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Wenjia Chen,1 Mohsen Sadatsafavi,2 Trung N Tran,3 Ruth B Murray,4 Chong Boon Nigel Wong,1 Nasloon Ali,4,5 Cono Ariti,4,5 Esther Garcia Gil,6 Anthony Newell,5,7 Marianna Alacqua,8 Mona Al-Ahmad,9 Alan Altraja,10 Riyad Al-Lehebi,11,12 Mohit Bhutani,13 Leif Bjermer,14 Anne Sofie Bjerrum,15 Arnaud Bourdin,16 Lakmini Bulathsinhala,4,5 Anna von Bülow,17 John Busby,18 Giorgio Walter Canonica,19,20 Victoria Carter,4,5 George C Christoff,21 Borja G Cosio,22 Richard W Costello,23 J Mark FitzGerald,24 João A Fonseca,25 Kwang Ha Yoo,26 Liam G Heaney,27 Enrico Heffler,19,20 Mark Hew,28,29 Ole Hilberg,30 Flavia Hoyte,31,32 Takashi Iwanaga,33 David J Jackson,34,35 Rupert C Jones,36 Mariko Siyue Koh,37,38 Piotr Kuna,39 Désirée Larenas-Linnemann,40 Sverre Lehmann,41 Lauri A Lehtimäki,42,43 Juntao Lyu,5,7 Bassam Mahboub,44,45 Jorge Maspero,46,47 Andrew N Menzies-Gow,48 Concetta Sirena,49 Nikolaos Papadopoulos,50,51 Andriana I Papaioannou,52 Luis Pérez de Llano,53,54 Diahn-Warng Perng,55,56 Matthew Peters,57 Paul E Pfeffer,58,59 Celeste M Porsbjerg,17 Todor A Popov,60 Chin Kook Rhee,61 Sundeep Salvi,62 Camille Taillé,63 Christian Taube,64 Carlos A Torres-Duque,65 Charlotte S Ulrik,66 Seung Won Ra,67 Eileen Wang,31,32 Michael E Wechsler,68 David B Price4,5,69 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 2Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3AstraZeneca, Gaithersburg, MD, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore, Singapore; 6AstraZeneca, Barcelona, Spain; 7Optimum Patient Care, Queensland, VIC, Australia; 8AstraZeneca, Cambridge, UK; 9Microbiology Department, Faculty of Medicine, Kuwait University, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 10Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 11Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 12College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 13Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Western Canada, AB, Canada; 14Department of Clinical Sciences, Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 15Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Jutland, Aarhus, Denmark; 16PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 17Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 18Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 19Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy; 20Department of Biomedical Sciences, Humanitas University, Milan, Italy; 21Medical University-Sofia, Faculty of Public Health, Sofia, Bulgaria; 22Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 23Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland; 24Department of Medicine, the University of British Columbia, Vancouver, BC, Canada; 25Comunity Health, Information and Decision Sciences Department (MEDCIDS) & Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine of University of Porto, Porto, Portugal; 26KonKuk University School of Medicine in Seoul, Seoul, Korea; 27Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 28Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia; 29Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 30Medical Department, Vejle University Hospital, Jutland, Vejle, Denmark; 31Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; 32Department of Internal Medicine, Division of Allergy & Clinical Immunology, University of Colorado School of Medicine, Aurora, CO, USA; 33Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 34UK Severe Asthma Network and National Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 35School of Immunology & Microbial Sciences, King’s College London, London, UK; 36Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 37Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 38SingHealth Duke-NUS Lung Centre, Singapore, Singapore; 39Division of Internal Medicine, Asthma and Allergy Medical University of &Lstrok;ód&zacute;, &Lstrok;ód&zacute;, Poland; 40Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 41Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway; 42Allergy Centre, Tampere University Hospital, Tampere, Finland; 43Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 44College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 45Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 46Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 47University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 48Royal Brompton & Harefield Hospitals, London, UK; 49Severe Asthma Network in Italy (SANI), Milano, Italy; 50Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 51Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 52 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 53Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Lugo, Spain; 54Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 55Division of Clinical Respiratory Physiology Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan; 56COPD Assembly of the Asian Pacific Society of Respirology Hongo, Bunkyo-ku, Tokyo, Japan; 57Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia; 58Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 59Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 60University Hospital ”sv. Ivan Rilski”, Sofia, Bulgaria; 61Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 62Pulmocare Research and Education Foundation, Pune, India; 63Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris, Paris, France; 64Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 65CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 66Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 67Department of Internal Medicine, Division of Pulmonology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea; 68Department of Medicine, NJH Cohen Family Asthma Institute, National Jewish Health, Denver, CO, USA; 69Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06 Midview City, Singapore, Singapore, 573969, Tel +65 3105 1489, Email dprice@opri.sgBackground: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥ 4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/μL, p=0.003), serious infections (49.0% vs 13.3%, p< 0.001), nasal polyps (35.2% vs 23.6%, p< 0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.Keywords: severe asthma, biologics, real-world, treatment pattern, patient characteristics

Importance: The optimal inhaled reliever therapy for asthma remains unclear., Objective: To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma., Data Sources: The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions., Study Selection: Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers)., Data Extraction and Synthesis: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence., Main Outcomes and Measures: Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events., Results: A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], -10.3% [95% CI, -11.8% to -8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, -4.7% [95% CI, -8.0% to -1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, -5.5% [95% CI, -8.4% to -2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, -0.6% [95% CI, -1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, -1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty)., Conclusions and Relevance: In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials., Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life., Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers., Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV 1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV 1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV 1 increase (adjusted R 2 : 0.751), compared to BEC (adjusted R 2 : 0.747) or FeNO alone (adjusted R 2 : 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE., Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline., Competing Interests: CP 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, MSD, Sanofi-Genzyme, GlaxoSmithKline, and Novartis; and has received educational and research grants from AstraZeneca, Novartis, TEVA, GlaxoSmithKline, ALK, and Sanofi-Genzyme. JT is an employee of the Observational and Pragmatic Research Institute OPRI. OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca. CB reports advisory board participation of Sanofi-Regeneron, AstraZeneca, Takeda, ValeoPharma, honorarium for presentations for AstraZeneca/Amgen, GlaxoSmithKline, Grifols, Sanofi-Regeneron, ValeoPharma and grants paid to UBC from BioHaven, Sanofi-Regeneron, AstraZeneca, GlaxoSmithKline. GCC declares relevant research support from AstraZeneca and Sanofi. GK has attended advisory boards for AstraZeneca, GlaxoSmithKline and Chiesi. He has also given lectures at meetings supported by Novartis, Sanofi-Genzyme, AstraZeneca, GlaxoSmithKline, and Boehringer-Ingelheim. DL reports personal fees from ALK-Abelló, AstraZeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GlaxoSmithKline national and global, Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Carnot, grants from Abbvie, Bayer, Lilly, Sanofi, AstraZeneca, Pfizer, Novartis, Circassia, UCB, GlaxoSmithKline, outside the submitted work. TNT is an employee of AstraZeneca and may own stock or stock options in AstraZeneca. AstraZeneca is a co-funder of ISAR. RA-L 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. SB-A has received honorarium for participation in expert advisory boards and given lectures for Teva Pharmaceuticals, AstraZeneca, GlaxoSmithKline, Meda, Mundipharma, Sanofi, Mylan and received