Once-daily budesonide/formoterol in a single inhaler in adults with moderate persistent asthma

Patients with moderate persistent asthma (n = 523; mean FEV1 77.4%) not fully controlled with inhaled corticosteroids (ICS; 400-1000 microg/day) were randomized to receive either once-daily budesonide/formoterol (160/4.5 microg, two inhalations); or twice-daily budesonide/formoterol (160/4.5 microg, one inhalation); or budesonide (400 microg) once-daily for 12 weeks. Once-daily dosing was administered in the evening and twice-daily dosing was administered in the morning and evening. All patients received twice-daily budesonide (200 microg) during a 2-week run-in. Compared with budesonide alone, change in mean morning and evening peak expiratory flow was greater in the once-daily budesonide/formoterol group (27 and 171 min(-1), respectively; P < 0.001) and twice-daily budesonide/formoterol group (23 and 24 l min(-1), respectively; P < 0.001). Night awakenings, symptom-free days, reliever-use-free days and asthma-control days were all improved during once-daily budesonide/formoterol therapy vs. budesonide (P < or = 0.05). Similar improvements were also seen with twice-daily budesonide/formoterol (P < or = 0.05). The risk of a mild exacerbation was reduced after once- and twice-daily budesonide/formoterol vs. budesonide (38% and 35%, respectively; P < 0.002). All treatments were well tolerated. Budesonide/formoterol, once- or twice-daily, in a single inhaler improved asthma symptoms and exacerbations compared with budesonide. In the majority of patients with moderate persistent asthma requiring ICS and long-acting beta-agonists, once-daily formoterol/budesonide provided sustained efficacy over 24 h, similar to twice-daily dosing.     

Tolerability of a high dose of budesonide/formoterol in a single inhaler in patients with asthma

This randomised, double-blind, double-dummy, crossover, placebo-controlled study assessed the acute tolerability of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler, AstraZeneca) administered as a high dose. Fourteen patients with asthma receiving budesonide/formoterol maintenance treatment (two inhalations of 160/4.5 microg twice daily) inhaled 10 additional doses of budesonide/formoterol 1600/45 microg (total daily dose including morning dose of maintenance treatment 1920/54 microg) or formoterol 45 microg (Oxis Turbuhaler, AstraZeneca; total daily dose including morning dose of maintenance treatment 54 microg formoterol) or placebo in addition to the morning dose of maintenance treatment on 3 separate study days. Serum potassium, pulse rate, blood pressure and ECG were assessed at regular intervals over a 12-h period following dosing. Blood glucose and plasma lactate were assessed over 3 h following dosing. Changes in serum potassium, pulse rate, blood pressure, QTc, blood glucose and plasma lactate occurring with budesonide/formoterol, though statistically significantly different from placebo (P<0.05), were considered clinically unimportant. No clinically relevant differences were identified between active treatments. In conclusion, budesonide/formoterol in a single inhaler is well tolerated at high doses such as might be used by patients using budesonide/formoterol for relief of symptoms of asthma.     

Onset of action of formoterol/budesonide in single inhaler vs. formoterol in patients with COPD

Formoterol is a beta(2)-agonist bronchodilator that combines a fast onset of action with a long duration of broncholytic effect. An increasing documentation is showing that the combination of a long acting beta(2)-adrenoceptor agonist bronchodilator and an inhaled corticosteroid targets the airways obstruction in patients with COPD. In this study, we have explored whether the acute addition of an inhaled corticosteroid influences the fast bronchodilator response to formoterol. A total of 20 patients with stable COPD were randomized. Single doses of formoterol/budesonide 2 x (4.5/160)microg or formoterol 2 x 4.5 microg were given via Turbuhaler. Serial measurements of FEV(1) were performed over 60 min. Formoterol/budesonide elicited a significantly larger mean FEV(1)-AUC(0-15 min) than formoterol alone. Also the change in FEV(1) 15 min after inhalation of formoterol/budesonide combination (0.197 l; 95% CI: to 0.142-0.252) was greater than that induced by formoterol alone (0.147 l; 95% CI: to 0.092-0.201). The mean increases in FEV(1) were always higher after budesonide/formoterol than formoterol alone, although both treatments induced a significant improvement over baseline at each explored time point. Even the FEV(1)-AUC(0-60 min) after formoterol/budesonide was significantly larger than that after formoterol. Both treatments induced a significant reduction in VAS score but did not modify heart rate in a statistically significant manner. This study indicates that the addition of budesonide influences the fast onset of action of formoterol, but does not induce systemic effects, in patients with stable COPD.     

