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.     

Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option?

This 12-month dose-titration study assessed the effectiveness of budesonide/formoterol for maintenance plus relief with a control group using salmeterol/fluticasone for maintenance plus salbutamol for relief. Adolescents and adults (n = 2,143; mean forced expiratory volume in one second (FEV1) 73% predicted; mean inhaled corticosteroid (ICS) 884 microg.day(-1)) were randomised to budesonide/formoterol 160/4.5 microg two inhalations b.i.d. plus additional inhalations as needed, or salmeterol/fluticasone 50/250 microg b.i.d. plus salbutamol as needed. Treatment was prescribed open label; after 4 weeks, physicians could titrate maintenance doses in accordance with normal clinical practice. Maintenance plus as-needed budesonide/formoterol prolonged the time to first severe exacerbation versus salmeterol/fluticasone (25% risk reduction). The total number of severe exacerbations was significantly reduced in the budesonide/formoterol group (255 versus 329). Both regimens provided sustained improvements in symptoms, as-needed use, quality of life and FEV1, with differences in favour of the budesonide/formoterol group for as-needed use (0.58 versus 0.93 inhalations.day(-1)) and FEV1 (post-beta2-agonist values). Mean ICS dose during treatment was similar in both groups (653 microg budesonide.day(-1) (maintenance plus as-needed) versus 583 microg fluticasone.day(-1)). The simplified strategy using budesonide/formoterol for maintenance and reliever therapy is feasible, safe and at least as effective as salmeterol/fluticasone plus salbutamol.     

Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial

STUDY OBJECTIVE: To compare a novel asthma management strategy--budesonide/formoterol in a single inhaler for both maintenance therapy and symptom relief--with a higher dose of budesonide plus as-needed terbutaline. METHODS: This was a 6-month, randomized, double-blind, parallel-group study in patients with mild-to-moderate asthma (n = 697; mean age, 38 years [range, 11 to 79 years]; mean baseline FEV1, 75% of predicted; mean inhaled corticosteroid [ICS] dosage, 348 microg/d). Following a 2-week run-in period, all patients received two blinded, dry powder inhalers, one containing maintenance medication and one containing medication to be used as needed for the relief of symptoms. Patients were randomized to receive either budesonide/formoterol (80 microg/4.5 microg, two inhalations qd) for maintenance plus additional inhalations as needed for symptom relief, or budesonide (160 microg, two inhalations qd) for maintenance medication plus terbutaline (0.4 mg) as needed. The primary efficacy variable was morning peak expiratory flow (PEF). RESULTS: Patients receiving budesonide/formoterol showed greater improvements in morning PEF than patients receiving budesonide (increases of 34.5 L/min vs 9.5 L/min, respectively; p < 0.001). The risk of having a severe exacerbation (hospitalization/emergency department [ED] treatment, oral steroids for asthma, or a > or = 30% decrease from baseline in morning PEF on 2 consecutive days) was 54% lower with budesonide/formoterol vs budesonide (p = 0.0011). Budesonide/formoterol patients experienced 90% fewer hospitalizations/ED treatments due to asthma than budesonide patients (1 vs 10, respectively; p = 0.026). The increased efficacy with budesonide/formoterol was achieved with less ICS than was used in the budesonide group (mean dose, 240 microg/d vs 320 microg/d, respectively) and with 77% fewer oral steroid treatment days vs budesonide (114 days vs 498 days, respectively). Both treatments were well tolerated. CONCLUSIONS: Budesonide/formoterol for both maintenance and relief improves asthma control with a lower steroid load compared with a higher dose of budesonide plus terbutaline.     

Budesonide/formoterol in a single inhaler rapidly relieves methacholine-induced moderate-to-severe bronchoconstriction

Inhalers containing corticosteroids and long-acting beta2-agonists are becoming increasingly important in asthma management. A rapid effect is important to patients, particularly during exacerbations. We compared the onset of bronchodilation and patient-perceived relief from dyspnoea following single-inhaler budesonide/formoterol or salmeterol/fluticasone in a model of acute bronchoconstriction. A randomised, double-blind, double-dummy, single-dose, crossover study included 27 outpatients with asthma (mean age 35 years; mean FEV1 90% predicted normal). Immediately following methacholine-induced bronchoconstriction (fall in FEV1 > or = 30%), patients inhaled budesonide/formoterol (160/4.5 microg, 1 or 2 inhalations; Symbicort Turbuhaler), salmeterol/fluticasone (50/250 microg; Seretide Diskus) or placebo on 4 study days. Lung function and Borg score were assessed for 30 min. During methacholine-induced provocation (final mean FEV1 62.5% of baseline), mean Borg score increased 10-fold (from 0.3 to 3.0 units). Hereafter, mean FEV1 at 3 min improved significantly more after budesonide/formoterol 1 and 2 inhalations (37 and 38%, respectively) than after salmeterol/fluticasone (23%; P < 0.001) or placebo (10%; P < 0.001). Median recovery times to 85% of baseline FEV1 were shorter for budesonide/formoterol (1 or 2 inhalations: 3.3 and 2.8 min, respectively) than salmeterol/fluticasone (8.9 min; P < 0.001) and placebo (> 30 min). One min after budesonide/formoterol, dyspnoea was significantly reduced (Borg score -0.86 units, both doses) compared with salmeterol/fluticasone (-0.55 units; P < 0.05) and placebo (-0.23 units; P < 0.001). Budesonide/formoterol provides immediate bronchodilation, faster than salmeterol/fluticasone, which patients can feel during acute methacholine-induced bronchoconstriction.     

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).     

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.     

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.     

Formoterol (OXIS) Turbuhaler as a rescue therapy compared with salbutamol pMDI plus spacer in patients with acute severe asthma

Formoterol has a similar onset of effect to salbutamol but a prolonged duration of action. However, the relative efficacy of the two drugs in acute severe asthma is not known. This double-blind, double-dummy study compared the safety and efficacy of the maximum recommended daily dose of formoterol and a predicted equivalent dose of salbutamol in 88 patients presenting to the emergency department with acute severe asthma. Patients were randomized to formoterol 54 microg via Turbuhaler or salbutamol 2400 microg via pressurized metered dose inhaler (pMDI) plus spacer in three equal doses over 1 h. Following the full dose, mean FEV1 at 75 min increased by 37% for formoterol and 28% for salbutamol (P = 0.18). The maximum increase in FEV1 over 4 h was significantly greater with formoterol compared with salbutamol (51% vs. 36%, respectively P < 0.05) and formoterol was as effective as salbutamol at improving symptoms and wellbeing. Both treatments were well tolerated. Formoterol caused a greater decrease in serum potassium (difference -0.2 mmol/l). In severe acute asthma, bronchodilator therapy with high-dose (54 microg) formoterol Turbuhaler provided equally rapid improvements in lung function of greater magnitude over 4 h than high-dose (2400 microg) salbutamol pMDI plus spacer.     

Onset of bronchodilation of budesonide/formoterol vs. salmeterol/fluticasone in single inhalers

Combinations of inhaled glucocorticoids and long-acting beta2-agonists in the same inhaler device have become available in recent years. In this double-blind, randomized, placebo-controlled and crossover study we have evaluated the onset of action of budesonide and formoterol in a single inhaler (Symbicort Turbuhaler) and that of the fixed combination of salmeterol and fluticasone (Seretide Diskus). Thirty patients with a mean FEV1 of 2.54 l (range: 1.48-4.28) and a mean inclusion reversibility in FEV1 of 19.1% were included. Single doses of budesonide/formoterol 160/4.5 microg and 2x (160/4.5) microg, salmeterol/fluticasone 50/250 microg, or placebo were given. Serial measurements of FEV1 were performed over 3 h. The combination of one or two inhalations of budesonide/formoterol showed a faster onset of action than salmeterol/fluticasone, both evaluated as mean FEV1 at 3 min (2.74, 2.75 and 2.56 l respectively P<0.001 for both doses of budesonide/formoterol), or as average FEV1 from 0 to 15 min (2.80, 2.83 and 2.67 l respectively P<0.001 for both doses of budesonide/formoterol). For placebo, mean FEV1 at 3 min was 2.46 l, and the average FEV1 at 0-15 min was 2.50 l. Furthermore, budesonide/formoterol at both doses resulted in higher FEV1 than salmeterol/fluticasone at 3 h. We conclude that the combination of budesonide/formoterol has a faster onset of action than salmeterol/fluticasone.     

Safety and tolerability of high-dose formoterol (Aerolizer) and salbutamol (pMDI) in patients with mild/moderate, persistent asthma

This double-blind, double-dummy, crossover study evaluated the tolerability of high-dose formoterol and salbutamol. Sixteen adults with mild/moderate persistent asthma (FEV1 > or = 70% predicted) were randomized to receive either formoterol 36 microg three times daily (TID) at 5-h intervals via Aerolizer (total daily dose 108 microg), or salbutamol 600 microg TID via pressurized metered-dose inhaler (total daily dose 1800 microg) for 3 consecutive days. After a 3-7-day washout period patients received the other treatment. FEV1 was measured 15 min pre-dose and 2 h post-dose. Both formoterol and salbutamol were associated with decreased plasma potassium (mean of minimum values: 3.4 and 3.6 mmol/L, respectively; P<0.001), increased serum glucose (mean of maximum values: 8.3 and 7.9 mmol/L, respectively; P=0.021), and small increases in mean QTc interval (mean of maximum values: 428.8 and 417.4 ms, respectively; P<0.001). However, none of these effects was clinically significant. Both treatments increased FEV1 to a mean maximum of 4.6 L (P=0.613), but the mean FEV1 AUC(0-72)h for formoterol was significantly greater than for salbutamol (302.2 L h, vs. 277.4 L h; P<0.001). No patients discontinued due to treatment-related adverse events. High-dose formoterol via Aerolizer did not produce any clinically significant systemic effects in patients with mild/moderate asthma.     

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.     

Adjustable maintenance dosing with budesonide/formoterol or budesonide: double-blind study

Adjustable maintenance dosing with either budesonide/formoterol or budesonide was compared in asthma patients. This double-blind trial randomized 133 patients (mean forced expiratory volume in 1s 66% predicted) to receive 2 inhalations twice daily of budesonide/formoterol 160/4.5 microg (640/18 microg/day) or budesonide 320 microg (1280 microg/day) for 4 weeks. The study drug was adjusted in both groups according to symptoms to 2-4 inhalations daily during Weeks 5-8 and 1-4 inhalations daily during Weeks 9-20. Asthma was well controlled in both groups, with minimal levels of treatment failure (5 budesonide/formoterol vs. 2 budesonide patients; P=NS) and minimal use of reliever therapy. Clinically important improvements in health-related quality of life (HRQL) occurred in the physical functioning and emotional role functioning domains (both P<0.05) for the budesonide/formoterol group compared with budesonide. Physician and patient treatment satisfaction favored budesonide/formoterol (both P<0.05). Budesonide/formoterol patients used fewer daily inhalations of study drug (P=0.024). The median average daily inhaled corticosteroid dose during the study was 448 microg with budesonide/formoterol and 1152 microg with budesonide. Adjustable maintenance dosing with budesonide/formoterol and budesonide resulted in high levels of asthma control. Adjustable budesonide/formoterol treatment achieved greater HRQL benefits and patient satisfaction, with lower overall drug use.     

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 following formoterol Turbuhaler and salbutamol pMDI in reversible chronic airway obstruction

Short-acting beta(2)-agonists are currently recommended for symptom relief in asthma and the treatment of mild, acute exacerbations in COPD. However, formoterol has as fast an onset of action as salbutamol with the additional benefit of longer-lasting bronchodilation (approximately 12 h). Furthermore, systemic side effects observed with formoterol are of a similar duration but less pronounced than with short-acting beta(2)-agonists. In this double-blind, randomized, cross-over study, 20 adult patients with reversible chronic airway obstruction (intrinsic asthma or COPD) inhaled single doses of formoterol 9 microg or salbutamol 100 microg (group A) or formoterol 18 microg or salbutamol 200 microg (group B). FEV(1) was measured prior to and 5, 10, 15, 20, 25 and 30 min following inhalation of study drug. No significant differences in FEV(1) values were observed between group A (P=0.704) or group B (P=0.270) at baseline, or at 5 (Group A: P=0.340; Group B: P=0.559) and 15 min (Group A: P=0.526; Group B: P=0.818) post dose. No adverse events were reported during the study. Formoterol Turbuhaler has as rapid an onset of action as salbutamol pMDI when given at the recommended doses.     

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.     

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.     

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.     

Comparison of the lung function change in patients with COPD and bronchial asthma before and after treatment with budesonide/formoterol

Objective

This study investigated the rapid onset of bronchodilation effect and compared lung function changes following budesonide/formoterol (Symbicort Turbuhaler®) inhalation in Chinese patients with moderate-severe chronic obstructive pulmonary disease (COPD) and bronchial asthma.

Methods

In this open-label, parallel-group clinical study, patients eligible for study were divided into COPD group (n=62, mean age 68.16±8.75 years) and asthma group (n=30, mean age 45.80±12.35 years). Lung function tests (include FEV1, FVC, FEV1/FVC, and IC) were performed at baseline (t=0 min time point, value before inhalation of budesonide/formoterol), and then eligible patients received two inhalations of budesonide/formoterol (160/4.5 μg). Lung function tests were reassessed at t=3, 10 and 30 min time point. The primary end-point was lung function change 3 min after drug inhalation, and the secondary end-points were comparison of the gas flow rate (ΔFEV1) and volume responses (ΔFVC, ΔIC) between COPD and asthma patients after inhalation of budesonide/formoterol.

Results

Compared with the baseline, all patients significantly improved their lung function (included FEV1, FVC, FEV1/FVC, and IC) at 3 min (P<0.05). Greater bronchodilation efficacy was found in the asthma group compared with the COPD group (P<0.05). In the asthmatic patients, the curves of FEV1, FVC, FEV1/FVC, IC, showed improvement with an ascending trend at all time points from 3 to 30 min. Whereas in the COPD patients, only the curves of FEV1, FVC, IC showed similar pattern. We found that ΔFVC was significantly higher than ΔFEV1 in both groups (P<0.05), but no significant difference between ΔIC and ΔFEV1 (P>0.05). Compared with COPD group, asthma group had higher level of ΔFEV1 and ΔIC (P<0.05), but no significant difference for ΔFVC can be found.

Conclusions

Budesonide/formoterol has a fast onset of bronchodilation effect in patients with moderate-severe COPD and asthma. Greater efficacy was found in the asthma group compared with the COPD group. The gas flow rate and volume responses in patients with COPD differ from those with asthma after inhalation of Budesonide/formoterol.KEY WORDS : Budesonide/formoterol, chronic obstructive pulmonary disease, bronchial asthma, lung function testChronic obstructive pulmonary disease (COPD) and bronchial asthma (asthma) have important similarities and differences. Both are chronic inflammatory diseases that cause airflow limitation (1,2). However, there are great difference between the two in terms of genetic basis, idiosyncratic reaction, airway hyper-responsiveness, inflammatory mediators and response to the treatment (3). There is neither study about the rapid onset of effect of ICS/LABA combination therapy (budesonide/formoterol) in China nor report about the differences of lung function change before and after treatment between patients with COPD and asthma all over the world.It is traditionally thought that the responses in bronchodilatation test of asthma and COPD are “gas flow rate responses” and “volume responses” respectively (1). But yet no report about the “gas flow rate responses” and “volume responses” of ICS/LABA such as budesonide/formoterol in patients with COPD and asthma is available.In this trial, we will determine the rapid onset of effect of budesonide/formoterol in patients with COPD and asthma by testing the lung function in several time points in a short time. In addition, we will discuss the differences of the gas flow rate and volume responses in patients with asthma and COPD after budesonide/formoterol inhalation.     

Bronchodilator response to albuterol after regular formoterol and effects of acute corticosteroid administration

BACKGROUND: There is controversy about the development of bronchodilator subsensitivity after regular administration of long-acting beta(2)-agonists. OBJECTIVES: The purpose of the study was to evaluate whether regular treatment with formoterol affects the bronchodilator response to repeated puffs of albuterol, and also to assess the effects of acute administration of a bolus dose of IV or inhaled corticosteroid. MATERIALS AND METHODS: Twelve patients (mean [SD] age, 43 [15] years; FEV(1), 57 [17] % predicted) with stable, moderate to severe persistent asthma who were all taking inhaled corticosteroids were evaluated in a randomized, placebo-controlled, double-blind, double-dummy, crossover study. Patients received treatments each for 2 weeks followed by a bolus (IV/inhaled) of corticosteroid or placebo: (1) placebo inhaler bid + bolus placebo; (2) formoterol Turbuhaler 24 microg metered dosage bid (delivered dosage 18 microg bid) + placebo; (3) formoterol 24 microg bid + bolus IV hydrocortisone, 200 mg; or (4) formoterol 24 microg bid + bolus inhaled budesonide, 1,600 microg. Bronchodilator response to repeated puffs of albuterol (200 to 1,600 microg) for > 80 min was measured at 2 h after bolus administration of placebo or corticosteroid. The study was powered at the 80% level to detect a 20% difference in area under curve between 20 and 80 min (AUC) for FEV(1) response to albuterol as change from baseline (primary end point). RESULTS: There was significant subsensitivity (p = 0.01) of the mean albuterol FEV(1) response (as AUC, L x s) after formoterol alone (737) as compared to placebo (1,453) along with partial reversal by steroid administration: formoterol + hydrocortisone (1, 050), and formoterol + budesonide (942). There was a similar pattern of subsensitivity (p = 0.03) for the mean albuterol forced expiratory flow between 25% and 75% of vital capacity response (as AUC, L): placebo (2,149), formoterol alone (1,002), formoterol + hydrocortisone (1,402), and formoterol + budesonide (1,271). CONCLUSION: Regular treatment with formoterol produced significant bronchodilator subsensitivity to repeated puffs of albuterol, which was partially reversed by a bolus dose of systemic or inhaled corticosteroid.     

Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort) 160/4.5 microg (delivered dose), budesonide 200 microg (metered dose), formoterol 4.5 microg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever beta2-agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever beta2-agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.