Biomarker profile and disease burden associated with intermittent and long-term oral corticosteroid use in patients with severe asthma prior to biologic initiation in real-life (STAR)

Florence Schleich¹, Désirée Larenas-Linnemann², Alan Altraja³, Luis Pérez de Llano^{4

5}, Konstantinos Kostikas⁶, Mohsen Sadatsafavi⁷, Arnaud Bourdin⁸, Roy Alton Pleasants^{9

10}, Mark Hew^{11

12}, Wenjia Chen¹³, Libardo Jiménez-Maldonado^{14

15}, Simon Couillard¹⁶, Charlotte Suppli Ulrik¹⁷, Adeeb A Bulkhi¹⁸, Ming-Ju Tsai^{19

20}, George C Christoff²¹, Nikolaos G Papadopoulos^{22

23}, Paul E Pfeffer^{24

25}, Dermot Ryan²⁶, Celine Bergeron^{27

28}, Mona S Al-Ahmad^{29

30}, Delbert R Dorscheid³¹, Eileen Wang^{32

33}, John D Blakey^{34

35}, Belinda Cochrane^{36

37}, Matthew J Peters^{38

39}, Todor A Popov⁴⁰, Carlos A Torres-Duque^{41

15}, Susanne Hansen^{42

43}, Francesca Puggioni⁴⁴, Kirsty Fletton^{45

46}, Laila Salameh^{47

48}, Peter G Middleton⁴⁹, Paulo Márcio Pitrez⁵⁰, Chin Kook Rhee⁵¹, Eve Denton^{11

52}, Kenneth R Chapman⁵³, Lauri Lehtimäki^{54

55}, Ruth B Murray^{45

46}, Chau-Chyun Sheu^{19

20}, David J Jackson⁵⁶, Riyad Al-Lehebi^{57

58}, Mariko Siyue Koh⁵⁹, Bassam Mahboub^{47

60}, Ledit R F Ardusso⁶¹, Athena Gogali⁶, Giorgio Walter Canonica^{44

62}, Piotr Kuna⁶³, Martin Sivori⁶⁴, Renaud Louis¹, Shelley Abercromby⁶⁵, Giuseppe Guida⁶⁶, Bernt Bøgvald Aarli^{67

68}, Aaron Beastall^{45

46}, Victoria Carter^{45

46}, Ghislaine Scelo^{45

46}, John Townend^{45

46}, Borja G Cosio⁶⁹, Pujan H Patel⁷⁰, Celine Yun Yi Goh^{45

46}, Zsuzsanna Csoma⁷¹, John W Upham⁷², João A Fonseca⁷³, Peter G Gibson^{74

75}, Christine Jenkins⁷⁶, Guy G Brusselle^{77

78}, Anne Chèvremont⁷⁹, Andréanne Côté⁸⁰, Carlos Andrés Celis-Preciado^{81

82}, Ivan Solarte^{81

82}, Celeste M Porsbjerg⁸³, Asger Sverrild^{83

84}, Paula Kauppi⁸⁵, Stelios Loukides⁸⁶, Michael P Makris⁸⁷, Andriana I Papaioannou⁸⁷, Enrico Heffler^{44

62}, Jeffrey Shi Kai Chan⁴⁵, Hyonsoo Joo⁸⁸, Liam G Heaney⁸⁹, Wei-Han Cheng⁹⁰, Njira Lugogo¹⁰, Michael E Wechsler⁹¹, Cláudia Chaves Loureiro^{92

93}, Bellanid Rodríguez-Cáceres⁹⁴, Tatsuya Nagano⁹⁵, Zhixiao Wang⁹⁶, Hao-Chien Wang⁹⁷, Jorge Máspero^{98

99}, Fernando Saldarini¹⁰⁰, Ana María Stok¹⁰¹, Anahi Yañez¹⁰², Philip G Bardin^{103

52}, Sinthia Z Bosnic-Anticevich^{104

39

105}, Vidya Navaratnam^{106

34

35}, Mohit Bhutani¹⁰⁷, M Diane Lougheed^{108

109

110}, Lyle Melenka¹¹¹, Petros Bakakos¹¹², Konstantinos P Exarchos⁶, Aggelos A Ladias¹¹³, Dóra Lúdvíksdóttir¹¹⁴, Takashi Iwanaga¹¹⁵, Elvia Angelica Contreras Contreras^{116

117}, Sverre Lehmann^{68

67}, José Alberto Ferreira¹¹⁸, Rebecca Gall⁹⁶, Pin-Kuei Fu¹¹⁹, Diahn-Warng Perng^{120

121}, Flavia Hoyte³², Rohit Katial³², Unnur S Björnsdóttir¹²², Camille Taillé¹²³, Christian Taube¹²⁴, Breda Cushen¹²⁵, Lakmini Bulathsinhala^{45

46}, Leif Bjermer¹²⁶, David B Price^{45

46

127}; ISAR STAR Working Group

Affiliations

¹ Department Pneumology CHU Liege, GIGA I3 Research Group, Exercise Physiology Lab, University of Liege, Liege, Belgium.
² Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico.
³ Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia.
⁴ Pneumology Service. Lucus Augusti University Hospital. EOXI (Sergas (Galician Healthcare Service) Integrated Management Structure): Lugo, Monforte, Cervo, Spain.
⁵ Department of Psychiatry, Radiology, Public Health, Nursery and Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
⁶ Respiratory Medicine Department, University of Ioannina School of Medicine, Ioannina, Greece.
⁷ Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
⁸ PhyMedExp, Univ Montpellier, CNRS (National Center for Scientific Research), INSERM (The National Institute of Health and Medical Research), CHU (Centre Hospitalier Universitaire) Montpellier, Montpellier, France.
⁹ Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA.
¹⁰ Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.
¹¹ Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia.
¹² Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹³ Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
¹⁴ Fundación Neumológica Colombiana, ASMAIRE REXPIRA Program, Bogotá, Colombia.
¹⁵ Departamento Cundinamarca, Universidad de La Sabana, Chia, Colombia.
¹⁶ Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Canada.
¹⁷ Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, Copenhagen, Denmark.
¹⁸ Department of Medicine, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
¹⁹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
²⁰ Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
²¹ Faculty of Public Health, Medical University, Sofia, Bulgaria.
²² Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
²³ Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
²⁴ Department of Respiratory Medicine, Barts Health NHS (National Health Services) Trust, London, UK.
²⁵ Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
²⁶ Usher Institute, University of Edinburgh, Edinburgh, UK.
²⁷ Department of Medicine, Centre for Lung Health, Vancouver General Hospital, Vancouver, British Columbia, Canada.
²⁸ Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
²⁹ Microbiology Department, College of Medicine, Kuwait University, Kuwait City, Kuwait.
³⁰ Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait.
³¹ Center for Heart Lung Innovation, The University of British Columbia, Vancouver, Canada.
³² Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, USA.
³³ Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
³⁴ Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
³⁵ Curtin University Medical School, Perth, Australia.
³⁶ Department of Respiratory and Sleep Medicine, Campbelltown Hospital (SWSLHD), Campbelltown, New South Wales, Australia.
³⁷ School of Medicine, Western Sydney University, Sydney, New South Wales, Australia.
³⁸ Department of Thoracic Medicine, Concord Hospital, Sydney, New South Wales, Australia.
³⁹ Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
⁴⁰ University Hospital St. Ivan Rilski, Sofia, Bulgaria.
⁴¹ CINEUMO (Centro Internacional de Investigación en Neumología), Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia.
⁴² Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
⁴³ Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
⁴⁴ Personalized Medicine, Asthma and Allergy Clinic, IRCCS Humanitas Research Hospital, Rozzano MI, Italy.
⁴⁵ Observational and Pragmatic Research Institute, Singapore, Singapore.
⁴⁶ Optimum Patient Care Global, Cambridge, UK.
⁴⁷ Rashid Hospital, Dubai Health (DH), Dubai, United Arab Emirates.
⁴⁸ Medical Education and Research Department, Dubai Health, Dubai, United Arab Emirates.
⁴⁹ CITRICA, Dept Resiratory & Sleep Medicine, Westmead Hospital, Sydney, Australia.
⁵⁰ Pulmonology Division, Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil.
⁵¹ 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.
⁵² Department of Medicine, Central Clinical School, Monash University, Clayton, Melbourne, Victoria, Australia.
⁵³ University of Toronto, Toronto, Ontario, Canada.
⁵⁴ Allergy Centre, Tampere University Hospital, Tampere, Finland.
⁵⁵ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁵⁶ Guy's Severe Asthma Centre, School of Immunology & Microbial Sciences, King's College London, London, UK.
⁵⁷ Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia.
⁵⁸ College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
⁵⁹ Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.
⁶⁰ College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
⁶¹ Pulmonology, Allergy and Immunology Department, Rosario School of Medicine, National University of Rosario, Rosario, SF, Argentina.
⁶² Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
⁶³ Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland.
⁶⁴ Neumonology Center of School of Medicine, University of Buenos Aires, Hospital "Dr.JM.Ramos Mejia", Buenos Aires, Argentina.
⁶⁵ The Centre for Lung Health, Vancouver Coastal Health Research Institute, UBC, Vancouver, Canada.
⁶⁶ Department of Clinical and Biological Sciences, Severe Asthma and Rare Lung Disease Unit, San Luigi Gonzaga University Hospital, University of Turin, Orbassano, Turin, TO, Italy.
⁶⁷ Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
⁶⁸ Department of Clinical Science, University of Bergen, Bergen, Norway.
⁶⁹ Son Espases University Hospital-IdISBa (Institut d'Investigació Sanitària Illes Balears)-Ciberes, Mallorca, Spain.
⁷⁰ Respiratory Medicine, Royal Brompton Hospital, London, UK.
⁷¹ Asthma Outpatient Clinic, National Koranyi Institute for Pulmonology, Budapest, Hungary.
⁷² Frazer Institute & PA-Southside Clinical Unit, The University of Queensland, Brisbane, Queensland, Australia.
⁷³ 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.
⁷⁴ Australian Severe Asthma Network, Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, New South Wales, Australia.
⁷⁵ Hunter Medical Research Institute, Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
⁷⁶ Respiratory Medicine, UNSW, Sydney, Head Respiratory Group, George Institute, Australia.
⁷⁷ Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
⁷⁸ Departments of Epidemiology and Respiratory Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
⁷⁹ CHU Sart-Tilman Liège, 4000 Liège, Belgium.
⁸⁰ Department of Medicine, Laval University, Quebec City, Quebec, Canada.
⁸¹ Pulmonary Unit, Hospital Universitario San Ignacio, Bogota, Colombia.
⁸² Faculty of Medicine, Pontificia Universidad Javeriana, Bogota, Colombia.
⁸³ Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
⁸⁴ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁸⁵ The Heart and Lung Center, Helsinki, University Hospital, University of Helsinki, Helsinki, Finland.
⁸⁶ 2nd Respiratory Medicine Department, Attikon University Hospital, University of Athens Medical School, Athens, Greece.
⁸⁷ Allergy Unit, National and Kapodistrian University of Athens, University General Hospital 'Attikon', Greece.
⁸⁸ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
⁸⁹ Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
⁹⁰ Sanofi, Cambridge, MA, USA.
⁹¹ National Jewish Health Cohen Family Asthma Institute, Department of Medicine, National Jewish Health, Denver, CO, USA.
⁹² Pneumology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
⁹³ Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
⁹⁴ Instituto Neumológico del Oriente, Bucaramanga, Colombia.
⁹⁵ Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
⁹⁶ Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
⁹⁷ Department of Medicine, Cancer Center, National Taiwan University, Taipei, Taiwan.
⁹⁸ Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina.
⁹⁹ University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina.
¹⁰⁰ Section Pulmonology, Hospital Santojanni Autonomous, City of Buenos Aires, Argentina.
¹⁰¹ Investigaciones en Patologias Respiratorias, San Miguel de Tucuman, Tucuman, Argentina.
¹⁰² The Allergy and Respiratory Medicine Research Center- InAER - Buenos Aires, Argentina.
¹⁰³ Lung, Sleep, Allergy and Immunology, Monash Health Clayton, Monash University, Clayton, Melbourne, Victoria, Australia.
¹⁰⁴ AstraZeneca Pty Ltd, Medical Affairs, Biopharmaceuticals Unit, Sydney, New South Wales, Australia.
¹⁰⁵ Woolcock Institute of Medical Research, Sydney, New South Wales, Australia.
¹⁰⁶ The University of Western Australia, Perth, Australia.
¹⁰⁷ Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
¹⁰⁸ Asthma Research Unit, Kingston General Hospital Research Institute, Kingston, ON, Canada.
¹⁰⁹ Department of Medicine, Queen's University, Kingston, ON, Canada.
¹¹⁰ Department of Public Health Sciences, Queen's University, Kingston, ON, Canada.
¹¹¹ Synergy Respiratory Care, Sherwood Park, Canada.
¹¹² 1st Department of Respiratory Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹¹³ Pulmonology Resident in the University Hospital of Ioannina, Ioannina, Greece.
¹¹⁴ Department of Respiratory Medicine, Landspitali University Hospital Reykjavik Iceland, University of Iceland, Reykjavik, Iceland.
¹¹⁵ Kindai University Hospital, Osakasayama, Japan.
¹¹⁶ Mexican Council of Clinical Immunology and Allergy, Mexico City, Mexico.
¹¹⁷ Lic. Adolfo López Mateos Regional Hospital of the Institute of Security and Social Services for State Workers (ISSSTE), Mexico City, Mexico.
¹¹⁸ Allergy Department - ULS Gaia e Espinho, Vila Nova de Gaia, Portugal.
¹¹⁹ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
¹²⁰ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹²¹ Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹²² Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland.
¹²³ Department of Respiratory Diseases, Bichat Hospital, Assistance publique - Hôpitaux de Paris), Université Paris Cité, Paris, France.
¹²⁴ Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany.
¹²⁵ Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland.
¹²⁶ Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
¹²⁷ Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.

PMID: 40524942
PMCID: PMC12169735
DOI: 10.1016/j.waojou.2025.101066

Biomarker profile and disease burden associated with intermittent and long-term oral corticosteroid use in patients with severe asthma prior to biologic initiation in real-life (STAR)

Florence Schleich et al. World Allergy Organ J. 2025.

