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Mario Cazzola - One of the best experts on this subject based on the ideXlab platform.
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Interaction between aclidinium bromide and Formoterol fumarate in small human airways
European Respiratory Journal, 2014Co-Authors: Mario Cazzola, L Calzetta, Clive P. Page, Paola Rogliani, Francesco Facciolo, Amadeu Gavaldà, Maria Gabriella MateraAbstract:Background Combining a long-acting β 2 -agonist (LABA) with a long-acting muscarinic antagonist (LAMA) may improve chronic obstructive pulmonary disease therapy. Aim To investigate the synergistic interaction of aclidinium (LAMA) and Formoterol (LABA) in small human bronchi. Methods Precision cut lung slices (PCLSs) from 8 patients were incubated inKrebs-Henseleit solution (37°C) aerated with O 2 /CO 2 (95:5%). The concentration response to aclidinium and Formoterol, administered alone and in combination, at isoeffective concentrations, was assessed at sub-maximal contraction (70% maximum, EC 70 ) induced by acetylcholine (ACh). PCLS relaxation was expressed as % of maximal response (lumen area enhancement) induced by papaverine (E max ) and potency as the negative logarithm of IC 50 or EC 50 (pD 2 ). Drug mixture effects were analyzed by Bliss Independence theory. Values (n=3) are mean±SEM. Results Aclidinium and Formoterol induced potent concentration-dependent relaxation of PCLSs (pD 2 : aclidinium 7.9±0.3, Formoterol 8.4±0.3). Only Formoterol eliminated ACh-induced bronchiolar contraction (E max : Formoterol 99.0±5.6%, aclidinium 68.1±4.5%; p Aclidinium and Formoterol at low-to-high concentrations (aclidinium 3.2 nM–1.0 µM, Formoterol 1.0–63.0 nM) had a synergistic relaxant response on PCLSs, enhancing relaxation by +19.7±0.8% compared with the expected response (p Low concentrations (EC 30 ) of aclidinium with Formoterol induced significant (p Conclusions Aclidinium and Formoterol had a synergistic interaction on the lumen area enhancement of bronchioles, mainly at low concentrations.
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Rapid onset of bronchodilation with Formoterol/beclomethasone Modulite and Formoterol/budesonide Turbuhaler as compared to Formoterol alone in patients with COPD.
Pulmonary pharmacology & therapeutics, 2010Co-Authors: Mario Cazzola, Franco Pasqua, Luigi Ferri, Gianluca Biscione, Vittorio Cardaci, Maria Gabriella MateraAbstract:In the present study, we examined whether there is a difference in the onset of bronchodilatation between Formoterol/beclomethasone 12/200 μg Modulite and Formoterol/budesonide 9/320 μg Turbuhaler in patients with COPD. We enrolled 28 patients with stable COPD. Both Formoterol/beclomethasone and Formoterol/budesonide elicited a larger mean FEV₁-AUC₀₋₁₅min than Formoterol alone, whereas there was no significant difference between their FEV₁-AUC₀₋₁₅min. Also the change in FEV₁ 15 min after inhalation of Formoterol/beclomethasone combination or Formoterol/budesonide combination was greater than that induced by Formoterol alone. This study confirms the rapid effect of the inhaled corticosteroid component when combined with Formoterol and indicates that the onset of bronchodilation of Formoterol/beclomethasone Modulite and Formoterol/budesonide Turbuhaler are similar and greater than Formoterol alone in patients with COPD.
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Combination of Formoterol and Tiotropium in the Treatment of COPD: Effects on Lung Function
COPD, 2009Co-Authors: Mario Cazzola, Donald P. TashkinAbstract:Bronchodilators are central in symptomatic management of all stages of COPD. For patients whose COPD is not sufficiently controlled by monotherapy, combining an inhaled anticholinergic and a ss(2)-agonist is a convenient way of delivering treatment and obtaining better lung function and improved symptoms. Formoterol (beta(2)-agonist) and tiotropium (anticholinergic) are long-acting bronchodilators with different mechanisms of action. Formoterol has a fast onset and a bronchodilator effect of approximately 12 h, while tiotropium has a 24-h bronchodilator effect and is given once daily. Currently, there is no documentation that tiotropium is superior to Formoterol or the contrary, but a combination of tiotropium and Formoterol is more effective than single drugs alone in inducing bronchodilation and a bronchodilator-mediated symptom benefit in patients suffering from COPD. Once-daily or twice-daily Formoterol, added to tiotropium, are both better than tiotropium alone, but the published evidence suggests twice-daily Formoterol is the best add-on option.
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Bronchodilator response to Formoterol after regular tiotropium or to tiotropium after regular Formoterol in COPD patients.
Respiratory Medicine, 2004Co-Authors: Mario Cazzola, Paolo Noschese, Antonello Salzillo, Carlo De Giglio, Gennaro D'amato, Maria Gabriella MateraAbstract:Summary We conducted a randomized, crossover trial with tiotropium 18 μg once daily (group A), and Formoterol 12 μg twice daily (group B) over a 5-day period for each drug, with a 10-day washout, in 20 COPD patients. At the end of each period, patients inhaled both drugs separated by 180 min in alternate sequence (group A: tiotropium 18 μg+Formoterol 12 μg; group B: Formoterol 12 μg+tiotropium 18 μg). FEV 1 and FVC were measured at baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. FEV 1 and FVC further improved after crossover with both sequences. The mean maximal change in FEV 1 over baseline was 0.226 L (0.154–0.298) after tiotropium+Formoterol and 0.228 L (0.165–0.291) after Formoterol+tiotropium; the mean maximal change in FEV 1 over pre-inhalation the second drug value was 0.081 L (0.029–0.133) after tiotropium+Formoterol and 0.054 L (0.016–0.092) after Formoterol+tiotropium. The mean maximal change in FVC over baseline was 0.519 L (0.361–0.676) after tiotropium+Formoterol and 0.495 L (0.307–0.683) after Formoterol+tiotropium; the mean maximal change in FVC over pre-inhalation of the second drug value was 0.159 L (0.048–0.270) after tiotropium+Formoterol and 0.175 L (0.083–0.266) after Formoterol+tiotropium. The FEV 1 AUCs 0–360 min were 62.70 (45.67–79.74) after tiotropium+Formoterol and 69.20 (50.84–87.57) after Formoterol+tiotropium, the FEV 1 AUCs 0–180 min were 24.70 (18.19–31.21) after tiotropium+Formoterol and 29.74 (21.02–38.46) after Formoterol+tiotropium, whereas the FEV 1 AUCs 180–360 min were 15.70 (10.88–20.52) after tiotropium+Formoterol and 11.71 (7.21–16.21) after Formoterol+tiotropium. Differences between the two treatments were not statistically significant ( P >0.05). The addition of second different long-acting bronchodilator to a regularly administered long-acting bronchodilator seems to be to patient's advantage.
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Bronchodilator response to Formoterol after regular tiotropium or to tiotropium after regular Formoterol in COPD patients.
Respiratory Medicine, 2004Co-Authors: Mario Cazzola, Paolo Noschese, Antonello Salzillo, Carlo De Giglio, Gennaro D'amato, Maria Gabriella MateraAbstract:Summary We conducted a randomized, crossover trial with tiotropium 18 μg once daily (group A), and Formoterol 12 μg twice daily (group B) over a 5-day period for each drug, with a 10-day washout, in 20 COPD patients. At the end of each period, patients inhaled both drugs separated by 180 min in alternate sequence (group A: tiotropium 18 μg+Formoterol 12 μg; group B: Formoterol 12 μg+tiotropium 18 μg). FEV 1 and FVC were measured at baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. FEV 1 and FVC further improved after crossover with both sequences. The mean maximal change in FEV 1 over baseline was 0.226 L (0.154–0.298) after tiotropium+Formoterol and 0.228 L (0.165–0.291) after Formoterol+tiotropium; the mean maximal change in FEV 1 over pre-inhalation the second drug value was 0.081 L (0.029–0.133) after tiotropium+Formoterol and 0.054 L (0.016–0.092) after Formoterol+tiotropium. The mean maximal change in FVC over baseline was 0.519 L (0.361–0.676) after tiotropium+Formoterol and 0.495 L (0.307–0.683) after Formoterol+tiotropium; the mean maximal change in FVC over pre-inhalation of the second drug value was 0.159 L (0.048–0.270) after tiotropium+Formoterol and 0.175 L (0.083–0.266) after Formoterol+tiotropium. The FEV 1 AUCs 0–360 min were 62.70 (45.67–79.74) after tiotropium+Formoterol and 69.20 (50.84–87.57) after Formoterol+tiotropium, the FEV 1 AUCs 0–180 min were 24.70 (18.19–31.21) after tiotropium+Formoterol and 29.74 (21.02–38.46) after Formoterol+tiotropium, whereas the FEV 1 AUCs 180–360 min were 15.70 (10.88–20.52) after tiotropium+Formoterol and 11.71 (7.21–16.21) after Formoterol+tiotropium. Differences between the two treatments were not statistically significant ( P >0.05). The addition of second different long-acting bronchodilator to a regularly administered long-acting bronchodilator seems to be to patient's advantage.
Maria Gabriella Matera - One of the best experts on this subject based on the ideXlab platform.