Budesonide/formoterol in a single inhaler versus inhaled corticosteroids alone in the treatment of asthma

The aim of this study was to evaluate the efficacy (expressed as effect on lung function) and tolerability of Symbicort (budesonide/formoterol in a single inhaler) in children with asthma. This was a double-blind, double-dummy, randomized, parallel-group, multicenter trial. After a 2-4-week run-in period, 286 asthmatic children (177 boys, 109 girls; mean age, 11 years; mean forced expiratory volume in 1 sec (FEV(1)), 75% predicted normal), previously treated with inhaled corticosteroids (average dose 548 microg/day), were randomized to 12 weeks' treatment with either budesonide/formoterol 80/4.5 microg, two inhalations twice daily (n = 148), or an equivalent dose of budesonide 100 microg, two inhalations twice daily (n = 138). Efficacy variables included morning and evening peak expiratory flow (PEF), spirometery, asthma symptoms, and use of rescue medication (beta(2)-agonists). Serial FEV(1) assessments were carried out on a subgroup of children (budesonide/formoterol, n = 41; budesonide, n = 40) at randomization and at week 12. Relative to baseline, morning PEF (primary variable) increased to a significantly greater extent with budesonide/formoterol than with budesonide alone (7.22% predicted normal vs 3.45% predicted normal; P < 0.001). Evening PEF also increased significantly with budesonide/formoterol (6.13% predicted normal vs. 2.73% predicted normal; P < 0.001), as did mean FEV(1) and serial FEV(1) measured over 12 hr (both P < 0.05). Similar improvements in asthma symptoms and rescue medication use were observed in both groups. The two treatment groups were similar in terms of their adverse-event profile and rates of discontinuation. Budesonide/formoterol in a single inhaler provided rapid improvements in PEF and FEV(1) compared to inhaled budesonide alone. These improvements were sustained throughout the study period. Budesonide/formoterol was well-tolerated in children with moderate persistent asthma.     

Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.     

Adjustable and fixed dosing with budesonide/ formoterol via a single inhaler in asthma patients: the ASSURE study

Patient-guided management of asthma using adjustable dosing of budesonide/formoterol in a single inhaler (Symbicort) was compared with fixed dosing in an open-label, multicentre, randomised study. Patients, uncontrolled on an inhaled corticosteroid (ICS) or controlled on an ICS and a long-acting beta2-agonist, entered a 4-week run-in period and received budesonide/formoterol (80/4.5 or 160/4.5 microg), 2 inhalations b.i.d. Following randomisation, the fixed-dosing group (n = 764) continued this regimen for a further 12 weeks. The adjustable-dosing group (n = 775) could step down to 1 inhalation b.i.d. if symptoms were controlled, and, at early signs of worsening symptoms, promptly step up to 4 inhalations b.i.d. for < or = 2 weeks. During run-in, National Heart, Lung and Blood Institute symptom-severity grading was maintained in 60% and improved in 31% of patients, clinic peak flow increased from 400 to 4191/min (P<0.001), and health-related quality of life (overall MiniAQLQ) improved from 4.6 to 5.4 (P<0.001). Patients effectively used the adjustable-dosing regimen; 79% reduced budesonide/formoterol dosage and, compared with fixed dosing, the number of inhalations were significantly lowered (3.2 vs. 3.8 inhalations/day, P<0.05). Both regimens were well tolerated. In both groups, symptom control was maintained or improved in 85-86% of patients, and 94% experienced no treatment failures. Consistent with current guidelines, adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma control at reduced medication doses.     

