[en] BACKGROUND: Asthma with low levels of type 2 (T2) biomarkers is poorly understood. OBJECTIVE: To characterize severe asthma phenotypes and compare changes in asthma outcomes from pre- to postbiologic treatment along a gradient of T2 involvement. METHODS: This was a registry-based cohort study including data from 24 countries. Biomarker distribution (blood eosinophil count, fractional exhaled nitric oxide, and IgE) was quantified before biologic initiation. Clusters were identified using a 5-component Gaussian finite mixture model and phenotypically characterized. Changes in asthma and health care utilization outcomes between 1-year pre- and postbiologic initiation were compared between clusters and by biologic class. RESULTS: Among 3675 patients, 5 biomarker clusters were identified along a gradient of T2 involvement: cluster A with the lowest T2 involvement (16.4%), cluster B (20.4%), cluster C (22.9%), cluster D (30.3%), and cluster E with the highest T2 involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in forced expiratory volume in 1 second compared with cluster A (difference 0.16 L [95% confidence interval: 0.08, 0.25]; P < .001). The odds of uncontrolled asthma were approximately 0.6 for all clusters compared with cluster A. Overall, exacerbation rates were lower, and greater improvements in lung function and asthma control were noted for anti-IL-5/5 receptor (R) (but not anti-IgE or anti-IL-4Rα) for all clusters compared with cluster A. CONCLUSION: T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. Further research is warranted to identify specific pathogenic pathways at the lower end of the T2 spectrum that can be effectively targeted by biologics.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Wang, Eileen; Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health, Denver, Colo, Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colo.
Henley, William; Observational and Pragmatic Research Institute, Singapore, Optimum Patient Care Global, Cambridge, United Kingdom, Department of Health and Community Sciences, University of Exeter Medical School, Exeter, United Kingdom.
Larenas-Linnemann, Désirée; Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Mexico City, Mexico.
Bulathsinhala, Lakmini; Observational and Pragmatic Research Institute, Singapore, Optimum Patient Care Global, Cambridge, United Kingdom.
Tran, Trung N; BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Md.
Wechsler, Michael E; Department of Medicine, NJH Cohen Family Asthma Institute, National Jewish Health, Denver, Colo.
Aaron, Shawn D; The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Al-Ahmad, Mona; Microbiology Department, College of Medicine, Kuwait University, Kuwait City, Kuwait, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait.
Al-Lehebi, Riyad; Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Altraja, Alan; Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia.
Beastall, Aaron; Observational and Pragmatic Research Institute, Singapore, Optimum Patient Care Global, Cambridge, United Kingdom.
Belevskiy, Andrey S; Department of Pulmonology, N.I. Pirogov Russian State National Research Medical University, Moscow, Russian Federation.
Bergeron, Celine; Centre for Lung Health, Vancouver General Hospital, Vancouver, BC, Canada, Department of Medicine, Centre for Lung Health, The University of British Columbia, Vancouver, BC, Canada.
Bjermer, Leif; Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
Björnsdóttir, Unnur S; Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland.
Bosnic-Anticevich, Sinthia Z; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia, Woolcock Institute of Medical Research, Sydney, NSW, Australia.
Bourdin, Arnaud; PhyMedExp, University of Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France.
Brusselle, Guy G; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium, Departments of Epidemiology and Respiratory Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
Busby, John; Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
Canonica, Giorgio Walter; Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy.
Carter, Victoria; Observational and Pragmatic Research Institute, Singapore, Optimum Patient Care Global, Cambridge, United Kingdom.
Chapman, Kenneth R; University of Toronto, Toronto, ON, Canada.
Chapman, Nicholas; Saint Joseph Hospital, Denver, Colo, National Jewish Health, Denver, Colo.
Christoff, George C; Bulgarian Alliance for Clinical and Translational Allergy, Sofia, Bulgaria.
Cosio, Borja G; Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain.
Costello, Richard W; Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland.
Fingleton, James; Capital and Coast District Health Board, Wellington, New Zealand.
Fonseca, João A; CINTESIS@RISE (Center for Health Technology and Services Research at Health Research Network), MEDCIDS (Departamento Medicina da Comunidade, Informação e Decisão em Saúde/Department of Community Medicine, Information and Health Decisions), Faculty of Medicine of the University of Porto, Porto, Portugal.
Gaga, Mina; 1st Respiratory Medicine Department, Hygeia Hospital, Athens, Greece.
Gibson, Peter G; Australian Severe Asthma Network, Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, NSW, Australia, Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, New Lambton Heights, NSW, Australia.
Hansen, Susanne; Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark, Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Heaney, Liam G; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom.
Heffler, Enrico; Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy.
Hew, Mark; Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia, Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Horiguchi, Takahiko; Toyota Regional Medical Center, Nishiyamacho, Toyota, Japan.
Hoyte, Flavia; Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health, Denver, Colo.
Hubbard, Richard B; Observational and Pragmatic Research Institute, Singapore, Optimum Patient Care Global, Cambridge, United Kingdom, Respiratory Medicine at the School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Iwanaga, Takashi; Kindai University Hospital, Osakasayama, Japan.
Jackson, David J; Guy's Severe Asthma Centre, School of Immunology & Microbial Sciences, King's College, London, United Kingdom.
Katial, Rohit; Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health, Denver, Colo.
Koh, Mariko Siyue; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore.
Kostikas, Konstantinos; Respiratory Medicine Department, University of Ioannina, Ioannina, Greece.
Kuna, Piotr; Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland.
Lehmann, Sverre; Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway, Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
Lehtimäki, Lauri; Allergy Centre, Tampere University Hospital, Tampere, Finland, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Louis, Renaud ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Lúdvíksdóttir, Dóra; Department of Respiratory Medicine, Landspitali University Hospital Reykjavik Iceland, University of Iceland, Reykjavik, Iceland.
Lugogo, Njira; Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Mich.
Mahboub, Bassam; Rashid Hospital, Dubai Health Authority (DHA), Dubai, United Arab Emirates, Dubai Academic and Health Corporation, Dubai, United Arab Emirates.
Martin, Neil; BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Md, Department of Respiratory Medicine, University of Leicester, Leicester, United Kingdom.
Máspero, Jorge; Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina, University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina.
Menzies-Gow, Andrew N; Lung Division, Royal Brompton & Harefield Hospital, London, United Kingdom, AstraZeneca, Cambridge, United Kingdom.
Mohan, Arjun; Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Mich.
Murray, Ruth B; Optimum Patient Care Global, Cambridge, United Kingdom.
Nagano, Tatsuya; Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Papadopoulos, Nikolaos G; Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, United Kingdom, Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
Papaioannou, Andriana I; 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece.
Patel, Pujan H; Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom.
Perez-de-Llano, Luis; Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Monforte, Cervo, Spain.
Perng, Diahn-Warng; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Peters, Matthew J; Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia, Faculty of Medicine, Health and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Pfeffer, Paul E; Department of Respiratory Medicine, Barts Health NHS Trust, London, United Kingdom, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Pitrez, Paulo Márcio; Pulmonology Division, Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil.
Pleasants, Roy Alton; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC.
Popov, Todor A; University Hospital St. Ivan Rilski, Sofia, Bulgaria.
Porsbjerg, Celeste M; Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
Puggioni, Francesca; Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy.
Quinton, Anna; AstraZeneca, Cambridge, United Kingdom.
Rhee, Chin Kook; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea.
Sadatsafavi, Mohsen; Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, the University of British Columbia, Vancouver, BC, Canada.
Salvi, Sundeep; Pulmocare Research and Education Foundation, Pune, India.
Scioscia, Giulia; Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Sheu, Chau-Chyun; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Sirena, Concetta; Severe Asthma Network Italy (SANI), Milano, Italy.
Taillé, Camille; Department of Respiratory Diseases, Bichat Hospital, AP-HP, Université Paris Cité, Paris, France.
Taube, Christian; Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany.
Torres-Duque, Carlos A; CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia, Universidad de La Sabana, Chia, Colombia.
Tsai, Ming-Ju; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Tunsäter, Alf; Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
Ulrik, Charlotte Suppli; Department of Respiratory Medicine, Copenhagen University Hospital, Hvidovre, Denmark.
Price, David B; Observational and Pragmatic Research Institute, Singapore, Optimum Patient Care Global, Cambridge, United Kingdom, Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom. Electronic address: dprice@opri.sg.
Global Initiative for Asthma. Global strategy for asthma management and prevention. https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf, 2024. (Accessed 23 July 2025)
Heaney, L.G., Perez de Llano, L., Al-Ahmad, M., Backer, V., Busby, J., Canonica, G.W., et al. Eosinophilic and non-eosinophilic asthma: an expert consensus framework to characterize phenotypes in a global real-life severe asthma cohort. Chest 160 (2021), 814–830.
Jackson, D.J., Busby, J., Pfeffer, P.E., Menzies-Gow, A.N., Brown, T., Gore, R., et al. Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era. Thorax 76 (2021), 220–227.
Ricciardolo, F.L.M., Sprio, A.E., Baroso, A., Gallo, F., Riccardi, E., Bertolini, F., et al. Characterization of T2-low and T2-high asthma phenotypes in real-life. Biomedicines, 9, 2021, 1684.
Heaney, L.G., Busby, J., Hanratty, C.E., Djukanovic, R., Woodcock, A., Walker, S.M., et al. Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med 9 (2021), 57–68.
Ricciardolo, F.L.M., Carriero, V., Bertolini, F., Which therapy for non-type(T)2/T2-low asthma. J Pers Med, 12, 2021, 10.
Lazarus, S.C., Krishnan, J.A., King, T.S., Lang, J.E., Blake, K.V., Covar, R., et al. Mometasone or tiotropium in mild asthma with a low sputum eosinophil level. N Engl J Med 380 (2019), 2009–2019.
Carr, T.F., Zeki, A.A., Kraft, M., Eosinophilic and Noneosinophilic Asthma. Am J Respir Crit Care Med 197 (2018), 22–37.
Loza, M.J., Djukanovic, R., Chung, K.F., Horowitz, D., Ma, K., Branigan, P., et al. Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study. Respir Res, 17, 2016, 165.
Denton, E., Price, D.B., Tran, T.N., Canonica, G.W., Menzies-Gow, A.N., FitzGerald, J.M., et al. Cluster analysis of inflammatory biomarker expression in the international severe asthma registry. J Allergy Clin Immunol Pract 9 (2021), 2680–2688.e7.
Rupani, H., Kyyaly, M.A., Azim, A., Abadalkareen, R., Freeman, A., Dennison, P., et al. Comprehensive characterization of difficult-to-treat asthma reveals near absence of T2-low status. J Allergy Clin Immunol Pract 11 (2023), 2812–2821.e4.
Moore, W.C., Meyers, D.A., Wenzel, S.E., Teague, G.W., Li, H., Li, X., et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 181 (2010), 315–323.
Douwes, J., Gibson, P., Pekkanen, J., Pearce, N., Non-eosinophilic asthma: importance and possible mechanisms. Thorax 57 (2002), 643–648.
Kyriakopoulos, C., Gogali, A., Bartziokas, K., Kostikas, K., Identification and treatment of T2-low asthma in the era of biologics. ERJ Open Res 7 (2021), 00309–2020.
Anderson, W.J., Short, P.M., Williamson, P.A., Lipworth, B.J., Inhaled corticosteroid dose response using domiciliary exhaled nitric oxide in persistent asthma: the FENOtype trial. Chest 142 (2012), 1553–1561.
Biener, L., Milger, K., Suhling, H., Korn, S., Pizarro, C., Skowasch, D., Impact of short-term pausing of oral corticosteroids on blood eosinophil count in patients with severe asthma. Pneumologie 77 (2023), 357–362.
Menzies-Gow, A.N., Corren, J., Bourdin, A., Chupp, G., Israel, E., Wechsler, M.E., et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med 384 (2021), 1800–1809.
Corren, J., Menzies-Gow, A.N., Chupp, G., Israel, E., Korn, S., Cook, B., et al. Efficacy of Tezepelumab in severe, uncontrolled asthma: pooled analysis of the PATHWAY and NAVIGATOR clinical trials. Am J Respir Crit Care Med 208 (2023), 13–24.
ISAR Study Group. International Severe Asthma Registry (ISAR): mission statement. Chest 157 (2020), 805–814.
FitzGerald, J.M., Tran, T.N., Alacqua, M., Altraja, A., Backer, V., Bjermer, L., et al. International severe asthma registry (ISAR): protocol for a global registry. BMC Med Res Methodol, 20, 2020, 212.
Cushen, B., Koh, M.S., Tran, T.N., Martin, N., Murray, R.B., Uthaman, T., Adult severe asthma registries: a global and growing inventory. Pragmat Obs Res 14 (2023), 127–147.
Wang, E., Wechsler, M.E., Tran, T.N., Heaney, L.G., Jones, R.C., Menzies-Gow, A.N., et al. Characterization of severe asthma worldwide: data from the International Severe Asthma Registry (ISAR). Chest 157 (2020), 790–804.
Campbell, J.D., Perry, R., Papadopoulos, N.G., Krishnan, J., Brusselle, G.G., Chisholm, A., et al. The REal Life EVidence AssessmeNt Tool (RELEVANT): development of a novel quality assurance asset to rate observational comparative effectiveness research studies. Clin Transl Allergy, 9, 2019, 21.
Global Initiative for Asthma. Global strategy for asthma prevention and treatment. https://ginasthma.org/wp-content/uploads/2019/01/2018-GINA.pdf, 2018. (Accessed 23 July 2025)
Nathan, R.A., Sorkness, C.A., Kosinski, M., Schatz, M., Li, J.T., Marcus, P., et al. Development of the Asthma Control Test: a survey for assessing asthma control. J Allergy Clin Immunol 113 (2004), 59–65.
Juniper, E.F., O'Byrne, P.M., Guyatt, G.H., Ferrie, P.J., King, D.R., Development and validation of a questionnaire to measure asthma control. Eur Respir J 14 (1999), 902–907.
Scrucca, L., Fop, M., Murphy, T., Raftery, A., mclust 5: clustering, classification and density estimation using Gaussian finite mixture models. R J 8 (2016), 289–317.
Gormley, I., Murphy, T., Raferty, A., Model-based clustering. Ann Rev Stat Appl 10 (2023), 573–595.
Prates, M., Lachos, V., Barbosa Cabral, C., mixsmsn: fitting finite mixture of scale mixture of skew-normal distributions. J Stat Softw 54 (2013), 1–20.
Fitzpatrick, A.M., Moore, W.C., Severe asthma phenotypes—how should they guide evaluation and treatment. J Allergy Clin Immunol Pract 5 (2017), 901–908.
Schiffers, C., Wouters, E.F.M., Breyer-Kohansal, R., Buhl, R., Pohl, W., Irvin, C.G., et al. Asthma prevalence and phenotyping in the general population: the LEAD (Lung, hEart, sociAl, boDy) study. J Asthma Allergy 16 (2023), 367–382.
van Bragt, J.J.M.H., Adcock, I.M., Bel, E.H.D., Braunstahl, G.J., Ten Brinke, A., Busby, J., et al. Characteristics and treatment regimens across ERS SHARP severe asthma registries. Eur Respir J, 55, 2020, 1901163.
Reddel, H.K., Vestbo, J., Agustí, A., Anderson, G.P., Bansal, A.T., Beasley, R., et al. Heterogeneity within and between physician-diagnosed asthma and/or COPD: NOVELTY cohort. Eur Respir J, 58, 2021, 2003927.
Louis, R., Louis, G., Bonhomme, O., NOVELTY: a landmark study in phenotyping and endotyping chronic obstructive airway diseases in real clinical practice. Eur Respir J, 58, 2021, 2100627.
Portel, L., Parrat, E., Nocent-Ejnaini, C., Mangiapan, G., Prud'homme, A., Oster, J.P., et al. FASE-CPHG study: a panoramic snapshot of difficult-to-treat, severe asthma in French nonacademic hospitals. ERJ Open Res 5 (2019), 00069–2019.
Green, R.H., Brightling, C.E., Woltmann, G., Parker, D., Wardlaw, A.J., Pavord, I.D., Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax 57 (2002), 875–879.
Ananth, S., Navarra, A., Vancheeswaran, R., Obese, non-eosinophilic asthma: frequent exacerbators in a real-world setting. J Asthma 59 (2022), 2267–2275.
Hanania, N.A., Wenzel, S., Rosén, K., Hsieh, H.J., Mosesova, S., Choy, D.F., et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med 187 (2013), 804–811.
Humbert, M., Taillé, C., Mala, L., Le Gros, V., Just, J., Molimard, M., Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Eur Respir J, 51, 2018, 1702523.
FitzGerald, J.M., Bleecker, E.R., Nair, P., Korn, S., Ohta, K., Lommatzsch, M., et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 388 (2016), 2128–2141.
Bleecker, E.R., FitzGerald, J.M., Chanez, P., Papi, A., Weinstein, S.F., Barker, P., et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 388 (2016), 2115–2127.
Wenzel, S., Castro, M., Corren, J., Maspero, J., Wang, L., Zhang, B., et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet 388 (2016), 31–44.
Corren, J., Parnes, J.R., Wang, L., Mo, M., Roseti, S.L., Griffiths, J.M., et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med 377 (2017), 936–946.
Gibson, P.G., Yang, I.A., Upham, J.W., Reynolds, P.N., Hodge, S., James, A.L., et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res 5 (2019), 00056–2019.
Gibson, P.G., Yang, I.A., Upham, J.W., Reynolds, P.N., Hodge, S., James, A.L., et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet 390 (2017), 659–668.