. 2025 Jun 3;18(7):101066.

doi: 10.1016/j.waojou.2025.101066. eCollection 2025 Jul.

Authors

Affiliations

¹ Department Pneumology CHU Liege, GIGA I3 Research Group, Exercise Physiology Lab, University of Liege, Liege, Belgium.
² Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico.
³ Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia.
⁴ Pneumology Service. Lucus Augusti University Hospital. EOXI (Sergas (Galician Healthcare Service) Integrated Management Structure): Lugo, Monforte, Cervo, Spain.
⁵ Department of Psychiatry, Radiology, Public Health, Nursery and Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
⁶ Respiratory Medicine Department, University of Ioannina School of Medicine, Ioannina, Greece.
⁷ Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
⁸ PhyMedExp, Univ Montpellier, CNRS (National Center for Scientific Research), INSERM (The National Institute of Health and Medical Research), CHU (Centre Hospitalier Universitaire) Montpellier, Montpellier, France.
⁹ Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA.
¹⁰ Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.
¹¹ Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia.
¹² Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹³ Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
¹⁴ Fundación Neumológica Colombiana, ASMAIRE REXPIRA Program, Bogotá, Colombia.
¹⁵ Departamento Cundinamarca, Universidad de La Sabana, Chia, Colombia.
¹⁶ Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Canada.
¹⁷ Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, Copenhagen, Denmark.
¹⁸ Department of Medicine, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
¹⁹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
²⁰ Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
²¹ Faculty of Public Health, Medical University, Sofia, Bulgaria.
²² Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
²³ Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
²⁴ Department of Respiratory Medicine, Barts Health NHS (National Health Services) Trust, London, UK.
²⁵ Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
²⁶ Usher Institute, University of Edinburgh, Edinburgh, UK.
²⁷ Department of Medicine, Centre for Lung Health, Vancouver General Hospital, Vancouver, British Columbia, Canada.
²⁸ Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
²⁹ Microbiology Department, College of Medicine, Kuwait University, Kuwait City, Kuwait.
³⁰ Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait.
³¹ Center for Heart Lung Innovation, The University of British Columbia, Vancouver, Canada.
³² Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, USA.
³³ Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
³⁴ Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
³⁵ Curtin University Medical School, Perth, Australia.
³⁶ Department of Respiratory and Sleep Medicine, Campbelltown Hospital (SWSLHD), Campbelltown, New South Wales, Australia.
³⁷ School of Medicine, Western Sydney University, Sydney, New South Wales, Australia.
³⁸ Department of Thoracic Medicine, Concord Hospital, Sydney, New South Wales, Australia.
³⁹ Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
⁴⁰ University Hospital St. Ivan Rilski, Sofia, Bulgaria.
⁴¹ CINEUMO (Centro Internacional de Investigación en Neumología), Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia.
⁴² Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
⁴³ Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
⁴⁴ Personalized Medicine, Asthma and Allergy Clinic, IRCCS Humanitas Research Hospital, Rozzano MI, Italy.
⁴⁵ Observational and Pragmatic Research Institute, Singapore, Singapore.
⁴⁶ Optimum Patient Care Global, Cambridge, UK.
⁴⁷ Rashid Hospital, Dubai Health (DH), Dubai, United Arab Emirates.
⁴⁸ Medical Education and Research Department, Dubai Health, Dubai, United Arab Emirates.
⁴⁹ CITRICA, Dept Resiratory & Sleep Medicine, Westmead Hospital, Sydney, Australia.
⁵⁰ Pulmonology Division, Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil.
⁵¹ 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.
⁵² Department of Medicine, Central Clinical School, Monash University, Clayton, Melbourne, Victoria, Australia.
⁵³ University of Toronto, Toronto, Ontario, Canada.
⁵⁴ Allergy Centre, Tampere University Hospital, Tampere, Finland.
⁵⁵ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁵⁶ Guy's Severe Asthma Centre, School of Immunology & Microbial Sciences, King's College London, London, UK.
⁵⁷ Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia.
⁵⁸ College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
⁵⁹ Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.
⁶⁰ College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
⁶¹ Pulmonology, Allergy and Immunology Department, Rosario School of Medicine, National University of Rosario, Rosario, SF, Argentina.
⁶² Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
⁶³ Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland.
⁶⁴ Neumonology Center of School of Medicine, University of Buenos Aires, Hospital "Dr.JM.Ramos Mejia", Buenos Aires, Argentina.
⁶⁵ The Centre for Lung Health, Vancouver Coastal Health Research Institute, UBC, Vancouver, Canada.
⁶⁶ Department of Clinical and Biological Sciences, Severe Asthma and Rare Lung Disease Unit, San Luigi Gonzaga University Hospital, University of Turin, Orbassano, Turin, TO, Italy.
⁶⁷ Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
⁶⁸ Department of Clinical Science, University of Bergen, Bergen, Norway.
⁶⁹ Son Espases University Hospital-IdISBa (Institut d'Investigació Sanitària Illes Balears)-Ciberes, Mallorca, Spain.
⁷⁰ Respiratory Medicine, Royal Brompton Hospital, London, UK.
⁷¹ Asthma Outpatient Clinic, National Koranyi Institute for Pulmonology, Budapest, Hungary.
⁷² Frazer Institute & PA-Southside Clinical Unit, The University of Queensland, Brisbane, Queensland, Australia.
⁷³ 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.
⁷⁴ Australian Severe Asthma Network, Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, New South Wales, Australia.
⁷⁵ Hunter Medical Research Institute, Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
⁷⁶ Respiratory Medicine, UNSW, Sydney, Head Respiratory Group, George Institute, Australia.
⁷⁷ Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
⁷⁸ Departments of Epidemiology and Respiratory Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
⁷⁹ CHU Sart-Tilman Liège, 4000 Liège, Belgium.
⁸⁰ Department of Medicine, Laval University, Quebec City, Quebec, Canada.
⁸¹ Pulmonary Unit, Hospital Universitario San Ignacio, Bogota, Colombia.
⁸² Faculty of Medicine, Pontificia Universidad Javeriana, Bogota, Colombia.
⁸³ Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
⁸⁴ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁸⁵ The Heart and Lung Center, Helsinki, University Hospital, University of Helsinki, Helsinki, Finland.
⁸⁶ 2nd Respiratory Medicine Department, Attikon University Hospital, University of Athens Medical School, Athens, Greece.
⁸⁷ Allergy Unit, National and Kapodistrian University of Athens, University General Hospital 'Attikon', Greece.
⁸⁸ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
⁸⁹ Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
⁹⁰ Sanofi, Cambridge, MA, USA.
⁹¹ National Jewish Health Cohen Family Asthma Institute, Department of Medicine, National Jewish Health, Denver, CO, USA.
⁹² Pneumology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
⁹³ Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
⁹⁴ Instituto Neumológico del Oriente, Bucaramanga, Colombia.
⁹⁵ Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
⁹⁶ Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
⁹⁷ Department of Medicine, Cancer Center, National Taiwan University, Taipei, Taiwan.
⁹⁸ Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina.
⁹⁹ University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina.
¹⁰⁰ Section Pulmonology, Hospital Santojanni Autonomous, City of Buenos Aires, Argentina.
¹⁰¹ Investigaciones en Patologias Respiratorias, San Miguel de Tucuman, Tucuman, Argentina.
¹⁰² The Allergy and Respiratory Medicine Research Center- InAER - Buenos Aires, Argentina.
¹⁰³ Lung, Sleep, Allergy and Immunology, Monash Health Clayton, Monash University, Clayton, Melbourne, Victoria, Australia.
¹⁰⁴ AstraZeneca Pty Ltd, Medical Affairs, Biopharmaceuticals Unit, Sydney, New South Wales, Australia.
¹⁰⁵ Woolcock Institute of Medical Research, Sydney, New South Wales, Australia.
¹⁰⁶ The University of Western Australia, Perth, Australia.
¹⁰⁷ Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
¹⁰⁸ Asthma Research Unit, Kingston General Hospital Research Institute, Kingston, ON, Canada.
¹⁰⁹ Department of Medicine, Queen's University, Kingston, ON, Canada.
¹¹⁰ Department of Public Health Sciences, Queen's University, Kingston, ON, Canada.
¹¹¹ Synergy Respiratory Care, Sherwood Park, Canada.
¹¹² 1st Department of Respiratory Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹¹³ Pulmonology Resident in the University Hospital of Ioannina, Ioannina, Greece.
¹¹⁴ Department of Respiratory Medicine, Landspitali University Hospital Reykjavik Iceland, University of Iceland, Reykjavik, Iceland.
¹¹⁵ Kindai University Hospital, Osakasayama, Japan.
¹¹⁶ Mexican Council of Clinical Immunology and Allergy, Mexico City, Mexico.
¹¹⁷ Lic. Adolfo López Mateos Regional Hospital of the Institute of Security and Social Services for State Workers (ISSSTE), Mexico City, Mexico.
¹¹⁸ Allergy Department - ULS Gaia e Espinho, Vila Nova de Gaia, Portugal.
¹¹⁹ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
¹²⁰ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹²¹ Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹²² Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland.
¹²³ Department of Respiratory Diseases, Bichat Hospital, Assistance publique - Hôpitaux de Paris), Université Paris Cité, Paris, France.
¹²⁴ Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany.
¹²⁵ Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland.
¹²⁶ Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
¹²⁷ Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.

PMID: 40524942
PMCID: PMC12169735
DOI: 10.1016/j.waojou.2025.101066

Abstract

Background: Asthma characterization using blood eosinophil count (BEC) (among other biomarkers and clinical indices) is recommended in severe asthma (SA), but the masking effect of oral corticosteroids (OCS), makes this challenging.

Aim: Our aim was to explore the effect of OCS use (both intermittent [iOCS] and long-term [LTOCS]) prior to biologic initiation on SA phenotype and biomarker profile in real-life and to characterize the burden of SA among patients prescribed LTOCS by biomarker profile.

Methods: This was a registry-based cohort study, including data from 23 countries collected between 2003 and 2023 and shared with the Internatonal Severe Asthma Registry (ISAR). Patients with SA were categorized into 3 cohorts, those with: (i) no prescription for OCS, (ii) prescription(s) for iOCS (ie, ≤90 days in previous 12-months, usually short courses for exacerbations), and (iii) prescriptions for LTOCS (ie, >90 days in previous 12-months). Biomarker distribution (ie, BEC, fractional exhaled nitric oxide [FeNO], and total Immunoglobulin E [IgE]) were quantified in the year prior to biologic initiation in patients with SA according to OCS prescription pattern. Phenotypes were characterized for those prescribed LTOCS according to BEC cut-off (<150 and ≥ 150 cells/μL).

Results: Of 4305 patients included, 5.0% (n = 215), 54.1% (n = 2330) and 40.9% (n = 1760) were prescribed no OCS, iOCS, and LTOCS, respectively. The BEC distribution varied by prescription pattern and LTOCS dose (<5 mg to ≥20 mg/day); BEC was <150 cells/μL in 28.6% (n = 369/1288) of LTOCS patients, compared to 19.5% (n = 284/1460) of iOCS patients and 14.0% (n = 21/150) of those in the no OCS group. Median BEC was also significantly lower in the LTOCS versus the iOCS group (310 vs 400 cells/μL; p < 0.001). A similar pattern was noted for IgE, but not FeNO. Among LTOCS patients with BEC <150 cells/μL, 39.9% experienced ≥4 exacerbations, 75.1% had uncontrolled asthma symptoms and 55.9% had evidence of persistent airflow obstruction (compared with 40.9%, 76.2% and 59.5% of those with BEC ≥150 cells/μL, respectively).

Conclusions: OCS, whether prescribed intermittently or long term, affect BEC distribution potentially leading to heightened risk of phenotype misclassification and influencing subsequent treatment decisions. FeNO appears to be less susceptible to OCS-induced suppression. Disease burden was high for those in the LTOCS group and was high independent of dose and BEC. Our findings highlight the importance of considering OCS use, even intermittent use, when characterizing SA, and suggests the need for earlier phenotyping and alternative treatment strategies for LTOCS patients with low BEC.

Keywords: BEC; Blood eosinophil count; FeNO; Fractional exhaled nitric oxide; IgE; Immunoglobulin E; Intermittent; Long-term.

