title: Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma.
abstract: Asthma control is improved by combining inhaled corticosteroids with long-acting beta2-agonists. However, fluctuating asthma control still occurs. We hypothesized that in patients receiving low maintenance dose budesonide/formoterol (bud/form), replacing short-acting beta2-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 microg twice a day (bud/form + SABA) or bud 320 microg twice a day (bud + SABA) or bud/form 80/4.5 microg twice a day with 80/4.5 microg 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.
authors.affiliation: Firestone Institute for Respiratory Health, St. Joseph's Hospital, Hamilton, Ontario, Canada. obyrnep@mcmaster.ca
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
authors.forename: Philippe P
authors.initials: PP
authors.lastname: Godard
authors.forename: Massimo
authors.initials: M
authors.lastname: Pistolesi
authors.forename: Mona
authors.initials: M
authors.lastname: Palmqvist
authors.forename: Yuanjue
authors.initials: Y
authors.lastname: Zhu
authors.forename: Tommy
authors.initials: T
authors.lastname: Ekström
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
mesh_terms: D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy*; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012449:Safety
chemical_list: D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate