Rhinitis associated with asthma is distinct from rhinitis alone: The <scp>ARIA‐MeDALL</scp> hypothesis
Jean Bousquet, Erik Melén, Tari Haahtela, Gerard H. Koppelman, Alkis Togias, Rudolf Valenta, Cezmi A. Akdiş, W. Czarlewski, Marc E. Rothenberg, Arūnas Valiulis, Magnus Wickman, Mübeccel Akdiş, D. Aguilar, Anna Bedbrook, Carsten Bindslev‐Jensen, Sinthia Bosnic‐Anticevich, Louis‐Philippe Boulet, Christopher E. Brightling, Luisa Brussino, Emilie Burte, Mariona Bustamante, Giorgio Walter Canonica, Lorenzo Cecchi, Juan C. Celedón, C. Chaves Loureiro, Elı́sio Costa, Álvaro A. Cruz, Marina Erhola, Bilun Gemicioğlu, Wytske J. Fokkens, Judith García‐Aymerich, Stefano Guerra, Joachim Heinrich, Juan Carlos Ivancevich, Thomas Keil, Ludger Klimek, Piotr Kuna, Maciej Kupczyk, Violeta Kvedarienė, Désirée Larenas‐Linnemann, Nicolas Lemonnier, Karin C. Lødrup Carlsen, Renaud Louis, Mika J. Mäkelä, Μichael Μakris, Marcus Maurer, Isabelle Momas, Mário Morais‐Almeida, Joaquim Mullol, Robert N. Naclerio, Kari C. Nadeau, Rachel Nadif, Marek Niedoszytko, Yoshitaka Okamoto, Markus Ollert, Nikolaos G. Papadopoulos, Giovanni Passalacqua, Vincenzo Patella, Ruby Pawankar, N. Pham‐Thi, Oliver Pfaar, Frederico S. Regateiro, Johannes Ring, Philip W. Rouadi, Bolesław Samoliński, J. Sastre, Marine Savouré, Nicola Scichilone, Mohamed H. Shamji, Aziz Sheikh, Valérie Siroux, Bernardo Sousa‐Pinto, Marie Standl, Jordi Sunyer, Luís Taborda‐Barata, Sanna Toppila‐Salmi, Maria J. Torres, Ioanna Tsiligianni, Erkka Valovirta, Olivier Vandenplas, Maria Teresa Ventura, Scott T. Weiss, Arzu Yorgancıoğlu, Luo Zhang, Amir Hamzah Abdul Latiff, Werner Aberer, Ioana Agache, Mona Al‐Ahmad, Isam Alobid, Ignacio J. Ansotegui, Syed Hasan Arshad, Estrella Asayag, Cristina Bárbara, Baharudin Abdullah, L. Battur, Kazi Saifuddin Bennoor, Camelia Elena Berghea, Karl‐Christian Bergmann, David I Bernstein, M. Bewick
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.