Received: 7 January 2021 DOI: 10.1002/clt2.12014 REVIEW - Accepted: 8 February 2021 ARIA‐EAACI care pathways for allergen immunotherapy in respiratory allergy Jean Bousquet1,2,3 | Oliver Pfaar4 | Ioana Agache5 | Anna Bedbrook3 | Cezmi A Akdis6 | G. Walter Canonica7,174 | Tomas Chivato8 | Mona Al‐Ahmad9,175 | Amir H Abdul Latiff10 | Ignacio J Ansotegui11 | Claus Bachert12,176,177 | Abdullah Baharuddin13 | Karl‐Christian Bergmann1 | Carsten Bindslev‐Jensen14,177,178 | Leif Bjermer15 | Matteo Bonini16,179 | Sinthia Bosnic‐Anticevich17,180 | Isabelle Bosse18 | Helen A. Brough19 | Luisa Brussino20 | Moises A Calderon21 | Luis Caraballo22,181 | Victoria Cardona23 | Pedro Carreiro‐Martins24,182 | Tomas Casale25 | Lorenzo Cecchi26 | Alfonso M Cepeda Sarabia27,183 | Ekaterine Chkhartishvili28 | Derek K Chu29 | Ieva Cirule30 | Alvaro A Cruz31 | Wienczyslawa Czarlewski32 | Stefano del Giacco33 | Pascal Demoly34,184 | Philippe Devillier35 | Dejan Dokic36 | Stephen L Durham37 | Motohiro Ebisawa38 | Yehia El‐Gamal✝39 | Regina Emuzyte40 | Amiran Gamkrelidze41 | Jean Luc Fauquert42 | Alessandro Fiocchi43 | Wytske J Fokkens44,185 | Joao A Fonseca45,186 | Jean‐François Fontaine46 | Radoslaw Gawlik47 | Asli Gelincik48 | Bilun Gemicioglu49 | Jose E Gereda50 | Roy Gerth van Wijk51 | R Maximiliano Gomez52 | Maia Gotua53 | Ineta Grisle54 | Maria‐Antonieta Guzmán55 | Tari Haahtela56 | Susanne Halken57 | Enrico Heffler7 | Karin Hoffmann‐Sommergruber58 | Elham Hossny59 | Martin Hrubiško60 | Carla Irani61 | Juan Carlos Ivancevich62 | Zhanat Ispayeva63 | Kaja Julge64 | Igor Kaidashev65 | Omer Kalayci66 | Musa Khaitov67 | Ludger Klimek68,187 | Edward Knol69 | Marek L Kowalski70 | Helga Kraxner71 | Inger Kull72,188 | Piotr Kuna73 | Violeta Kvedariene74,189 | Vicky Kritikos75,190 | Antti Lauerma76 | Susanne Lau77 | Daniel Laune78 | Michael Levin79 | Desiree E Larenas‐Linnemann80 | Karin C Lodrup Carlsen81,191 | Carlo Lombardi82 | Olga M Lourenço83 | Bassam Mahboub84 | Hans‐Jørgen Malling85 | Patrick Manning86 | Gailen D Marshall87 | Erik Melén88,188 | Eli O Meltzer89 | Neven Miculinic90 | Branislava Milenkovic91,193 | Mostafa Moin92 | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2021 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology. Clin Transl Allergy. 2021;e12014. wileyonlinelibrary.com/journal/clt2 1 of 11 https://doi.org/10.1002/clt2.12014 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2 of 11 - BOUSQUET ET AL. Stephen Montefort93 | Mario Morais‐Almeida94 | Charlotte G Mortz14 | Ralph Mösges95 | Joaquim Mullol96,194 | Leyla Namazova Baranova97 | Hugo Neffen98 | Kristof Nekam99 | Marek Niedoszytko100 | Mikaëla Odemyr101 | Robyn E O'Hehir102,195 | Markus Ollert103,196 | Liam O'Mahony104 | Ken Ohta105 | Yoshitaka Okamoto106 | Kimi Okubo107 | Giovanni B Pajno108 | Oscar Palomares109 | Susanna Palkonen110 | Petr Panzner110 | Nikolaos G Papadopoulos111 | Hae‐Sim Park112 | Giovanni Passalacqua113 | Vincenzo Patella114 | Ruby Pawankar115 | Nhân Pham‐Thi116 | Davor Plavec117 | Todor A Popov118 | Marysia Recto192 | Frederico S Regateiro119,197,198 | Carmen Riggioni120,199 | Graham Roberts121 | Monica Rodriguez‐Gonzales122 | Nelson Rosario123 | Menachem Rottem124,200 | Philip W Rouadi125 | Dermot Ryan126 | Boleslaw Samolinski127 | Mario Sanchez‐Borges✝128 | Faradiba S Serpa129 | Joaquin Sastre130 | Glenis K. Scadding131 | Mohamed H Shamji132,201 | Peter Schmid‐Grendelmeier133 | Holger J Schünemann29 | Aziz Sheikh134 | Nicola Scichilone135 | Juan Carlos Sisul136 | Mikhail Sofiev137 | Dirceu Solé138 | Talant Sooronbaev139 | Manuel Soto‐Martinez140 | Manuel Soto‐Quiros141 | Milan Sova142 | Jürgen Schwarze143 | Isabel Skypala144 | Charlotte Suppli‐Ulrik145,202 | Luis Taborda‐Barata146,203 | Ana Todo‐Bom147,204 | Maria J Torres148 | Marylin Valentin‐Rostan149 | Peter‐Valentin Tomazic150 | Antonio Valero151 | Sanna Toppila‐Salmi56 | Ioanna Tsiligianni152,172 | Eva Untersmayr153 | Marilyn Urrutia‐Pereira154 | Arunas Valiulis155,173 | Erkka Valovirta156,205 | Olivier Vandenplas157 | Maria Teresa Ventura158 | Pakit Vichyanond159 | Martin Wagenmann160 | Dana Wallace161 | Jolanta Walusiak‐Skorupa162 | De Yun Wang163 | Susan Waserman164 | Gary WK Wong165 | Arzu Yorgancioglu166 | Osman M Yusuf167 | Mario Zernotti168 | Luo Zhang169,206 | Mihaela Zidarn170 | Torsten Zuberbier1 | Marek Jutel171,207 1 Department of Dermatology and Allergy, Comprehensive Allergy Center, Charité Universitätsmedizin Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany 2 Allergology, University Hospital Montpellier, Montpellier, France 3 MACVIA‐France, Montpellier, France 4 Department of Otorhinolaryngology, Head and Neck Surgery Section of Rhinology and Allergy, University Hospital Marburg, Philipps‐Universität Marburg, Germany 5 Allergy and Clinical Immunology, Transylvania University Brasov, Brasov, Romania 6 Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland 7 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, (MI) and Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milano, Italy 8 School of Medicine, University CEU San Pablo, Madrid, Spain 9 Department of Allergy and Microbiology, Faculty of Medicine, Al‐Rashed Allergy Center, Kuwait University, Kuwait City, Kuwait 10 Allergy & Immunology Centre, Pantai Hospital Kuala Lumpur, Malaysia 11 Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Erandio, Spain 12 ENT Department, Upper Airways Research Laboratory, Ghent University Hospital, Ghent, Belgium 13 Department of Otorhinolaryngology—Head and Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia 14 Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark 15 Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden 16 Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy 17 Woolcock Institute of Medical Research, University of Sydney, Australia 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License BOUSQUET ET AL. - 3 of 11 18 Allergist, La Rochelle, France 19 Paediatric Allergy, Department of Asthma, Allergy and Respiratory Science, Guys' Hospital, King's College London, London, UK 20 Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, Torino, Italy 21 Imperial College and National Heart and Lung Institute, London, UK 22 Institute for Immunological Research, University of Cartagena, Cartagena, Colombia 23 Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron & ARADyAL Research Network, Barcelona, Spain 24 Serviço de Imunoalergologia, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, Lisbon, Portugal 25 Division of Allergy/immunology, University of South Florida, Tampa, Fla, USA 26 SOS Allergology and Clinical Immunology, USL Toscana Centro, Prato, Italy 27 Allergy and Immunology Laboratory, Metropolitan University, Simon Bolivar University, Barranquilla, Colombia 28 David Tatishvili Medical Center, David Tvildiani Medical University‐AIETI Medical School, Tbilisi, Georgia 29 Departments of Medicine and Health Research Methods, McMaster University, Hamilton, ON, Canada 30 Latvain Association of Allergists, University Children Hospital, Riga, Latvia 31 Fundação ProAR, Federal University of Bahia and GARD/WHO Planning Group, Salvador, Brazil 32 Medical Consulting Czarlewski, Levallois, France 33 Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital “Duilio Casula”, University of Cagliari, Cagliari, Italy 34 Department of Pulmonology, Division of Allergy, Hô pital Arnaud de Villeneuve, University Hospital of Montpellier, France 35 Unité de Recherche en Pharmacologie Respiratoire, Pôle des Maladies des Voies Respiratoires, Hôpital Foch, Université Paris Saclay, Suresnes, France 36 Medical Faculty, University Clinic of Pulmology and Allergy, Skopje, Republic of Macedonia 37 National Heart and Lung Institute, Imperial College London, UK 38 Clinical Reserch Center for Allergy and Rheumatology, NHO Sagamihara National Hospital, Sagamihara, Japan 39 Pediatric Allergy and Immunology Unit, Children's Hospital, Ain Shams University, Cairo, Egypt 40 Faculty of Medicine, Clinic of Children's Diseases, Vilnius University, Vilnius, Lithuania 41 National Center for Disease Control and Public Health of Georgia, Tbilisi, Georgia 42 CHU Clermont‐Ferrand, Unité d'Allergologie de l'Enfant, Pole pédiatrique, Hopital Estaing, Clermont‐Ferrand, France 43 Division of Allergy, The Bambino Gesu Children's Hospital IRCCS, Rome, Italy 44 Department of Otorhinolaryngology, Academic Medical Centers, Amsterdam, The Netherland 45 Faculdade de Medicina, CINTESIS, Center for Health Technology and Services Research, Universidade do Porto, Porto, Portugal 46 Allergist, Reims, France 47 Department of Internal Medicine, Allergology and Clinical Immunology, Silesian University of Medicine, Katowice, Poland 48 Division of Allergy and Immunology, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey 49 Department of Pulmonary Diseases, Cerrahpasa Faculty of Medicine, Istanbul University‐Cerrahpasa, Istanbul, Turkey 50 Allergy and Immunology Division, Clinica Ricardo Palma, Lima, Peru 51 Department of Internal Medicine, Section of Allergology, Erasmus MC, Rotterdam, the Netherlands 52 Fundacion Ayre, Instituto Medico Alas, Salta, Argentina 53 Center of Allergy and Immunology, Georgian Association of Allergology and Clinical Immunology, Tbilisi, Georgia 54 Latvian Association of Allergists, Center of Tuberculosis and Lung Diseases, Riga, Latvia 55 Immunology and Allergy Division, Clinical Hospital, University of Chile, Santiago, Chile 56 Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland 57 Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark 58 Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria 59 Pediatric Allergy and Immunology Unit, Children's Hospital, Ain Shams University, Cairo, Egypt 60 Department of Clinical Immunology and Allergy, Oncology Institute of St