High-Dose Inhaled Budesonide May Substitute for Oral Therapy After an Acute Asthma Attack

Patients attending the emergency room with acute asthma, participating in a study comparing salbutamol (albuterol in the United States) via a dry powder inhaler (Turbuhaler®) with pressurized metered-dose inhaler (pMDI), were included in this 1-week follow-up study with the aim of assessing whether inhaled budesonide via Turbuhaler may be an alternative to prednisolone tablets after an acute asthma attack. Eighty-one patients with a mean age of 38 years and forced expiratory volume in 1 sec (FEV₁) of 64% predicted normal value after treatment with salbutamol were randomized in this double-blind, double-dummy, parallel-group study. The doses given were budesonide 1600 μg b.i.d. or prednisolone in daily doses from 40 mg (day 1) decreased to 5 mg (day 7). FEV₁ was recorded before and after the 7-day treatments and peak expiratory flow (PEF) morning and evening, clinical symptoms (visual analogue scale 0-100), and doses of rescue medication (terbutalineTurbuhaler 0.25 mg/dose) were recorded daily. The mean increase in FEV, from baseline to day 7 was 1 7.3% in the budesonide Turbuhaler group and 1 7.6% in the prednisolone group. Mean values of morning PEF increased from day 1 to day 7 by 67 L/min in the budesonide Turbuhaler group and by 57 L/min in the prednisolone group (not significant). There were no statistically significant differences between the groups in clinical symptoms and in the number of doses of rescue medication. Because of disease deterioration, five patients in the Turbuhaler group and three in the prednisolone group needed additional symptomatic as well as corticosteroid treatment. Inhaled budesonide in high doses may be a substitute for oral therapy as follow-up treatment after an acute asthma attack.     

Comparison of two budesonide powder inhalers,Easyhaler and Turbuhaler,in steroid-naïve asthmatic patients

The objective of this multicenter study was to compare the clinical efficacy, safety, and acceptability of Easyhaler and Turbuhaler for the delivery of budesonide 200 micrograms/dose twice daily in steroid-na?ve asthmatic patients. Three hundred and twenty-six newly diagnosed, steroid-na?ve adult patients with mild-to-moderate asthma were recruited into this randomized, double-blind, double-dummy, parallel-group study, comprising a 2-week run-in period and 8 weeks of treatment. Patients received budesonide inhalation powder 400 micrograms/day either via Easyhaler (n = 159) or via Turbuhaler (n = 167), plus salbutamol inhalation powder (100 micrograms/dose) via Easyhaler as rescue therapy. The study was completed by 292 patients: 143 in the Easyhaler group and 149 in the Turbuhaler group. The primary outcome variable, mean morning peak expiratory flow (PEF), improved significantly and almost similarly by 36.3 and 30.6 l/min, respectively, from run-in to weeks 7-8. At weeks 7-8, the mean (SE) difference in morning PEF between the two treatments was 7.1 (9.4) l/min (90% CI from -8.4 to 22.6) on per protocol analysis, which was within the defined limits for therapeutic equivalence. There were no significant differences between treatments in terms of secondary efficacy variables or adverse events. However, patients found Easyhaler more acceptable than Turbuhaler. The results show that budesonide via Easyhaler is clinically as effective as Pulmicort Turbuhaler when equal daily doses of budesonide are delivered to steroid-na?ve asthmatic patients. Moreover, patients found Easyhaler more acceptable than Turbuhaler, and a majority would prefer Easyhaler if given a choice.     

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.     

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone.

Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.     

Formoterol Turbuhaler as reliever medication in patients with acute asthma.