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Interaction between aclidinium bromide and Formoterol fumarate in small human airways
European Respiratory Journal, 2014Co-Authors: Mario Cazzola, L Calzetta, Clive P. Page, Paola Rogliani, Francesco Facciolo, Amadeu Gavaldà, Maria Gabriella MateraAbstract:Background Combining a long-acting β 2 -agonist (LABA) with a long-acting muscarinic antagonist (LAMA) may improve chronic obstructive pulmonary disease therapy. Aim To investigate the synergistic interaction of aclidinium (LAMA) and Formoterol (LABA) in small human bronchi. Methods Precision cut lung slices (PCLSs) from 8 patients were incubated inKrebs-Henseleit solution (37°C) aerated with O 2 /CO 2 (95:5%). The concentration response to aclidinium and Formoterol, administered alone and in combination, at isoeffective concentrations, was assessed at sub-maximal contraction (70% maximum, EC 70 ) induced by acetylcholine (ACh). PCLS relaxation was expressed as % of maximal response (lumen area enhancement) induced by papaverine (E max ) and potency as the negative logarithm of IC 50 or EC 50 (pD 2 ). Drug mixture effects were analyzed by Bliss Independence theory. Values (n=3) are mean±SEM. Results Aclidinium and Formoterol induced potent concentration-dependent relaxation of PCLSs (pD 2 : aclidinium 7.9±0.3, Formoterol 8.4±0.3). Only Formoterol eliminated ACh-induced bronchiolar contraction (E max : Formoterol 99.0±5.6%, aclidinium 68.1±4.5%; p Aclidinium and Formoterol at low-to-high concentrations (aclidinium 3.2 nM–1.0 µM, Formoterol 1.0–63.0 nM) had a synergistic relaxant response on PCLSs, enhancing relaxation by +19.7±0.8% compared with the expected response (p Low concentrations (EC 30 ) of aclidinium with Formoterol induced significant (p Conclusions Aclidinium and Formoterol had a synergistic interaction on the lumen area enhancement of bronchioles, mainly at low concentrations.
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Rapid onset of bronchodilation with Formoterol/beclomethasone Modulite and Formoterol/budesonide Turbuhaler as compared to Formoterol alone in patients with COPD.
Pulmonary pharmacology & therapeutics, 2010Co-Authors: Mario Cazzola, Franco Pasqua, Luigi Ferri, Gianluca Biscione, Vittorio Cardaci, Maria Gabriella MateraAbstract:In the present study, we examined whether there is a difference in the onset of bronchodilatation between Formoterol/beclomethasone 12/200 μg Modulite and Formoterol/budesonide 9/320 μg Turbuhaler in patients with COPD. We enrolled 28 patients with stable COPD. Both Formoterol/beclomethasone and Formoterol/budesonide elicited a larger mean FEV₁-AUC₀₋₁₅min than Formoterol alone, whereas there was no significant difference between their FEV₁-AUC₀₋₁₅min. Also the change in FEV₁ 15 min after inhalation of Formoterol/beclomethasone combination or Formoterol/budesonide combination was greater than that induced by Formoterol alone. This study confirms the rapid effect of the inhaled corticosteroid component when combined with Formoterol and indicates that the onset of bronchodilation of Formoterol/beclomethasone Modulite and Formoterol/budesonide Turbuhaler are similar and greater than Formoterol alone in patients with COPD.
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effect of Formoterol budesonide combination on arterial blood gases in patients with acute exacerbation of copd
Respiratory Medicine, 2006Co-Authors: M Cazzola, Paolo Noschese, F De Michele, G Damato, Maria Gabriella MateraAbstract:Summary Background Patients with severe chronic airway obstruction might suffer dangerous hypoxemia after administration of a β -agonist despite bronchodilation. Methods We first compared the acute effects on gas exchange of two doses of Formoterol Turbuhaler (9 and 18μg) in 10 patients with acute exacerbation of COPD. Afterwards, we compared the acute effects of Formoterol Turbuhaler 9μg with those of Formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320μg in 10 other patients with acute exacerbation of COPD. Finally, we compared the changes in P aO 2 induced by Formoterol Turbuhaler 9μg or Formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320μg with those in FEV 1 in 10 other patients with acute exacerbation of COPD. Each agent was given on separate days, and the patients' arterial blood gases were measured at baseline and at intervals of 120min. Results Small but statistically significant declines in P aO 2 were found after administration of both Formoterol 9 and 18μg. In the second group of patients, Formoterol 9μg alone again induced a significant decrease in P aO 2 . However, the simultaneous administration of budesonide 320μg significantly reduced the acute effect of Formoterol on P aO 2 . In a third group of 10 patients we confirmed a small but significant decrease in P aO 2 after Formoterol alone and the reduction of this effect when budesonide was administered simultaneously. Moreover, we also documented that addition of budesonide amplified the fast onset of action of Formoterol. Conclusions These results suggest that when treating patients suffering from acute exacerbation of COPD with Formoterol, it is prudent to check their arterial blood gases. In any case, combined administration of Formoterol and budesonide reduces the potential for acute effects of Formoterol on blood-gas tensions.
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Bronchodilator response to Formoterol after regular tiotropium or to tiotropium after regular Formoterol in COPD patients.
Respiratory Medicine, 2004Co-Authors: Mario Cazzola, Paolo Noschese, Antonello Salzillo, Carlo De Giglio, Gennaro D'amato, Maria Gabriella MateraAbstract:Summary We conducted a randomized, crossover trial with tiotropium 18 μg once daily (group A), and Formoterol 12 μg twice daily (group B) over a 5-day period for each drug, with a 10-day washout, in 20 COPD patients. At the end of each period, patients inhaled both drugs separated by 180 min in alternate sequence (group A: tiotropium 18 μg+Formoterol 12 μg; group B: Formoterol 12 μg+tiotropium 18 μg). FEV 1 and FVC were measured at baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. FEV 1 and FVC further improved after crossover with both sequences. The mean maximal change in FEV 1 over baseline was 0.226 L (0.154–0.298) after tiotropium+Formoterol and 0.228 L (0.165–0.291) after Formoterol+tiotropium; the mean maximal change in FEV 1 over pre-inhalation the second drug value was 0.081 L (0.029–0.133) after tiotropium+Formoterol and 0.054 L (0.016–0.092) after Formoterol+tiotropium. The mean maximal change in FVC over baseline was 0.519 L (0.361–0.676) after tiotropium+Formoterol and 0.495 L (0.307–0.683) after Formoterol+tiotropium; the mean maximal change in FVC over pre-inhalation of the second drug value was 0.159 L (0.048–0.270) after tiotropium+Formoterol and 0.175 L (0.083–0.266) after Formoterol+tiotropium. The FEV 1 AUCs 0–360 min were 62.70 (45.67–79.74) after tiotropium+Formoterol and 69.20 (50.84–87.57) after Formoterol+tiotropium, the FEV 1 AUCs 0–180 min were 24.70 (18.19–31.21) after tiotropium+Formoterol and 29.74 (21.02–38.46) after Formoterol+tiotropium, whereas the FEV 1 AUCs 180–360 min were 15.70 (10.88–20.52) after tiotropium+Formoterol and 11.71 (7.21–16.21) after Formoterol+tiotropium. Differences between the two treatments were not statistically significant ( P >0.05). The addition of second different long-acting bronchodilator to a regularly administered long-acting bronchodilator seems to be to patient's advantage.
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Bronchodilator response to Formoterol after regular tiotropium or to tiotropium after regular Formoterol in COPD patients.
Respiratory Medicine, 2004Co-Authors: Mario Cazzola, Paolo Noschese, Antonello Salzillo, Carlo De Giglio, Gennaro D'amato, Maria Gabriella MateraAbstract:Summary We conducted a randomized, crossover trial with tiotropium 18 μg once daily (group A), and Formoterol 12 μg twice daily (group B) over a 5-day period for each drug, with a 10-day washout, in 20 COPD patients. At the end of each period, patients inhaled both drugs separated by 180 min in alternate sequence (group A: tiotropium 18 μg+Formoterol 12 μg; group B: Formoterol 12 μg+tiotropium 18 μg). FEV 1 and FVC were measured at baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. FEV 1 and FVC further improved after crossover with both sequences. The mean maximal change in FEV 1 over baseline was 0.226 L (0.154–0.298) after tiotropium+Formoterol and 0.228 L (0.165–0.291) after Formoterol+tiotropium; the mean maximal change in FEV 1 over pre-inhalation the second drug value was 0.081 L (0.029–0.133) after tiotropium+Formoterol and 0.054 L (0.016–0.092) after Formoterol+tiotropium. The mean maximal change in FVC over baseline was 0.519 L (0.361–0.676) after tiotropium+Formoterol and 0.495 L (0.307–0.683) after Formoterol+tiotropium; the mean maximal change in FVC over pre-inhalation of the second drug value was 0.159 L (0.048–0.270) after tiotropium+Formoterol and 0.175 L (0.083–0.266) after Formoterol+tiotropium. The FEV 1 AUCs 0–360 min were 62.70 (45.67–79.74) after tiotropium+Formoterol and 69.20 (50.84–87.57) after Formoterol+tiotropium, the FEV 1 AUCs 0–180 min were 24.70 (18.19–31.21) after tiotropium+Formoterol and 29.74 (21.02–38.46) after Formoterol+tiotropium, whereas the FEV 1 AUCs 180–360 min were 15.70 (10.88–20.52) after tiotropium+Formoterol and 11.71 (7.21–16.21) after Formoterol+tiotropium. Differences between the two treatments were not statistically significant ( P >0.05). The addition of second different long-acting bronchodilator to a regularly administered long-acting bronchodilator seems to be to patient's advantage.
H Olsson - One of the best experts on this subject based on the ideXlab platform.
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maintenance therapy with budesonide and Formoterol in chronic obstructive pulmonary disease
European Respiratory Journal, 2003Co-Authors: P M Calverley, S Peterson, W Boonsawat, Z Cseke, Nanshan Zhong, H OlssonAbstract:Lung function in chronic obstructive pulmonary disease (COPD) can be improved acutely by oral corticosteroids and bronchodilators. Whether clinical improvement can be maintained by subsequent inhaled therapy is unknown. COPD patients (n=1,022, mean prebronchodilator forced expiratory volume in one second (FEV1) 36% predicted) initially received Formoterol (9 microg b.i.d.) and oral prednisolone (30 mg o.d.) for 2 weeks. After this time, patients were randomised to b.i.d. inhaled budesonide/Formoterol 320/9 microg, budesonide 400 microg, Formoterol 9 microg or placebo for 12 months. Postmedication FEV1 improved by 0.21 L and health-related quality of life using the St George's Respiratory Questionnaire (SGRQ) by 4.5 units after run-in. Fewer patients receiving budesonide/Formoterol withdrew from the study than those receiving budesonide, Formoterol or placebo. Budesonide/Formoterol patients had a prolonged time to first exacerbation (254 versus 96 days) and maintained higher FEV1 (99% versus 87% of baseline), both primary variables versus placebo. They had fewer exacerbations (1.38 versus 1.80 exacerbations per patient per year), had higher prebronchodilator peak expiratory flow, and showed clinically relevant improvements in SGRQ versus placebo (-7.5 units). Budesonide/Formoterol was more effective than either monocomponent in both primary variables. Budesonide/Formoterol in a single inhaler (Symbicort) maintains the benefit of treatment optimisation, stabilising lung function and delaying exacerbations more effectively than either component drug alone or placebo.
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efficacy and safety of budesonide Formoterol in the management of chronic obstructive pulmonary disease
European Respiratory Journal, 2003Co-Authors: W Szafranski, A Cukier, Andrea Ramirez, G Menga, R Sansores, S Nahabedian, S Peterson, H OlssonAbstract: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 µg (delivered dose), budesonide 200 µg (metered dose), Formoterol 4.5 µg 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 β2‐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 β2‐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. This study was supported by AstraZeneca.
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Efficacy and safety of budesonide/Formoterol in the management of chronic obstructive pulmonary disease
The European respiratory journal, 2003Co-Authors: W Szafranski, A Cukier, Andrea Ramirez, G Menga, R Sansores, S Nahabedian, S Peterson, H OlssonAbstract: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 µg (delivered dose), budesonide 200 µg (metered dose), Formoterol 4.5 µg 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 β2‐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 β2‐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. This study was supported by AstraZeneca.
Donald P. Tashkin - One of the best experts on this subject based on the ideXlab platform.
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Formoterol for the Treatment of Chronic Obstructive Pulmonary Disease.
International journal of chronic obstructive pulmonary disease, 2020Co-Authors: Donald P. TashkinAbstract:Bronchodilators, including long-acting β2-agonists and long-acting muscarinic antagonists, are the mainstay for treatment of patients with chronic obstructive pulmonary disease (COPD) to prevent exacerbations or reduce symptoms. Formoterol is a highly selective and potent β2-agonist that relaxes airway smooth muscle to significantly improve lung function. Inhaled Formoterol works within 5 minutes of administration and provides improvements in spirometry measurements over 12 hours. The lipophilicity of Formoterol allows it to form a depot within the smooth muscle to provide a prolonged duration of action. Following therapeutic doses, plasma concentrations are very low or undetectable. Determination of the pharmacokinetics of Formoterol following high-dose administration to healthy volunteers revealed that the drug was rapidly absorbed and excreted unchanged in the urine with a half-life of 10 hours. Inhaled Formoterol, as monotherapy or in combination with other agents, is an effective and safe treatment option for patients with moderate to severe COPD. Clinical studies have demonstrated improvements in lung function and COPD symptoms, particularly dyspnea; reductions in the risk of exacerbations; and improvement in patients' health status. The adverse event profile of inhaled Formoterol is similar to that of placebo, with few adverse cardiovascular events. Formoterol is a valuable bronchodilator used in the maintenance treatment of COPD. This review describes the mechanism of action, pharmacodynamics, and pharmacokinetics of inhaled Formoterol. It also reviews the results of large, randomized, controlled clinical trials that evaluated the use of Formoterol as monotherapy and in combination with inhaled corticosteroids, long-acting muscarinic antagonists, and triple therapy regimens in the treatment of patients with moderate to severe COPD.
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effect of budesonide Formoterol pressurized metered dose inhaler on exacerbations versus Formoterol in chronic obstructive pulmonary disease the 6 month randomized rise revealing the impact of symbicort in reducing exacerbations in copd study
Respiratory Medicine, 2017Co-Authors: Gary T Ferguson, Carin Jorup, Donald P. Tashkin, Tor Skarby, Kristina Sandin, Mike Greenwood, Kristine Pemberton, Frank TrudoAbstract:Abstract Background Prevention of exacerbations is a primary goal for chronic obstructive pulmonary disease (COPD) therapy. This randomized, double-blind, double-dummy, parallel-group, multicenter study evaluated the effect of budesonide/Formoterol pressurized metered-dose inhaler (pMDI) versus Formoterol dry powder inhaler (DPI) on reducing COPD exacerbations. Methods 1219 patients aged ≥40 years with moderate-to-very-severe COPD (per lung function) and a history of ≥1 COPD exacerbation received budesonide/Formoterol pMDI 320/9 μg twice daily (BID) during a 4-week run-in. Patients were then randomized 1:1 to receive budesonide/Formoterol pMDI 320/9 μg BID (n = 606) or Formoterol DPI 9 μg BID (n = 613) for 26 weeks. Exacerbations were identified using predefined criteria for symptom worsening and treatment with systemic corticosteroids and/or antibiotics and/or hospitalization. The primary endpoint was annual rate of exacerbations. Results Budesonide/Formoterol pMDI resulted in a 24% reduction in annual rate of exacerbations (0.85 vs 1.12; rate ratio: 0.76 [95% CI: 0.62, 0.92]; P = 0.006), and a significant risk reduction for time to first exacerbation (hazard ratio: 0.78 [95% CI: 0.64, 0.96]; P = 0.016) versus Formoterol DPI. The most commonly reported adverse events (AEs; ≥3%) in budesonide/Formoterol and Formoterol groups were COPD (4.5% vs 8.6%) and nasopharyngitis (5.0% vs 5.2%). Pneumonia AEs were reported in 0.5% and 1.0% of budesonide/Formoterol-treated and Formoterol-treated patients, respectively. Conclusions Budesonide/Formoterol pMDI is an effective treatment option for reducing exacerbation rates in COPD patients with moderate-to-very-severe airflow limitation and history of exacerbations. No increase in pneumonia was observed with budesonide/Formoterol; safety data were consistent with its established profile.
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Bronchodilator responsiveness and onset of effect with budesonide/Formoterol pMDI in COPD
Respiratory medicine, 2011Co-Authors: Bartolome R. Celli, Donald P. Tashkin, Stephen I. Rennard, Jennifer Mcelhattan, Ubaldo J. MartinAbstract:Summary Background Chronic obstructive pulmonary disease (COPD) patients are thought to have limited bronchodilator response, determined by changes in forced expiratory volume in 1s (FEV 1 ). In this study, we assessed bronchodilator response in patients with COPD using not only FEV 1 but also changes in lung volume expressed as forced vital capacity (FVC) and inspiratory capacity (IC). We also evaluated the speed of onset of bronchodilation. Methods Data were from 2 randomized, double-blind, placebo-controlled studies (6-months [NCT00206154]; 12-months [NCT00206167]) in patients with moderate to very severe COPD. Treatments: twice daily budesonide/Formoterol pressurized metered-dose inhaler (pMDI) 320/9μg, budesonide/Formoterol pMDI 160/9μg, Formoterol dry powder inhaler (DPI) 9μg, placebo. Results The percentage of patients with FEV 1 improvement (≥12% and ≥200mL; American Thoracic Society [ATS] criterion) was 34–39% post-albuterol (screening). On day of randomization (DOR), a larger proportion receiving Formoterol-containing treatment exhibited reversibility within 60min: FEV 1 (57–59%). Similar results were seen for IC (50–61%) and FVC (57–67%) using the same improvement criteria. The time to ≥15% FEV 1 improvement on DOR was 5.0, 4.8, and 7.3min for budesonide/Formoterol 320/9, budesonide/Formoterol 160/9, and Formoterol, respectively. Time to ≥15% FEV 1 improvement was better maintained with budesonide/Formoterol than Formoterol at treatment end (6 and 12 months). Conclusions Most patients with moderate to very severe COPD exhibit ATS-defined bronchodilator reversibility based on flow and lung volume measures after budesonide/Formoterol pMDI or Formoterol treatment. Budesonide/Formoterol pMDI also has a rapid (within 5min) onset of bronchodilation that is maintained over time compared with Formoterol alone.
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Combination of Formoterol and Tiotropium in the Treatment of COPD: Effects on Lung Function
COPD, 2009Co-Authors: Mario Cazzola, Donald P. TashkinAbstract:Bronchodilators are central in symptomatic management of all stages of COPD. For patients whose COPD is not sufficiently controlled by monotherapy, combining an inhaled anticholinergic and a ss(2)-agonist is a convenient way of delivering treatment and obtaining better lung function and improved symptoms. Formoterol (beta(2)-agonist) and tiotropium (anticholinergic) are long-acting bronchodilators with different mechanisms of action. Formoterol has a fast onset and a bronchodilator effect of approximately 12 h, while tiotropium has a 24-h bronchodilator effect and is given once daily. Currently, there is no documentation that tiotropium is superior to Formoterol or the contrary, but a combination of tiotropium and Formoterol is more effective than single drugs alone in inducing bronchodilation and a bronchodilator-mediated symptom benefit in patients suffering from COPD. Once-daily or twice-daily Formoterol, added to tiotropium, are both better than tiotropium alone, but the published evidence suggests twice-daily Formoterol is the best add-on option.
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Efficacy and Tolerability of Budesonide/Formoterol in One Hydrofluoroalkane Pressurized Metered-Dose Inhaler in Patients with Chronic Obstructive Pulmonary Disease
Drugs, 2009Co-Authors: Stephen I. Rennard, Donald P. Tashkin, Sulabha Ramachandran, Ubaldo J. Martin, Mitchell Goldman, Jennifer Mcelhattan, Philip E. SilkoffAbstract:Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. The efficacy and tolerability of the combination of budesonide/Formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study. Objective: This study assessed the long-term efficacy and tolerability of budesonide/Formoterol HFA pMDI in patients with moderate to very severe COPD. Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico. After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/Formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/Formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); Formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo. Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV_1) and 1-hour post-dose FEV_1. Results: Budesonide/Formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV_1 versus Formoterol (p = 0.008), and both budesonide/Formoterol doses demonstrated greater improvements in 1-hour post-dose FEV_1 versus placebo (p < 0.001). The rate of COPD exacerbations was lower in both budesonide/Formoterol groups compared with Formoterol and placebo (p ≤ 0.004). Both budesonide/Formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire). All treatments were generally well tolerated. The incidence of pneumonia was not different for active (3.4–4.0%) and placebo (5.0%) groups. Conclusions: Budesonide/Formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD. Only budesonide/Formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with Formoterol DPI 9 μg. Both budesonide/Formoterol pMDI dosages were well tolerated relative to Formoterol and placebo.
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effect of budesonide Formoterol pmdi on copd exacerbations a double blind randomized study
Respiratory Medicine, 2012Co-Authors: Amir Sharafkhaneh, Mitchell Goldman, John G Southard, Tom Uryniak, Ubaldo J. MartinAbstract:Summary Background Treatment with an inhaled corticosteroid (ICS) and long-acting bronchodilator is recommended for severe/very severe chronic obstructive pulmonary disease (COPD) patients with repeated exacerbations. This randomized, double-blind, double-dummy, parallel-group, 12-month multicenter study evaluated the effect of budesonide/Formoterol pressurized metered-dose inhaler (pMDI) on COPD exacerbations. Methods Following a 2-week run-in during which COPD patients aged ≥40 years with an exacerbation history discontinued medications except ICSs, 1219 patients were randomized 1:1:1 to twice-daily budesonide/Formoterol pMDI 320/9 μg, budesonide/Formoterol pMDI 160/9 μg, or Formoterol dry powder inhaler 9 μg. An exacerbation was defined as COPD worsening requiring oral corticosteroids and/or hospitalization. A post hoc analysis, with antibiotic treatment added to the exacerbation definition, was also performed. Results Budesonide/Formoterol 320/9 and 160/9 reduced exacerbation rates (number per patient-treatment year) by 34.6% and 25.9%, respectively, versus Formoterol ( p ≤ 0.002). Budesonide/Formoterol 320/9 prolonged time to first exacerbation versus Formoterol, corresponding to a 21.2% reduction in hazard ratio (0.788 [95% CI: 0.639, 0.972]; p = 0.026). Exacerbation rates (number per patient-treatment year) including antibiotic treatment (post hoc analysis) were reduced by 25.9% and 18.7% with budesonide/Formoterol 320/9 and 160/9, respectively, versus Formoterol ( p ≤ 0.023). Both budesonide/Formoterol doses were well tolerated with safety profiles similar to Formoterol. Pneumonia adverse events occurred in 6.4%, 4.7%, and 2.7% of patients in the budesonide/Formoterol 320/9, 160/9, and Formoterol groups. Conclusions Over 12 months, both budesonide/Formoterol doses reduced the exacerbation rate (defined with or without antibiotic treatment) versus Formoterol. Budesonide/Formoterol pMDI is an appropriate treatment for reducing exacerbations in COPD patients with a history of exacerbations. (NCT00419744).
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Effect of budesonide/Formoterol pMDI on COPD exacerbations: A double-blind, randomized study
Respiratory medicine, 2011Co-Authors: Amir Sharafkhaneh, Mitchell Goldman, John G Southard, Tom Uryniak, Ubaldo J. MartinAbstract:Summary Background Treatment with an inhaled corticosteroid (ICS) and long-acting bronchodilator is recommended for severe/very severe chronic obstructive pulmonary disease (COPD) patients with repeated exacerbations. This randomized, double-blind, double-dummy, parallel-group, 12-month multicenter study evaluated the effect of budesonide/Formoterol pressurized metered-dose inhaler (pMDI) on COPD exacerbations. Methods Following a 2-week run-in during which COPD patients aged ≥40 years with an exacerbation history discontinued medications except ICSs, 1219 patients were randomized 1:1:1 to twice-daily budesonide/Formoterol pMDI 320/9 μg, budesonide/Formoterol pMDI 160/9 μg, or Formoterol dry powder inhaler 9 μg. An exacerbation was defined as COPD worsening requiring oral corticosteroids and/or hospitalization. A post hoc analysis, with antibiotic treatment added to the exacerbation definition, was also performed. Results Budesonide/Formoterol 320/9 and 160/9 reduced exacerbation rates (number per patient-treatment year) by 34.6% and 25.9%, respectively, versus Formoterol ( p ≤ 0.002). Budesonide/Formoterol 320/9 prolonged time to first exacerbation versus Formoterol, corresponding to a 21.2% reduction in hazard ratio (0.788 [95% CI: 0.639, 0.972]; p = 0.026). Exacerbation rates (number per patient-treatment year) including antibiotic treatment (post hoc analysis) were reduced by 25.9% and 18.7% with budesonide/Formoterol 320/9 and 160/9, respectively, versus Formoterol ( p ≤ 0.023). Both budesonide/Formoterol doses were well tolerated with safety profiles similar to Formoterol. Pneumonia adverse events occurred in 6.4%, 4.7%, and 2.7% of patients in the budesonide/Formoterol 320/9, 160/9, and Formoterol groups. Conclusions Over 12 months, both budesonide/Formoterol doses reduced the exacerbation rate (defined with or without antibiotic treatment) versus Formoterol. Budesonide/Formoterol pMDI is an appropriate treatment for reducing exacerbations in COPD patients with a history of exacerbations. (NCT00419744).