unrestricted research grants from Mylan, AstraZeneca, Teva, Mundipharma International, GlaxoSmithKline, and Viatris. JB has received research grants from AstraZeneca and personnel fees from NuvoAir, outside the submitted work. MH declares grants and other advisory board fees made to his institutional employer from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva, and Seqirus, for unrelated projects. KK received honoraria for presentations and consultancy fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, ELPEN, Gilead, GlaxoSmithKline, Menarini, Novartis, Sanofi, Specialty Therapeutics, WebMD. His department has received funding and grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GlaxoSmithKline, Menarini, Novartis and NuvoAir. NP 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, MSD, Novartis, Nutricia, OM Pharma, Regeneron, Sanofi, Takeda, and Viatris. PEP 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 a current research grant funded by GlaxoSmithKline. TP declares relevant research support from Novartis and Chiesi Pharma. CR received consulting/lecture fees from MSD, AstraZeneca, GlaxoSmithKline, Novartis, Takeda, Mundipharma, Boehringer-Ingelheim, Teva, Sanofi, and Bayer. MS 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. M-JT 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. CU 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, and Pfizer, outside the submitted work. MA-A 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. AA has received lecture fees from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, MSD, Norameda, Novartis, Orion, Sanofi, and Zentiva; sponsorships from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, GlaxoSmithKline, MSD, Norameda, Novartis, and Sanofi; and has participated in advisory boards for AstraZeneca, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, MSD, Novartis, Sanofi, and Teva. ABe is an employee of Optimum Patient Care Global, a co-funder of the International Severe Asthma Registry. LBu is an employee of the Observational and Pragmatic Research Institute OPRI. OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca. VC is an employee of Optimum Patient Care OPC. OPC is a co-funder of the International Severe Asthma Registry. BC declares grants from Chiesi 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. KF is an employee of Optimum Patient Care Global OPCG, a co-funder of the International Severe Asthma Registry. LH 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, and GlaxoSmithKline, Amgen, Genentech/Hoffman la Roche, AstraZeneca, MedImmune, GlaxoSmithKline, 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. RH is an employee for Observational and Pragmatic Research Institute OPRI which conducted this study in collaboration with Optimum Patient Care and AstraZeneca. PK reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, FAES, Glenmark, Novartis, Polpharma, Boehringer Ingelheim, Teva, Zentiva, outside the submitted work. RM is a consultant for Observational and Pragmatic Research Institute OPRI which conducted this study in collaboration with Optimum Patient Care and AstraZeneca. TN received lecture fees from Kyorin, GlaxoSmithKline, Novartis, Sanofi, and AstraZeneca. LP received research grants and lecture fees from GlaxoSmithKline, Menarini, Chiesi, AstraZeneca and Grifols. DC has received speaker fees from AstraZeneca, Boehringer Ingelheim, and has acted as an investigator for trials sponsored by AstraZeneca. FS reports consultancy work for GlaxoSmithKline, AstraZeneca, Sanofi - Advisory board, received speaker fees from GlaxoSmithKline, AstraZeneca, Chiesi, Amgen, Teva and research grants from GlaxoSmithKline, AstraZeneca, and Chiesi. MW 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. ABo 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. GB 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, MSD Merck sharp & Dohme, Novartis, and Sanofi/Regeneron. LC has received speaker and consultancy fees and conference expenses from AstraZeneca, Novartis, GlaxoSmithKline, Boehringer Ingelheim and Menarini. ED declares grants to her institution from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva, and Seqirus, for unrelated projects and speaker fees from Sanofi. JF 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. FH declares honoraria from AstraZeneca, Sanofi, TEVA, GSK, and Genentech. She has been an investigator on clinical trials sponsored by GlaxoSmithKline, Genentech, and Sanofi, for which her institution has received funding. DJ has received speaker fees and consultancy fees from AstraZeneca, GlaxoSmithKline, Sanofi Regeneron, Boehringer Ingelheim and research funding from AstraZeneca. MK 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. LL has received personal fees from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Orion Pharma and Sanofi. NM is an employee of AstraZeneca and may own stock or stock options in AstraZeneca. AstraZeneca is a co-funder of ISAR. AM-G is an employee of AstraZeneca and may own stock or stock options in AstraZeneca. AstraZeneca is a co-funder of ISAR. PHwP has received honoraria for talks and advisory board meetings from GlaxoSmithKline, AstraZeneca, and Sanofi. AP has received fees and honoraria from Menarini, GlaxoSmithKline, Novartis, Elpen, Boehringer Ingelheim, AstraZeneca, and Chiesi. PHP has received advisory board and speaker fees from AstraZeneca, GlaxoSmithKline, Novartis, and Sanofi/Regeneron. LP-d-L 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 MSD, 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. MP declares personal fees and non-financial support from AstraZeneca, GlaxoSmithKline, and Sanofi. LR received fees as a speaker from AstraZeneca, GlaxoSmithKline, Novartis, and Sanofi. IS has received fees as advisory board participant and/or speaker from GlaxoSmithKline and Sanofi. CT-D 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. EW has received honoraria from AstraZeneca, GlaxoSmithKline, and Genentech. She has been an investigator on studies sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Sanofi, Novartis, and Teva, for which her institution has received funding. RC has received honoraria for lectures from Aerogen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Teva. He is a member of advisory boards for GlaxoSmithKline and Novartis, has received grant support from GlaxoSmithKline and Aerogen and has patents in the use of acoustics in the diagnosis of lung disease, assessment of adherence and prediction of exacerbations. PG has received speaker fees and grants to his institution from AstraZeneca, GlaxoSmithKline, and Novartis. EH 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. JM reports speaker fees, grants or advisory boards for AstraZeneca, Sanofi, GlaxoSmithKline, Novartis, Inmunotek, Menarini and Noucor. D-WP 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. FP 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. SS declares research support and speaker fees from Cipla, Glenmark, and GlaxoSmithKline. C-CS has received 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. CT has received lecture or advisory board fees and grants to her institution from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi and Novartis, for unrelated projects. TT is an advisory Board Member for Boehringer Ingelheim, AstraZeneca, Takeda, GlaxoSmithKline, MSD, Mundipharma, and Janssen. Honoraria were received for these advisory boards. Honoraria were received for speaking at CMEs for AstraZeneca in the past. Conference sponsorships from AstraZeneca, Boehringer Ingelheim, Merck Serono, GlaxoSmithKline, Norvatis, Mundipharma and MSD. Research grants from Merck Serono Concor Study, MSD Apbord study. LBj has in the last three years received lecture or advisory board fees from Alk-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Novartis, Sanofi, Genzyme/Regeneron, and Teva. GWC 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, MSD, Mundipharma, Novartis, Orion, Sanofi Aventis, Sanofi, Genzyme/Regeneron, Stallergenes, UCB Pharma, Uriach Pharma, Teva, Thermo Fisher, and Valeas. TI received speaker bureau fees from Kyorin, GlaxoSmithKline, Novartis, Boehringer Ingelheim, AstraZeneca and Sanofi. LJ-M 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. DP 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, Commune Digital, 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; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; 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; 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation Programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Porsbjerg, Townend, Bergeron, Christoff, Katsoulotos, Larenas-Linnemann, Tran, Al-Lehebi, Bosnic-Anticevich, Busby, Hew, Kostikas, Papadopoulos, Pfeffer, Popov, Rhee, Sadatsafavi, Tsai, Ulrik, Al-Ahmad, Altraja, Beastall, Bulathsinhala, Carter, Cosio, Fletton, Hansen, Heaney, Hubbard, Kuna, Murray, Nagano, Pini, Cano Rosales, Schleich, Wechsler, Amaral, Bourdin, Brusselle, Chen, Chung, Denton, Fonseca, Hoyte, Jackson, Katial, Kirenga, Koh, Ławkiedraj, Lehtimäki, Liew, Mahboub, Martin, Menzies-Gow, Pang, Papaioannou, Patel, Perez-De-Llano, Peters, Ricciardi, Rodríguez-Cáceres, Solarte, Tay, Torres-Duque, Wang, Zappa, Abisheganaden, Assing, Costello, Gibson, Heffler, Máspero, Nicola, Perng (Steve), Puggioni, Salvi, Sheu, Sirena, Taillé, Tan, Bjermer, Canonica, Iwanaga, Jiménez-Maldonado, Taube, Brussino and Price.)