PubMed Disclaimer

Conflict of interest statement

Florence Schleich reports consultancy work for GlaxoSmithKline, AstraZeneca, Sanofi - Advisory board, received speaker fees from GlaxoSmithKline, AstraZeneca, Chiesi, Teva, ALK and research grants from GlaxoSmithKline, AstraZeneca, and Chiesi. Désirée Larenas-Linnemann reports personal fees from ALK-Abelló, AstraZeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GlaxoSmithKline national and global, Viatris, Novartis, Pfizer, Sanofi, Siegfried, and Carnot, grants for guideline development from Abbvie, Bayer, Chiesi, Lilly, Sanofi, AstraZeneca, Pfizer, Novartis, Circassia, UCB, and GlaxoSmithKline, outside the submitted work. Alan Altraja has received lecture fees from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, Merck, Sharp & Dohme, Norameda, Novartis, Orion, Sanofi, Takeda, Teva, and Zentiva; sponsorships from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, Merck, Sharp & Dohme, Norameda, Novartis, Takeda, Teva, and Sanofi; and has participated in advisory boards for AstraZeneca, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, Merck, Sharp & Dohme, Novartis, Sanofi, Shire Pharmaceuticals, and Teva. Luis PérezdeLlano reports grants, personal fees, and non-financial support from AstraZeneca, personal fees and non-financial support from GlaxoSmithKline, grants, personal fees and non-financial support from Teva, personal fees and non-financial support from Chiesi, grants, personal fees and non-financial support from Sanofi, personal fees from Merck Sharp & Dohme, personal fees from Techdow Pharma, grants, personal fees and non-financial support from Faes Farma, personal fees from Leo-Pharma, grants and personal fees from Gebro, personal fees from Gilead, outside the submitted work. Konstantinos Kostikas received honoraria for presentations and consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GlaxoSmithKline, Guidotti, Menarini, Pfizer, Sanofi, Specialty Therapeutics. He was an employee of AstraZeneca from 2 September to 29 November2024. Mohsen Sadatsafavi has received honoraria from AstraZeneca, Boehringer Ingelheim, Teva, and GlaxoSmithKline for purposes unrelated to the content of this manuscript and has received research funding from AstraZeneca and Boehringer Ingelheim directly into his research account from AstraZeneca for unrelated projects. Arnaud Bourdin has received industry-sponsored grants from AstraZeneca/MedImmune, Boehringer Ingelheim, Cephalon/Teva, GlaxoSmithKline, Novartis, Sanofi-Regeneron, and consultancies with AstraZeneca/MedImmune, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Regeneron-Sanofi, Med-in-Cell, Actelion, Merck, Roche, and Chiesi. Roy Alton Pleasants is a consultant for AstraZeneca and Grifols and receives research support through institutions from AstraZeneca and GlaxoSmithKline. Mark Hew declares grants and other advisory board fees (made to his institutional employer) from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva, and Seqirus, for unrelated projects. Wenjia Chen reports no conflict of interest. Libardo Jiménez-Maldonado has received fees as advisory board participant and/or speaker from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, and Sanofi-Aventis; has participated in clinical trials for AstraZeneca, Novartis and GlaxoSmithKline. Simon Couillard reports the following: he has received non-restricted research grants from the NIHR Oxford BRC, the Quebec Respiratory Health Research Network, the Fondation Québécoise en Santé Respiratoire, AstraZeneca, bioMérieux, and Sanofi-Genyme-Regeneron; he is the holder of the Association Pulmonaire du Québec's Research Chair in Respiratory medicine and is a Clinical research scholar of the Fonds de recherche du Québec; he received speaker honoraria from AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, and Valeo Pharma; he received consultancy fees for FirstThought, AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, Access Biotechnology and Access Industries; he has received sponsorship to attend/speak at international scientific meetings by/for AstraZeneca and Sanofi-Regeneron. He is an advisory board member and will have stock options for Biometry Inc – a company which is developing a FeNO device (myBiometry). He advised the Institut national d'excellence en santé et services sociaux (INESSS) for an update of the asthma general practice information booklet for general practitioners. Charlotte Suppli Ulrik reports personal fees for talks, participation in advisory boards etc. from AstraZeneca, GlaxoSmithKline, Teva, Boehringer Ingelheim, Orion Pharma, Sanofi Genzyme, TFF Pharmaceuticals, Covis Pharma, Berlin-Chemie, Takeda, Chiesi, Pfizer, Hikma Pharmaceuticals, and Novo Nordisk, outside the submitted work. Adeeb A. Bulkhi has received speaker lecture fees from AstraZeneca, GlaxoSmithKline, Sanofi, Novartis, Takeda, and ALK. He also participated in advisory boards with GlaxoSmithKline, Sanofi, and Novartis. Ming-Ju Tsai has received sponsorship to attend or speak at conferences, honoraria for lecturing or attending advisory boards, and research grants from the following companies: AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Shionogi and Orient EuroPharma. George C. Christoff declares relevant research support from AstraZeneca and Sanofi. Nikolaos G. Papadopoulos has been a speaker and/or advisory board member for Abbott, Abbvie, ALK, Asit Biotech, AstraZeneca, Biomay, Boehringer Ingelheim, GlaxoSmithKline, HAL, Faes Farma, Medscape, Menarini, Merck Sharp & Dohme, Novartis, Nutricia, OM Pharma, Regeneron, Sanofi, Takeda, and Viatris. Paul E. Pfeffer has attended advisory boards for AstraZeneca, GlaxoSmithKline, and Sanofi; has given lectures/webinars at meetings supported by AstraZeneca, Chiesi, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, GlaxoSmithKline, Novartis, Regeneron, and Sanofi, for which his institution received remuneration; and has current research grants funded by GlaxoSmithKline and a quality improvement grant funded by AstraZeneca. Dermot Ryan has (in the last 3 years) lectured on behalf of, received sponsorship from, or acted as a paid advisor to Mylan, AZ, Chiesi, Novartis, GlaxoSmithKline, Boehringer Ingelheim and Regeneron. Celine Bergeron reports advisory board participation of Sanofi-Regeneron, AstraZeneca, Takeda, ValeoPharma, consultant for Areteia, honorarium for presentations for AstraZeneca/Amgen, GlaxoSmithKline, Grifols, Sanofi-Regeneron, ValeoPharma and grants paid to The University of British Columbia from BioHaven, Sanofi-Regeneron, AstraZeneca, and GlaxoSmithKline. Mona S. Al-Ahmad has received advisory board and speaker fees from AstraZeneca, Sanofi, Novartis, and GlaxoSmithKline, and received a grant from Kuwait Foundation for the Advancement of Sciences (KFAS). Delbert R. Dorscheid is on faculty at the University of British Columbia and is supported by the following grants: Canadian Institutes of Health Research, British Columbia Lung Association, and Michael Smith Foundation for Health Research. In addition, he has received speaking fees, travel grants, unrestricted project grants, writing fees and is a paid consultant for Pharma including Sanofi Regeneron, Novartis Canada, AstraZeneca, GlaxoSmithKline and ValeoPharma. He is an active member of Canadian Thoracic Society, American Thoracic Society, European Respiratory Society, and the Allergen Research Network. Dr. Dorscheid does not believe that any of the disclosed potential conflicts represent true conflicts with respect to the information and recommendations included in this manuscript. Eileen Wang has received honoraria from AstraZeneca, GlaxoSmithKline, Amgen, and Genentech. She has been an investigator on studies sponsored by AstraZeneca, GlaxoSmithKline, Genentech, and Sanofi, for which her institution has received funding. John D. Blakey has received grants or contracts from Asthma Australia, MRFF, FHRI, Telethon Kids Institute, International Primary Care Respiratory Group, and the Charlies Foundation for Research. He has received payment or honoraria for lectures, presentations, or speaker bureaus from Chiesi, The Limbic, Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, and Sanofi. He has received support for attending meetings and/or travel from GlaxoSmithKline, Centre for Research Excellence in Treatable Traits, AstraZeneca, and The George Institute. He has participated in the study steering committee of GlaxoSmithKline, unrelated to this work. He has taken a leadership role in the Thoracic Society of Australia and New Zealand, and Asthma Australia. He has received medical writing/equipment from GlaxoSmithKline, and Novartis. Belinda Cochrane has received advisory fees from GlaxoSmithKline and Sanofi, speaker fees from AstraZeneca, Moderna and Chiesi, and research grant funding from GlaxoSmithKline. Matthew J. Peters declares personal fees and non-financial support from AstraZeneca, GlaxoSmithKline, and Sanofi. Todor A. Popov declares