Budesonide and formoterol in a single inhaler improves asthma control compared with increasing the dose of corticosteroid in adults with mild-to-moderate asthma

BACKGROUND: We evaluated the efficacy and safety of low-dose budesonide/formoterol, 80 micro g/4.5 micro g, bid in a single inhaler (Symbicort Turbuhaler; AstraZeneca; Lund, Sweden) compared with an increased dose of budesonide, 200 micro g bid, in adult patients with mild-to-moderate asthma not fully controlled on low doses of inhaled corticosteroid alone. METHODS: All patients received budesonide, 100 micro g bid, during a 2-week run-in period. At the end of the run-in phase, 467 patients with a mean FEV(1) of 82% predicted received 12 weeks of treatment with budesonide/formoterol in a single inhaler or budesonide alone in a higher dose. Patients kept daily records of their morning and evening peak expiratory flow (PEF), nighttime and daytime symptom scores, and use of reliever medication. RESULTS: The increase in mean morning PEF-the primary efficacy measure-was significantly higher for budesonide/formoterol compared with budesonide alone (16.5 L/min vs 7.3 L/min, p = 0.002). Similarly, evening PEF was significantly greater in the budesonide/formoterol group (p < 0.001). In addition, the percentage of symptom-free days and asthma-control days (p = 0.007 and p = 0.002, respectively) were significantly improved in the budesonide/formoterol group. Budesonide/formoterol decreased the relative risk of an asthma exacerbation by 26% (p = 0.02) compared with budesonide alone. Adverse events were comparable between the two treatment groups. CONCLUSION: This study shows that in adult patients whose mild-to-moderate asthma is not fully controlled on low doses of inhaled corticosteroids, single-inhaler therapy with budesonide and formoterol provides greater improvements in asthma control than increasing the maintenance dose of inhaled corticosteroid.     

Adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma symptom control at a lower dose than fixed maintenance dosing

Asthma guidelines suggest a stepwise approach to maintenance pharmacological treatment of persistent asthma until control is attained, and a 3 month review of the fixed maintenance dosing for step-up or step-down adjustment. This 12-week study compared the efficacy and safety of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler 160/4.5 or 80/4.5 microg) given as adjustable maintenance or fixed maintenance dosing. Patients (n = 2358) were randomised to budesonide/formoterol fixed maintenance dosing (two inhalations bid) or adjustable maintenance dosing (two inhalation bid; stepping up to four inhalations bid if asthma worsened for a maximum of 14 days; stepping down to two inhalations once nocte or one inhalation bid if symptoms were controlled) for 12 weeks, following a 4-week run-in period on budesonide/formoterol two inhalations bid. Primary efficacy variables were frequency of asthma exacerbations and changes in patients' asthma symptom severity. Secondary variables were asthma control, safety and health economics. Both adjustable maintenance dosing and fixed maintenance dosing were associated with similar low frequency of exacerbations (5% both groups; ns) and similarly improved lung function, with similarly fewer nocturnal awakenings and less asthma symptoms compared with the mean value of the run-in period. However, patients on adjustable maintenance dosing used 24% fewer study drug compared with fixed maintenance dosing (2.95 versus 3.86 inhalations daily; p < 0.0001) and incurred in a significant (p <0.0001) reduction in total costs (direct+indirect) compared with fixed maintenance dosing. In conclusion, adjustable maintenance dosing with budesonide/formoterol effectively controls asthma at a reduced drug load with lower costs than fixed maintenance dosing.     

Efficacy and safety of high-dose budesonide/formoterol (Symbicort) compared with budesonide administered either concomitantly with formoterol or alone in patients with persistent symptomatic asthma

OBJECTIVE AND BACKGROUND: Budesonide/formoterol 160/4.5 microg, two inhalations bd, is an effective and well-tolerated maintenance therapy for patients not controlled on inhaled corticosteroids alone. The authors assessed the efficacy and safety of a higher dose of budesonide/formoterol in patients with persistent symptomatic asthma. METHODS: This was a 24-week, double-blind, double-dummy randomized study. Budesonide/formoterol 320/9 microg, two inhalations bd (1280/36 microg/day), was compared with corresponding doses of budesonide during weeks 1-12 and budesonide plus formoterol via separate inhalers during weeks 1-24. Efficacy was assessed during weeks 1-12; the primary variable was morning PEF. Safety was assessed over weeks 1-24. RESULTS: Patients (n=456; aged 12-79 years) had a mean reversibility in FEV1 of 28% and mean pre-study inhaled corticosteroid dose of 1038 microg/day. Mean morning PEF increased by 37 L/min and 36 L/min with budesonide/formoterol and budesonide plus formoterol, respectively, versus an increase of 5 L/min with budesonide (P<0.001 for both vs. budesonide). Budesonide/formoterol increased time to first mild exacerbation (P<0.005) versus budesonide. Budesonide/formoterol and budesonide plus formoterol had similar efficacy. All treatments were well tolerated and the incidence of class-related adverse events was similarly low in all groups. Changes in serum potassium and plasma cortisol were comparable across treatments. CONCLUSIONS: High-dose budesonide/formoterol (320/9 microg, two inhalations bd) is effective and well tolerated in patients with persistent symptomatic asthma. The findings also support the safety of regular high-dose formoterol (36 microg/day).     

Cost-effectiveness analysis of budesonide/formoterol compared with fluticasone in moderate-persistent asthma

In this economic evaluation, conducted alongside a randomized, double-blind clinical trial, economic data were collected from 339 patients with moderate-persistent asthma randomized to receive twice-daily, double-blind treatment with budesonide/formoterol 160/4.5 microg in a single inhaler (n=166) or fluticasone propionate 250 microg (n=173) for 12 weeks. The mean number of episode-free days (EFD) per patient was significantly greater in the budesonide/formoterol group than the fluticasone group (48.71 compared with 42.34, P=0.0185). Data on medication use, visits to healthcare professionals, and hospitalization were pooled across all six countries and combined with German and Dutch unit cost data to calculate total healthcare costs. Using German unit costs, budesonide/formoterol was associated with significantly lower total healthcare costs per patient over the 12-week period compared with fluticasone (euro 131 compared with euro 210, P=0.0043). Using Dutch unit costs, total healthcare costs were slightly numerically lower in the budesonide/formoterol group than the fluticasone group (euro 102 compared with euro 104), but the difference did not reach statistical significance. Budesonide/formoterol in a single inhaler is more effective than a higher microgram dose of fluticasone alone. It is cost-neutral and may provide cost-savings in some countries.     

Comparable long-term safety and efficacy of a novel budesonide/formoterol pressurized metered-dose inhaler versus budesonide/formoterol Turbuhaler in adolescents and adults with asthma

Budesonide/formoterol in one inhaler is an established therapy for asthma and chronic obstructive pulmonary disease. The long-term safety and efficacy profile of a novel hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) formulation of budesonide/formoterol was compared with that of budesonide/formoterol in a dry powder inhaler (DPI; Turbuhaler). This multinational, 52-week, randomized, open, parallel-group study included patients aged > or = 12 years with asthma who had a forced expiratory volume in 1s (FEV1)> or = 50% of predicted normal; all patients used inhaled corticosteroids (400-1200 microg/day) and needed additional short-acting beta 2-agonist therapy. Patients were randomized to receive budesonide/formoterol pMDI or DPI 160/4.5 microg, two inhalations twice daily. Safety endpoints included assessment of adverse events and laboratory parameters. Efficacy endpoints included change from baseline in FEV1 and time to first severe asthma exacerbation. Overall, 673 patients (446pMDI, 227DPI) were included. There were no clinically significant differences between treatment groups in the nature, incidence or severity of adverse events or laboratory parameters. The number of patients experiencing adverse events was comparable in the pMDI (332/446 [74%]) and DPI (175/227 [77%]) groups; the most commonly reported adverse event was upper respiratory tract infection. The proportion of patients discontinuing as a result of adverse events was low in both groups (pMDI 12/446 [3%], DPI 2/227 [1%]). Lung function was improved to a similar extent in both groups and there was no detectable difference in time to first severe asthma exacerbation. The novel HFA pMDI formulation of budesonide/formoterol is an equally well tolerated and effective treatment for adults and adolescents with asthma as the budesonide/formoterol DPI.     