Elisabeth, Bratislava, Slovakia 61 Department of Internal Medicine and Infectious Diseases, St Joseph University, Hotel Dieu de France Hospital, Beirut, Lebanon 62 Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina 63 Department of Allergology and Clinical Immunology of the Kazakh National Medical University, Kazakhstan Association of Allergology and Clinical Immunology, Kazakhstan 64 Allergy Center of Childrens's Clinic of Tartu University Hospital, Tartu, Estonia 65 Ukrainina Medical Stomatological Academy, Poltava, Ukraine 66 Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey 67 National Research Center, Institute of Immunology, Federal Medicobiological Agency, Laboratory of Molecular Immunology, Russia 68 Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz, Germany 69 Departments of Immunology and Dermatology/Allergology, University Medical Center Utrecht, The Netherlands 70 Department of Immunology and Allergy, Healthy Ageing Research Center, Medical University of Lodz, Poland 71 Department of Otorhinolaryngology, Head and Neck Surgery, Semmelweis University, Budapest, Hungary 72 Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden 73 Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Poland 74 Department of Pathology, Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University Vilnius, Lithuania 75 Quality Use of Respiratory Medicines Group, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia 76 Department of Dermatology and Allergology, University of Helsinki and Helsinki University, Helsinki, Finland 77 Department of Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin, Germany 78 KYomed INNOV, Montpellier, France 79 Division of Paediatric Allergology, University of Cape Town, Cape Town, South Africa 80 Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico 81 Department of Paediatrics, Oslo University Hospital, Oslo, Norway 82 Departmental Unit of Allergology & Respiratory Diseases, Fondazione Poliambulanza, Brescia, Italy 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 11 - BOUSQUET ET AL. 83 Faculty of Health Sciences and CICS – UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal 84 Department of Pulmonary Medicine, Rashid Hospital, Dubai, UAE 85 Danish Allergy Centre, University of Copenhagen, Copenhagen, Denmark 86 Department of Medicine (RCSI), Bon Secours Hospital, Dublin, Ireland 87 The University of Mississippi Medical Center, Division of Clinical Immunology and Allergy, Laboratory of Behavioral Immunology Research, Jackson, Mississippi, USA 88 Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden 89 Allergy, Allergy and Asthma Medical Group and Research Center, San Diego, California, USA 90 Croatian Pulmonary Society, Zagreb, Croatia 91 Faculty of Medicine, Clinic for Pulmonary Diseases, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia 92 Immunology and Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 93 Faculty of Medicine and Surgery, Mater Dei Hospital Malta, University of Medicine, La Valette, Malta 94 Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal 95 CRI‐Clinical Research International‐Ltd, Hamburg, Germany 96 ENT Department, Rhinology Unit & Smell Clinic, Hospital Clínic, Barcelona, Spain 97 Scientific Centre of Children's Health, Russian National Research Medical University, Moscow, Russia 98 Center of Allergy, Immunology and Respiratory Diseases, Santa Fe, Argentina 99 Hospital of the Hospitaller Brothers in Buda, Budapest, Hungary 100 Department of Allergology, Medical University of Gdańsk, Gdańsk, Poland 101 EFA, European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium 102 Department of Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, Victoria, Australia 103 Department of Infection and Immunity, Luxembourg Institute of Health, Esch‐sur‐Alzette, Luxembourg 104 Departments of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland 105 National Hospital Organization, Tokyo National Hospital, Tokyo, Japan 106 Department of Otorhinolaryngology, Chiba University Hospital, Chiba, Japan 107 Department of Otolaryngology, Nippon Medical School, Tokyo, Japan 108 Department of Pediatrics, Allergy Unit, University of Messina, Messina, Italy 109 Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain 110 Department of Immunology and Allergology, Faculty of Medicine and Faculty Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic 111 Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, UK 112 Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea 113 Allergy and Respiratory Diseases, Ospedale Policlino San Martino ‐University of Genoa, Italy 114 Department of Medicine, Division of Allergy and Clinical Immunology, Agency of Health ASL Salerno, “Santa Maria della Speranza” Hospital, Battipaglia, Salerno, Italy 115 Department of Pediatrics, Nippon Medical School, Tokyo, Japan 116 Ecole Polytechnique Palaiseau, IRBA (Institut de