research support from Novartis and Chiesi Pharma, not related to this particular work. Carlos A. Torres-Duque has received fees as advisory board participant and/or speaker from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, and Sanofi-Aventis; has taken part in clinical trials from AstraZeneca, Novartis and Sanofi-Aventis; has received unrestricted grants for investigator-initiated studies at Fundacion Neumologica Colombiana from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Grifols, and Novartis. Susanne Hansen declares no relevant conflict of interest. Francesca Puggioni reports having received lectures or advisory board fees from Menarini, Mundipharma, Chiesi, Alk Abello, AstraZeneca, Boehringer Ingelheim, Guidotti, Malesci, GlaxoSmithKline, Hal Allergy, Novartis, Sanofi, Regeneron, Stallergenes Greer, Valeas, and Almirall. Kirsty Fletton is an employee of Optimum Patient Care Global (OPCG), a co-funder of the International Severe Asthma Registry. Laila Salameh declares no relevant conflict of interest. Peter G. Middleton declares grant support from HCF Australia, Canadian Institutes of Health, Board membership of the CF Foundation DSMB, and lecture fees and advisory boards for AstraZeneca, Limbic, MedEd, and Vertex, all unrelated to this work. Paulo Márcio Pitrez received fees as a speaker or for consultations from GlaxoSmithKline, AstraZeneca, Sanofi, and Aché. Chin Kook Rhee received consulting/lecture fees from Merck Sharp & Dohme, AstraZeneca, GlaxoSmithKline, Novartis, Takeda, Mundipharma, Boehringer-Ingelheim, Teva, Sanofi, Organon, Roche, and Bayer. Eve Denton declares grants to her institution from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva, and Seqirus, for unrelated projects and speaker fees from Sanofi, and Boehringer Ingelheim. Kenneth R. Chapman has received grants from AstraZeneca, Boehringer Ingelheim, Bellus, CSL Behring, GlaxoSmithKline, Grifols, Inhibrx, Novartis, Regeneron, Sanofi, Takeda, Vertex, consulting fees from AstraZeneca, CSL Behring, GlaxoSmithKline, Grifols, Inhibrx, Novartis, Sanofi, Takeda. He has a leadership or fiduciary role in Alpha-1 Canada, Canadian Thoracic Society, Alpha-1 Foundation, and AlphaNet Canada. Lauri Lehtimäki has received personal fees from ALK, AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Orion Pharma and Sanofi. Ruth B. Murray is a consultant for Observational and Pragmatic Research Institute (OPRI) which conducted this study in collaboration with Optimum Patient Care, a co-funder of the International Severe Asthma Registry. Chau-Chyun Sheu has received advisory board and speaker fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Pfizer, and has acted as an investigator for trials sponsored by AstraZeneca, Novartis, Roche, Sanofi-Regeneron, Galapagos, Shionogi, Aridis, Bristol Myers Squibb, Insmed, United Therapeutics, Enanta Pharmaceuticals, Areteia Therapeutics, Meiji, and Horizon Therapeutics. David J. Jackson has received speaker fees and consultancy fees from AstraZeneca, GlaxoSmithKline, Sanofi Regeneron, and Boehringer Ingelheim, and research funding from AstraZeneca. Riyad Al-Lehebi has given lectures at meetings supported by AstraZeneca, Boehringer Ingelheim, Novartis, GlaxoSmithKline, and Sanofi, and participated in advisory board fees from GlaxoSmithKline, AstraZeneca, Novartis, and Abbott. Mariko Siyue Koh reports grant support from AstraZeneca, and honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GlaxoSmithKline, AstraZeneca, Novartis, Sanofi, and Boehringer Ingelheim, outside the submitted work. Bassam Mahboub reports no conflict of interest. Ledit R. F. Adrusso is an investigator and/or speaker for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Amgen, Chiesi, Bellus, Areteria, Insmed, and Optinose. Athena Gogali received honoraria for presentations and consultancy fees from: AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GlaxoSmithKline, Novartis, and Menarini. Giorgio Walter Canonica has received research grants, as well as lecture or advisory board fees from A. Menarini, Alk-Albello, Allergy Therapeutics, Anallergo, AstraZeneca, MedImmune, Boehringer Ingelheim, Chiesi Farmaceutici, Circassia, Danone, Faes, Genentech, Guidotti Malesci, GlaxoSmithKline, Hal Allergy, Merck, Merck Sharp & Dohme, Mundipharma, Novartis, Orion, Sanofi Aventis, Sanofi, Genzyme/Regeneron, Stallergenes, UCB Pharma, Uriach Pharma, Teva, Thermo Fisher, and Valeas. Piotr Kuna reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, FAES, Glenmark, Novartis, Polpharma, Boehringer Ingelheim, Teva, Zentiva, outside the submitted work. Martin Sivori has received lecture fees for medical education programs of AstraZeneca, GlaxoSmithKline, and TEVA. Renaud Louis has received grants and lecture fees from AstraZeneca, GlaxoSmithKline, and Sanofi. Shelley Abercromby declares no relevant conflict of interest. Giuseppe Guida received lecture fees from GlaxoSmithKline and AstraZeneca. Bernt Bøgvald Aarli reports grants from AstraZeneca and Novartis, honoraria for presentations from AstraZeneca, GlaxoSmithKline, Sanofi-Aventis, and Orion, consulting fees from AstraZeneca, Grifols, and IM Medical Education Nordic AB, and has participated in advisory boards for AstraZeneca, GlaxoSmithKline, Chiesi, Sanofi-Aventis, Grifols, Orion, and Celltrion Healthcare, and he reports owning stocks in KBB Medic (Medical app company), outside the submitted work. His institution has received funding from Novartis and AstraZeneca. Aaron Beastall is an employee of Optimum Patient Care Global, a co-funder of the International Severe Asthma Registry. Victoria Carter is an employee of Optimum Patient Care (OPC). OPC is a co-funder of the International Severe Asthma Registry. Ghislaine Scelo is a consultant for Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care, a co-funder of the International Severe Asthma Registry. John Townend is an employee of the Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care, a co-funder of the International Severe Asthma Registry. Borja G. Cosio declares grants from Chiesi, Menarini, and GlaxoSmithKline; personal fees for advisory board activities from Chiesi, GlaxoSmithKline, Novartis, Sanofi, Teva, and AstraZeneca; and payment for lectures/speaking engagements from Chiesi, Novartis, GlaxoSmithKline, Menarini, and AstraZeneca, outside the submitted work. Pujan H. Patel has received advisory board and speaker fees from AstraZeneca, GlaxoSmithKline, Novartis, and Sanofi/Regeneron. Celine Yun Yi Goh is an employee of Optimum Patient Care Global (OPCG), a co-funder of the International Severe Asthma Registry. Zsuzsanna Csoma declares no relevant conflict of interest. John W. Upham has received speaker and consulting fees from Novartis, AstraZeneca, GlaxoSmithKline, Sanofi, and Boehringer Ingelheim. João A. Fonseca reports grants from research agreements with AstraZeneca, Mundipharma, Sanofi Regeneron, and Novartis. Personal fees for lectures and attending advisory boards: AstraZeneca, GlaxoSmithKline, Mundipharma, Novartis, Sanofi Regeneron, and Teva. Peter G. Gibson has received speaker fees and grants to his institution from AstraZeneca, GlaxoSmithKline, and Novartis. Christine Jenkins is a member of advisory boards for AstraZeneca, GlaxoSmithKline and Chiesi. She has received payment for Advisory board attendance, honoraria, lectures and meeting participation as a speaker. She has no conflicts in relation to this work. Guy G. Brusselle has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Novartis. He is a member of advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck Sharp & Dohme (MSD), Novartis, and Sanofi/Regeneron. Anne Chèvremont declares no conflict of interest. Andréanne Côté declares she has received speaking fees and consultant fees from Sanofi, Regeneron, AstraZeneca, and GlaxoSmithKline. She received unrestricted grant support from GlaxoSmithKline, and AstraZeneca. Carlos Andrés Celis-Preciado declares no relevant conflict of interest. Ivan Solarte has received fees as an advisory board participant and/or speaker from GlaxoSmithKline, AstraZenca, and Sanofi. Celeste M. Porsbjerg has attended advisory boards for AstraZeneca, Novartis, TEVA, and Sanofi-Genzyme; has given lectures at meetings supported by AstraZeneca, Novartis, TEVA, Sanofi-Genzyme, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, Novartis, Merck Sharp & Dohme, Sanofi-Genzyme, GlaxoSmithKline, and Novartis; and has received educational and research grants from AstraZeneca, Novartis, TEVA, GlaxoSmithKline, ALK, and Sanofi-Genzyme. Asger Sverrild has attended advisory boards for Sanofi, and GSK, has given lectures at meetings supported by AstraZeneca, GSK, and Sanofi, and has taken part in clinical trials sponsored by AstraZeneca, Sanofi, and Eli Lilly. Paula Kauppi has received lecture fees from GlaxoSmithKline, consultancy fees from Sobi, and PI fees from Theravance. Stelios Loukides has received fees and honoraria from