Budesonide/Formoterol Combination Therapy as Both Maintenance and Reliever Medication in Asthma
Abstract
Asthma control is improved by combining inhaled corticosteroids with long-acting β2-agonists. However, fluctuating asthma control still occurs. We hypothesized that in patients receiving low maintenance dose budesonide/formoterol (bud/form), replacing short-acting β2-agonist (SABA) reliever with as-needed bud/form would provide rapid symptom relief and simultaneous adjustment in antiinflammatory therapy, thereby reducing exacerbations. In this double-blind, randomized, parallel-group study, 2,760 patients with asthma aged 4–80 years (FEV1 60–100% predicted) received either terbutaline 0.4 mg as SABA with bud/form 80/4.5 μg twice a day (bud/form + SABA) or bud 320 μg twice a day (bud + SABA) or bud/form 80/4.5 μg twice a day with 80/4.5 μg as-needed (bud/form maintenance + relief). Children used a once-nocte maintenance dose. Bud/form maintenance + relief prolonged time to first severe exacerbation (p < 0.001; primary endpoint), resulting in a 45–47% lower exacerbation risk versus bud/form + SABA (hazard ratio, 0.55; 95% confidence interval, 0.44, 0.67) or bud + SABA (hazard ratio, 0.53; 95% confidence interval 0.43, 0.65). Bud/form maintenance + relief also prolonged the time to the first, second, and third exacerbation requiring medical intervention (p < 0.001), reduced severe exacerbation rate, and improved symptoms, awakenings, and lung function compared with both fixed dosing regimens.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The pandemic 2009 H1N1 influenza virus is extremely sensitive to the antiviral actions of type I and type III IFNs.
“The pandemic 2009 (H1N1) influenza virus is extremely sensitive to the antiviral actions of type I and type III IFNs (200).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [200]
Cites
Lung volumes and forced ventilatory flows
Quanjer, P. H., Tammeling, G. J., Cotes, J. E., Pedersen, O. F., Peslin, R., & Yernault, J. (1993) · European Respiratory Journal · doi:10.1183/09041950.005s1693 · Cited by 5,484 · see citing works
(1993) · PubMed · Cited by 3,827 · see citing works
Effect of Inhaled Formoterol and Budesonide on Exacerbations of Asthma
PAUWELS, R. A., Löfdahl, C., Postma, D. S., Tattersfield, A. E., O’Byrne, P. M., Barnes, P. J., & Ullman, A. (1997) · New England Journal of Medicine · doi:10.1056/nejm199711133372001 · Cited by 1,518 · see citing works
Self-citationClinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study
Rabe, K. F., Vermeire, P., Soriano, J. B., & Maier, W. (2000) · European Respiratory Journal · doi:10.1183/09031936.00.16580200 · Cited by 1,024 · see citing works
Effect of Inhaled Formoterol and Budesonide on Exacerbations of Asthma
(1998) · New England Journal of Medicine · doi:10.1056/nejm199801083380222 · Cited by 864 · see citing works
Low Dose Inhaled Budesonide and Formoterol in Mild Persistent Asthma
O’Byrne, P. M., Barnes, P. J., Rodriguez‐Roisin, R., Runnerström, E., Sandström, T., Svensson, K., & Tattersfield, A. E. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.8.2104102 · Cited by 678 · see citing works
Self-citationA Cohort Analysis Of Excess Mortality In Asthma And The Use Of Inhaled Beta-Agonists
Suissa, S., Ernst, P., Boivin, J.-F., Horwitz, R. I., Habbick, B. F., Cockroft, D. W., Blais, L., McNutt, M., Buist, A. S., & Spitzer, W. O. (1994) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.149.3.8118625 · Cited by 420 · see citing works
Exacerbations of Asthma: A Descriptive Study of 425 Severe Exacerbations
Tattersfield, A. E., Postma, D. S., Barnes, P. J., Svensson, K., Bauer, C., O’Byrne, P. M., Löfdahl, C., PAUWELS, R. A., & Ullman, A. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.160.2.9811100 · Cited by 395 · see citing works
Self-citationPotential Masking Effects of Salmeterol on Airway Inflammation in Asthma
McIvor, R. A., Pizzichini, E., TURNER, M. O., et al. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.158.3.9802069 · Cited by 283 · see citing works
Harrison, T. W., Oborne, J., Newton, S., & Tattersfield, A. (2004) · The Lancet · doi:10.1016/s0140-6736(03)15384-6 · Cited by 228 · see citing works
ZETTERSTRÖM, O., Buhl, R., Mellem, H., et al. (2001) · European Respiratory Journal · doi:10.1183/09031936.01.00065801 · Cited by 195 · see citing works
Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations
FitzGerald, J. M. (2004) · Thorax · doi:10.1136/thx.2003.014936 · Cited by 193 · cited 1× · see citing works
“Studies that simply doubled the maintenance dose of ICS well into the course of an exacerbation have generally failed to show added benefits (11, 12).”
Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial
Tattersfield, A. E., Löfdahl, C., Postma, D. S., Eivindson, A., Schreurs, A. J. M., Rasidakis, A., & Ekström, T. (2001) · The Lancet · doi:10.1016/s0140-6736(00)03611-4 · Cited by 180 · see citing works
Aubier, M., Pieters, W. R., Schlösser, N. J. J., et al. (1999) · Respiratory Medicine · doi:10.1016/s0954-6111(99)90053-7 · Cited by 161 · see citing works
Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial
Pauwels, R., Sears, M. R., Campbell, M., Villasante, C., Huang, S., Lindh, A., Petermann, W., Aubier, M., Schwabe, G., & Bengtsson, T. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00055803 · Cited by 134 · see citing works
Aalbers, R., Backer, V., Kava, T., et al. (2004) · Current Medical Research and Opinion · doi:10.1185/030079903125002928 · Cited by 128 · see citing works
Effect of long‐acting β2 agonists on exacerbation rates of asthma in children
Bisgaard, H. (2003) · Pediatric Pulmonology · doi:10.1002/ppul.10381 · Cited by 111 · see citing works
Self-citationAziz, I., Wilson, A. M., & Lipworth, B. J. (2000) · CHEST Journal · doi:10.1378/chest.118.4.1049 · Cited by 72 · see citing works
Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma
Ind, P. W., NEGRO, R. D., Colman, N. C., et al. (2003) · Respiratory Medicine · doi:10.1053/rmed.2003.1483 · Cited by 69 · see citing works
Beta agonists, inhaled steroids, and the risk of intensive care unit admission for asthma
Eisner, M. D., Lieu, T. A., Chi, F., Capra, A. M., Mendoza, G. R., Selby, J. V., & Blanc, P. D. (2001) · European Respiratory Journal · doi:10.1183/09031936.01.17202330 · Cited by 68 · see citing works
van der Woude, H. J., Boorsma, M., Bergqvist, P. B. F., et al. (2003) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2003.11.001 · Cited by 61 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Global strategy for asthma management and prevention: GINA executive summary
Bateman, E. D., Hurd, S. S., Barnes, P. J., Bousquet, J., Drazen, J. M., FitzGerald, M., Gibson, P., Ohta, K., O'Byrne, P., Pedersen, S. E., et al. (2008) · European Respiratory Journal · doi:10.1183/09031936.00138707 · Cited by 3,203 · see citing works
Self-citationAfter asthma: redefining airways diseases
Pavord, I. D., Beasley, R., Agusti, A., Anderson, G. P., Bel, E., Brusselle, G., Cullinan, P., Custovic, A., Ducharme, F. M., Fahy, J. V., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)30879-6 · Cited by 1,073 · see citing works
Cloutier, M. M., Baptist, A. P., Blake, K. V., Brooks, E. G., Bryant-Stephens, T., DiMango, E., Dixon, A. E., Elward, K. S., Hartert, T., Krishnan, J. A., et al. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.10.003 · Cited by 854 · see citing works
The airway epithelium: soldier in the fight against respiratory viruses
Vareille, M., Kieninger, E., Edwards, M. R., & Regamey, N. (2011) · Clinical Microbiology Reviews · doi:10.1128/cmr.00014-10 · Cited by 655 · see citing works
Skevaki, C. L., Christodoulou, I., Spyridaki, I. S., Tiniakou, I., Georgiou, V., Xepapadaki, P., Kafetzis, D. A., & Papadopoulos, N. G. (2009) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2009.03307.x · Cited by 67 · see citing works
Edwards, M. R., Saglani, S., Schwarze, J., Skevaki, C., Smith, J. A., Ainsworth, B., Almond, M., Andreakos, E., Belvisi, M. G., Chung, K. F., et al. (2017) · European Respiratory Journal · doi:10.1183/13993003.02448-2016 · Cited by 55 · see citing works
New treatment regimes for virus-induced exacerbations of asthma
Edwards, M. R., Kebadze, T., Johnson, M. W., & Johnston, S. L. (2006) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2005.09.005 · Cited by 30 · see citing works
- Authors
- O'Byrne, P. M., Bisgaard, H., Godard, P. P., Pistolesi, M., Palmqvist, M., Zhu, Y., Ekström, T., & Bateman, E. D.
- Affiliations
- Firestone Institute for Respiratory Health, St. Joseph's Hospital, Hamilton, Ontario, Canada; COPSAC Clinical Research Unit, University Hospital of Copenhagen, Gentofte, Denmark; Hôpital Arnaud de Villeneuve, Service des Maladies Respiratoires and Bronchomotricité, Montpellier, France; Department of Critical Care, Section of Respiratory Medicine, University of Florence, Florence, Italy; Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden; Respiratory Department, Peking Union Medical College Hospital, Beijing, China; AstraZeneca R&D, Lund, Sweden; and University of Cape Town, Cape Town, South Africa
- University of Copenhagen (DK)
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-01
- Volume
- 171
- Issue
- 2
- Pages
- 129-136
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2110658984
- Cited by
- 657
- References
- 21
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 14 · 2023: 18 · 2022: 31 · 2021: 27 · 2020: 29 · 2019: 20 · 2018: 18 · 2017: 23 · 2016: 20 · 2015: 22 · 2014: 23 · 2013: 22 · 2012: 27
- FWCI
- 30.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
- Keywords
- budesonide/formoterol, asthma, maintenance and reliever therapy, inhaled corticosteroids, long-acting beta2-agonists, terbutaline, asthma exacerbations, asthma control, lung function, nocturnal symptoms
- MeSH terms
- Formoterol Fumarate, Adolescent, Adrenergic beta-Agonists, Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Asthma, Child, Child, Preschool, Double-Blind Method, Drug Combinations, Ethanolamines, Female, Humans, Male, Middle Aged, Peak Expiratory Flow Rate, Regression Analysis, Safety, Proportional Hazards Models, Budesonide, Metered Dose Inhalers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