Effects of budesonide/formoterol combination therapy versus budesonide alone on airway dimensions in asthma

Background and objective: Combination therapy with inhaled corticosteroids and long‐acting β₂‐agonists results in improved asthma symptom control compared with the use of inhaled corticosteroids alone. However, the effects of combination therapy on structural changes and inflammation of the airways are still unknown. The aim of this study was to compare the effects of budesonide/formoterol with those of budesonide alone on airway dimensions and inflammation in individuals with asthma. Methods: Fifty asthmatic patients were randomized to treatment with budesonide/formoterol (200/6 µg, two inhalations bd) or budesonide (200 µg, two inhalations bd) for 24 weeks. Airway dimensions were assessed using a validated computed tomography technique, and airway wall area (WA) corrected for body surface area (BSA), percentage WA (WA%), wall thickness/Ösquare root BSA, and luminal area (Ai)/BSA at the right apical segmental bronchus, were measured. The percentage of eosinophils in induced sputum, pulmonary function, and Asthma Quality of Life Questionnaires (AQLQ) were also evaluated. Results: There were significantly greater decreases in WA/BSA (P < 0.05), WA% (P < 0.001) and wall thickness/square root BSA (P < 0.05), and increases in Ai/BSA (P < 0.05), in subjects treated with budesonide/formoterol compared with those treated with budesonide. The reduction in sputum eosinophils and increase in per cent of predicted forced expiratory volume in 1 s (FEV₁%) were greater for subjects treated with budesonide/formoterol compared with those treated with budesonide alone. In the budesonide/formoterol group, the changes in WA% were significantly correlated with changes in sputum eosinophils and FEV_1% (r = 0.84 and r = 0.64, respectively). There were improvements in the AQLQ scores after treatment with budesonide/formoterol. Conclusions: Budesonide/formoterol combination therapy is more effective than budesonide alone for reducing airway wall thickness and inflammation in individuals with asthma.     

Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma.

The present study was designed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite (Chiesi Farmaceutici, Parma, Italy) pressurised metered-dose inhaler (pMDI), with a combination of budesonide and formoterol administered via a Turbuhaler (AstraZeneca, Lund, Sweden) dry powder inhaler (DPI). This was a phase III, multinational, multicentre, double-blind, double-dummy, randomised, two-arm parallel groups, controlled study design. After a 2-week run-in period, 219 patients with moderate-to-severe asthma were randomised to a 12-week treatment with beclomethasone 200 microg plus formoterol 12 microg b.i.d. delivered via a pMDI or budesonide 400 microg plus formoterol 12 microg b.i.d. delivered via a DPI. The analysis of noninferiority on primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups. A statistically significant improvement from baseline in lung function, symptoms and rescue medication use was observed in both groups at all time-points. No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events. The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile.     

