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.

High or standard initial dose of budesonide to control mild-to-moderate asthma? P. Chanez, R. Karlstrom, P. Godard. #ERS Journals Ltd 2001. ABSTRACT: Guidelines on the use of inhaled steroids in asthma advocate that the daily dose should be chosen according to the severity of the disease. However, the question of the optimal starting dose remains to be properly addressed, as does the issue of the adjustment in dose required for a given patient.Whether a high initial dose of budesonide (800 mg b.i.d) was more efficacious than a standard dose (200 mg b.i.d) in controlling mild-to-moderate asthma was investigated, and whether the dose could be decreased, based on peak expiratory flow (PEF), symptom-score, b 2 -agonist use in a double-blind, randomized, parallel-group 18-week study.One-hundred and sixty-nine patients (mean age 38 yrs, mean forced expiratory volume in one second 74% predicted) were enrolled. No difference was detected between the two groups in improvement in morning PEF (z61 L?min -1 in the high-dose group, z60 L?min -1 in the standard-dose group by 16 weeks). Morning and evening PEF values stabilized before the end of the first 4 weeks.No difference between groups was observed in symptom score, b 2 -agonist use, number of exacerbation per interval and the best forced expiratory volume in one second achieved. The proportion of subjects being able to decrease the doses of budesonide was similar in both treatment strategies. It is concluded that both high and standard initial doses are equally effective in controlling symptoms and improving lung function in mildto-moderate asthma. It is well established that inhaled corticosteroids (ICSs) effectively control symptoms and improve lung function in asthmatic patients [1,2]. Over recent years, guidelines have varied in their recommendations for starting doses of ICSs. When the present study was performed, most of the current guidelines advocated a stepwise approach, starting with low doses [3,4]. However, the benefit of starting with a high dose of ICSs was illustrated in a long-term study investigating the effect of budesonide pressurized metered-dose inhaler (pMDI) 1,200 mg daily in newly diagnosed mild asthma; a clear improvement in daily peak expiratory flow (PEF) was seen within a few days in the group treated with budesonide. On the other hand, in another study in patients with mild asthma, a low dose of budesonide, 400 mg daily, was also seen to increase morning PEF and decrease nocturnal symptoms and b 2 -agonist use [5,6]. A few well-controlled studies in severe asthma have succeeded in demonstrating a dose-response to inhaled steroids [7][8][9], but this has been difficult to show in mild-to-moderate asthma.Thus, the question of the optimal starting dose still remains to be properly addressed, as does the issue of the adjustment in dose required for a given patient. Therefore, the present double-blind, randomized study was undertaken to assess if: 1) a high initial dose of ICSs (budesonide 800 mg b.i.d.) was more efficacious than a standard dose ...