Background: Investigation for the presence of asthma comorbidities is recommended by the Global Initiative for Asthma because their presence can complicate asthma management., Objective: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes., Methods: This was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. A total of 30 comorbidities were identified and categorized a priori as any of the following: (1) potentially type 2-related comorbidities, (2) potentially oral corticosteroid (OCS)-related comorbidities, or (3) comorbidities mimicking or aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex (ie male or female)., Results: Of the 11,821 patients, 69%, 67%, and 55% had at least 1 potentially type 2-related, potentially OCS-related, or mimicking or aggravating comorbidities, respectively; 57% had 3 or more comorbidities, and 33% had comorbidities in all 3 categories. Patients with allergic rhinitis, nasal polyposis, and chronic rhinosinusitis experienced 1.12 (P = .003), 1.16 (P < .001), and 1.29 times (P < .001) more exacerbations per year, respectively, than those without. Patients with nasal polyposis and chronic rhinosinusitis were 40% and 46% more likely (P < .001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with a greater likelihood of LTOCS use (odds ratios [ORs]: 1.23-2.77) and, except for dyslipidemia, with a greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking or aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81), and all (except chronic obstructive pulmonary disease) with increased likelihood of LTOCS use (ORs: 1.37-1.57). A greater number of comorbidities was associated with worse outcomes., Conclusion: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes., Clinical Trial Registration: The International Severe Asthma Registry database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization Studies (European Network Centres for Pharmacoepidemiology and Pharmacovigilance [ENCEPP]/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EMA 2014; EUPAS44024) and with all applicable local and international laws and regulations, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=48848). Governance was provided by ADEPT (registration number: ADEPT1121)., Competing Interests: Disclosures Dr Scelo and Dr Murray are consultants for the Observational and Pragmatic Research Institute (OPRI). Dr Torres-Duque has received fees as an 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; and has received unrestricted grants for investigator-initiated studies at Fundacion Neumologica Colombiana from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, and Novartis. Dr Maspero reports receiving speaker fees, grants, or fees for serving on advisory boards for AstraZeneca, Sanofi, GlaxoSmithKline, Novartis, Inmunotek, Menarini, and Noucor. Dr Tran, Dr Menzies-Gow, and Dr Martin are employees of AstraZeneca and may own stock or stock options in AstraZeneca. Dr Hew reports receiving grants and other advisory board fees (made to his institutional employer) from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva, and Seqirus for unrelated projects. Dr Peters reports receiving personal fees and nonfinancial support from AstraZeneca and GlaxoSmithKline. Dr Gibson has received speaking fees and grants to his institution from AstraZeneca, GlaxoSmithKline, and Novartis. Dr Popov reports receiving relevant research support from Novartis and Chiesi Pharma. Dr Côté reports receiving speaking fees and consultant fees from Sanofi, Regeneron, AstraZeneca, GlaxoSmithKline, and ValeoPharma and reports receiving unrestricted grant support from GlaxoSmithKline; Dr Bergeron reports advisory board participation in Sanofi, AstraZeneca, Takeda, and ValeoPharma and honorarium for presentations for GlaxoSmithKline, AstraZeneca, Amgen, Grifols, Sanofi, Regeneron, and ValeoPharma. Dr Dorscheid is on faculty at the University of British Columbia and is supported by grants from the 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, and writing fees and is a paid consultant for Sanofi-Regeneron, Novartis Canada, AstraZeneca, GlaxoSmithKline, and ValeoPharma and is an active member of the Canadian Thoracic Society, American Thoracic Society, European Respiratory Society, and the Allergen Research Network. Dr FitzGerald previously reported receiving grants from AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, and Novartis paid directly to UBC and personal fees for lectures and attending advisory boards for AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, and Teva. Dr Chapman reports receiving grants from AstraZeneca, Boehringer Ingelheim, Bellus, CSL Behring, GlaxoSmithKline, Grifols, Inhibrx, Novartis, Regeneron, Sanofi, Takeda, and Vertex and consulting fees from AstraZeneca, CSL Behring, GlaxoSmithKline, Grifols, Inhibrx, Novartis, Sanofi, and Takeda; he has a leadership or fiduciary role in Alpha-1 Canada, the Canadian Thoracic Society, and Alpha-1 Foundation. Dr Boulet has received grants for participation in clinical studies from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis, Sanofi-Regeneron, and BioHaven; for consulting and advisory boards from AstraZeneca, Novartis, GlaxoSmithKline, Merck, and Sanofi-Regeneron; and lecture fees from AstraZeneca, Covis, Cipla, GlaxoSmithKline, Novartis, Merck, and Sanofi. Dr Bhutani has received speaker and consultant fees for AstraZeneca, GlaxoSmithKline, Sanofi, Covis, Boehringer Ingelheim, and Valeo. Dr 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. Dr Jiménez-Maldonado has received fees as an advisory board participant and/or speaker from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Sanofi-Aventis and has participated in clinical trials for AstraZeneca, Novartis, and GlaxoSmithKline. Dr Duran-Silva has received fees as an advisory board participant and/or speaker from Boehringer Ingelheim, Novartis, and Sanofi-Aventis and has taken part in clinical trials from AstraZeneca, Novartis, and Sanofi-Aventis. Dr Solarte received fees from GlaxoSmithKline for participation on advisory boards. Dr Fernandez-Sanchez is a part-time employee of GlaxoSmithKline and does not hold shares in the company. Dr Bülow reports receiving speakers fees and consultancy fees from AstraZeneca and Novartis outside the submitted work and has also attended the advisory board for Novartis and AstraZeneca. Dr Bjerrum has received lecture fees from AstraZeneca, GlaxoSmithKline, and Novartis. Dr Ulrik reports receiving personal fees for talks and participation in advisory boards, among others, from AstraZeneca, GlaxoSmithKline, Teva, Boehringer Ingelheim, Orion Pharma, Sanofi-Genzyme, TFF Pharmaceuticals, Covis Pharma, Berlin-Chemie, Takeda, Chiesi, and Pfizer outside the submitted work. Dr Rasmussen declares receiving speaker fees from AstraZeneca, Boehringer Ingelheim, Teva, ALK, and Mundipharma outside the submitted work and attended advisory board for AstraZeneca, Sanofi, and Teva. Dr Altraja has received lecture fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MSD, Norameda, Novartis, Orion, Sanofi, and Zentiva; sponsorships from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MSD, Norameda, Novartis, and Sanofi; and has participated in advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi, and Teva. Dr Bourdin has received industry-sponsored grants from AstraZeneca-MedImmune, Boehringer Ingelheim, Cephalon/Teva, GlaxoSmithKline, Novartis, and Sanofi-Regeneron and consultancies with AstraZeneca-MedImmune, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Regeneron-Sanofi, Med-in-Cell, Actelion, Merck, Roche, and Chiesi. Dr Taille has received lecture or advisory board fees and grants to her institution from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi, and Novartis for unrelated projects. Dr Charriot reports receiving advisory board and lecture fees from AstraZeneca, GlaxoSmithKline, Sanofi; consulting fees for Chiesi; and serving as a trial coinvestigator for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Sanofi. Dr Roche reports receiving grants and personal fees from Austral, Biosency, Boehringer Ingelheim, Novartis, and Pfizer and personal fees from MSD, GlaxoSmithKline, AstraZeneca, Chiesi, Sanofi, Menarini, and Zambon. Dr Papaioannou has received fees and honoraria from Menarini, GlaxoSmithKline, Novartis, Elpen, Boehringer Ingelheim, AstraZeneca, and Chiesi. Dr Kostikas received honoraria for presentations and consultancy fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, ELPEN, GILEAD, GlaxoSmithKline, Menarini, Novartis, Sanofi, Specialty Therapeutics, and WebMD; and received funding and grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GlaxoSmithKline, Menarini, Novartis, and NuvoAir (paid to the University of Ioannina). Dr 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, MSD, Novartis, Nutricia, OM Pharma, Regeneron, Sanofi, Takeda, and Viatris. Dr Salvi reports receiving research support and speaker fees from Cipla, Glenmark, and GlaxoSmithKline. Dr Mitchell has received speaker fees from GlaxoSmithKline, AstraZeneca, Teva, and Novartis and has received grants from AstraZeneca and Teva. Dr Costello has received honoraria for lectures from Aerogen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Teva; is a member of advisory boards for GlaxoSmithKline and Novartis; has received grant support from GlaxoSmithKline and Aerogen; and has patents in the use of acoustics in the diagnosis of lung disease, assessment of adherence, and prediction of exacerbations. Dr Heffler declares receiving personal fees from Sanofi, Regeneron, GlaxoSmithKline, Novartis, AstraZeneca, Stallergenes, and Circassia. Dr 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. Dr Canonica has received research grants and 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, MSD, Mundipharma, Novartis, Orion, Sanofi-Aventis, Sanofi, Genzyme/Regeneron, Stallergenes, UCB Pharma, Uriach Pharma, Teva, Thermo Fisher, and Valeas. Dr Iwanaga received lecture fees from Kyorin, GlaxoSmithKline, Novartis, Boehringer Ingelheim, and AstraZeneca. Dr Mona Al-Ahmad has received advisory board and speaker fees from AstraZeneca, Sanofi, Novartis, and GlaxoSmithKline and received a grant from the Kuwait Foundation for the Advancement of Sciences (KFAS). Dr Linnemann reports receiving personal fees from ALK-Abelló, AstraZeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GlaxoSmithKline national and global, Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, and Carnot and grants from AbbVie, Bayer, Lilly, Sanofi, AstraZeneca, Pfizer, Novartis, Circassia, UCB, and GlaxoSmithKline outside the submitted work. Dr Garcia Ramirez received fees as a speaker and advisory board participant from AstraZeneca, GlaxoSmithKline, Sanofi-Genzyme, Chiesi, and Novartis. Dr Kuna reports receiving personal fees from Adamed, AstraZeneca, Berlin-Chemie Menarini, FAES, Glenmark, Novartis, Polpharma, Boehringer Ingelheim, Teva, and Zentiva outside the submitted work. Dr Fonseca reports receiving grants from or has research agreements with AstraZeneca, Mundipharma, Sanofi-Regeneron, and Novartis and has received personal fees for lectures and attending advisory boards for AstraZeneca, GlaxoSmithKline, Mundipharma, Novartis, Sanofi-Regeneron, and Teva. Dr 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. Dr Koh reports receiving 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. Dr Kook Rhee received consulting/lecture fees from MSD, AstraZeneca, GlaxoSmithKline, Novartis, Takeda, Mundipharma, Boehringer Ingelheim, Teva, Sanofi, and Bayer. Dr Cosio declares receiving grants from Chiesi 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. Dr de Llano reports receiving grants, personal fees and nonfinancial support from AstraZeneca, Teva, Faes, and Sanofi; personal fees and nonfinancial support from GlaxoSmithKline and Chiesi; personal fees from MSD, Techdow Pharma, GILEAD, and Leo Pharma; and grants and personal fees from GEBRO outside the submitted work. Dr 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. Dr Tsai has received grants from Boehringer Ingelheim and has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Orient EuroPharma. Dr Jackson has received speaker fees and consultancy fees from AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, and Boehringer Ingelheim and research funding from AstraZeneca. Dr Busby has received research grants from AstraZeneca and personnel fees from NuvoAir outside the submitted work. Dr 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; has received grants from MedImmune, Novartis UK, Roche/Genentech Inc, GlaxoSmithKline, Amgen, Genentech/Hoffman la Roche, AstraZeneca, Aerocrine, and Vitalograph; has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Napp Pharmaceuticals; has taken part in asthma clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Hoffmann la Roche, and GlaxoSmithKline, for which his institution received remuneration; and 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. Dr Pfeffer has attended advisory boards for AstraZeneca, GlaxoSmithKline, and Sanofi; has given lectures at meetings supported by AstraZeneca and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, GlaxoSmithKline, Novartis, and Sanofi, for which his institution received remuneration; and has a current research grant funded by GlaxoSmithKline. Dr Goddard reports receiving lecture fees from Sanofi. Dr Wang has received honoraria from AstraZeneca, GlaxoSmithKline, and Genentech; and has been an investigator on studies sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Sanofi, Novartis, and Teva, for which her institution has received funding. Dr Hoyte reports receiving honoraria from AstraZeneca and Genentech and has been an investigator on clinical trials sponsored by GlaxoSmithKline, Genentech, Teva, and Sanofi, for which her institution has received funding. Dr Wechsler reports receiving 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 biologic, Incyte, and Kinaset. Ms Carter is an employee of Optimum Patient Care (OPC) (OPC is a cofounder of the International Severe Asthma Registry and a cofounder of the APEX-COPD initiative). Ms Bulathsinhala is an employee of OPRI. Ms Eleangovan and Mr Ariti were employees of OPRI. Dr Lyu was an employee of OPC. Dr Price has advisory board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi-Genzyme, Teva Pharmaceuticals, Thermofisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, Theravance; received grants and unrestricted funding for investigator-initiated studies (conducted through