, Humans, Female, Sinusitis
Abstract: Item does not contain fulltext BACKGROUND: Endoscopic sinus surgery (ESS) is a common operation for patients with chronic rhinosinusitis with nasal polyps (CRSwNP) when medical therapy alone is insufficient. No randomised controlled trials on the efficacy of ESS have been published. We aimed to assess the efficacy of ESS plus medical therapy versus medical therapy alone in patients with CRSwNP. METHODS: We performed an open-label, multicentre, pragmatic, randomised, controlled trial in three tertiary care centres and 12 secondary care centres in 11 cities in the Netherlands (Almere, Amstelveen, Amsterdam, Blaricum, Den Haag, Deventer, Haarlem, Hoofddorp, Hoorn, Leiderdorp, and Rotterdam). Adults (aged ≥18 years) with CRSwNP and an indication for ESS were randomly assigned (1:1) using block randomisation (block sizes of six), stratified by study centre, to receive either ESS plus medical therapy or medical therapy. ESS was performed according to local practice, although anterior ethmoidectomy was mandatory. Medical therapy was prescribed at the patient's otorhinolaryngologist's discretion, and could be, but was not limited to, nasal corticosteroids, nasal rinsing, systemic corticosteroids, or systemic antibiotics. The primary outcome was disease-specific health-related quality of life (HRQoL) at 12 months of follow up, measured with the validated Sinonasal Outcome Test 22 (SNOT-22; where each item is scored from 0 to 5, where 0 indicated no problems and 5 indicates problems as bad as can be, with a total score of 0-110 points), and the minimal clinically important difference of the SNOT-22 is 9·0 points. Primary and safety analyses were performed on an intention-to-treat (ITT) basis. The ITT population comprised all patients who were randomly assigned to treatment according to their randomisation group and without any protocol violation. This study is registered with the Netherlands Trial Register, NTR4978, and is ongoing. FINDINGS: Between Feb 15, 2015, and Aug 27, 2019, 371 patients were screened for eligibility, of whom 238 were eligible, willing to participate, and randomly assigned to ESS plus medical therapy (n=121) or medical therapy (n=117) and 234 were included in the baseline ITT population (n=118 ESS plus medical therapy; n=116 medical therapy). 142 (61%) of 234 patients at baseline were men and 92 (39%) were women, and the mean age was 50·4 years (SD 12·7). 206 participants were analysed at 12 months for the primary outcome (n=103 in the ESS plus medical therapy group; n=103 in the medical therapy group). At 12 months follow-up, the mean SNOT-22 score in the ESS plus medical therapy group was 27·9 (SD 20·2; n=103) and in the medical therapy group was 31·1 (20·4; n=103), with an adjusted mean difference of -4·9 (95% CI -9·4 to -0·4), favouring ESS plus medical therapy. Adverse events were similar between the groups. The most common adverse events were minor epistaxis or gastrointestinal problems. No treatment-related deaths occurred, but one patient died due to congestive heart failure. INTERPRETATION: ESS plus medical therapy is more efficacious than medical therapy alone in patients with CRSwNP, although the minimal clinically important difference was not met. Long-term follow-up data are needed to determine whether the effect persists. The current results are a basis for further development of evidence-based guidelines. FUNDING: The Netherlands Organisation for Health Research and Development (ZonMw).
Published: 2022
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21. Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference

Author: Bernardo Sousa‐Pinto, Holger J. Schünemann, Ana Sá‐Sousa, Rafael José Vieira, Rita Amaral, Josep M. Anto, Ludger Klimek, Wienczyslawa Czarlewski, Joaquim Mullol, Oliver Pfaar, Anna Bedbrook, Luisa Brussino, Violeta Kvedariene, Desirée Larenas‐Linnemann, Yoshitaka Okamoto, Maria Teresa Ventura, Ioana Agache, Ignacio J. Ansotegui, Karl C. Bergmann, Sinthia Bosnic‐Anticevich, Jan Brozek, G. Walter Canonica, Victoria Cardona, Pedro Carreiro‐Martins, Thomas Casale, Lorenzo Cecchi, Tomas Chivato, Derek K. Chu, Cemal Cingi, Elísio M. Costa, Alvaro A. Cruz, Stefano Del Giacco, Philippe Devillier, Patrik Eklund, Wytske J. Fokkens, Bilun Gemicioglu, Tari Haahtela, Juan Carlos Ivancevich, Zhanat Ispayeva, Marek Jutel, Piotr Kuna, Igor Kaidashev, Musa Khaitov, Helga Kraxner, Daniel Laune, Brian Lipworth, Renaud Louis, Michael Makris, Riccardo Monti, Mario Morais‐Almeida, Ralph Mösges, Marek Niedoszytko, Nikolaos G. Papadopoulos, Vincenzo Patella, Nhân Pham‐Thi, Frederico S. Regateiro, Sietze Reitsma, Philip W. Rouadi, Boleslaw Samolinski, Aziz Sheikh, Milan Sova, Ana Todo‐Bom, Luis Taborda‐Barata, Sanna Toppila‐Salmi, Joaquin Sastre, Ioanna Tsiligianni, Arunas Valiulis, Olivier Vandenplas, Dana Wallace, Susan Waserman, Arzu Yorgancioglu, Mihaela Zidarn, Torsten Zuberbier, Joao A. Fonseca, Jean Bousquet, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Comprehensive Health Research Centre (CHRC) - pólo NMS, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Publica
Subjects: allergic rhinitis, real-world data, allergen immunotherapy, co-medication, multivariable mixed-effects model, Immunology, Allergen immunotherapy, Rhinitis, Allergic, Adrenal Cortex Hormones, Desensitization, Immunologic, HDE ALER, Immunology and Allergy, Fluticasone, Humans, Rhinitis
Abstract: Funding Information: IA reports personal fees from Roxall, Menarini, UCB, Faes Farma, Sanofi, Bial, Amgen, Abbott, Bayer, Organon. SBA reports grants from TEVA, personal fees from TEVA, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, Mylan. JB reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi‐Aventis, Takeda, Teva, Uriach, other from KYomed‐Innov, personal fees from Purina, other from MASK‐air. VC reports personal fees from Thermofisher. PCM reports personal fees from Abbvie, AZ, Bial, GSK, Mylan, Medinfar, Novartis, Sanofi. LC reports personal fees from Malesci, Menarini, Astra Zeneca, Novartis. AC reports grants and personal fees from Astrazeneca, GSK, Sanofi, personal fees from Boehringer‐Ingelheim, Chiesi, Glenmark, Novartis, personal fees from Mylan, Abdi‐Ibrahim. PD reports personal fees and non‐financial support from Stallergenes Greer, ALK‐Abello, Astra Zeneca, CHIESI, MYLAN/Meda Pharma, Novartis, GlaxoSmithKline, Sanofi, IQVIA personal fees from MENARINI. JAFonseca reports participation in SME that has mHealth technologies for patients with asthma. JCI reports personal fees from Abbott Ecuador, Bago Bolivia, Faes Farma, Laboratorios Casasco, Sanofi. LK reports grants and personal fees from Allergopharma, LETI Pharma,MEDA/Mylan, Sanofi, personal fees from HAL Allergie, Allergy Therapeut., Cassella med, grants from ALK Abelló, Stallergenes, Quintiles, ASIT biotech, Lofarma, AstraZeneca, GSK, Inmunotk, and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. VK reports other from Norameda, BerlinCHemie Menarini. PK reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, Boehringer Ingelheim, Chiesi, GSK, Novartis, Polpharma. DLL reports personal fees from Allakos, Amstrong, Astrazeneca, Chiesi, DBV Technologies, Grunenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, Carnot, grants from Sanofi, Astrazeneca, Novartis, Circassia, UCB, GSK, Purina institute, Abvvie, Lilly, Pfizer. BL reports grants and personal fees from Meda, personal fees from Glenamrk. RL reports grants and personal fees from GSK, AZ, Chiesi, personal fees from Novartis, Sanofi. MM reports personal fees from Novartis, Gsk, Menarini, Az, Chiesi, Sanofi, Pfizer. RM reports personal fees from Angelini Pharma ALK, Allergopharma, Allergy Therapeutics, Friulchem, Hexal, Servier, Klosterfrau, Bayer, FAES, GSK, MSD, Johnson&Johnson, Meda, Stada, UCB, Nuvo, Menarini, Mundipharma, Pohl‐Boskamp, Laboratoire de la Mer, Sidroga, Lek, PRO‐AdWise, grants and personal fees from Bencard, Stallergenes, Ursapharm, HAL BV, grants from Leti, Optima, BitopAG, Hulka, Inmunotek, Cassella‐med GmbH & Co. KG, ASIT biotech, grants, personal fees and non‐financial support from Lofarma, non‐financial support from Roxall, Atmos, Bionorica, Otonomy, Ferrero, personal fees and non‐financial support from Novartis. OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., GlaxoSmithKline, personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS, Paul‐Martini‐Stiftung (PMS), Regeneron Pharmaceuticals Inc., RG Aerztefortbildung, Institut für Disease Management, Springer GmbH, AstraZeneca, IQVIA Commercial, Ingress Health, grants from Pohl‐Boskamp, Inmunotek S.L., Biomay, Circassia. NGPapadopoulos reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. ATB reports personal fees from AstraZeneca, GSK, Novartis, IQVIA/Abbvie, Mylan, Bial, Leti, grants and personal fees from Teva. STS reports personal fees from ERT, Roche products, Novartis, Sanofi Pharma, AstraZeneca, ALK‐ Abelló grants from Glaxo Smith Kline. IT reports grants from GSK, Boehringer Ingelheim, AZ, personal fees from Novartis, Astra Zeneca, Chiesi, TZ reports Organizational affiliations: Committee member: WHO‐Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA); Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI); Head: European Centre for Allergy Research Foundation (ECARF). President: Global Allergy and Asthma European Network (GA2LEN); Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). Funding Information: MASK‐air® has been supported by EU grants (POLLAR, EIT Health; Structural and Development Funds, Twinning, EIP on AHA and H2020) and educational grants from Mylan‐Viatris, ALK, GSK, Novartis and Uriach 1 1 Publisher Copyright: © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., “real-world data”). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. Methods: We assessed the MASK-air® app data (May 2015–December 2020) by users self-reporting AR (16–90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. Results: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71–0.80). Conclusion: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines. publishersversion published
Published: 2022
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22. Behavioural patterns in allergic rhinitis medication in Europe: A study using MASK-air

Author: Bernardo, Sousa-Pinto, Ana, Sá-Sousa, Rafael José, Vieira, Rita, Amaral, Ludger, Klimek, Wienczyslawa, Czarlewski, Josep M, Antó, Oliver, Pfaar, Anna, Bedbrook, Violeta, Kvedariene, Maria Teresa, Ventura, Ignacio J, Ansotegui, Karl-Christian, Bergmann, Luisa, Brussino, G Walter, Canonica, Victoria, Cardona, Pedro, Carreiro-Martins, Tomas, Casale, Lorenzo, Cecchi, Tomás, Chivato, Derek K, Chu, Cemal, Cingi, Elísio M, Costa, Alvaro A, Cruz, Giulia, De Feo, Philippe, Devillier, Wytske J, Fokkens, Mina, Gaga, Bilun, Gemicioğlu, Tari, Haahtela, Juan Carlos, Ivancevich, Zhanat, Ispayeva, Marek, Jutel, Piotr, Kuna, Igor, Kaidashev, Helga, Kraxner, Désirée E, Larenas-Linnemann, Daniel, Laune, Brian, Lipworth, Renaud, Louis, Michael, Makris, Riccardo, Monti, Mario, Morais-Almeida, Ralph, Mösges, Joaquim, Mullol, Mikaëla, Odemyr, Yoshitaka, Okamoto, Nikolaos G, Papadopoulos, Vincenzo, Patella, Nhân, Pham-Thi, Frederico S, Regateiro, Sietze, Reitsma, Philip W, Rouadi, Boleslaw, Samolinski, Milan, Sova, Ana, Todo-Bom, Luis, Taborda-Barata, Peter Valentin, Tomazic, Sanna, Toppila-Salmi, Joaquin, Sastre, Ioanna, Tsiligianni, Arunas, Valiulis, Olivier, Vandenplas, Dana, Wallace, Susan, Waserman, Arzu, Yorgancioglu, Mihaela, Zidarn, Torsten, Zuberbier, João A, Fonseca, and Jean, Bousquet
Subjects: Europe, Habits, Histamine Antagonists, Humans, Rhinitis, Allergic, Rhinitis
Abstract: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data.We analysed 2015-2020 MASK-airWe analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p .001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral HAllergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severity.
Published: 2022

23. Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study

Author: Bernardo Sousa‐Pinto, Holger J. Schünemann, Ana Sá‐Sousa, Rafael José Vieira, Rita Amaral, Josep M. Anto, Ludger Klimek, Wienczyslawa Czarlewski, Joaquim Mullol, Oliver Pfaar, Anna Bedbrook, Luisa Brussino, Violeta Kvedariene, Désirée E. Larenas‐Linnemann, Yoshitaka Okamoto, Maria Teresa Ventura, Ioana Agache, Ignacio J. Ansotegui, Karl C. Bergmann, Sinthia Bosnic‐Anticevich, G. Walter Canonica, Victoria Cardona, Pedro Carreiro‐Martins, Thomas Casale, Lorenzo Cecchi, Tomas Chivato, Derek K. Chu, Cemal Cingi, Elísio M. Costa, Alvaro A. Cruz, Stefano Del Giacco, Philippe Devillier, Patrik Eklund, Wytske J. Fokkens, Bilun Gemicioglu, Tari Haahtela, Juan Carlos Ivancevich, Zhanat Ispayeva, Marek Jutel, Piotr Kuna, Igor Kaidashev, Musa Khaitov, Helga Kraxner, Daniel Laune, Brian Lipworth, Renaud Louis, Michael Makris, Riccardo Monti, Mario Morais‐Almeida, Ralph Mösges, Marek Niedoszytko, Nikolaos G. Papadopoulos, Vincenzo Patella, Nhân Pham‐Thi, Frederico S. Regateiro, Sietze Reitsma, Philip W. Rouadi, Boleslaw Samolinski, Aziz Sheikh, Milan Sova, Ana Todo‐Bom, Luis Taborda‐Barata, Sanna Toppila‐Salmi, Joaquin Sastre, Ioanna Tsiligianni, Arunas Valiulis, Olivier Vandenplas, Dana Wallace, Susan Waserman, Arzu Yorgancioglu, Mihaela Zidarn, Torsten Zuberbier, Joao A. Fonseca, Jean Bousquet, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Ear, Nose and Throat, AII - Inflammatory diseases, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Helsinki University Hospital Area, and Department of Pathology
Subjects: Patient-reported outcomes, real-world data, Respiratory Medicine and Allergy, Immunology, Oto-rino-laryngologi, Rhinitis* / epidemiology, Real-world data, rhinitis, Otorhinolaryngology, patient-reported outcomes, Surveys and Questionnaires, HDE ALER, 3121 General medicine, internal medicine and other clinical medicine, Humans, Immunology and Allergy, Longitudinal Studies, Mobile health, mobile health, Telemedicine, Lungmedicin och allergi, Rhinitis
Abstract: Data de publicació electrònica: 03-11-2022 Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. Methods: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. Results: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. Conclusions: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.
Published: 2022
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24. Combined medical and surgical therapy for chronic rhinosinusitis with nasal polyposis - Authors' reply

Author: Evelijn S Lourijsen, Sietze Reitsma, Gerjon Hannink, Wytske J Fokkens, Ear, Nose and Throat, Graduate School, and AII - Inflammatory diseases
Subjects: Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Pulmonary and Respiratory Medicine, Nasal Polyps, Chronic Disease, Humans, Sinusitis
Abstract: Item does not contain fulltext
Published: 2022
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25. Cutoff Values of MASK-air Patient-Reported Outcome Measures

Author: Bernardo Sousa-Pinto, Ana Sá-Sousa, Rafael José Vieira, Rita Amaral, Ana Margarida Pereira, Josep M. Anto, Ludger Klimek, Wienczyslawa Czarlewski, Joaquim Mullol, Oliver Pfaar, Anna Bedbrook, Luisa Brussino, Violeta Kvedariene, Desirée E. Larenas-Linnemann, Yoshitaka Okamoto, Maria Teresa Ventura, Ignacio J. Ansotegui, Sinthia Bosnic-Anticevich, G. Walter Canonica, Victoria Cardona, Lorenzo Cecchi, Tomas Chivato, Cemal Cingi, Elísio M. Costa, Alvaro A. Cruz, Stefano Del Giacco, Philippe Devillier, Wytske J. Fokkens, Bilun Gemicioglu, Tari Haahtela, Juan Carlos Ivancevich, Piotr Kuna, Igor Kaidashev, Helga Kraxner, Daniel Laune, Renaud Louis, Michael Makris, Riccardo Monti, Mario Morais-Almeida, Ralph Mösges, Marek Niedoszytko, Nikolaos G. Papadopoulos, Vincenzo Patella, Nhân Pham-Thi, Frederico S. Regateiro, Sietze Reitsma, Philip W. Rouadi, Boleslaw Samolinski, Aziz Sheikh, Milan Sova, Luis Taborda-Barata, Sanna Toppila-Salmi, Joaquin Sastre, Ioanna Tsiligianni, Arunas Valiulis, Arzu Yorgancioglu, Mihaela Zidarn, Torsten Zuberbier, Joao A. Fonseca, and Jean Bousquet
Subjects: Asthma, Conjunctivitis, Cutoffs, MASK-air, Rhinitis, Immunology and Allergy
Published: 2022

26. Academic Productivity of Young People With Allergic Rhinitis: A MASK-air Study

Author: Rafael José Vieira, Nhân Pham-Thi, Josep M. Anto, Wienczyslawa Czarlewski, Ana Sá-Sousa, Rita Amaral, Anna Bedbrook, Sinthia Bosnic-Anticevich, Luisa Brussino, G. Walter Canonica, Lorenzo Cecchi, Alvaro A. Cruz, Wytske J. Fokkens, Bilun Gemicioglu, Tari Haahtela, Juan Carlos Ivancevich, Ludger Klimek, Piotr Kuna, Violeta Kvedariene, Désirée Larenas-Linnemann, Mario Morais-Almeida, Joaquim Mullol, Marek Niedoszytko, Yoshitaka Okamoto, Nikolaos G. Papadopoulos, Vincenzo Patella, Oliver Pfaar, Frederico S. Regateiro, Sietze Reitsma, Philip W. Rouadi, Boleslaw Samolinski, Aziz Sheikh, Luis Taborda-Barata, Sanna Toppila-Salmi, Joaquin Sastre, Ioanna Tsiligianni, Arunas Valiulis, Maria Teresa Ventura, Susan Waserman, Arzu Yorgancioglu, Mihaela Zidarn, Torsten Zuberbier, João A. Fonseca, Jean Bousquet, Bernardo Sousa-Pinto, Publica, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: Adolescent, Visual Analog Scale, MASK, Academic productivity, Allergic rhinitis, Mobile health, Real-world data, Efficiency, Rhinitis, Allergic, Surveys and Questionnaires, Quality of Life, Humans, Immunology and Allergy, Rhinitis
Abstract: Background: Several studies have suggested an impact of allergic rhinitis on academic productivity. However, large studies with real-world data (RWD) are not available. Objective: To use RWD to assess the impact of allergic rhinitis on academic performance (measured through a visual analog scale [VAS] education and the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific [WPAI+CIQ:AS] questionnaire), and to identify factors associated with the impact of allergic rhinitis on academic performance. Methods: We assessed data from the MASK-air mHealth app of users aged 13 to 29 years with allergic rhinitis. We assessed the correlation between variables measuring the impact of allergies on academic performance (VAS education, WPAI+CIQ:AS impact of allergy symptoms on academic performance, and WPAI+CIQ:AS percentage of education hours lost due to allergies) and other variables. In addition, we identified factors associated with the impact of allergic symptoms on academic productivity through multivariable mixed models. Results: A total of 13,454 days (from 1970 patients) were studied. VAS education was strongly correlated with the WPAI+CIQ:AS impact of allergy symptoms on academic productivity (Spearman correlation coefficient = 0.71 [95% confidence interval (CI) = 0.58; 0.80]), VAS global allergy symptoms (0.70 [95% CI = 0.68; 0.71]), and VAS nose (0.66 [95% CI = 0.65; 0.68]). In multivariable regression models, immunotherapy showed a strong negative association with VAS education (regression coefficient = -2.32 [95% CI = -4.04; -0.59]). Poor rhinitis control, measured by the combined symptom-medication score, was associated with worse VAS education (regression coefficient = 0.88 [95% CI = 0.88; 0.92]), higher impact on academic productivity (regression coefficient = 0.69 [95% CI = 0.49; 0.90]), and higher percentage of missed education hours due to allergy (regression coefficient = 0.44 [95% CI = 0.25; 0.63]). Conclusion: Allergy symptoms and worse rhinitis control are associated with worse academic productivity, whereas immunotherapy is associated with higher productivity.
Published: 2022
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27. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

