Low Dose Inhaled Budesonide and Formoterol in Mild Persistent Asthma . The OPTIMA Randomized Trial

Low Dose Inhaled Budesonide and Formoterol in Mild Persistent Asthma
The OPTIMA Randomized Trial

PAUL M. O'BYRNE, PETER J. BARNES, ROBERTO RODRIGUEZ-ROISIN, EVA RUNNERSTROM, THOMAS SANDSTROM, KLAS SVENSSON, and ANNE TATTERSFIELD

Department of Medicine, McMaster University, Hamilton, Ontario, Canada; National Heart and Lung Institute, Imperial College, London, Division of Respiratory Medicine, City Hospital, Nottingham, United Kingdom; Servei de Pneumologia i Allergia Respiratoria, Hospital Clinic, University of Barcelona, Spain; Clinical Research and Development, AstraZeneca, Lund, and Department of Respiratory Disease, University of Umea, Sweden

The optimal treatment for mild asthma is uncertain. We assessed the effects of adding a long-acting inhaled beta-agonist,formoterol, to low doses of an inhaled corticosteroid, budesonide,for 1 yr in subjects with mild asthma, receiving no or only asmall dose of inhaled corticosteroid. The 698 corticosteroid freepatients (Group A) were assigned to twice daily treatment with100 µg budesonide, 100 µg budesonide plus 4.5 µg formoterol, orplacebo. The 1,272 corticosteroid-treated patients (Group B) wereassigned to twice daily treatment with 100 µg budesonide, 100µg budesonide plus 4.5 µg formoterol, 200 µg budesonide, or 200µg budesonide plus 4.5 µg formoterol. The main outcome variableswere time to the first severe asthma exacerbation and poorly controlledasthma days. In Group A, budesonide alone reduced the risk forsevere exacerbations by 60% and poorly controlled days by 48%;adding formoterol increased lung function with no change in otherend points. By contrast, in Group B, adding formoterol reducedthe risk for the first severe exacerbation and for poorly controlleddays by 43 and 30%, respectively. Thus, in corticosteroid-freepatients, low dose inhaled budesonide alone reduced severe exacerbationsand improved asthma control, and in patients already receivinginhaled corticosteroid, adding formoterol was more effective thandoubling the corticosteroiddose.

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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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[Full Text] [PDF]

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Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1212 - 1217.
[Abstract] [Full Text] [PDF]

C. Lemiere, A. Becker, L.-P. Boulet, D. Bowie, A. Cartier, D. Cockroft, R. Cowie, P. Ernst, M. Fitzgerald, M. Sears, et al.
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Can. Med. Assoc. J., October 29, 2002; 167(9): 1008 - 1009.
[Full Text] [PDF]

P.W. Ind, C. Villasante, R.J. Shiner, A. Pietinalho, N.G. Boszormenyi, S. Soliman, and O. Selroos
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Eur. Respir. J., October 1, 2002; 20(4): 859 - 866.
[Abstract] [Full Text] [PDF]

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DTB, August 1, 2002; 40(8): 62 - 64.
[Abstract] [Full Text] [PDF]

D. Grosser and B. Smith
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[Full Text] [PDF]

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BUDESONIDE DOSE-RESPONSE IN MILD PERSISTENT ASTHMA
Am. J. Respir. Crit. Care Med., April 15, 2002; 165(8): 1188a - 1189.
[Full Text]

M. J. TOBIN
Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2001
Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 598 - 618.
[Full Text] [PDF]

P.J. Barnes
Scientific rationale for inhaled combination therapy with long-acting {beta}2-agonists and corticosteroids
Eur. Respir. J., January 1, 2002; 19(1): 182 - 191.
[Abstract] [Full Text] [PDF]

J. C. Kips
Treating Asthma, or Is Simple Too Simple?
Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1336 - 1338.
[Full Text] [PDF]