Recherche bio‐Médicale des Armées), Bretigny, France 117 School of Medicine, Children's Hospital Srebrnjak, Zagreb, University J.J. Strossmayer, Osijek, Croatia 118 University Hospital ‘Sv Ivan Rilski’, Sofia, Bulgaria 119 Allergy and Clinical Immunology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Coimbra, Portugal 120 Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, Spain 121 Salford Royal NHS Foundation Trust NHS England North, Salford, UK 122 Pediatric Allergy and Clinical Immunology, Hospital Angeles Pedregal, Mexico City, Mexico 123 Hospital de Clinicas, University of Parana, Brazil 124 Division of Allergy Asthma and Clinical Immunology, Emek Medical Center, Afula, Israel 125 Department of Otolaryngology‐Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon 126 Usher Institute, Medical School, University of Edinburgh, Edinburgh, UK 127 Department of Prevention of Environmental Hazards, Allergology and Immunology, Medical University of Warsaw, Warsaw, Poland 128 Allergy and Clinical Immunology Department, Centro Medico‐Docente La Trinidad, Caracas, Venezuela 129 Asthma Reference Center ‐ Escola Superior de Ciencias, Santa Casa de Misericórdia of Vitória‐Espírito Santo, Vitoria, Brazil 130 Faculty of Medicine, Fundacion Jimenez Diaz, CIBERES, Autonoma University of Madrid, Spain 131 The Royal National ENT Hospital, University College London, UK 132 Immunomodulation and Tolerance Group, Imperial College London, London, UK 133 Department of Dermatology, Allergy Unit, University Hospital of Zurich, Zürich, Switzerland 134 The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK 135 PROMISE Department, University of Palermo, Palermo, Italy 136 Sociedad Paraguaya de Alergia Asma e Inmunologıa, Clinica Sisul, Allergy & Asthma, Asuncion, Paraguay 137 Finnish Meteorological Institute (FMI), Helsinki, Finland 138 Department of Pediatrics, Division of Allergy, Clinical Immunology and Rheumatology, Federal University of São Paulo, São Paulo, Brazil 139 Kyrgyzstan National Centre of Cardiology and Internal Medicine, Euro‐Asian Respiratory Society, Bishkek, Kyrgyzstan 140 Department of Pediatrics, Division of Respiratory Medicine, Hospital Nacional de Niños, Universidad de Costa Rica, San Jose, Costa Rica 141 Department of Pediatrics, Hospital Nacional de Niños, San José, Costa Rica 142 Department of Respiratory Medicine, University Hospital Olomouc, Czech Republic 143 Centre for Inflammation Research, Child Life and Health, The University of Edinburgh, Edinburgh, UK 144 Royal Brompton and Harefield NHS Foundation Trust, London, UK 145 Department of Respiratory Medicine, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark 146 Department of Immunoallergology, Faculty of Health Sciences, Cova da Beira, Covilhã, Portugal 147 Imunoalergologia, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal 148 Allergy Unit, Málaga Regional University Hospital‐IBIMA, Málaga, Spain 149 Allergist, Montevideo, Uruguay 150 Department of General ORL, H&NS, ENT‐University Hospital Graz, Medical University of Graz, Graz, Austria 151 Pneumology and Allergy Department, CIBERES, Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, University of Barcelona, Barcelona, Spain 152 Department of Social Medicine, Health Planning Unit, Faculty of Medicine, University of Crete, Crete, Greece 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License BOUSQUET ET AL. - 5 of 11 153 Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria 154 Universidade Federal dos Pampa, Uruguaiana, Brazil 155 Faculty of Medicine, Vilnius University, Institute of Clinical Medicine & Institute of Health Sciences, Vilnius, Lithuania 156 Department of Lung Diseases and Clinical Immunology, University of Turku, Turku, Finland 157 Department of Chest Medicine, Centre Hospitalier Universitaire UCL Namur, Université Catholique de Louvain, Yvoir, Belgium 158 Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy 159 Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand 160 Department of Otorhinolaryngology, HNO‐Klinik, Universitätsklinikum Düsseldorf, Germany 161 Nova Southeastern University, Fort Lauderdale, Florida, USA 162 Department of Occupational Diseases and Environmental Health, Nofer Institute of Occupational Medicine, Lodz, Poland 163 Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 164 Department of Medicine, Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario, Canada 165 Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China 166 Department of Pulmonology, Celal Bayar University, Manisa, Turkey 167 The Allergy and Asthma Institute, Islamabad, Pakistan 168 Universidad Católica de Córdoba, Universidad Nacional de Villa Maria, Argentina 169 Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Beijing, China 170 Respiratory and Allergic Diseases, University Clinic, Golnik, Slovenia 171 Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland 172 International Primary Care Respiratory Group IPCRG, Aberdeen, Scotland 173 European Academy of Paediatrics (EAP/UEMS‐SP), Brussels, Belgium 174 Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Rozzano, Milano, Italy 175 Department of Allergy, Al‐Rashed Allergy Center, Kuwait City, Kuwait 176 International Airway Research Center, First Affiliated Hospital Guangzou, Sun Yat‐sen University, Guangzhou, China 177 Division of ENT Diseases, Department of ENT Diseases, CLINTEC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden 178 Research Center for Anaphylaxis (ORCA), Odense, Denmark 179 National Heart and Lung Institute, Royal Brompton Hospital & Imperial College London, UK 180 Woolcock Emphysema Centre and Sydney Local Health District, Glebe, New South Wales, Australia 181 Foundation for the Development of Medical and Biological Sciences (Fundemeb), Cartagena, Colombia 182 NOVA Medical School, CEDOC, Comprehensive Health Research Center (CHRC), Lisboa, Portugal 183 SLaai, Sociedad Latinoamericana de Allergia, Asma e Immunologia, Branquilla, Colombia 184 Equipe EPAR ‐ IPLESP, Sorbonne Université , Paris, France 185 EUFOREA, Brussels, Belgium 186 Allergy Unit, CUF Porto, Portugal 187 Center for Rhinology and Allergology, Wiesbaden, Germany 188 Sach´s Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden 189 Faculty of Medicine, Institute of Clinical Medicine, Clinic of Chest Diseases and Allergology, Vilnius University, Vilnius, Lithuania 190 Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia 191 Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway 192 Department of Pediatrics, Section of Allergy and Immunology, UP‐PGH, Manila, Philipinnes 193 Serbian Association for Asthma and COPD, Belgrade, Serbia 194 Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Spain 195 Alfred Health, Melbourne, Victoria, Australia 196 Department of Dermatology and Allergy Centre, Odense Research Center for Anaphylaxis (ORCA), Odense University Hospital, Odense, Denmark 197 Faculty of Medicine, Institute of Immunology, University of Coimbra, Coimbra, Portugal 198 Faculty of Medicine, ICBR ‐ Coimbra Institute for Clinical and Biomedical Research, CIBB, University of Coimbra, Coimbra, Portugal 199 Institut de Recerca Sant Joan de Déu, Barcelona, Spain 200 Rappaport Faculty of Medicine, Technion‐Israel Institute of Technology, Haifa, Israël 201 Allergy and Clinical Immunology, Imperial College London, London, UK 202 Institute of Cinical Medicine, University of Copenhagen, Copenhagen, Denmark 203 University Hospital Centre, Covilhã, Portugal 204 Faculty of Medicine, University of Coimbra, Coimbra, Portugal 205 Terveystalo Allergy Clinic, Turku, Finland 206 Otolaryngology, Beijing Institute of Otolaryngology, Beijing, China 207 ALL‐MED Medical Research Institute, Wroclaw, Poland Funding information ARIA, Grant/Award Number: N/A KEYWORDS allergic rhinitis, asthma, immunotherapy, precision medicine 1 | INTRODUCTION the potential for immune tolerance against reactions to the natural exposures to specific allergens. AIT may lead to the long‐lasting Allergen immunotherapy (AIT), the gradually increasing repeated remission of allergic symptoms and is the only disease‐modifying administration of high doses of allergens to allergic patients, offers intervention in IgE‐mediated allergic respiratory diseases. 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 11 - BOUSQUET ET AL. 3 | STRATIFICATION OF ALLERGIC PATIENTS This Pocket Guide was developed by an ARIA and EAACI Precision medicine aims at the customisation of healthcare, tailored to joint study group from a background paper of the ARIA‐ the characteristics of each individual patient. The stratification of pa- MASK study group and from the EAACI guidelines on tients into subpopulations is the basis of clinical decision making allergen immunotherapy. (Figure 2). Bousquet J, Pfaar O, Togias A, et al. (2019). ARIA Care In allergic diseases, patient stratification is required to: pathways for allergen immunotherapy. Allergy 2019; 74: 2087–2102. � Propose the appropriate pharmacotherapy. Agache, Lau S, Akdis CA, et al. EAACI guidelines on allergen � Identify the most suitable candidates for AIT. immunotherapy: house dust mite‐driven allergic asthma. � Reduce the amount of time and resources needed to match the Allergy, 2019;74:855‐73. right patient to an optimal care management programme. � Optimise costs as expensive therapeutic interventions are not necessary or suitable for all patients. AIT is a proven therapeutic option for the treatment of allergic rhinitis, conjunctivitis, and/or asthma using sublingual (SLIT) or sub- Patient stratification may also help to improve the patient's cutaneous (SCIT) routes. engagement. However, AIT is more expensive than symptomatic treatments for allergic diseases (excluding biologicals). It is justified (i) in patients with rhinitis