OPRI Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi-Genzyme, Teva Pharmaceuticals, Theravance, and the UK National Health Service; received payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi-Genzyme, Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma, Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; funding for patient enrollment or completion of research from Novartis; has stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise OPC Ltd (Australia and UK) and 74% of OPRI Pte Ltd (Singapore); has 5% shareholding in Timestamp, which develops adherence monitoring technology; is a peer reviewer for grant committees of the Efficacy and Mechanism Evaluation program and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. Dr 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, MSD, Sanofi-Genzyme, GlaxoSmithKline, and Novartis; and has received educational and research grants from AstraZeneca, Novartis, Teva, GlaxoSmithKline, ALK, and Sanofi-Genzyme. The remaining authors have no conflicts of interest to report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone., Objective: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS., Methods: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models., Results: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48])., Conclusions: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life., Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions., Results: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43)., Conclusions: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

In Australia, the Teaching Performance Assessment (TPA) is a relatively new, mandatory hurdle which must be completed just prior to the graduation stage of initial teacher education (ITE) programmes. This high-stakes task is one of a growing number of requirements to come out of the standards and accountability regime as outlined in the Australian Institute for Teaching and School Leadership (AITSL) document for accreditation for ITE programmes. We delve into the public commentary about the broader commission of preservice and graduate teacher quality in general and the TPA in particular. We draw on Bernstein's pedagogic identities and deductively apply this theory to explore this phenomenon. We use a data set of publicly available legacy media and social media tweets made over a ten-month period from August 2019 to May 2020 to reveal the focus, inherent bias and pedagogic identities promoted by these public discourses. The paper concludes with discussion about the implications of these drivers on the public perception of quality in ITE and on the status of teaching more broadly., Competing Interests: Competing interestThere is no conflict of interest for any of the authors associated with this submission to The Australian Educational Researcher., (© Crown 2023.)

Despite previous findings of therapeutic effects for heart rate variability biofeedback (HRVB) on asthma, it is not known whether HRVB can substitute either for controller or rescue medication, or whether it affects airway inflammation. Sixty-eight paid volunteer steroid naïve study participants with mild or moderate asthma were given 3 months of HRVB or a comparison condition consisting of EEG alpha biofeedback with relaxing music and relaxed paced breathing (EEG+), in a two-center trial. All participants received a month of intensive asthma education prior to randomization. Both treatment conditions produced similar significant improvements on the methacholine challenge test (MCT), asthma symptoms, and asthma quality of life (AQOL). MCT effects were of similar size to those of enhanced placebo procedures reported elsewhere, and were 65% of those of a course of a high-potency inhaled steroid budesonide given to a sub-group of participants following biofeedback training. Exhaled nitric oxide decreased significantly only in the HRVB group, 81% of the budesonide effect, but with no significant differences between groups. Participants reported becoming more relaxed during practice of both techniques. Administration of albuterol after biofeedback sessions produced a large improvement in pulmonary function test results, indicating that neither treatment normalized pulmonary function as a potent controller medication would have done. Impulse oscillometry showed increased upper airway (vocal cord) resistance during biofeedback periods in both groups. These data suggest that HRVB should not be considered an alternative to asthma controller medications (e.g., inhaled steroids), although both biofeedback conditions produced some beneficial effects, warranting further research, and suggesting potential complementary effects. Various hypotheses are presented to explain why HRVB effects on asthma appeared smaller in this study than in earlier studies. Clinical Trial Registration NCT02766374.