Author: Bousquet, Jean, Cristol, Jean-Paul, Czarlewski, Wienczyslawa, Anto, Josep M, Martineau, Adrian, Haahtela, Tari, Fonseca, Susana C, Iaccarino, Guido, Blain, Hubert, Fiocchi, Alessandro, Canonica, G Walter, Fonseca, Joao A, Vidal, Alain, Choi, Hak-Jong, Kim, Hyun Ju, Le Moing, Vincent, Reynes, Jacques, Sheikh, Aziz, Akdis, Cezmi A, Zuberbier, Torsten, Amir Hamzah Abdul Latiff, Baharudin, Abdullah, Werner, Aberer, Nancy, Abusada, Ian, Adcock, Alejandro, Afani, Ioana, Agache, Xenofon, Aggelidis, Jenifer, Agustin, Cezmi, A Akdis, Mübeccel, Akdis, Mona, Al-Ahmad, Abou Al-Zahab Bassam, Hussam, Alburdan, Oscar, Aldrey-Palacios, Emilio Alvarez Cuesta, Hiba Alwan Salman, Ashraf, Alzaabi, Salma, Amade, Gene, Ambrocio, Rosana, Angles, Isabella, Annesi-Maesano, Ignacio, J Ansotegui, Josep, M Anto, Paula Ara Bardajo, Stefania, Arasi, Margarete, Arrais, Hasan, Arshad, Maria-Cristina, Artesani, Estrella, Asayag, Francesca, Avolio, Khuzama, Azhari, Claus, Bachert, Diego, Bagnasco, Ilaria, Baiardini, Nissera, Bajrović, Petros, Bakakos, Sergio Bakeyala Mongono, Christine, Balotro-Torres, Sergio, Barba, Cristina, Barbara, Elsa, Barbosa, Bruno, Barreto, Joan, Bartra, Xavier, Basagana, Eric, D Bateman, Lkhagvaa, Battur, Anna, Bedbrook, Martín Bedolla Barajas, Bianca, Beghé, Antra, Bekere, Elizabeth, Bel, Ali Ben Kheder, Mikael, Benson, Elena-Camelia, Berghea, Karl-Christian, Bergmann, Roberto, Bernardini, David, Bernstein, Mike, Bewick, Slawomir, Bialek, Artur, Białoszewski, Thomas, Bieber, Nils, E Billo, Maria-Beatrice, Bilo, Carsten, Bindslev-Jensen, Leif, Bjermer, Hubert, Blain, Irina, Bobolea, Malgorzata Bochenska Marciniak, Christine, Bond, Attilio, Boner, Matteo, Bonini, Sergio, Bonini, Sinthia, Bosnic-Anticevich, Isabelle, Bosse, Sofia, Botskariova, Jacques, Bouchard, Louis-Philippe, Boulet, Rodolphe, Bourret, Philippe, Bousquet, Fulvio, Braido, Andrew, Briggs, Christopher, E Brightling, Jan, Brozek, Luisa, Brussino, Roland, Buhl, Roxana, Bumbacea, Rosalva, Buquicchio, María-Teresa Burguete Cabañas, Andrew, Bush, William, W Busse, Jeroen, Buters, Fernan, Caballero-Fonseca, Moïses, A Calderon, Mario, Calvo, Paulo, Camargos, Thierry, Camuzat, R Canevari, F, Antonio, Cano, G Walter Canonica, Arnaldo, Capriles-Hulett, Luis, Caraballo, Vicky, Cardona, Kai-Hakon, Carlsen, Jonas Carmona Pirez, Jorge, Caro, Warner, Carr, Pedro, Carreiro-Martins, Fredelita, Carreon-Asuncion, Ana-Maria, Carriazo, Carme Carrion, Y Ribas, Thomas, Casale, Mary-Ann, Castor, Elizabeth, Castro, G Caviglia, A, Lorenzo, Cecchi, Alfonso Cepeda Sarabia, Maciej, Chalubinski, Ramanathan, Chandrasekharan, Yoon-Seok, Chang, Victoria, Chato-Andeza, Lida, Chatzi, Christina, Chatzidaki, Niels, H Chavannes, Claudia Chaves Loureiro, Aurora-Alejandra Chavez Garcia, Marta, Chelninska, Yuzhi, Chen, Lei, Cheng, Sharon, Chinthrajah, Tomas, Chivato, Ekaterine, Chkhartishvili, George, Christoff, Henry, Chrystyn, Derek, K Chu, Antonio, Chua, Alexander, Chuchalin, Kian Fan Chung, Alberto, 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Romano, Jan, Romantowski, Philippe, Rombaux, Joel, Romualdez, Jose, Rosado-Pinto, Nelson, Rosario, Lanny, Rosenwasser, Oliviero, Rossi, Menachem, Rottem, Philip, W Rouadi, Nikoleta, Rovina, Irma Rozman Sinur, Mauricio, Ruiz, Lucy Tania Ruiz Segura, Dermot, Ryan, Hironori, Sagara, Daiki, Sakai, Daiju, Sakurai, Wafaa, Saleh, Johanna, Salimaki, Konstantinos, Samitas, Boleslaw, Samolinski, María Guadalupe Sánchez Coronel, Mario, Sanchez-Borges, Jaime, Sanchez-Lopez, Melissa, Sansonna, Codrut, Sarafoleanu, Faradiba Sarquis Serpa, Joaquin, Sastre, Eleonora, Savi, Agne, Savonyte, Bisher, Sawaf, Glenis, K Scadding, Sophie, Scheire, Peter, Schmid-Grendelmeier, Juan Francisco Schuhl, Holger, Schunemann, Maria, Schvalbová, Jorgen, Schwarze, Nicola, Scichilone, Gianenrico, Senna, Cecilia, Sepúlveda, Elie, Serrano, Sara, Shamai, Aziz, Sheikh, Mike, Shields, Vasil, Shishkov, Nikos, Siafakas, Alexander, Simeonov, Estelle Fer Simons, Juan Carlos Sisul, Brigita, Sitkauskiene, Ingelbjorg, Skrindo, Tanja Soklič Košak, Dirceu, Solé, Martin, Sondermann, Talant, Sooronbaev, Manuel, Soto-Martinez, Manuel, Soto-Quiros, Barnaro Sousa Pinto, Milan, Sova, Michael, Soyka, Krzysztof, Specjalski, Annette, Sperl, Otto, Spranger, Sofia, Stamataki, Lina, Stefanaki, Cristiana, Stellato, Rafael, Stelmach, Timo, Strandberg, Petra, Stute, Abirami, Subramaniam, Charlotte Suppli Ulrik, Michael, Sutherland, Silvia, Sylvestre, Aikaterini, Syrigou, Luis Taborda Barata, Nadejda, Takovska, Rachel, Tan, Frances, Tan, Vincent, Tan, Ing Ping Tang, Masami, Taniguchi, Line, Tannert, Pongsakorn, Tantilipikorn, Jessica, Tattersall, Filippo, Tesi, Uta, Thieme, Carel, Thijs, Mike, Thomas, Teresa, To, Ana Maria Todo-Bom, Alkis, Togias, Peter-Valentin, Tomazic, Vesna, Tomic-Spiric, Sanna, Toppila-Salmi, Maria-José Torres Jaen, Elina, Toskala, Massimo, Triggiani, Nadja, Triller, Katja, Triller, Ioanna, Tsiligianni, Uberti, M, Ruxandra, Ulmeanu, Jure, Urbancic, Marilyn Urrutia Pereira, Martina, Vachova, Felipe, Valdés, Rudolf, Valenta, Marylin Valentin Rostan, Antonio, Valero, Arunas, Valiulis, Mina, Vallianatou, Erkka, Valovirta, Michiel Van Eerd, Eric Van Ganse, Marianne van Hage, Olivier, Vandenplas, Tuula, Vasankari, Dafina, Vassileva, Cesar Velasco Munoz, Maria Teresa Ventura, Cécilia, Vera-Munoz, Frédéric, Viart, Dilyana, Vicheva, Pakit, Vichyanond, Petra, Vidgren, Giovanni, Viegi, Claus, Vogelmeier, Leena Von Hertzen, Theodoros, Vontetsianos, Dimitris, Vourdas, Vu Tran Thien Quan, Martin, Wagenmann, Samantha, Walker, Dana, Wallace, Yun De Wang, Susan, Waserman, Katrin, Wehner, Magnus, Wickman, Sian, Williams, Dennis, Williams, Nicola, Wilson, Gary, Wong, Kent, Woo, Lucyna, Wozniak, John, Wright, Piotr, Wroczynski, Paraskevi, Xepapadaki, Plamen, Yakovliev, Masao, Yamaguchi, Kwok, Yan, Yoke Yeow Yap, Mais, Yassin, Barbara, Yawn, Panayiotis, Yiallouros, Arzu, Yorgancioglu, Shigemi, Yoshihara, Ian, Young, Osman, B Yusuf, Asghar, Zaidi, Fares, Zaitoun, Petra, Zalud, Heather, Zar, T Zedda, M, Mario, E Zernotti, Luo, Zhang, Nanshan, Zhong, Mihaela, Zidarn, Torsten, Zuberbier, Celia, Zubrinich, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Barts & The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Central Hospital [Finland] (HUCH), Departamento de Geociencias, Ambiente e Ordenamento do Territorio (DGAOT), Universidade do Porto = University of Porto, University of Naples Federico II = Università degli studi di Napoli Federico II, Euromov (EuroMov), Université de Montpellier (UM), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Center of Research in Health Technologies and Information Systems (CINTESIS), AgroParisTech, World Institute of Kimchi [Gwangju], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Edinburgh, Universität Zürich [Zürich] = University of Zurich (UZH), Humboldt-Universität zu Berlin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Universidade do Porto, University of Naples Federico II, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), MORNET, Dominique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet J., Cristol J.-P., Czarlewski W., Anto J.M., Martineau A., Haahtela T., Fonseca S.C., Iaccarino G., Blain H., Fiocchi A., Canonica G.W., Fonseca J.A., Vidal A., Choi H.-J., Kim H.J., Le Moing V., Reynes J., Sheikh A., Akdis C.A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Alburdan H., Aldrey-Palacios O., Alvarez Cuesta E., Alwan Salman H., Alzaabi A., Amade S., Ambrocio G., Angles R., Annesi-Maesano I., Ansotegui I.J., Ara Bardajo P., Arasi S., Arrais M., Arshad H., Artesani M.-C., Asayag E., Avolio F., Azhari K., Bachert C., Bagnasco D., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Basagana X., Bateman E.D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bekere A., Bel E., Ben Kheder A., Benson M., Berghea E.-C., Bergmann K.-C., Bernardini R., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N.E., Bilo M.-B., Bindslev-Jensen C., Bjermer L., Bobolea I., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C.E., Brozek J., Brussino L., Buhl R., Bumbacea R., Buquicchio R., Burguete Cabanas M.-T., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Canevari F., Cano A., Canonican G.W., Capriles-Hulett A., Caraballo L., Cardona V., Carlsen K.-H., Carmona Pirez J., Caro J., Carr W., Carreiro-Martins P., Carreon-Asuncion F., Carriazo A.-M., CarrionyRibas C., Casale T., Castor M.-A., Castro E., Caviglia A.G., Cecchi L., Cepeda Sarabia A., Chalubinski M., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chaves Loureiro C., Chavez Garcia A.-A., Chelninska M., Chen Y., Cheng L., Chinthrajah S., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A.-C., Compalati E., Constantinidis J., Correia de Sousa J., Costa E.M., Costa D., del Carmen Costa Dominguez M., Coste A., Cottini M., Cox L., Crisci C., Crivellaro M.A., Cruz A.A., Cullen J., Custovic A., Cvetkovski B., D'Amato G., da Silva J., Dahl R., Dahlen S.-E., Daniilidis V., Darjazini Nahhas L., Darsow U., Davies J., de Blay F., De Feo G., De Guia E., De la Torre Navarrete J.-R., De los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimic Janjic S., Dimou M., Dinh-Xuan A.T., Djukanovic R., Do Ceu Texeira M., Dokic D., Dominguez Silva M.G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Dupas E., Durham S., Duse M., Dykewicz M., Ebo D., Edelbaher N., Eiwegger T., Eklund P., El-Gamal Y., El-Sayed Z.A., El-Sayed S.S., El-Seify M., Emuzyte R., Enecilla L., Erhola M., Espinoza H., Espinoza Contreras J.G., Farrell J., Fernandez L., Fimbres Jimenez P., Fink Wagner A., Fokkens W.J., Folletti L., Fontaine J.-F., Forastiere F., Fuentes Perez J.M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J.L., Gamkrelidze A., Garcia A., Garcia Cobas C.Y., de la Luz Hortensia Garcia Cruz M., Ortiz V.G., Gayraud J., Gelardi M., Gemicioglu B., Gennimata D., Genova S., Gereda J., Gerth van Wijk R., Giuliano A., Gomez R.-M., Gonzalez Ballester M.-A., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Halpin D., Hamelmann E., Hammadi S., Harvey R., Heffler E., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y.R., Humbert M., Husain S., Hyland M., Ibrahim M., Ilina N., Illario M., Incorvaia C., Infantino A., Irani C., Ispayeva Z., Ivancevich J.C., Jares E.E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R.D., Johnston S.L., Joos G., Jost M., Julge K., Jung K.-S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kavaliukaite L., Bennoor K.S., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kirenga B., Kleine-Tebbe J., Klimek L., Ko F.W., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Koskinen S., Kosnik M., Kostka T., Kostov K.V., Kowalski M.L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kuitunen M., Kull I., Kuna P., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Landi M., Lane S., Larenas-Linnemann D.E., Lau S., Laune D., Lavrut J., Le L., Lenzenhuber M., Leo G., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Maggi E., Magnan A., Mahboub B., Mair A., Maitland van der Zee A.-H., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marseglia G., Marshall G., Masjedi M.R., Maspero J.F., Matta Campos J.J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melioli G., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Micheli Y., Miculinic N., Midao L., Mihaltan F., Mikos N., Milanese M., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M.D., Mohammad Y., Moharra F.-M., Moin M., Molimard M., Momas I., Mommers M., Monaco A., Montefort S., Montenegro L.-E., Monti R., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Mullol J., Munter L., Muraro A., Murray R., Musarra A., Mustakov T., Naclerio R., Nadeau K.C., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nettis E., Neuberger D., Nicod L., Nicola S., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R.E., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Padilla F.-J., Paggiaro P.L., Pagkalos A., Pajno G., Pala G., Palaniappan S., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papadopoulos N.G., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.-S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pellegino S., Pereira A., Pereira M., Perez T., Perna A., Peroni D., Pfaar O., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puggioni F., Puig-Domenech E., Puy R., Rabe K., Rabotti S., Raciborski F., Ramos J., Recalcati C., Recto M.T., Reda S.M., Regateiro F.S., Reider N., Reitsma S., Repka-Ramirez S., Ridolo E., Rimmer J., Rivero Yeverino D., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Robles K., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolla G., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Romantowski J., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rossi O., Rottem M., Rouadi P.W., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L.T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Samitas K., Samolinski B., Sanchez Coronel M.G., Sanchez-Borges M., Sanchez-Lopez J., Sansonna M., Sarafoleanu C., Sarquis Serpa F., Sastre J., Savi E., Savonyte A., Sawaf B., Scadding G.K., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Schwarze J., Scichilone N., Senna G., Sepulveda C., Serrano E., Shamai S., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Soklic Kosak T., Sole D., Sondermann M., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Pinto B.S., Sova M., Soyka M., Specjalski K., Sperl A., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Taborda Barata L., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tantilipikorn P., Tattersall J., Tesi F., Thieme U., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Tomic-Spiric V., Toppila-Salmi S., Torres Jaen M.-J., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Uberti M., Ulmeanu R., Urbancic J., Urrutia Pereira M., Vachova M., Valdes F., Valenta R., Valentin Rostan M., Valero A., Valiulis A., Vallianatou M., Valovirta E., Van Eerd M., Van Ganse E., van Hage M., Vandenplas O., Vasankari T., Vassileva D., Velasco Munoz C., Ventura M.T., Vera-Munoz C., Viart F., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Von Hertzen L., Vontetsianos T., Vourdas D., Tran Thien Quan V., Wagenmann M., Walker S., Wallace D., De Wang Y., Waserman S., Wehner K., Wickman M., Williams S., Williams D., Wilson N., Wong G., Woo K., Wozniak L., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yassin M., Yawn B., Yiallouros P., Yorgancioglu A., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zalud P., Zar H., Zedda M.T., Zernotti M.E., Zhang L., Zhong N., and Zidarn M.
Subjects: MAPK/ERK pathway, ARIA group, Allergy, [SDV]Life Sciences [q-bio], NF-KAPPA-B, debelost, Review, Pharmacology, Resveratrol, PROTECTS, chemistry.chemical_compound, 0302 clinical medicine, RESPIRATORY SYNDROME CORONAVIRUS, ENDOPLASMIC-RETICULUM STRESS, Medicine and Health Sciences, Immunology and Allergy, Medicine, OXIDATIVE STRESS, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, 2. Zero hunger, 0303 health sciences, RESPIRATORY, INSULIN-RESISTANCE, Muscle cell proliferation, SULFORAPHANE, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SIGNALING PATHWAY, Signal transduction, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, NRF2 ACTIVATORS, MUSCLE-CELL PROLIFERATION, Immunology, 610 Medicine & health, Lung injury, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ACUTE LUNG INJURY, 03 medical and health sciences, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, udc:616.9, odpornost proti inzulinu, SULFORAPHANE PROTECTS, Transcription factor, PI3K/AKT/mTOR pathway, 030304 developmental biology, Science & Technology, business.industry, SARS-CoV-2, food, medicine.disease, chemistry, hranila, SYNDROME CORONAVIRUS, business, hrana, GREEN TEA
Abstract: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Published: 2020
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28. 国际过敏与鼻科学共识声明 : 变应性鼻炎

Author: Sarah K. Wise, Sandra Y. Lin, Elina Toskala, Richard R. Orlandi, Cezmi A. Akdis, Jeremiah A. Alt, Antoine Azar, Fuad M. Baroody, Claus Bachert, G. Walter Canonica, Thomas Chacko, Cemal Cingi, Giorgio Ciprandi, Jacquelynne Corey, Linda S. Cox, Peter Socrates Creticos, Adnan Custovic, Cecelia Damask, Adam DeConde, John M. DelGaudio, Charles S. Ebert, Jean Anderson Eloy, Carrie E. Flanagan, Wytske J. Fokkens, Christine Franzese, Jan Gosepath, Ashleigh Halderman, Robert G. Hamilton, Hans Jürgen Hoffman, Jens M. Hohlfeld, Steven M. Houser, Peter H. Hwang, Cristoforo Incorvaia, Deborah Jarvis, Ayesha N. Khalid, Maritta Kilpeläinen, Todd. T. Kingdom, Helene Krouse, Desiree Larenas‐Linnemann, Adrienne M. Laury, Stella E. Lee, Joshua M. Levy, Amber U. Luong, Bradley F. Marple, Edward D. McCoul, K. Christopher McMains, Erik Melén, James W. Mims, Gianna Moscato, Joaquim Mullol, Harold S. Nelson, Monica Patadia, Ruby Pawankar, Oliver Pfaar, Michael P. Platt, William Reisacher, Carmen Rondón, Luke Rudmik, Matthew Ryan, Joaquin Sastre, Rodney J. Schlosser, Russell A. Settipane, Hemant P. Sharma, Aziz Sheikh, Timothy L. Smith, Pongsakorn Tantilipikorn, Jody R. Tversky, Maria C. Veling, De Yun Wang, Marit Westman, Magnus Wickman, Mark Zacharek, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: Otorhinolaryngology, 1107 Immunology, Immunology and Allergy
Published: 2018

29. 过敏和鼻科学国际共识声明 : 鼻窦炎

Author: Richard R. Orlandi, Todd T. Kingdom, Peter H. Hwang, Timothy L. Smith, Jeremiah A. Alt, Fuad M. Baroody, Pete S. Batra, Manuel Bernal-Sprekelsen, Neil Bhattacharyya, Rakesh K. Chandra, Alexander Chiu, Martin J. Citardi, Noam A. Cohen, John DelGaudio, Martin Desrosiers, Hun-Jong Dhong, Richard Douglas, Berrylin Ferguson, Wytske J. Fokkens, Christos Georgalas, Andrew Goldberg, Jan Gosepath, Daniel L. Hamilos, Joseph K. Han, Richard Harvey, Peter Hellings, Claire Hopkins, Roger Jankowski, Amin R. Javer, Robert Kern, Stilianos Kountakis, Marek L. Kowalski, Andrew Lane, Donald C. Lanza, Richard Lebowitz, Heung-Man Lee, Sandra Y. Lin, Valerie Lund, Amber Luong, Wolf Mann, Bradley F. Marple, Kevin C. McMains, Ralph Metson, Robert Naclerio, Jayakar V. Nayak, Nobuyoshi Otori, James N. Palmer, Sanjay R. Parikh, Desiderio Passali, Anju Peters, Jay Piccirillo, David M. Poetker, Alkis J. Psaltis, Hassan H. Ramadan, Vijay R. Ramakrishnan, Herbert Riechelmann, Hwan-Jung Roh, Luke Rudmik, Raymond Sacks, Rodney J. Schlosser, Brent A. Senior, Raj Sindwani, James A. Stankiewicz, Michael Stewart, Bruce K. Tan, Elina Toskala, Richard Voegels, De Yun Wang, Erik K. Weitzel, Sarah Wise, Bradford A. Woodworth, Peter-John Wormald, Erin D. Wright, Bing Zhou, and David W. Kennedy
Subjects: Otorhinolaryngology, Immunology and Allergy
Published: 2016
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30. Treatment of allergic rhinitis using mobile technology with real world data: The MASK observational pilot study

Author: Valérie Siroux, Cristiana Stellato, Olivier Vandenplas, Isabella Annesi-Maesano, P V Tomazic, A. Bedbrook, Luís Nogueira-Silva, M. Morais Almeida, Maddalena Illario, Wytske J. Fokkens, Piotr Kuna, Isabelle Bosse, Erik Melén, Joaquim Mullol, G Alexis-Alexandre, Esben Eller, Nikolaos G. Papadopoulos, Pascal Demoly, B. Samolinski, D. Larenas-Linnemann, Carsten Bindslev-Jensen, Peter McDowall, Ana Margarida Pereira, M. Bewick, Josep M. Antó, Torsten Zuberbier, A. Todo Bom, Pedro Carreiro-Martins, R. Murray, A. Yorgancioglu, F. Portejoie, Robyn E O'Hehir, E Murphy, Inger Kull, D. Laune, A. Valiulis, G. Passalacqua, T. Keil, Peter Hellings, M. L. Kowalski, Bilun Gemicioglu, Alvaro A. Cruz, P. Devillier, A. Valero, L. Klimek, Aziz Sheikh, G. De Vries, J. Just, Davide Caimmi, Niels H. Chavannes, K. C. Bergmann, João Fonseca, Erkka Valovirta, J. F. Fontaine, Dermot Ryan, S. Shamai, Massimo Triggiani, Enrica Menditto, Giorgio Walter Canonica, M. Wickman, Jean Bousquet, Sinthia Bosnic-Anticevich, Gabrielle L. Onorato, M. van Eerd, S. Arnavielhe, E Mathieu-Dupas, David Price, Tari Haahtela, O. Spranger, V. Kvedariene, Claus Bachert, R Mösgues, AII - Inflammatory diseases, Ear, Nose and Throat, AII - Amsterdam institute for Infection and Immunity, Other departments, Bousquet, J, Arnavielhe, S, Bedbrook, A, Alexis-Alexandre, G, van Eerd, M, Murray, R, Canonica, G W, Illario, M, Menditto, E, Passalacqua, G, Stellato, C, Triggiani, M, Carreiro-Martins, P, Fonseca, J, Morais Almeida, M, Nogueira-Silva, L, Pereira, A M, Todo Bom, A, Bosse, I, Caimmi, D, Demoly, P, Devillier, P, Fontaine, J F, Just, J, Onorato, G L, Kowalski, M L, Kuna, P, Samolinski, B, Anto, J M, Mullol, J, Valero, A, Tomazic, P V, Bergmann, K C, Keil, T, Klimek, L, Mösgues, R, Shamai, S, Zuberbier, T, Murphy, E, Mcdowall, Peter, Price, D, Ryan, D, Sheikh, A, Chavannes, N H, Fokkens, W J, Kvedariene, V, Valiulis, A, Bachert, C, Hellings, P W, Kull, I, Melén, E, Wickman, M, Bindslev-Jensen, C, Eller, E, Haahtela, T, Valovirta, E, Papadopoulos, N G, Annesi-Maesano, I, Bewick, M, Bosnic-Anticevich, S, Cruz, A A, De Vries, G, Gemicioglu, B, Larenas-Linnemann, D, Laune, D, Mathieu-Dupas, E, O'Hehir, R E, Portejoie, F, Siroux, V, Spranger, O, Vandenplas, O, Yorgancioglu, A, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], 'Federico II' University of Naples Medical School, CHU Montpellier, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Barcelona, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University Hospital of Cologne [Cologne], Department of Computer Science [Haifa], University of Haifa [Haifa], University of Edinburgh, Vilnius University [Vilnius], Ghent University Hospital, University Hospitals Leuven [Leuven], The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], University of Helsinki, The University of Sydney, Heidelberg University, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), University of Turku, Department of Dermatology, Allergology and Venereology, Clinicum, and HUS Inflammation Center
Subjects: Research design, Male, IMPACT, Pilot Projects, Review, Global Health, law.invention, DOUBLE-BLIND, 0302 clinical medicine, FLUTICASONE, Randomized controlled trial, law, QUALITY-OF-LIFE, HDE ALER, Immunology and Allergy, Medicine, AZELASTINE, 030212 general & internal medicine, Prospective Studies, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, mHealth, Randomized Controlled Trials as Topic, treatment, Disease Management, mobile technology, observational study, rhinitis, Middle Aged, Combined Modality Therapy, Mobile Applications, 3. Good health, rhiniti, Research Design, GUIDED SELF-MANAGEMENT, [SDV.IMM]Life Sciences [q-bio]/Immunology, Over-the-counter, Female, mHealth, mobile technology, observational study, rhinitis, treatment, medicine.drug, Adult, medicine.medical_specialty, Immunology, CONTROLLED-TRIAL, Drug Prescriptions, Medication Adherence, 03 medical and health sciences, Young Adult, Quality of life (healthcare), Journal Article, Humans, Asthma, business.industry, CARE, medicine.disease, Azelastine, Rhinitis, Allergic, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, Physical therapy, ASTHMA, Observational study, business, TRADITIONAL TREATMENT
Abstract: BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials (RCTs) as they reflect "real world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real life treatment of allergic rhinitis using mobile technology.METHODS: A mobile phone app (Allergy Diary, freely available Google Play and Apple App stores) collects the data of daily visual analogue scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries.RESULTS: A total of 2,871 users filled in 17,091 days of VAS in 2015 and 2016. Medications were reported for 9,634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single or multiple treatments (worst control).CONCLUSIONS: The present study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in allergic rhinitis. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings and generates new hypotheses. This article is protected by copyright. All rights reserved.
Published: 2018
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31. A chest physician's guide to mechanisms of sinonasal disease

Author: C. van Drunen, Claus Bachert, P W Hellings, Ben Nemery, Wouter Huvenne, Tania Maes, Valérie Hox, Jeroen Vanoirbeek, Jan Ceuppens, Guy Joos, and Wytske J. Fokkens
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Endogenous Factors, Inflammation, Air Pollution, Occupational Exposure, medicine, Humans, Respiratory system, Sinusitis, Primary ciliary dyskinesia, Rhinitis, Chest physician, business.industry, Bacterial Infections, Allergens, respiratory system, medicine.disease, Sinonasal disease, respiratory tract diseases, Mycoses, Mucociliary Clearance, Virus Diseases, Immunology, medicine.symptom, Airway, business, Upper airway disease
Abstract: The upper and lower airways are closely linked from an anatomical, histological and immunological point of view, with inflammation in one part of the airways influencing the other part. Despite the concept of global airway disease, the upper airways tend to be overlooked by respiratory physicians. We provide a clinical overview of the most important and recent insights in rhinitis and rhinosinusitis in relation to lower airway disease. We focus on the various exogenous and endogenous factors that play a role in the development and aggravation of chronic upper airway inflammation. In addition to the classical inhaled allergens or microorganisms with well-defined pathophysiological mechanisms in upper airway disease, environmental substances such as cigarette smoke, diesel exhaust particles and occupational agents affecting lower airway homeostasis have recently gained attention in upper airway research. We are only at the beginning of understanding the complex interplay between exogenous and endogenous factors like genetic, immunological and hormonal influences on chronic upper airway inflammation. From a clinical perspective, the involvement of upper and lower airway disease in one patient can only be fully appreciated by doctors capable of understanding the interplay between upper and lower airway inflammation.
Published: 2015
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32. Activity of Bacteriophages in Removing Biofilms of

Author: Stephanie A, Fong, Amanda, Drilling, Sandra, Morales, Marjolein E, Cornet, Bradford A, Woodworth, Wytske J, Fokkens, Alkis J, Psaltis, Sarah, Vreugde, and Peter-John, Wormald
Subjects: Cystic Fibrosis, chronic rhinosinusitis, multidrug resistant, Australia, Microbial Sensitivity Tests, Microbiology, biofilm, Anti-Bacterial Agents, bacteriophage, Biofilms, Drug Resistance, Multiple, Bacterial, Pseudomonas aeruginosa, Humans, Bacteriophages, Pseudomonas Infections, Phage Therapy, Sinusitis, Phylogeny, Multilocus Sequence Typing, Original Research
Abstract: Introduction: Pseudomonas aeruginosa infections are prevalent amongst chronic rhinosinusitis (CRS) sufferers. Many P. aeruginosa strains form biofilms, leading to treatment failure. Lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death. Aim: To assess the activity of a phage cocktail in eradicating biofilms of ex vivo P.aeruginosa isolates from CRS patients. Methods: P. aeruginosa isolates from CRS patients with and without cystic fibrosis (CF) across three continents were multi-locus sequence typed and tested for antibiotic resistance. Biofilms grown in vitro were treated with a cocktail of four phages (CT-PA). Biofilm biomass was measured after 24 and 48 h, using a crystal violet assay. Phage titrations were performed to confirm replication of the phages. A linear mixed effects model was applied to assess the effects of treatment, time, CF status, and multidrug resistance on the biomass of the biofilm. Results: The isolates included 44 strain types. CT-PA treatment significantly reduced biofilm biomass at both 24 and 48 h post-treatment (p < 0.0001), regardless of CF status or antibiotic resistance. Biomass was decreased by a median of 76% at 48 h. Decrease in biofilm was accompanied by a rise in phage titres for all except one strain. Conclusion: A single dose of phages is able to significantly reduce biofilms formed in vitro by a range of P.aeruginosa isolates from CRS patients. This represents an exciting potential and novel targeted treatment for P. aeruginosa biofilm infections and multidrug resistant bacteria.
Published: 2017

33. Nasal polyposis and asthma: the otorhinolaryngologist's view

Author: Wytske J. Fokkens and Peter W. Hellings
Published: 2017
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34. New Findings in Nonallergic Rhinitis and Local Allergic Rhinitis

Author: Ingrid Terreehorst, Carmen Rondon, Cornelis M. van Drunen, Wytske J. Fokkens, Peter Hellings, and Christine L. Segboer
Subjects: Allergy, medicine.medical_specialty, business.industry, Rhinitis medicamentosa, Disease, medicine.disease, Dermatology, Mixed rhinitis, Nonallergic rhinitis, Otorhinolaryngology, Inflammatory cascade, Immunology and Allergy, Medicine, Surgery, Neurology (clinical), business
Abstract: Research in rhinitis has primarily focused on allergic rhinitis and important aspects of the disease such as the IgE-mediated inflammatory cascade, the impact on quality of life, the impact on the lower airways, and control and severity of the disease, especially in those patients in which control is not easily obtained. However, a significant number of patients with persistent rhinitis do not show systemic sensitization to aeroallergens or signs of infection. These patients are defined under the umbrella term “nonallergic rhinitis” or “noninfectious rhinitis.” Nonallergic rhinitis comprises a large number of phenotypes and endotypes, such as rhinitis medicamentosa, drug-induced rhinitis, rhinitis of the elderly, idiopathic rhinitis, and local allergic rhinitis. This review describes the new pathophysiology and clinical insights into these different forms of nonallergic rhinitis with special emphasis on local allergy. New recommendations in diagnosis and treatment are given.
Published: 2013
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35. Safety and efficacy of a bioabsorbable fluticasone propionate-eluting sinus dressing in postoperative management of endoscopic sinus surgery: a randomized clinical trial

Author: Gwijde F J P M, Adriaensen, Keng-Hua, Lim, and Wytske J, Fokkens
Subjects: Adult, Aged, 80 and over, Drug Implants, Male, Nasal Surgical Procedures, Anti-Inflammatory Agents, Endoscopy, Middle Aged, Young Adult, Treatment Outcome, Double-Blind Method, Absorbable Implants, Paranasal Sinuses, Fluticasone, Humans, Female, Postoperative Period, Aged
Abstract: Postoperative wound healing after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS) is an important factor in procedural success. Local steroids and separation of opposing mucosa are commonly implemented to optimize healing. A bioabsorbable, fluticasone propionate (FP)-eluting implant, SinuBand FP, was assessed for its safety and efficacy when used in patients with CRS and nasal polyps, who were indicated for ESS including bilateral anterior and posterior ethmoidectomy.A first-in-human, randomized, partially double-blind, single-tertiary-referral-center, controlled trial enrolling 30 patients receiving 2 of 3 treatments (1 per sinus, intrapatient control): SinuBand FP, SinuBand (without FP), or standard nasal pack (Merocel®). Primary outcome measures were local safety, ocular safety (intraocular pressure [IOP], lens opacity), and 24-hour urine cortisol. Secondary measures (evaluated by independent review of postoperative video endoscopies) were ethmoid inflammation, polyp score, adhesion formation, and Lund-Kennedy score. Patient-reported outcomes of postoperative pain, nasal congestion, and nasal discharge were collected.Of 30 enrolled patients (used for safety analysis), 27 patients completed the trial. SinuBand FP showed local safety, ocular safety, and no significant change in 24-hour urine cortisol. SinuBand FP showed a trend to do better concerning inflammation. Concerning polyp score SinuBand FP did significantly better compared to Merocel (p = 0.03). No significance compared to SinuBand without corticosteroids (p = 0.97). Adhesions were comparable across treatments. Patient reported pain was nominally lower in the SinuBand group.SinuBand FP was well tolerated and showed evidence of efficacy. A larger study is needed to further evaluate and confirm the benefits of SinuBand FP.
Published: 2016

36. Dendritic Cell Subsets in Oral Mucosa of Allergic and Healthy Subjects

Author: Esther J. J. de Groot, Danielle van Egmond, Susanne M. Reinartz, Joost van Tongeren, Cornelis M. van Drunen, Wytske J. Fokkens, MUMC+: MA Keel Neus Oorheelkunde (9), RS: GROW - School for Oncology and Reproduction, RS: FHML non-thematic output, RS: GROW - R2 - Basic and Translational Cancer Biology, Ear, Nose and Throat, Other departments, and AII - Amsterdam institute for Infection and Immunity
Subjects: 0301 basic medicine, Male, Allergy, Pathology, Myeloid, BLOOD, Physiology, medicine.medical_treatment, Biopsy, Respiratory System, lcsh:Medicine, Mucous membrane of nose, Cell Count, INHALED ANTIGEN, Epithelium, 0302 clinical medicine, Animal Cells, hemic and lymphatic diseases, Medicine and Health Sciences, Group-Specific Staining, Oral mucosa, lcsh:Science, Immune Response, Staining, Multidisciplinary, INDUCTION, Cell Staining, LANGERHANS CELLS, hemic and immune systems, Middle Aged, Immunohistochemistry, Healthy Volunteers, Body Fluids, medicine.anatomical_structure, MAST-CELLS, Female, Anatomy, Cellular Types, Research Article, Adult, medicine.medical_specialty, Adolescent, Immune Cells, Immunology, Antigen-Presenting Cells, Surgical and Invasive Medical Procedures, Research and Analysis Methods, 03 medical and health sciences, Young Adult, Immune system, RATIO, medicine, Hypersensitivity, Humans, NASAL, IMMUNOTHERAPY, Lamina propria, business.industry, lcsh:R, Hematoxylin Staining, Mouth Mucosa, Biology and Life Sciences, Dendritic cell, Immunotherapy, Dendritic Cells, Cell Biology, medicine.disease, Nasal Mucosa, 030104 developmental biology, Biological Tissue, Specimen Preparation and Treatment, Case-Control Studies, T-CELLS, lcsh:Q, business, SKIN, 030215 immunology
Abstract: Immunohistochemistry was used to identify, enumerate, and describe the tissue distribution of Langerhans type (CD1a and CD207), myeloid (CD1c and CD141), and plasmacytoid (CD303 and CD304) dendritic cell subsets in oral mucosa of allergic and non-allergic individuals. Allergic individuals have more CD141+ myeloid cells in epithelium and more CD1a + Langerhans cells in the lamina propria compared to healthy controls, but similar numbers for the other DC subtypes. Our data are the first to describe the presence of CD303+ plasmacytoid DCs in human oral mucosa and a dense intraepithelial network of CD141+ DCs. The number of Langerhans type DCs (CD1a and CD207) and myeloid DCs (CD1c), was higher in the oral mucosa than in the nasal mucosa of the same individual independent of the atopic status.
Published: 2016

37. Role of Innate Immunity in the Pathogenesis of Chronic Rhinosinusitis: Progress and New Avenues

Author: Christine L. Segboer, Wytske J. Fokkens, Jenny Mjösberg, Cornelis M. van Drunen, and Marjolein E. Cornet
Subjects: Pulmonary and Respiratory Medicine, Immunology, Microorganisms, Sinusitis (ML Kowalski, Section Editor), Pattern-recognition receptors, Pathogenesis, Disease, Biology, Epithelium, ILC2, Anti-Infective Agents, medicine, Humans, Immunology and Allergy, Sinusitis, Rhinitis, Innate immunity, Nasal polyposis, Polymorphism, Genetic, Innate immune system, Bacteria, Fungi, Pattern recognition receptor, Fibroblasts, medicine.disease, Immunity, Innate, Pathophysiology, Chronic rhinosinusitis, Receptors, Pattern Recognition, Chronic Disease, Etiology
Abstract: Chronic rhinosinusitis is a heterogeneous and multifactorial disease with unknown etiology. Aberrant responses to microorganisms have been suggested to play a role in the pathophysiology of the disease. Research has focused on the presence, detection, response to, and eradication of these potential threats. Main topics seem to center on the contribution of structural cells such as epithelium and fibroblasts, on the consequences of activation of pattern-recognition receptors, and on the role of antimicrobial agents. This research should be viewed not only in the light of a comparison between healthy and diseased individuals, but also in a comparison between patients who do or do not respond to treatment. New players that could play a role in the pathophysiology seem to surface at regular intervals, adding to our understanding (and the complexity) of the disease and opening new avenues that may help fight this incapacitating disease.
Published: 2012
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38. Practical guide to skin prick tests in allergy to aeroallergens

Author: Lucie Heinzerling, Thomas B. Casale, Carsten Bindslev-Jensen, O. Kalayci, Philippe-Jean Bousquet, Marek L. Kowalski, Carlos E. Baena-Cagnani, Rudolf Valenta, Antonino Romano, Peter Burney, L. Nazamova-Baranova, Torsten Zuberbier, Adriano Mari, Osman M. Yusuf, K. C. Bergmann, J. Ring, Ana Todo-Bom, Kai-Håkon Carlsen, K. Ohta, J Mullol, R. Gerth-Van-Wijk, Stephen R. Durham, L. Cox, Isabella Annesi-Maesano, Anca-Mirela Chiriac, Magnus Wickman, Dermot Ryan, Peter Schmid-Grendelmeier, K. C. Lødrup Carlsen, Robyn E O'Hehir, David Price, Ruta Dubakiene, Tari Haahtela, Jean Bousquet, Barbara Rogala, Claus Bachert, P. Panzner, Wytske J. Fokkens, Giovanni Passalacqua, Alvaro A. Cruz, B. Samolinski, Pascal Demoly, Stefan Woehrl, F. E. R. Simons, Giorgio Walter Canonica, and Nikolaos G. Papadopoulos
Subjects: Intoxicative inhalant, medicine.medical_specialty, Allergy, Pathology, Clinical immunology, business.industry, Immunology, Skin test, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Air pollutants, Daily practice, Family medicine, medicine, Immunology and Allergy, 030212 general & internal medicine, Allergists, business, Asthma
Abstract: To cite this article: Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Lodrup Carlsen KC, Price D, Samolinski B, Simons FER, Wickman M, Annesi-Maesano I, Baena-Cagnani CE, Bergmann KC, Bindslev-Jensen C, Casale TB, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth-van-Wijk R, Kalayci O, Kowalski ML, Mari A, Mullol J, Nazamova-Baranova L, O'Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Rogala B, Romano A, Ryan D, Schmid-Grendelmeier P, Todo-Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Demoly P. Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02728.x ABSTRACT: This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.
Published: 2011
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39. Dendritic cells in nasal mucosa of subjects with different allergic sensitizations

Author: Susanne M. Reinartz, Cornelis M. van Drunen, Wytske J. Fokkens, Danielle van Egmond, Joost van Tongeren, Esther J. J. de Groot, Amsterdam institute for Infection and Immunity, and Ear, Nose and Throat
Subjects: Adult, Male, Adolescent, business.industry, Immunology, Rhinitis, Allergic, Seasonal, Mucous membrane of nose, Dendritic Cells, Allergens, Middle Aged, Nasal Mucosa, Text mining, Humans, Immunology and Allergy, Medicine, Female, business
Published: 2011
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40. Complications of balloon packing in epistaxis

Author: Dirk Jan Menger, Lenka Vermeeren, W Derks, Wytske J. Fokkens, Other departments, Amsterdam institute for Infection and Immunity, and Ear, Nose and Throat
Subjects: Male, medicine.medical_specialty, Time Factors, Treatment outcome, Mucous membrane of nose, Case Reports, Balloon, Cartilaginous skeleton, Packing, Necrosis, Nasal Cartilages, medicine, Journal Article, Humans, Tampons, Surgical, Balloon packing, Nasal cartilages, Aged, 80 and over, Medicine(all), Wound Healing, business.industry, Hemostatic Techniques, General Medicine, Middle Aged, Hemostatic technique, Surgery, Nasal Mucosa, Treatment Outcome, Epistaxis, Otorhinolaryngology, Head and neck surgery, Female, business
Abstract: Although balloon packing appears to be efficient to control epistaxis, severe local complications can occur. We describe four patients with local lesions after balloon packing. Prolonged balloon packing can cause damage to nasal mucosa, septum and alar skin (nasal mucosa, the cartilaginous skeleton and the overlying soft-tissue envelope) and should, therefore, be avoided. We suggest early nasendoscopy in general anesthesia to identify and treat the bleeding focus, if bleeding cannot be controlled with regular packing.
Published: 2015

41. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Author: Richard R, Orlandi, Todd T, Kingdom, Peter H, Hwang, Timothy L, Smith, Jeremiah A, Alt, Fuad M, Baroody, Pete S, Batra, Manuel, Bernal-Sprekelsen, Neil, Bhattacharyya, Rakesh K, Chandra, Alexander, Chiu, Martin J, Citardi, Noam A, Cohen, John, DelGaudio, Martin, Desrosiers, Hun-Jong, Dhong, Richard, Douglas, Berrylin, Ferguson, Wytske J, Fokkens, Christos, Georgalas, Andrew, Goldberg, Jan, Gosepath, Daniel L, Hamilos, Joseph K, Han, Richard, Harvey, Peter, Hellings, Claire, Hopkins, Roger, Jankowski, Amin R, Javer, Robert, Kern, Stilianos, Kountakis, Marek L, Kowalski, Andrew, Lane, Donald C, Lanza, Richard, Lebowitz, Heung-Man, Lee, Sandra Y, Lin, Valerie, Lund, Amber, Luong, Wolf, Mann, Bradley F, Marple, Kevin C, McMains, Ralph, Metson, Robert, Naclerio, Jayakar V, Nayak, Nobuyoshi, Otori, James N, Palmer, Sanjay R, Parikh, Desiderio, Passali, Anju, Peters, Jay, Piccirillo, David M, Poetker, Alkis J, Psaltis, Hassan H, Ramadan, Vijay R, Ramakrishnan, Herbert, Riechelmann, Hwan-Jung, Roh, Luke, Rudmik, Raymond, Sacks, Rodney J, Schlosser, Brent A, Senior, Raj, Sindwani, James A, Stankiewicz, Michael, Stewart, Bruce K, Tan, Elina, Toskala, Richard, Voegels, De Yun, Wang, Erik K, Weitzel, Sarah, Wise, Bradford A, Woodworth, Peter-John, Wormald, Erin D, Wright, Bing, Zhou, and David W, Kennedy
Subjects: Consensus, Evidence-Based Medicine, Nasal Polyps, Acute Disease, Chronic Disease, Humans, Sinusitis, Child, Rhinitis
Abstract: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS).Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus.The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS.As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.
Published: 2015

42. Shape of the Osseous External Auditory Canal and Its Relationship to Troublesome Cavities

Author: Erik, van Spronsen, Huibert F, van Waegeningh, Simon, Geerse, Wytske J, Fokkens, and Fenna A, Ebbens
Subjects: Adult, Aged, 80 and over, Male, Temporal Bone, Middle Aged, Otitis Externa, Risk Assessment, Severity of Illness Index, Mastoid, Cohort Studies, Logistic Models, Multidetector Computed Tomography, Multivariate Analysis, Humans, Female, Otologic Surgical Procedures, Ear Canal, Aged, Follow-Up Studies, Retrospective Studies
Abstract: On the basis of clinical observations, the shape of the osseous external auditory canal (OEAC) has often been seen as an etiological factor in troublesome cavities after modified radical mastoidectomy.Retrospective analysis of CT scans.To assess the role of the shape of the OEAC in troublesome modified radical cavities using computed tomographic scans of three groups of patients (without pathology and with or without draining cavities), we determined the depth of the pretympanic recess (DPTR) and its anterior curvature (ACPTR). In addition to looking at the shape of the OEAC, we also studied the role of any remaining mastoid air cells in relation to troublesome radical cavities, as well as the consultation frequency.The DPTR was significantly deeper in draining cavities than in ears without pathology and dry cavities. No difference in the ACPTR was observed. The presence of remaining mastoid air cells is significantly associated with the presence of a troublesome radical cavity.The shape of the OEAC (i.e., the DPTR) is a contributory factor to the drainage of modified radical cavities.4. Laryngoscope, 126:693-698, 2016.
Published: 2015

43. Challenges in the Management of Inverted Papilloma: A Review of 72 Revision Cases

Author: Gwijde F J P M, Adriaensen, Keng-Hua, Lim, Christos, Georgalas, Susanne M, Reinartz, and Wytske J, Fokkens
Subjects: Male, Papilloma, Inverted, Time Factors, Disease Management, Endoscopy, Middle Aged, Otorhinolaryngologic Surgical Procedures, Treatment Outcome, Humans, Female, Fluorouracil, Paranasal Sinus Neoplasms, Follow-Up Studies, Retrospective Studies
Abstract: We report on the treatment outcome of endoscopically managed sinonasal inverted papilloma, focusing on revision cases. Our aim was to identify the properties of revision cases that affect treatment outcome by comparing them to primary cases in a single center. We propose using 5-fluorouracil (5-FU) in the postoperative management of inverted papilloma.A retrospective single-center case series. This study met the criteria for approval by the local medical ethics committee.We performed a retrospective chart review identifying patients operated on between January 2003 and September 2013. Data were collected about patient demographics, symptoms, tumor attachment site, imaging, intraoperative and pathological findings, surgical approaches, postoperative treatment, follow-up, and recurrence.One hundred and twenty-one (72 revision and 49 primary) cases were retrieved with a minimum follow-up of 1 year. Revision cases have significantly higher Krouse staging (P = 0.003), different distribution of tumor attachment sites, and higher recurrence rates. The recurrence rate was 4.1% for primary cases (mean follow-up 35.5 months) and 18.1% for revision cases (mean follow-up 45 months). Eight of the recurrent cases recurred within the first year. 5-fluorouracil was applied postoperatively in 18 (5 primary and 13 revision) cases, which included one (5.6%) recurrence and one minor complication (transient periorbital swelling).The most important factors in preventing the recurrence of inverted papilloma are the determination of the location of the attachment and the completeness of resection in the primary endoscopic surgery. Revision cases have a higher recurrence rate, and the attachment sites are surgically more challenging. The use of 5-FU might have a place in the postoperative treatment of surgically challenging inverted papilloma.4.
Published: 2015

44. Objective measurements of nasal function: necessary before nasal surgery?

Author: Wytske J, Fokkens, Peter W, Hellings, Amsterdam institute for Infection and Immunity, and Ear, Nose and Throat
Subjects: Otorhinolaryngology, Nasal Surgical Procedures, otorhinolaryngologic diseases, Humans, General Medicine, Nose, respiratory system
Abstract: When we discuss nasal dysfunction, we think primarily of nasal obstruction. However, other clinical signs like rhinorrheoa, sneezing, itching, burning and loss of smell, as well as perception of the form and aesthetics of the nose should not be neglected. During the last decades, we have significantly increased our knowledge on nasal function. We are more aware of the role of questioning the patients about their symptoms, about their most bothersome symptoms and also their quality of life, and we more often report on objective measure- ments of nasal obstruction like PNIF, acoustic rhinometry and rhinomanometry. It has clearly been shown that the correlation between symptoms of nasal obstruction and objective measu- rements is low
Published: 2014
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45. Direct navigation on 3D rotational x-ray data acquired with a mobile propeller C-arm: accuracy and application in functional endoscopic sinus surgery

Author: Wytske J Fokkens, Bart Carelsen, Wiro J. Niessen, Everine B. van de Kraats, Sjirk N. Boon, Niels Noordhoek, Theo van Walsum, Biomedical Engineering and Physics, Amsterdam institute for Infection and Immunity, and Ear, Nose and Throat
Subjects: Radiological and Ultrasound Technology, business.industry, Computer science, Phantoms, Imaging, Propeller, Navigation system, Endoscopy, Functional endoscopic sinus surgery, Direct navigation, Imaging phantom, Imaging, Three-Dimensional, Surgery, Computer-Assisted, Cadaver, X ray data, Calibration, Image Processing, Computer-Assisted, Humans, Radiology, Nuclear Medicine and imaging, Computer vision, Artificial intelligence, business, Tomography, X-Ray Computed, Head, Algorithms
Abstract: Recently, three-dimensional (3D) rotational x-ray imaging has been combined with navigation technology, enabling direct 3D navigation for minimally invasive image guided interventions. In this study, phantom experiments are used to determine the accuracy of such a navigation set-up for a mobile C-arm with propeller motion. After calibration of the C-arm system, the accuracy is evaluated by pinpointing divots on a special-purpose phantom with known geometry. This evaluation is performed both with and without C-arm motion in between calibration and registration for navigation. The variation caused by each of the individual transformations in the calibration and registration process is also studied. The feasibility of direct navigation on 3D rotational x-ray images for functional endoscopic sinus surgery has been evaluated in a cadaver navigation experiment. Navigation accuracy was approximately 1.0 mm, which is sufficient for functional endoscopic sinus surgery. C-arm motion in between calibration and registration slightly degraded the registration accuracy by approximately 0.3 mm. Standard deviations of each of the transformations were in the range 0.15-0.31 mm. In the cadaver experiment, the navigation images were considered in good correspondence with the endoscopic images by an experienced ENT surgeon. Availability of 3D localization information provided by the navigation system was considered valuable by the ENT surgeon.
Published: 2005
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46. Evaluation of an intranasal house dust mite provocation model as a tool in clinical research

Author: Paul G.H. Mulder, N. B. Oldenbeuving, Wytske J. Fokkens, Alex KleinJan, P. Lumley, E. J. J. de Groot, C. M. van Drunen, Other departments, Ear, Nose and Throat, Amsterdam institute for Infection and Immunity, Otorhinolaryngology and Head and Neck Surgery, Pulmonary Medicine, and Epidemiology
Subjects: Adult, Male, Allergy, medicine.medical_specialty, Nasal Provocation Tests, Rhinitis, Allergic, Perennial, Time Factors, Adolescent, medicine.medical_treatment, Immunology, Provocation test, Mucous membrane of nose, Nasal provocation test, Fluticasone propionate, Leukocyte Count, Animals, Humans, Immunology and Allergy, Medicine, Eosinophilia, Administration, Intranasal, House dust mite, Mites, biology, business.industry, Reproducibility of Results, Dust, Middle Aged, medicine.disease, biology.organism_classification, Dermatology, Androstadienes, Eosinophils, Nasal Mucosa, Nasal spray, Fluticasone, Female, medicine.symptom, business, medicine.drug
Abstract: Background: As a result of the all-year-round exposure to house dust mite (HDM), perennial rhinitis patients never have a clear symptom-free period. In this study, we investigated whether, despite these symptoms, we can still use nasal HDM provocations to study perennial allergic rhinitis and the effects of treatment. Methods: In a parallel-group study, after 1 week treatment with either fluticasone propionate aqueous nasal spray (FPANS) or placebo, 20 patients, allergic to HDM, registered symptoms (nasal obstruction, rhinorrhoea, sneezing, pruritus and eye symptoms) using three different scoring methods [Lebel, categorical and visual analogue scale (VAS)] and peak nasal inspiratory flow (PNIF) after HDM provocations. Provocations were performed with 1000 biological units/ml and 24 h later with 10 000 biological units/ml of HDM. Before and after the provocations, nasal mucosa biopsies were taken for immunohistochemical staining to determine the number of eosinophils. Results: House dust mite provocations resulted in an increase in symptoms and a decrease in PNIF. Even at high-dose provocation, the FPANS group registered significantly lower symptoms than the placebo group for nasal blockage, sneezing, eye symptoms, and PNIF in both early and late phases. FPANS also suppressed rhinorrhoea during the late phase and the influx of eosinophils in the lamina propria. Conclusion: Despite the high background of symptoms, allergic responses can be induced in this perennial rhinitis model. The VAS score seems most suited to detect these changes and the suppression of symptoms by 7 days of FPANS treatment. Epithelial eosinophilia at baseline was correlated positively with the severity of the reaction after the first provocation.
Published: 2005
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47. Nasal involvement in allergic asthma

Author: Wytske J. Fokkens, Gert-Jan Braunstahl, Pulmonary Medicine, and Dermatology
Subjects: Allergy, business.industry, Immunology, Respiratory disease, Chronic sinusitis, Allergic asthma, Respiratory Mucosa, respiratory system, medicine.disease, Pathophysiology, Asthma, respiratory tract diseases, medicine.anatomical_structure, Nasal Polyps, Immunopathology, Immunology and Allergy, Medicine, Humans, Sinusitis, business, Nose, Rhinitis
Abstract: Even since the late 19th century, a relationship has been suspected between upper airway disease and the subsequent development or aggravation of asthma symptoms. To date, it has been generally accepted that pathologic conditions of the upper airways, e.g. allergic rhinitis, chronic sinusitis and nasal polyposis, may influence the lower airways. However, the mechanisms underlying this relationship were, for a long time, poorly understood. Recently, evidence has been accumulating which indicates a systemic connection as one of the responsible mechanisms in nasobronchial crosstalk. In this review, the pathophysiologic and immunologic aspects of the interaction between upper and lower airways will be discussed.
Published: 2003
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48. How I changed my practice in the last five years and what is likely to change in the next five years

Author: Wytske J, Fokkens, Amsterdam institute for Infection and Immunity, and Ear, Nose and Throat
Subjects: Otolaryngology, Otorhinolaryngology, Paranasal Sinus Diseases, Practice Management, Medical, otorhinolaryngologic diseases, Humans, Endoscopy, General Medicine
Abstract: The fast development of our field in the last decades has had significant impact on the way we practice our profession. This year my editorials will focus on the impact of these develop- ments on my own daily practice. When I started in otorhinolaryngology functional endoscopic sinus surgery was the new kid on the Block. We learned to operate as functional as possible. The primary goal of FESS was to restore normal ventilation and remove irreversibly changed mucosa. The concept was that by restoring proper ventilation the sinus would heal itself. In the past decades, we have more and more discovered that CRS and especially CRS with nasal polyps is a mucosal disease that needs intensive medical treat- ment if necessary combined with ESS. The concept of FESS has moved from improving ventilation to opening up sinus for local medical treatment. Local medical treatment has been shown to be more effective when it is able to enter the sinus. Although we do not have all data available yet, rinsing with saline in which local corticosteroids have been dissolved seems to be more effective than using nasal drops and certainly more effective than nasal spray
Published: 2015

49. Molecular Mechanisms of Nasal Epithelium in Rhinitis and Rhinosinusitis

Author: Wytske J. Fokkens, Sakari Joenväärä, Risto Renkonen, Sanna Toppila-Salmi, Cornelis M. van Drunen, Pirkko Mattila, Jutta Renkonen, and Korneliuz Golebski
Subjects: Pulmonary and Respiratory Medicine, Allergy, Rhinosinusitis (J Mullol, Section Editor), Rhinosinusitis, Immunology, Allergic rhinitis, Epithelium, Nonallergic rhinitis, Risk Factors, medicine, Immunology and Allergy, Animals, Humans, Sinusitis, Asthma, Rhinitis, business.industry, Nasal polyp, Innate lymphoid cell, Genomics, respiratory system, medicine.disease, 3. Good health, Airway, Nasal Mucosa, medicine.anatomical_structure, Chronic Disease, Respiratory, Respiratory epithelium, business
Abstract: Allergic rhinitis, nonallergic rhinitis, and chronic rhinosinusitis are multifactorial upper airway diseases with high prevalence. Several genetic and environmental factors are proposed to predispose to the pathogenesis of the inflammatory upper airway diseases. Still, the molecular mechanisms leading toward the onset and progression of upper airway diseases are largely unknown. The upper airway epithelium has an important role in sensing the environment and regulating the inhaled air. As such, it links environmental insults to the host immunity. Human sinonasal epithelium serves as an excellent target for observing induced early-phase events, in vivo, and with a systems biological perspective. Actually, increasing number of investigations have provided evidence that altered homeostasis in the sinonasal epithelium might be important in the chronic upper airway inflammation.
Published: 2014

50. Synergy between TLR-2 and TLR-3 signaling in primary human nasal epithelial cells

Author: Wytske J. Fokkens, Danielle van Egmond, Korneliusz Golebski, Joost van Tongeren, Cornelis M. van Drunen, Esther J. J. de Groot, Other departments, Graduate School, Ear, Nose and Throat, and AII - Amsterdam institute for Infection and Immunity
Subjects: Agonist, medicine.drug_class, Immunology, Cell, Stimulation, Biology, Ligands, Cell Line, Gene expression, medicine, Immunology and Allergy, Humans, RNA, Messenger, Receptor, Gene, Toll-Like Receptors, Epithelial Cells, Hematology, In vitro, Toll-Like Receptor 2, Toll-Like Receptor 3, Nasal Mucosa, medicine.anatomical_structure, Poly I-C, Gene Expression Regulation, Cell culture, Cytokines, Inflammation Mediators, Signal Transduction
Abstract: Introduction Although we have a detailed understanding of how single microbial derived triggers activate specialized Toll-like receptors (TLR) on airway epithelial cells, we know little of how these receptors react in a more complex environment. In everyday life, nasal epithelial cells are exposed to multiple TLR agonists, therefore we explored whether exposure to one trigger could affect the responsiveness to another TLR trigger. Methods Primary nasal epithelium from healthy individuals and the bronchial epithelium cell line NCI-H292 were exposed in vitro to different TLR specific agonists. The effect on the expression of different TLRs was determined using the q-PCR. We also evaluated the effect of TLR-3 stimulation on TLR-2, functionally using ELISA to determine levels of secreted mediators. Results Stimulation of airway epithelial cells with a specific TLR agonist affects gene expression of other TLRs. In primary nasal epithelium, poly(I:C) challenge results in an up-regulation of the TLR-1, TLR-2, and TLR-3 genes and reduction of expression of TLR-5. Poly(I:C) induced activation of TLR-2 contributes to stronger cell responses to a TLR-2 agonist and regulation of these synergistic responses may take place at the mRNA level of IL-6 and IL-8. The effect of TLR-3 stimulation on TLR-2 functionality and most of the effects on the expression of other TLRs could be replicated in NCI-H292. Poly(I:C) failed to up-regulate TLR-1 and showed an additional up-regulation of TLR-4. Conclusion Our data suggest that to better understand TLR mediated innate responses we need to consider the impact of the presence of multiple triggers.
Published: 2014

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