otherwise uncontrolled by symptomatic treatment or (ii) 3.1 | Precision medicine in the indication of AIT as an add‐on to regular asthma treatment in controlled or partially‐ controlled asthmatic patients sensitised to house dust mites aiming 1. Precise diagnosis with history, skin prick tests and/or spe- to decrease asthma exacerbations, rescue and controller medication, cific IgE and, if applicable, component‐resolved in vitro and to improve quality of life. testing. In some cases, where the above‐mentioned diagnostic Care pathways are structured multi‐disciplinary care plans de- tools do not allow for precise diagnosis, allergen provocation tailing the key steps of patient care. They promote the translation testing (nasal, ocular and, in some cases, bronchial) may be of guideline recommendations to their application in clinical needed. practice. 2. Proven indications: Allergic rhinitis, conjunctivitis and/or asthma. Although many international and national AIT guidelines have 3. Symptoms predominantly induced by the relevant allergen been produced, this is the first care pathway for AIT. exposure. This pocket guide applies to sublingual (SLIT) and sub‐cutaneous 4. Patient stratification: (SCIT) immunotherapy for allergic rhinitis. � Poor control of nasal or ocular symptoms despite optimal It has been revised by members from 65 countries (Figure 1). medications according to guidelines with documented adher- ence to treatment. � Exceptions to requiring optimum symptomatic treatment prior 2 | ALLERGENS TO BE ADMINISTERED to considering AIT include unacceptable side effects of the medications. The decision to prescribe AIT should be based on relevant symptoms � Allergic asthma fully controlled under background asthma during allergen exposure, demonstration of sensitisation to the rele- medication (see EAACI HDM‐AIT GL) vant allergens, and availability of good‐quality extracts with proven � However, for partially controlled asthma, HDM‐AIT efficacy and safety. may facilitate achieving asthma control (see EAACI HDM‐ Some allergen extracts are approved for marketing in the EU (list AIT GL) in annex) with some others also approved by national health 5. Good clinical documentation of efficacy and safety for the AIT agencies. product with relevant trials. For certain products, efficacy and safety have been demon- 6. The patient's (and caregiver's) views represent an essential strated in appropriate clinical studies on adults and children. The component. extrapolation to untested products, allergens or a different popula- tion from the one evaluated in the trial is not appropriate and not in line with current guidelines as there is no class‐effect in AIT. 3.2 | Biomarkers Both monosensitised and polysensitised patients can be treated. However, in the latter case, the most clinically relevant allergen(s) There are currently no in vivo or in vitro biomarkers validated for should be used when symptoms are clearly present with allergen monitoring the efficacy of AIT although several potential candidates source exposure and when allergy tests confirm clinical findings. are currently being investigated. 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 7 of 11 F I G U R E 2 Proposed Flow of Precision Medicine approach in allergic diseases. *examples of exceptions: Thunderstorm‐induced asthma, - patient with moderate rhinitis and severe asthma during pollen season Countries with Pocket Guide members ET AL. FIGURE 1 BOUSQUET 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 11 - BOUSQUET ET AL. 4 | mHEALTH 6 | RHINITIS (WITH OR WITHOUT CONJUNCTIVITIS) IN CHILDREN Apps can be used: AIT is effective, has long‐term beneficial effects after cessation, and � To acquire real‐world evidence to confirm the efficacy of AIT in may delay or prevent the onset of asthma. AIT can be initiated in situations where randomised controlled trials are difficult to children with moderate/severe rhinitis that is not controlled by perform. appropriate medications according to guidelines. � To assess air quality index including pollen exposure and air pollution. � By physicians and patients for stratification of patients and follow‐ 7 | ASTHMA up. An algorithm for HDM‐driven allergic asthma diagnosis and man- agement is proposed by the EAACI guidelines. For patients with concomitant allergic rhinitis and sensitised to 5 | RHINITIS (WITH OR WITHOUT house dust mite—with persisting asthma symptoms despite low‐ CONJUNCTIVITIS) IN ADOLESCENTS AND ADULTS moderate dose of inhaled corticosteroids—SLIT can be considered, provided FEV1 is >70% predicted. The selection of pharmacotherapy and AIT for patients with House dust mite SLIT should initially be considered as an add‐ AR and/or allergic conjunctivitis may be better supported by on therapy to controller treatment, and reduction in asthma con- evidence algorithms to aid patients and healthcare pro- trollers should be performed gradually under the supervision of a fessionals jointly determine the treatment and its step‐up or step‐ physician. down strategy depending on rhinitis control (shared decision‐ Immunotherapy is not indicated for the treatment of acute ex- making). acerbations, and patients must be informed of the need to seek A simple algorithm is proposed as an aid for physicians to medical attention immediately if their asthma deteriorates suddenly determine the treatment of their patients (Figure 3). (Figure 4). 