Liam G Heaney1, Luis Perez de Llano2, Mona Al-Ahmad3, Vibeke Backer4, John Busby1, Giorgio Walter Canonica5, George C Christoff6, Borja G Cosio7, J Mark FitzGerald8, Enrico Heffler5, Takashi Iwanaga9, David J Jackson10, Andrew N Menzies-Gow11, Nikolaos G Papadopoulos12, Andriana I Papaioannou13, Paul E Pfeffer14, Todor A Popov15, Celeste M Porsbjerg16, Chin Kook Rhee17, Mohsen Sadatsafavi18, Yuji Tohda9, Eileen Wang19, Michael E Wechsler20, Marianna Alacqua21, Alan Altraja22, Leif Bjermer23, Unnur S Björnsdóttir24, Arnaud Bourdin25, Guy G Brusselle26, Roland Buhl27, Richard W Costello28, Mark Hew29, Mariko Siyue Koh30, Sverre Lehmann31, Lauri Lehtimäki32, Matthew Peters33, Camille Taillé34, Christian Taube35, Trung N Tran36, James Zangrilli36, Lakmini Bulathsinhala37, Victoria A Carter37, Isha Chaudhry37, Neva Eleangovan37, Naeimeh Hosseini37, Marjan Kerkhof37, Ruth B Murray37, Chris A Price37, David B Price38. 1. UK Severe Asthma Network and National Registry, Queen's University Belfast, Belfast, United Kingdom. 2. Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Monforte, Cervo, Lugo, Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Spain. 3. Al-Rashed Allergy Center, Ministry of Health, Microbiology Department, Faculty of Medicine, Kuwait University, Kuwait. 4. Centre for Physical Activity Research, Rigshospitalet, Copenhagen University, Copenhagen, Denmark; Department of ENT, Rigshospitalet, Copenhagen University, Copenhagen, Denmark. 5. Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. 6. Faculty of Public Health, Medical University - Sofia, Sofia, Bulgaria. 7. Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain. 8. Centre for Lung Health, Vancouver, BC, Canada. 9. Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan. 10. UK Severe Asthma Network and National Registry, Guy's and St Thomas' NHS Trust, London, United Kingdom; School of Immunology & Microbial Sciences, King's College London, London, United Kingdom. 11. UK Severe Asthma Network and National Registry, Royal Brompton & Harefield Hospitals, London, UK. 12. Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, United Kingdom; Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece. 13. 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece. 14. Department of Respiratory Medicine, Barts Health NHS Trust, The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; UK Severe Asthma Network, Barts Health NHS Trust, London, United Kingdom. 15. University Hospital "Sv. Ivan Rilski", Sofia, Bulgaria. 16. Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark. 17. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. 18. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. 19. Division of Allergy & Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO; Division of Allergy & Clinical Immunology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, CO. 20. NJH Cohen Family Asthma Institute, Department of Medicine, National Jewish Health, Denver, CO. 21. AstraZeneca, Cambridge, United Kingdom. 22. Department of Pulmonary, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia. 23. Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden. 24. Department of Respiratory Medicine and Allergy, Landspitali The University Hospital of Iceland, Reykjavik, Iceland. 25. PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France. 26. Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Epidemiology and Respiratory Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands. 27. Pulmonary Department, Mainz University Hospital, Mainz, Germany. 28. Clinical Research Centre, Smurfit Building Beaumont Hospital and Department of Respiratory Medicine, RCSI, Dublin, Ireland. 29. Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, Australia; Public Health and Preventive Medicine, Monash University, Melbourne, Australia. 30. Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Republic of Singapore; SingHealth Duke-NUS Lung Centre, Singapore, Republic of Singapore. 31. Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway. 32. Allergy Centre, Tampere University Hospital, and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. 33. Department of Thoracic Medicine, Concord Hospital, Sydney, Australia. 34. Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris; Paris, France. 35. Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany. 36. AstraZeneca, Gaithersburg, MD. 37. Optimum Patient Care, Cambridge, United Kingdom. 38. Optimum Patient Care, Cambridge, United Kingdom; Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom; Observational and Pragmatic Research Institute, Singapore, Republic of Singapore. Electronic address: dprice@opri.sg.
Abstract
BACKGROUND: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. RESEARCH QUESTION: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? STUDY DESIGN AND METHODS: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). RESULTS: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. INTERPRETATION: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
BACKGROUND: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. RESEARCH QUESTION: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? STUDY DESIGN AND METHODS: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). RESULTS: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. INTERPRETATION: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
Authors: Andrew Menzies-Gow; Flavia L Hoyte; David B Price; David Cohen; Peter Barker; James Kreindler; Maria Jison; Christopher L Brooks; Peggy Papeleu; Rohit Katial Journal: Adv Ther Date: 2022-03-14 Impact factor: 4.070
Authors: David J Jackson; Praveen Akuthota; Rebeca Andradas; Albert J Bredenoord; Amanda Cordell; Sarah Gray; Joyce Kullman; Sameer K Mathur; Ian Pavord; Florence Roufosse; Christian Rubio; Irena Clisson Rusek; Dagmar Simon; Mary Jo Strobel; Tonya Winders Journal: Adv Ther Date: 2022-04-30 Impact factor: 4.070
Authors: Diana Betancor; José María Olaguibel; José Manuel Rodrigo-Muñoz; Ebymar Arismendi; Pilar Barranco; Blanca Barroso; Irina Bobolea; Blanca Cárdaba; María Jesús Cruz; Elena Curto; Victoria Del Pozo; Francisco-Javier González-Barcala; Carlos Martínez-Rivera; Joaquim Mullol; Xavier Muñoz; Cesar Picado; Vicente Plaza; Santiago Quirce; Manuel Jorge Rial; Lorena Soto; Antonio Valero; Marcela Valverde-Monge; Joaquin Sastre Journal: Clin Transl Allergy Date: 2022-08-20 Impact factor: 5.657
Authors: Cristiano Caruso; Paolo Cameli; Elena Altieri; Maria Aliani; Pietro Bracciale; Luisa Brussino; Maria Filomena Caiaffa; Giorgio Walter Canonica; Stefano Centanni; Maria D'Amato; Stefano Del Giacco; Fausto De Michele; Elide Anna Pastorello; Girolamo Pelaia; Paola Rogliani; Micaela Romagnoli; Pietro Schino; Marco Caminati; Alessandra Vultaggio; Alessandro Zullo; Sara Rizzoli; Silvia Boarino; Gianfranco Vitiello; Francesco Menzella; Fabiano Di Marco Journal: Front Med (Lausanne) Date: 2022-09-02
Authors: Maria D'Amato; Francesco Menzella; Elena Altieri; Elena Bargagli; Pietro Bracciale; Luisa Brussino; Maria Filomena Caiaffa; Giorgio Walter Canonica; Cristiano Caruso; Stefano Centanni; Fausto De Michele; Fabiano Di Marco; Elide Anna Pastorello; Girolamo Pelaia; Paola Rogliani; Micaela Romagnoli; Pietro Schino; Gianenrico Senna; Alessandra Vultaggio; Alessandra Ori; Lucia Simoni; Silvia Boarino; Gianfranco Vitiello; Maria Aliani; Stefano Del Giacco Journal: Front Allergy Date: 2022-05-18
Authors: Luis A Pérez de Llano; Borja G Cosío; Ignacio Lobato Astiárraga; Gregorio Soto Campos; Miguel Ángel Tejedor Alonso; Nuria Marina Malanda; Alicia Padilla Galo; Isabel Urrutia Landa; Francisco J Michel de la Rosa; Ismael García-Moguel Journal: J Asthma Allergy Date: 2022-01-14