One-year safety and efficacy of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler) for the treatment of asthma

BACKGROUND: A budesonide/formoterol single inhaler has been developed for convenient treatment of patients whose asthma is inadequately controlled by inhaled glucocorticosteroids alone. OBJECTIVES: To compare long-term safety and efficacy of budesonide/formoterol single inhaler with budesonide plus formoterol via separate inhalers in adults with asthma. METHODS: In this open, randomized, parallel-group 6-month extension conducted in a subset of centres from a previous 6-month study, patients (n=321) received two inhalations bid of budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg delivered dose or corresponding doses of budesonide (Pulmicort Turbuhaler) plus formoterol (Oxis Turbuhaler) via separate inhalers. RESULTS: Significantly fewer patients receiving budesonide/formoterol single inhaler withdrew compared with budesonide plus formoterol (9 vs. 19%, P=0.008). Incidence and severity of AEs were low and similar in both groups. No clinically important differences between groups, or changes, were identified in laboratory measurements, vital signs or ECG. Treatments produced similar improvements in lung function, ACQ scores and Mini AQLQ domains that were maintained throughout 12 months. CONCLUSIONS: Budesonide/formoterol in a single inhaler is as safe and effective in the long-term treatment of asthma as budesonide plus formoterol via separate inhalers. The lower number of withdrawals with budesonide/formoterol may reflect better adherence to treatment compared with budesonide plus formoterol.     

Difference in time-course of improvement in asthma control measures between budesonide and budesonide/formoterol

Combinations of inhaled corticosteroids (ICS) and inhaled long-acting beta₂-agonists (LABA) have become widely used for the initiation of maintenance treatment for asthma. However, it has not been fully elucidated whether ICS/LABA alters the time-course of different control outcome measures in steroid-naive patients with asthma compared to the treatment with ICS alone.We compared the time-response in Asthma Control Questionnaire (ACQ), forced expiratory volume in 1 s (FEV1), exhaled nitric oxide fraction (FE_NO), and airway responsiveness to methacholine (PD₂₀₀) between budesonide (BUD) and budesonide/formoterol (BUD/FM).BUD/FM therapy significantly improved the ACQ score at week 2 and week 4 (p < 0.01 and p < 0.05), and increased FEV1 and the methacholine threshold at week 8 and week 24 (all p < 0.05) compared to BUD alone. A logistic function model showed that the BUD/FM combination significantly improved ACQ, FEV1, FE_NO and PD₂₀₀ at a faster rate than BUD over 24 weeks (p < 0.001 for ACQ, FEV1, PD₂₀₀, and p < 0.05 for FE_NO, z-test). A significant variance in the time-response was also found in the outcomes of the two treatment groups (FE_NO and ACQ > FEV1 and PD₂₀₀, p < 0.001, z-test).The present study provides evidence that ICS/LABA combination therapy results in a more rapid improvement in asthma symptoms, lung function, and airway inflammation compared to ICS monotherapy in steroid-naive patients with asthma.     

Efficacy and safety of budesonide/formoterol compared with salbutamol in the treatment of acute asthma

This study compared the efficacy and safety of budesonide/formoterol (Symbicort) Turbuhaler)) with salbutamol pressurized metered-dose inhaler (pMDI) with spacer for relief of acute bronchoconstriction in patients with asthma. In this randomized, double-blind, parallel-group study, patients (n = 104 allocated to treatment; n = 103 received treatment; mean age 45 years) seeking medical attention for acute asthma (mean FEV(1) 43% of predicted) received two doses repeated at t = -5 and 0 min of either budesonide/formoterol (320/9 microg, two inhalations) or salbutamol (100 microg x eight inhalations); total doses 1280/36 microg and 1600 microg, respectively. All patients received prednisolone 60 mg at 90 min and FEV(1) was assessed over 3h. FEV(1) 90 min after dosing (primary variable) increased compared with pre-dose FEV(1) by an average of 30% and 32% for budesonide/formoterol and salbutamol, respectively (P = 0.66), with similar increases at all timepoints from 3 to 180 min for both groups. Mean pulse rate over 3h was significantly higher in the salbutamol group versus the budesonide/formoterol group (92 vs. 88 bpm; P < 0.01). No treatment differences were seen for other vital signs, including ECG. High-dose budesonide/formoterol was effective and well tolerated for the treatment of acute asthma, with rapid onset of efficacy and a safety profile over 3h similar to high-dose salbutamol.