Menarini, GlaxoSmithKline, Novartis, Elpen, Pfizer, Gilead, Guidotti, AstraZeneca, and Chiesi. Michael P. Makris reports honoraria for presentations and consultancy fees from Novartis, GlaxoSmithKline, Menarini, AstraZeneca, Chiesi, Sanofi, Pfizer, outside the submitted work. Andriana I. Papaioannou has received fees and honoraria from Menarini, GlaxoSmithKline, Novartis, Elpen, Boehringer Ingelheim, AstraZeneca, Demo, and Chiesi. Enrico Heffler declares personal fees for advisory boards participation and/or speaker activities from: Sanofi, Regeneron, GlaxoSmithKline, Novartis, AstraZeneca, Stallergenes-Greer, Circassia, Bosch, Celltrion-Healthcare, Chiesi, and Almirall. Jeffrey Shi Kai Chan is an employee of the Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care, a co-funder of the International Severe Asthma Registry. Hyonsoo Joo reports no conflict of interest. Liam G. Heaney has received grant funding, participated in advisory boards and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Hoffmann la Roche, GlaxoSmithKline, Novartis, Theravance, Evelo Biosciences, Sanofi, and Teva; he has received grants from MedImmune, Novartis UK, Roche/Genentech Inc, GlaxoSmithKline, Amgen, Genentech/Hoffman la Roche, AstraZeneca, MedImmune, Aerocrine, and Vitalograph; he has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Napp Pharmaceuticals; he has also taken part in asthma clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Hoffmann la Roche, and GlaxoSmithKline for which his institution received remuneration; he is the Academic Lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma which involves industrial partnerships with a number of pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffmann la Roche, and Janssen. Wei-Han Cheng was an employee of Sanofi and may hold stock and/or stock options in the company. Njira Lugogo received consulting fees from Amgen, AstraZeneca, Avillion, Genentech, GSK, Niox, Novartis, Regeneron, Sanofi, and Teva; honoraria for non-speakers bureau presentations from GSK, TEVA and Astra Zeneca; and travel support from Astra Zeneca, SANOFI, TEVA, Regeneron and GSK; her institution received research support from Amgen, AstraZeneca, Avillion, Bellus, Evidera, Gossamer Bio, Genentech, GSK, Janssen, Niox, Regeneron, Sanofi, Novartis and Teva. She is an honorary faculty member of Observational and Pragmatic Research Institute (OPRI) but does not receive compensation for this role. Michael E. Wechsler reports grants and/or personal fees from Novartis, Sanofi, Regeneron, Genentech, Sentien, Restorbio, Equillium, Genzyme, Cohero Health, Teva, Boehringer Ingelheim, AstraZeneca, Amgen, GlaxoSmithKline, Cytoreason, Cerecor, Sound Biologics, Incyte, and Kinaset. Cláudia Chaves Loureiro has received (in the last 3 years) lecture or advisory board fees from AstraZeneca, GlaxoSmithKline, Menarini, Sanofi, and Teva, outside this work. Bellanid Rodríguez-Cáceres declares no relevant conflict of interest. Tatsuya Nagano received lecture fees from Kyorin, Sanofi, GlaxoSmithKline, Novartis, and AstraZeneca. Zhixiao Wang is an employee of Regeneron Pharmaceuticals, Inc, and holds stock and/or stock options in the company. Hao-Chien Wang reports no conflict of interest. Jorge Máspero reports speaker fees, grants, or advisory boards for AstraZeneca, Sanofi, GlaxoSmithKline, Novartis, Inmunotek, Menarini, and Noucor. Fernando Saldarini is a speaker of GlaxoSmithKline, AstraZeneca, and SANOFI. Ana María Stok has acted as an investigator for GlaxoSmithKline, AstraZeneca, Sanofi, Chiesi, Novartis, and Bago. She reports speaker fees from GlaxoSmithKline, AstraZeneca, and Sanofi. Anahi Yañez has received grants/research supports from GlaxoSmithKline, AstraZeneca, Sanofi, Chiessi, Novartis, MDS, Roche, Faes, TEVA, Avillon, Janssen, Bayer, Sanofi Gynzene, and he has received consultation fees from GlaxoSmithKline, AstraZeneca, Sanofi, and Eurofarma. He has participated in a company sponsored speaker's bureau from Sanofi, GlaxoSmithKline, Faes, Sanofi Gynzene, and AstraZeneca. Philip G. Bardin declares no relevant conflict of interest. Sinthia Z. Bosnic-Anticevich has received honorarium for participation in expert advisory boards and given lectures for Teva Pharmaceuticals, AstraZeneca, GlaxoSmithKline, Meda/Mylan, Sanofi, Mylan, Chiesi, Menarini, Sanofi, Boehringer Ingelheim, Abbvie and received unrestricted research grants from Mylan, AstraZeneca, Teva, AstraZeneca, GlaxoSmithKline, and Viatris. Vidya Navaratnam was an employee of OPCA when she worked on this manuscript, but she has left OPCA. She has received payment for lectures/speaking engagements from Boehringer Ingelheim as well as payment for travel/accommodation/meeting expenses from Boehringer Ingelheim and Bristol Myer Squibs. Mohit Bhutani has received speaker and consultant fees for AstraZeneca, GlaxoSmithKline, Sanofi, Covis, Boerhinger Ingelheim, Takeda and Valeo. He has leadership roles within the Canadian Thoracic Society. M. Diane Lougheed has (in the past 3 years) received grants outside the submitted work paid directly to Queen's University from the Canadian Institutes of Health Research (sub-grant from Ottawa Health Research Institute), Manitoba Workers Compensation Board, Ontario Lung Association, Ontario Thoracic Society, the Government of Ontario's Innovation Fund, Queen's University, Astra Zeneca and GlaxoSmithKline; and honoraria from the Canadian Thoracic Society for co-development and co-presentation of as Severe Asthma PREP course, from MD Breifcase for co-development of an accredited CME module on Severe Asthma; and from AstraZeneca for participation in the Precision Program Advisory Board. She has also served as a member and past-chair of the Canadian Thoracic Society (CTS) Asthma Clinical Assembly, member of the CTS Asthma Clinical Assembly Steering Committee, CTS representative on the Lung Association's Board of Directors, CTS representative to the European Respiratory Society, and member of Health Quality Ontario's Asthma in Adults and Asthma in Children Quality Standard Advisory Committee. Lyle Melenka † declares no conflict of interest. Petros Bakakos declares no conflict of interest. Konstantinos P. Exarchos declares no relevant conflict of interest. Aggelos A. Ladias declares no conflict of interest. Dóra Lúdvíksdóttir has received lecture fees from GlaxoSmithKline, Sanofi and AstraZeneca. Takashi Iwanaga received speaker bureau fees from Kyorin, GlaxoSmithKline, Novartis, Boehringer Ingelheim, AstraZeneca, and Sanofi. Elvia Angelica Contreras Contreras declares no relevant conflict of Interest. Sverre Lehmann has been an investigator on clinical trials sponsored by GlaxoSmithKline and AstraZeneca, for which his institution has received funding. José Alberto Ferreira declares no conflict of interest. Rebecca Gall is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Pin-Kuei Fu declares no relevant conflict of interest. Diahn-Warng Perng received sponsorship to attend or speak at international meetings, honoraria for lecturing or attending advisory boards, and research grants from the following companies: AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Daiichi Sankyo, Shionogi, and Orient Pharma. Flavia Hoyte declares honoraria from AstraZeneca and Genentech. She has been an investigator on clinical trials sponsored by GlaxoSmithKline, Genentech, Teva, Sanofi, for which her institution has received funding. Rohit Katial declares no relevant conflict of interest. Unnur S. Björnsdóttir receives gratuities for lectures/presentations from AstraZeneca, Sanofi and Novartis. Camille Taillé has received lecture or advisory board fees and grants to her institution from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi, Stallergenes, Celltrion and Novartis, for unrelated projects. Christian Taube declares no relevant conflict of interest. Breda Cushen has received honoraria for lectures and received sponsorship for attending meetings from AstraZeneca, Novartis, and Boehringer Ingelheim. She has participated in advisory boards, and provided consultancy,for Chiesi and Sanofi. Lakmini Bulathsinhala is an employee of the Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care, a co-funder of the International Severe Asthma Registry. Leif Bjermer has (in the last 3 years) received lecture or advisory board fees from Alk-Abello, AstraZeneca, Chiesi, GlaxoSmithKline, Sanofi, and Genzyme/Regeneron. David B. Price has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; consultancy agreements with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Chiesi, Viatris, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Inside Practice, GlaxoSmithKline, Medscape, Viatris, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme, Teva Pharmaceuticals; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Novartis, Medscape, Teva Pharmaceuticals.; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation Programme, and Health Technology Assessment; and he was an expert witness for GlaxoSmithKline.