8 | MULTIMORBIDITY 5.1 | Treatment algorithm using visual analogue scale (VAS) One strength of AIT is that it has the potential to control all allergic diseases related to a specific allergen, including rhinitis, conjunctivitis In the case of remaining ocular symptoms, add intra‐ocular and asthma. treatment. F I G U R E 3 Treatment algorithm using visual analogue scale (VAS) for adolescents and adults AIT, allergen immunotherapy; VAS, visual analogue scale. 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License BOUSQUET ET AL. - 9 of 11 FIGURE 4 Algorithm for AIT in asthma 9 | SAFETY develop within 30 min after the injection, and patients are advised to wait in their doctor's surgery for at least 30 min after an injection. 9.1 | Subcutaneous immunotherapy (SCIT) Severe bronchospasm can also occur, especially in patients where asthma is not controlled. Local reactions: A typical reaction is redness and swelling at the in- jection site immediately or several hours after the injection. Some- times, sneezing, nasal congestion or hives can occur. 9.2 | Sublingual immunotherapy (SLIT) Systemic reactions: Serious reactions to injections are very rare and require immediate medical attention. Symptoms of an anaphy- Allergen drops or tablets have a more favourable safety profile than lactic reaction can include swelling in the throat, wheezing or tight- injections. The initial dose should be performed in the doctor's surgery, ness in the chest, nausea and dizziness. The most serious reactions and patients are advised to remain in the surgery for at least 30 min 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 10 of 11 - BOUSQUET ET AL. after administration. Thereafter, SLIT can be administered at home VK reports other from GSK, non‐financial support from Mylan, once the first dose has been given under the supervision of a physician. AstraZeneca, Dimuna, Norameda. Allergic reactions: The majority of patients will experience mild SL reports personal fees from DBV, Sanofi Aventis, Allergo- local reactions of the oropharyngeal passage. This is usually pharma, ALK, Nutricia, Bencard. controlled by predosing with an antihistamine 30 min before the EM reports personal fees from Sanofi, Novartis, AstraZeneca and administration of SLIT. Sometimes, sneezing, nasal congestion or Chiesi. hives can occur. Anaphylaxis is rarely described. JM reports personal fees and other from SANOFI‐GENZYME & In some countries, SLIT tablets include a warning about possible REGENERON, NOVARTIS, ALLAKOS, MITSUBISHI‐TANABE, severe allergic reactions, and adrenaline auto‐injectors are routinely MENARINI, UCB, ASTRAZENECA, GSK, MSD, grants and personal recommended. This is not the case in Europe. fees from MYLAN‐MEDA Pharma, URIACH Group. MO reports personal fees from Hycor Diagnostics, Thermo C ON F LI C T O F IN T ER E S T Fisher Phadia. IAgache is an Associate Editor Allergy and CTA. YO reports personal fees from Torii Pharmaceutical Co., Ltd., CA reports grants from Allergopharma, grants from Idorsia, Shionogi Pharmaceutical Co.,Ltd. Swiss National Science Foundation, Christine Kühne‐Center for Al- OP received research grants from Inmunotek S.L., Novartis and lergy Research and Education, European Commission's Horison's MINECO and has received fees for giving scientific lectures or 2020 Framework Programme, Cure, Novartis Research Institutes, participation in Advisory Boards from: Allergy Therapeutics, Amgen, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from AstraZeneca, Diater, GlaxoSmithKline, S.A, Inmunotek S.L, Novartis, Glakso Smith‐Kline, advisory role in scibase. Sanofi‐Genzyme and Stallergenes. IA reports personal fees from Hikma, Roxall, Astra Zeneca, NGP reports personal fees from Novartis, Nutricia, HAL, Menarini, UCB, Faes Farma, Sanofi, Mundipharma, Bial, Amgen, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, Stallergenes. AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, SBA reports grants from TEVA, personal fees from TEVA, grants from Gerolymatos International SA, Capricare. AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, Mylan. OP reports grants and personal fees from ALK‐Abelló, Aller- VC reports personal fees from ALK, Allergy Therapeutics, LETI, gopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Thermofisher, Merck, Astrazeneca, GSK. Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, TC reports grants and personal fees from Stallergenes. Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, PD reports personal fees from ALK‐Abello, Stallergenes‐Greer, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Astra Zeneca, GlaxoSmithKline, Mylan, Sanofi. Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/ SD reports personal fees and non‐financial support from ALK MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Abello, personal fees from Adiga, Biomay, Allergopharma, Anergis, Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Allergy Therapeutics. Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med TH reports personal fees from GSK, Mundipharma, Orion Pharma. Update Europe GmbH, streamedup! GmbH, John Wiley and SH reports other from ALK‐Abelló, other from ALK‐Abelló. Sons, AS. EH reports personal fees from Sanofi, Novartis, GSK, AstraZe- DPreports grants and personal fees from GlaxoSmithKline, per- neca, Circassia, Nestlè Purina. sonal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, JCI reports personal fees from Faes Farma, Laboratorios Casasco Chiesi, Revenio, personal fees and non‐financial support from Argentina, Abbott de Ecuador, EuroFarma Argentina. Boehringer Ingelheim, non‐financial support from Philips. MJ reports personal fees from ALK‐Abello, Allergopharma, MR is on the Advisory board‐ A. Menarini ‐ Speaker ‐ Astra Stallergenes, Anergis, Allergy Therapeutics, Circassia, Leti, Biomay, Zeneca, Novartis, Sanofi, Mylan. HAL, during the conduct of the study; personal fees from Astra‐ FSRreports speaker and advisory fees from AstraZeneca, Zeneka, GSK, Novartis, Teva, Vectura, UCB, Takeda, Roche, Novartis, Sanofi, GSK, Teva and Lusomedicamenta. Janssen, Medimmune, Chiesi,. GR reports payment to his Institution from Allergo Pharma. LK reports grants and personal fees from Allergopharma, BSreports personal fees from Allergopharma, during the conduct MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quin- of the study; grants from National Health Programm, grant, personal tiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, patient ombudsman, national Centre for Research and Development, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akade- Polish Allergology Society. mie für Allergologie und klinische Immunologie, HNO‐BV, GPA, JS reports grants and personal fees from Sanofi, personal EAACI. fees from GSK, Novartis, Astra Zeneca, Mundipharma, Faes PK reports personal fees from Adamed, Berlin Chemie Menarini, Farma. Boehringer Ingelheim, AstraZeneca, Lekam, Novartis, Polpharma, GS reports personal fees from ALK, and leds on the BSACI GSK, Polpharma, Sanofi, teva. Rhinitis Guidelines and lead for EUFOREA on Allergic Rhinitis. 20457022, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014 by Consorci De Serveis Universitaris De Catalunya, Wiley Online Library on [28/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License BOUSQUET ET AL. - 11 of 11 PSG reports personal fees from Allergopharma, ALK, grants from Immunology (DGAKI). Head: European Centre for Allergy Research Bencard, grants and personal fees from Stallergenes. Foundation (ECARF). Secretary General: Global Allergy and Asthma JS reports personal fees from Mylan, F2F events. European Network (GA2LEN). Member: Committee on Allergy Diag- ATB reports grants and personal fees from Teva, AstraZeneca, nosis and Molecular Allergology, World Allergy Organization (WAO). GSK Sanofi, Mundipharma, personal fees from Bial, Novartis. O RC I D MJTreports grants from European Commission, SEAIC, ISCIII, Jean Bousquet https://orcid.org/0000-0002-4061-4766 personal fees from Diater laboratory, Leti laboratory, Aimmune Victoria Cardona https://orcid.org/0000-0003-2197-9767 Therapeutics. Ralph Mösges https://orcid.org/0000-0002-1928-810X MW reports personal fees from ALK‐Abello, Allergopharma, Dermot Ryan https://orcid.org/0000-0002-4115-7376 AstraZeneca, Bencard, Genzyme, GlaxoSmithKline, HAL Allergy, Manuel Soto‐Quiros https://orcid.org/0000-0003-3425-3463 LETI, Meda Pharma, Novartis, Sanofi, Stallergenes, Teva. Isabel Skypala https://orcid.org/0000-0003-3629-4293 DW reports other from Optinose, ALK, Sanofi; past Co‐Chair of the Mihaela Zidarn https://orcid.org/0000-0003-0515-5207 Joint Task Force on Practice Parameters of the AAAAI and ACAAI. Second author of a recently published practice parameter on Rhinitis. MW reports other from Aralez (Medexus), Pediapharm, Pfizer, Astra Zeneca, GSK, Alk. How to cite this article: Bousquet J, Pfaar O, Agache I, et al. MZ reports personal fees from Takeda. ARIA‐EAACI care pathways for allergen immunotherapy in TZ reports and Organizational affiliations: Commitee member: respiratory allergy. Clin Transl Allergy. 2021;e12014. https:// WHO‐Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA). doi.org/10.1002/clt2.12014 Member of the Board: German Society for Allergy and Clinical