The aim of this study was to compare the efficacy and safety of formoterol versus salbutamol as reliever medication in patients presenting at an emergency dept with acute asthma. A randomised, double-blind, double-dummy, parallel group study was performed in four Australian emergency treatment centres. The study included a total of 78 adult patients (mean baseline forced expiratory volume in one second (FEV1) 1.83 L; 59% predicted) with acute asthma. Based on the expected dose equivalence of formoterol Turbuhaler 4.5 microg (delivered dose) and salbutamol pressurised metered-dose inhaler 200 microg (metered dose), patients received a total of formoterol Turbuhaler 36 microg (delivered) or salbutamol pressurised metered-dose inhaler with spacer 1,600 microg (metered), divided into two equal doses at 0 and 30 min. FEV1, peak expiratory flow and systemic beta2-agonist effects were monitored for 4 h. The primary variable was FEV1% pred at 45 min. At 45 min, mean increases in FEV1 expressed in % pred were 6.6% and 9.3%, respectively, with a small adjusted mean difference in favour of salbutamol (3.0%, 95% confidence interval -2.0-8.0). Transient increases in systemic beta2-agonist effects occurred predominantly with salbutamol, although no significant treatment differences were observed. Eight patients discontinued due to adverse events. In this study of patients presenting at emergency depts with acute asthma, formoterol Turbuhaler 36 microg was well tolerated and, as rescue therapy, had an efficacy that was not different from that of salbutamol pressurised metered-dose inhaler with spacer 1,600 microg in the number of patients studied.     

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.     

Salmeterol/fluticasone propionate combination therapy 50/250 microg twice daily is more effective than budesonide 800 microg twice daily in treating moderate to severe asthma

Three hundred and fifty-three asthmatic patients who remained symptomatic despite treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized to a new combination therapy comprising salmeterol 50 microg and fluticasone propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of their morning and evening peak expiratory flow (PEF), daytime and night-time symptom scores and daytime and night-time use of rescue salbutamol. Mean morning PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1) (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P < 0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided significantly better control of daytime symptoms and a significantly greater reduction in the requirement for rescue salbutamol compared with budesonide. These results demonstrate that SFC 50/250 microg twice daily is superior to budesonide 800 microg twice daily in the management of patients with moderate to severe asthma who are symptomatic on their existing dose of corticosteroid.     

Efficacy and Tolerability of Budesonide Clickhaler® and Turbuhaler® in Adult Asthma

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler® or Turbuhaler® dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (≤ 1600 µg/day) via either Clickhaler (n = 110) or Turbuhaler (n = 112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting β₂-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of ? 2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval ? 7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.     

Efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI in Japanese patients with moderately persistent asthma

OBJECTIVE: The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler with that of beclomethasone dipropionate (BDP) pMDI. METHODOLOGY: Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (< 80% predicted normal)), taking BDP via pressurized metered-dose inhaler (pMDI), 400 microg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 microg or 400 microg twice daily via Turbuhaler or continued treatment with BDP, 100 microg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials. RESULTS: At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 microg and 800 microg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 microg budesonide and 400 microg BDP treatment in the effect on PEF (P = 0.29), but 800 microg budesonide was significantly superior to BDP (P < 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P < 0.001). All treatments were well tolerated. CONCLUSION: Budesonide Turbuhaler (200 microg) was as effective as 400 microg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 microg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose-response curve. Without that information, comparative studies are usually inconclusive.     

A double-blind, placebo-controlled dose-response study with budesonide Turbuhaler in Japanese asthma patients. Japanese Pulmicort Turbuhaler study group

OBJECTIVE: The aim of this study was to investigate the dose-response for inhaled budesonide via Turbuhaler in Japanese patients with mild to moderate asthma. METHODOLOGY: Inhaled budesonide 100 microg, 200 microg, 400 microg or placebo was administered twice daily via Turbuhaler for 6 weeks, to 267 adult Japanese patients (mean age 51 years) with mild-to-moderate, non-steroid-dependent bronchial asthma, in a double-blind, placebo-controlled, randomized, parallel group study. The patients had to be symptomatic for more than 3 days/week and have an average morning peak expiratory flow (PEF) 50-80% of predicted normal value. RESULTS: The response to budesonide was rapid, all treatments showing a significant improvement in morning PEF after 1 week (P<0.05). During week 6, mean improvements of 15, 45, 53 and 71 L/min were observed for the placebo, 200 microg, 400 microg and 800 microg budesonide groups, respectively. Compared with placebo all improvements in the budesonide groups were statistically significant and a significant dose-response was demonstrated (P<0.001). The difference between the 200 microg and 800 microg doses was significant. Also, for several secondary efficacy variables (e.g. evening PEF, symptom score, treatment score, daily activity score and sleep score) significant dose-responses were shown. Other variables included the investigators' assessments of improvement and usefulness. They also showed statistically significant dose-response relationships and confirmed the rapid onset of action. Budesonide was well tolerated at all tested doses, with a low incidence of adverse events, all of which were minor in severity. CONCLUSIONS: Budesonide Turbuhaler in the doses 100 microg to 400 microg twice daily was effective, well tolerated and showed a rapid onset of action in patients with mild-to-moderate asthma. Dose-response was demonstrated for several variables of clinical efficacy.     

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.     

Efficacy and Tolerability of Budesonide Clickhaler® and Turbuhaler® in Adult Asthma

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler® or Turbuhaler® dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (≤ 1600 µg/day) via either Clickhaler (n = 110) or Turbuhaler (n = 112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting β₂-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of - 2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval - 7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.     

Efficacy of nebulized fluticasone propionate compared with oral prednisolone in children with an acute exacerbation of asthma

The aim of the present study was to investigate the efficacy and safety of nebulized fluticasone propionate (FP Nebules) compared with oral soluble prednisolone in children with an acute exacerbation of asthma. The study used an international, multi-centre, randomized, double-blind, parallel group design. Three hundred and twenty-one patients, aged 4-16 years old, who presented with an acute exacerbation of asthma, were randomly allocated to either nebulized FP (1 mg b.d.) or oral prednisolone (2 mg kg(-1) day(-1) for 4 days then 1 mg kg(-1) day(-1) for 3 days) for 7 days. Patients in the FP group showed a significantly greater increase in diary card morning peak expiratory flow (PEF) over 7 days compared with patients in the prednisolone group (difference = 9.51 min(-1), CI = 2.1, 16.8, P = 0.034). Similar increases for both treatments were shown for evening PEF. Clinic PEF improved with both treatments, but was significantly greater in patients taking FP after 7 days (difference = 11.41 min(-1), CI = 2.8, 20.0, P = 0.029). Both treatments reduced symptom scores to a similar extent. The two treatments were well tolerated, and there was no difference in the incidence of adverse events. The present study demonstrated that nebulized FP is at least as effective as oral prednisolone in the treatment of children presenting with an acute exacerbation of asthma.     

Efficacy of once- and twice-daily administration of budesonide via Turbuhaler as initial therapy in patients with mild persistent asthma.

Inhaled glucocorticosteroids such as budesonide have an important role in the management of asthma. Although these agents have traditionally been given twice daily, evidence is accumulating that once-daily treatment may be as effective as twice-daily administration. The efficacy of budesonide Turbuhaler (Astra, Lund, Sweden), 400 micrograms once daily in the evening or 200 micrograms twice daily, was compared in a randomized, double-blind study involving 181 patients (75 men, 106 women; mean age 30.8 years) with mild asthma [mean forced expiratory volume in 1 s (FEV1) 92.8% pred.] who had not previously been treated with inhaled glucocorticosteroids. After a 2-week run-in period, patients were randomized to either regimen and treated for 6 weeks. This was followed by two 8-week open treatment periods, during which all patients received budesonide Turbuhaler, 200 micrograms once daily during the first period and 100 micrograms once daily during the second period. The mean change in morning peak expiratory flow (PEF) during the double-blind treatment period was 16.9 l min-1 in patients receiving once-daily treatment and 17.2 l min-1 in those receiving twice-daily treatment. Similarly, there were no significant differences in evening PEF, symptom scores, bronchodilator use or spirometry data between patients receiving once- and twice-daily treatments. The improvements in morning PEF, symptom scores and bronchodilator use seen during the double-blind treatment period were maintained during the two open treatment periods. It is concluded that once-daily treatment with budesonide Turbuhaler is as effective as an initial therapy twice-daily treatment in patients with mild persistent asthma and that the initial dose can be reduced to maintenance levels (including 100 micrograms) without loss of asthma control.     

Clinical equivalence trial on budesonide delivered either by the Novolizer multidose dry powder inhaler or the Turbuhaler in asthmatic patients

BACKGROUND AND OBJECTIVES: To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer, i.e. a multidose dry powder inhaler, or by the Pulmicort Turbuhaler in asthmatic patients in terms of efficacy, safety and tolerability during a 12-week treatment. METHODS: A total of 315 patients were randomised in this open, multicentre study. Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity (ranging from 60% to a maximum of 90% predicted FEV(1)), need for anti-inflammatory therapy, inhalation of beta(2)-sympathomimetics on an as needed to regular basis, reversibility of airway obstruction of >12% after inhalation of 2 actuations of 100 microg salbutamol. Primary variable was FEV(1), secondary were other pulmonary function test variables, PC(20)FEV(1) for histamine challenge, morning and evening PEFR, salbutamol usage, asthma symptoms, reactions after inhalation, standard safety variables. RESULTS: The comparison of the FEV(1) at study endpoint indicated that the Novolizer was at least as efficacious as the Turbuhaler (p < 0.001). All other variables of the pulmonary function tests as well as the asthma symptoms, nocturnal awakenings, PEFR measurements, or salbutamol usage indicated no relevant difference. Only 1 patient (Turbuhaler discontinued prematurely due to lack of efficacy. None of the other safety variables (adverse events, laboratory variables, vital signs, etc.) indicated any difference between the groups. CONCLUSIONS: The budesonide Novolizer is therapeutically equivalent to the Pulmicort Turbuhaler for the long-term treatment of patients with mild to moderate persistent asthma.     

Budesonide turbuhaler delivered once daily improves health-related quality of life in adult patients with non-steroid-dependent asthma.

Budesonide inhalation powder via the dry-powder multidose inhaler Turbuhaler (budesonide Turbuhaler) has been shown to improve lung function and symptoms in adults with asthma. In this double-blind, placebo-controlled, multicenter trial, we evaluated the effects of once-daily budesonide Turbuhaler on health-related quality of life (HRQL) in 177 adults (aged 18-70 years) with non-steroid-dependent asthma. Patients were randomized to receive budesonide Turbuhaler (400 micrograms) once daily or placebo for 12 weeks. HRQL was assessed at baseline and weeks 4 and 12 using the Asthma Quality of Life Questionnaire (AQLQ). In addition to assessment based on the four AQLQ domains (activity limitations, asthma symptoms, emotional function, and response to exposure to environmental stimuli), AQLQ overall scores were analyzed for both treatment groups. Compared with placebo, patients using budesonide Turbuhaler once daily had statistically significant (p < 0.001) improvements from baseline to weeks 4 and 12 in AQLQ overall scores. Statistically significant improvements from baseline to weeks 4 and 12 in all four individual domains also were observed in the budesonide Turbuhaler group compared with placebo. Differences between the two treatment groups in mean changes from baseline in AQLQ overall, asthma symptoms, and emotional function reached the level required for patients to achieve a minimal important difference of change (> or = 0.5 U) at week 12. A retrospective analysis of the data showed that approximately 70% of patients treated with budesonide Turbuhaler experienced a minimal important difference of change in AQLQ overall scores. Overall, improvements in AQLQ correlated significantly (p < or = 0.04) with improvements in forced expiratory volume in 1 second, morning peak expiratory flow measurements, asthma symptoms, and breakthrough bronchodilator use at the study end. Thus, patients with corticosteroid-na?ve asthma can experience improved HRQL when using budesonide Turbuhaler.     

Efficacy and safety of a new pressurised metered-dose inhaler formulation of budesonide/formoterol in children with asthma: a superiority and therapeutic equivalence study

AIM: This paediatric asthma study evaluated the efficacy and safety of a novel hydrofluoroalkane pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol versus budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI). METHODS: The study was a 12-week, multinational, double-blind trial involving children (aged 6-11 years) with symptomatic asthma on inhaled corticosteroids (375-1000 microg/day), with a history of exercise-induced bronchoconstriction and peak expiratory flow (PEF) > or =50% of predicted. Patients were randomised (two inhalations twice daily) to budesonide pMDI 100 microg, budesonide/formoterol DPI 80/4.5 microg or budesonide/formoterol pMDI 80/4.5 microg. The primary endpoint was change from baseline in morning PEF. RESULTS: Overall, 622 patients were randomised. Increases in morning PEF with budesonide/formoterol pMDI and budesonide/formoterol DPI were therapeutically equivalent (29.5 versus 30.2l/min, respectively; 95% confidence interval: -6.0 to 4.6; P=0.78, also confirmed by per-protocol analysis). Improvements in secondary efficacy endpoints with both budesonide/formoterol formulations were not significantly different. Significantly greater improvement was achieved with budesonide/formoterol pMDI versus budesonide pMDI for morning PEF (+9.6l/min; P<0.001) and other lung function parameters. The safety profile of budesonide/formoterol pMDI was favourable and similar to that of budesonide/formoterol DPI and budesonide pMDI. CONCLUSION: Budesonide/formoterol, administered via the therapeutically equivalent hydrofluoroalkane pMDI or DPI, is an effective and well-tolerated treatment for children with asthma.     

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.     

Effects of 4-week treatment with low-dose budesonide (100 micrograms BID) from a novel inhaler Airmax and from a conventional inhaler on bronchial hyper-responsiveness,lung function and symptoms in patients with mild asthma

This study investigated the effect of low dose of budesonide 100 micrograms b.d from a new multi-dose dry powder inhaler (Airmax) and from a conventional inhaler (Turbuhaler) on bronchial hyper-responsiveness, lung function and asthma symptoms in mild stable asthmatics. Twenty-five patients were enrolled into a double-blind double-dummy crossover study with two 4-week treatment periods separated by a 4-week washout. Patients had a mean forced expiratory volume in 1 s (FEV1) of 91 +/- 13% predicted, had previously received inhaled short-acting beta 2-agonists only and had a PC20 to adenosine 5' monophosphate (AMP) < 40 mg/ml. PC20 AMP was assessed at baseline, and at the start and end of each treatment period. Patients recorded peak expiratory flow and symptoms throughout the study. There was a mean increase in PC20AMP from start to end of 3.49 doubling dilutions (DD) in the Airmax group and 2.90 DD in the Turbuhaler group. The difference was 0.60 DD (95% CI--0.47, 1.69) favouring Airmax and the upper limit exceeded the equivalence limit of +/- 1 DD. There were similar improvements in FEV1, daily PEF and symptoms in both groups. The majority of patients preferred treatment with Airmax to Turbuhaler (64 vs. 23%). Both treatments were equally well tolerated. In conclusion, 100 micrograms budesonide bid during 4 weeks from Airmax effectively attenuates the response to AMP in mild asthmatics. Overall Airmax offers equal clinical benefit to Turbuhaler.     

Formoterol used as needed in patients with intermittent or mild persistent asthma

OBJECTIVE: To study the effectiveness and safety of as-needed treatment of formoterol compared with the short-acting alternative terbutaline. METHODS: Two double-blind, 12-month, parallel-group, non-inferiority trials comparing as-needed use of formoterol (Oxis) 4.5 microg and terbutaline (Bricanyl) 0.5 mg via dry-powder inhaler (Turbuhaler), one in 675 patients with intermittent and one in 455 patients with mild persistent asthma, overall 6-87 years of age. Peak expiratory flow (PEF), symptoms, rescue medication use, exacerbations, airway responsiveness (metacholine challenge; subgroup of 127 patients), systemic effects (high single-dose test; subgroup of 87 patients), and safety (adverse events) were assessed. RESULTS: Formoterol 4.5 microg was as effective as terbutaline 0.5 mg with regard to morning PEF (non-inferiority; lower 95% confidence interval limit above -10 L/min). Metacholine sensitivity, exacerbation rates or use of rescue medication did not differ between treatments. Formoterol 54 microg was shown to give less systemic effects than terbutaline 6 mg. Both treatments were safe and well tolerated. CONCLUSIONS: Formoterol 4.5 microg used as needed was at least as effective and safe as terbutaline 0.5 mg used as needed in intermittent and mild persistent asthma, and was associated with less systemic effects when administered as high single doses.