Figures

**Fig. 1**
Pre-biologic (A) BEC, (B) FeNO, and (C) IgE distribution according to OCS use for patients with severe asthma. A leftward shift in the BEC distribution was observed in the intermittent and, especially, in the long-term OCS groups compared to no OCS users (A). The impact of OCS prescription was less apparent for FeNO (B). The IgE concentration was significantly lower in patients long-term OCS compared to those, who were prescribed intermittent OCS (p < 0.001) (C). BEC: blood eosinophil count; FeNO: fractional exhaled nitric oxide; IgE: Immunoglobulin E; OCS: oral corticosteroid; Intermittent use: ≤90 days; Long-term use: >90 days; Index date: date of biologic initiation

**Fig. 2**
Severe asthma phenotypes by pattern of OCS use BEC: blood eosinophil count; ED: emergency department; exac: exacerbation; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; IgE: immunoglobulin E; Hosp: asthma-related hospitalization; iOCS: intermittent oral corticosteroid; LAMA: long-acting muscarinic antagonist; LTOCS: long-term oral corticosteroid; OCS: oral corticosteroid; Intermittent: OCS use for ≤90 days; Long-term: OCS use for >90 days; Exacerbation: an asthma-related hospital attendance/admission and/or an asthma related emergency room attendance, and/or an acute OCS course of ≥3 days; Uncontrolled: assessed by GINA control criteria, ACT or ACQ (country specific) ACT and ACQ converted to GINA control criteria as outlined in Table 1 footer; Obese: BMI ≥30 kg/m²

**Fig. 3**
Disease characteristics of patients with severe asthma treated with LTOCS by BEC cut-off BEC: blood eosinophil count; ED: asthma related emergency department visit; exac: exacerbation; FeNO: fractional exhaled nitric oxide; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; Hosp: asthma-related hospitalization; IgE: immunoglobulin E; LTOCS: long-term oral corticosteroid (>90 days) Obese: >30 kg/m²; Adult onset: onset at ≥18 years; Exacerbation: an asthma-related hospital attendance/admission and/or an asthma related emergency room attendance, and/or an acute OCS course of ≥3 days; Uncontrolled: assessed by GINA control criteria, ACT or ACQ (country specific) ACT and ACQ converted to GINA control criteria as outlined in Table 1 footer; ICS dose: BDP equivalent

See this image and copyright information in PMC

References

1. Kuruvilla M.E., Lee F.E.H., Lee G.B. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219–233. doi: 10.1007/s12016-018-8712-1. - DOI - PMC - PubMed
1. Bakakos A., Loukides S., Bakakos P. Severe eosinophilic asthma. J Clin Med. 2019;8(9) doi: 10.3390/jcm8091375. - DOI - PMC - PubMed
1. Global Strategy for Asthma Management and Prevention . Global Initiative for Asthma; 2024. https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Repo... Published online.
1. Heaney L.G., Perez de Llano L., Al-Ahmad M., et al. Eosinophilic and non-eosinophilic asthma: an expert consensus framework to characterize phenotypes in a global real-life severe asthma cohort. Chest. 2021;160(3):814–830. doi: 10.1016/j.chest.2021.04.013. - DOI - PubMed
1. Price D.B., Bosnic-Anticevich S., Pavord I.D., et al. Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations. Clin Transl Allergy. 2019;9:41. doi: 10.1186/s13601-019-0282-7. - DOI - PMC - PubMed

LinkOut - more resources

Full Text Sources
- Elsevier Science
- PubMed Central

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Biomarker profile and disease burden associated with intermittent and long-term oral corticosteroid use in patients with severe asthma prior to biologic initiation in real-life (STAR)

Affiliations

Biomarker profile and disease burden associated with intermittent and long-term oral corticosteroid use in patients with severe asthma prior to biologic initiation in real-life (STAR)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources