Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis
J Bousquet 1 2 3 4, E Melén 5 6, T Haahtela 7, G H Koppelman 8, A Togias 9, R Valenta 10, C A Akdis 11, W Czarlewski 12 13, M Rothenberg 14, A Valiulis 15 16, M Wickman 17, M Akdis 11, D Aguilar 18, A Bedbrook 13 19, C Bindslev-Jensen 20 21, S Bosnic-Anticevich 22 23 24, L P Boulet 25, C E Brightling 26, L Brussino 27 28, E Burte 4 29, M Bustamante 30 31 32, G W Canonica 33 34, L Cecchi 35, J C Celedon 36, C Chaves Loureiro 37, E Costa 38, A A Cruz 39, M Erhola 40, B Gemicioglu 41, W J Fokkens 42, J Garcia-Aymerich 30 31, S Guerra 43, J Heinrich 44, J C Ivancevich 45, T Keil 46 47 48, L Klimek 49 50, P Kuna 51, M Kupczyk 51, V Kvedariene 52 53, D E Larenas-Linnemann 54, N Lemonnier 55, K C Lodrup Carlsen 56, R Louis 57 58, M Makela 7, M Makris 59, M Maurer 1 2, I Momas 60 61, M Morais-Almeida 62, J Mullol 63 64, R N Naclerio 65, K Nadeau 66, R Nadif 4 29, M Niedoszytko 67, Y Okamoto 68 69, M Ollert 20 21 70, N G Papadopoulos 71, G Passalacqua 72, V Patella 73 74 75, R Pawankar 76, N Pham-Thi 77 78 79, O Pfaar 80, F S Regateiro 81 82 83, J Ring 84 85, P W Rouadi 86 87, B Samolinski 88, J Sastre 89, M Savouré 4 29 90, N Scichilone 91, M H Shamji 92 93, A Sheikh 94, V Siroux 95, B Sousa-Pinto 96 97, M Standl 98 99, J Sunyer 30 31 32 100, L Taborda-Barata 101 102, S Toppila-Salmi 7, M J Torres 103, I Tsiligianni 104 105, E Valovirta 106, O Vandenplas 107 108, M T Ventura 109 110, S Weiss 111, A Yorgancioglu 112, L Zhang 113, A H Abdul Latiff 114, W Aberer 115, I Agache 116, M Al-Ahmad 117, I Alobid 118 119, I J Ansotegui 120, S H Arshad 121 122, E Asayag 123, C Barbara 124, A Baharudin 125, L Battur 126, K S Bennoor 127, E C Berghea 128, K C Bergmann 1 2, D Bernstein 129, M Bewick 130, H Blain 131, M Bonini 132 133 134, F Braido 135 136, R Buhl 137, R S Bumbacea 138, A Bush 139, M Calderon 140, M Calvo-Gil 141, P Camargos 142, L Caraballo 143, V Cardona 144 145, W Carr 146, P Carreiro-Martins 147 148, T Casale 149, A M Cepeda Sarabia 150 151, R Chandrasekharan 152, D Charpin 153, Y Z Chen 154, I Cherrez-Ojeda 155 156, T Chivato 157, E Chkhartishvili 158, G Christoff 159, D K Chu 160, C Cingi 161, J Correia de Sousa 162, C Corrigan 163, A Custovic 164, G D'Amato 165, S Del Giacco 166, F De Blay 167 168, P Devillier 169, A Didier 170, M do Ceu Teixeira 171 172, D Dokic 173, H Douagui 174, M Doulaptsi 175, S Durham 176, M Dykewicz 177, T Eiwegger 178, Z A El-Sayed 179, R Emuzyte 180, A Fiocchi 181, N Fyhrquist 182, R M Gomez 183, M Gotua 184, M A Guzman 185, J Hagemann 49, S Hamamah 186, S Halken 187, D M G Halpin 188, M Hofmann 1 189, E Hossny 179, M Hrubiško 190, C Irani 191, Z Ispayeva 192, E Jares 193, T Jartti 194, E Jassem 195, K Julge 196, J Just 197, M Jutel 198 199, I Kaidashev 200, O Kalayci 201, A F Kalyoncu 202, P Kardas 203, B Kirenga 204, H Kraxner 205, I Kull 5 6, M Kulus 206, S La Grutta 207, S Lau 208, L Le Tuyet Thi 209, M Levin 210, B Lipworth 211, O Lourenço 212, B Mahboub 213, E Martinez-Infante 214, P Matricardi 215, N Miculinic 216, N Migueres 167, F Mihaltan 217, Y Mohammad 218 219, M Moniuszko 220, S Montefort 221, H Neffen 222, K Nekam 223, E Nunes 224, D Nyembue Tshipukane 225, R O'Hehir 226, I Ogulur 11, K Ohta 227, K Okubo 228, S Ouedraogo 229, H Olze 230 189, I Pali-Schöll 231, O Palomares 232, K Palosuo 233, C Panaitescu 234, P Panzner 235, H S Park 236, C Pitsios 237, D Plavec 238 239, T A Popov 240, F Puggioni 241, S Quirce 242, M Recto 243, M S Repka-Ramirez 244, C Robalo Cordeiro 37, N Roche 245 246, M Rodriguez-Gonzalez 247, J Romantowski 67, N Rosario Filho 248, M Rottem 249, H Sagara 250, F S Serpa 251, Z Sayah 252, S Scheire 253, P Schmid-Grendelmeier 254, J C Sisul 255, D Sole 256, M Soto-Martinez 257, M Sova 258, A Sperl 50, O Spranger 259, R Stelmach 260, C Suppli Ulrik 261 262, M Thomas 263, T To 264, A Todo-Bom 265, P V Tomazic 266, M Urrutia-Pereira 267, M Valentin-Rostan 268, E Van Ganse 269, M van Hage 270 271, T Vasankari 272 273, P Vichyanond 274, G Viegi 275, D Wallace 276, D Y Wang 277, S Williams 278, M Worm 279, P Yiallouros 237, O Yusuf 280, F Zaitoun 281, M Zernotti 282, M Zidarn 283 284, J Zuberbier 230 189, J A Fonseca 96 97, T Zuberbier 1 2, J M Anto 30 31 32
Affiliations
Affiliations
- Institute of Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
- Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany.
- University Hospital Montpellier, Montpellier, France.
- Inserm, Equipe d'Epidémiologie Respiratoire Intégrative, CESP, Villejuif, France.
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
- Sach´s Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
- Skin and Allergy Hospital, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland.
- Department of Pediatric Pulmonology and Pediatric Allergology, GRIAC Research Institute, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
- Division of Allergy, Immunology, and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
- Medical Consulting Czarlewski, Levallois, France.
- MASK-air, Montpellier, France.
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
- Institute of Clinical Medicine and Institute of Health Sciences, Vilnius, Lithuania.
- Medical Faculty of Vilnius University, Vilnius, Lithuania.
- Institute of Environmental medicine, Karolinska Institutet, Stockholm, Sweden.
- 6AM Data Mining, Barcelona, Spain.
- ARIA, Montpellier, France.
- Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
- Odense Research Center for Anaphylaxis « ORCA », Odense, Denmark.
- Quality Use of Respiratory Medicines Group, Woolcock Institute of Medical Research, Sydney, NSW, Australia.
- Sydney Local Health District, Sydney, NSW, Australia.
- Sydney Pharmacy School, The University of Sydney, Sydney, NSW, Australia.
- Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada.
- Institute of Lung Health, NIHR Biomedical Research Centre, Department of Respiratory and Infection Sciences, University of Leicester, Leicester, UK.
- Department of Medical Sciences, University of Torino, Torino, Italy.
- Allergy and Clinical Immunology Unit, Mauriziano Hospital, Torino, Italy.
- Université Paris-Saclay, UVSQ, UnivParis-Sud, Villejuif, France.
- Universitat Pompeu Fabra (UPF), Barcelona, Spain.
- ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
- Personalized medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
- SOS Allergology and Clinical Immunology, USL Toscana Centro, Prato, Italy.
- Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- Pneumology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
- UCIBIO, REQUINTE, Faculty of Pharmacy and Competence Center on Active and Healthy Ageing of University of Porto (Porto4Ageing), Porto, Portugal.
- Fundaçao ProAR, Federal University of Bahia and GARD/WHO Planning Group, Salvador, Bahia, Brazil.
- Pirkanmaa Welfare district, Tampere, Finland.
- Department of Pulmonary Diseases, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey.
- Department of Otorhinolaryngology, Amsterdam University Medical Centres, Amsterdam, the Netherlands.
- Asthma and Airway Disease Research Center, University of Arizona, Tucson, Arizona, USA.
- Ludwig Maximilians University Munich, University Hospital Munich - Instituteand Outpatient Clinic for Occupationa, Social and Environmental Medicine, Munich, Germany.
- Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina.
- Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
- Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
- State Institute of Health, Bavarian Health and Food Safety Authority, Erlangen, Germany.
- Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz, Germany.
- Center for Rhinology and Allergology, Wiesbaden, Germany.
- Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland.
- Institute of Clinical Medicine, Clinic of Chest Diseases and Allergology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
- Institute of Biomedical Sciences, Department of Pathology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
- Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico.
- Institute for Advanced Biosciences, UGA - INSERM U1209 - CNRS UMR5309, Site Santé, La Tronche, France.
- Department of Paediatrics, Oslo University Hospital, Oslo, Norway.
- Department of Pulmonary Medicine, CHU Liège, Liège, Belgium.
- GIGA I3 Research Group, University of Liège, Liège, Belgium.
- Allergy Unit "D Kalogeromitros", 2nd Department of Dermatology and Venereology, National & Kapodistrian University of Athens, "Attikon" University Hospital, Athens, Greece.
- Department of Public Health and Health Products, Paris Descartes University-Sorbonne Paris Cité, EA 4064, Paris, France.
- Paris Municipal Department of Social Action, Childhood, and Health, Paris, France.
- Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal.
- ENT Department, Rhinology Unit & Smell Clinic, Hospital Clínic, Barcelona, Spain.
- Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain.
- Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California, USA.
- Department of Allergology, Medical University of Gdańsk, Gdansk, Poland.
- Chiba Rosai Hospital, Chiba, Japan.
- Chiba University Hospital, Chiba, Japan.
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
- Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
- Allergy and Respiratory Diseases, IRCCS Policlinico San Martino - University of Genoa, Genoa, Italy.
- Division of Allergy and Clinical Immunology, Department of Medicine, "Santa Maria della Speranza" Hospital, Battipaglia, Salerno, Italy.
- Agency of Health ASL, Salerno, Italy.
- Postgraduate Programme in Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy.
- Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
- Ecole Polytechnique de Palaiseau, Palaiseau, France.
- IRBA (Institut de Recherche Bio-Médicale des Armées), Brétigny sur Orge, France.
- Université Paris Cité, Paris, France.
- Section of Rhinology and Allergy, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany.
- Allergy and Clinical Immunology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
- Coimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
- Institute of Immunology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
- Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University of Munich, Munich, Germany.
- Christine Kühne Center for Allergy Research and Education (CK-Care), Davos, Switzerland.
- Department of Otolaryngology-Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon.
- Department of Otorhinolaryngology-Head and Neck Surgery, Dar Al Shifa Hospital, Salmiya, Kuwait.
- Department of Prevention of Environmental Hazards, Allergology and Immunology, Medical University of Warsaw, Warsaw, Poland.
- Allergy Service, Fundacion Jimenez Diaz, Autonoma University of Madrid, CIBERES-ISCIII, Madrid, Spain.
- French Environment and Energy Management Agency, Angers, France.
- PROMISE Department, University of Palermo, Palermo, Italy.
- National Heart and Lung Institute, Imperial College, London, UK.
- NIHR Imperial Biomedical Research Centre, London, UK.
- Usher Institute, The University of Edinburgh, Edinburgh, UK.
- INSERM, Université Grenoble Alpes, IAB, U 1209, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Université Joseph Fourier, Grenoble, France.
- MEDCIDS - Department of Community Medicine, Information and Health Decision Sciences; Faculty of Medicine, University of Porto, Porto, Portugal.
- CINTESIS@RISE- Health Research Network, Faculty of Medicine, University of Porto, Porto, Portugal.
- Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
- German Center of Lung Research (DZL), Munich, Germany.
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Abstract
Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
Keywords: IL-33; Toll-like receptors; asthma; multimorbidity; rhinitis.
References
https://pubmed.ncbi.nlm.nih.gov/