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Efficacy and Tolerability of Budesonide/Formoterol in One Hydrofluoroalkane Pressurized Metered-Dose Inhaler in Patients with Chronic Obstructive Pulmonary Disease
Drugs, 2009Co-Authors: Stephen I. Rennard, Donald P. Tashkin, Sulabha Ramachandran, Ubaldo J. Martin, Mitchell Goldman, Jennifer Mcelhattan, Philip E. SilkoffAbstract:Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. The efficacy and tolerability of the combination of budesonide/Formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study. Objective: This study assessed the long-term efficacy and tolerability of budesonide/Formoterol HFA pMDI in patients with moderate to very severe COPD. Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico. After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/Formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/Formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); Formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo. Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV_1) and 1-hour post-dose FEV_1. Results: Budesonide/Formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV_1 versus Formoterol (p = 0.008), and both budesonide/Formoterol doses demonstrated greater improvements in 1-hour post-dose FEV_1 versus placebo (p < 0.001). The rate of COPD exacerbations was lower in both budesonide/Formoterol groups compared with Formoterol and placebo (p ≤ 0.004). Both budesonide/Formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire). All treatments were generally well tolerated. The incidence of pneumonia was not different for active (3.4–4.0%) and placebo (5.0%) groups. Conclusions: Budesonide/Formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD. Only budesonide/Formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with Formoterol DPI 9 μg. Both budesonide/Formoterol pMDI dosages were well tolerated relative to Formoterol and placebo.
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Efficacy and tolerability of once-daily budesonide/Formoterol pressurized metered-dose inhaler in adults and adolescents with asthma previously stable with twice-daily budesonide/ Formoterol dosing.
Annals of allergy asthma & immunology : official publication of the American College of Allergy Asthma & Immunology, 2009Co-Authors: Edward Kerwin, Bhash Parasuraman, Christopher J. Miller, John J. Oppenheimer, C. Laforce, L. O'dowd, Mitchell GoldmanAbstract:Background The goal of asthma therapy is to control symptoms using minimal pharmacologic intervention. Objective To evaluate the efficacy and tolerability of once-daily budesonide/Formoterol vs once-daily budesonide in patients stable with twice-daily budesonide/Formoterol. Methods This double-blind, 12-week study enrolled 619 patients 12 years and older with mild to moderate asthma. After 4 to 5 weeks of twice-daily budesonide/Formoterol pressurized metered-dose inhaler (pMDI), 80/4.5 μg × 2 inhalations (320/18 μg/d), stable patients were randomized 1:1:1:1 to 2 inhalations twice daily of budesonide/Formoterol pMDI, 80/4.5 μg (320/18 μg/d), or 2 inhalations once daily (evening) of budesonide/Formoterol pMDI, 160/4.5 μg or 80/4.5 μg (320/9 μg or 160/9 μg/d), or budesonide pMDI, 160 μg (320 μg/d). Results All budesonide/Formoterol groups maintained significantly more favorable evening predose forced expiratory volume in 1 second (FEV 1 ), morning peak expiratory flow (PEF), daytime/nighttime asthma symptoms, nighttime rescue medication use, and rescue medication–free days vs budesonide. Variables evaluated during the end of the once-daily dosing interval (evening predose FEV 1 , evening PEF, daytime asthma symptoms, and daytime rescue medication use) significantly favored twice-daily budesonide/Formoterol vs all treatments. Twice-daily budesonide/Formoterol demonstrated significantly more favorable results for symptom-free and asthma control days vs all treatments and awakening-free nights vs budesonide. Asthma Quality of Life Questionnaire and Asthma Control Questionnaire results significantly favored twice-daily budesonide/Formoterol vs budesonide ( P ≤ .018). All treatments were well tolerated. Conclusions Pulmonary function and asthma control were more effectively maintained with all budesonide/Formoterol regimens vs once-daily budesonide and with twice-daily budesonide/Formoterol at twice the daily Formoterol dose vs both once-daily budesonide/Formoterol doses.
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efficacy and tolerability of budesonide Formoterol in one hydrofluoroalkane pressurized metered dose inhaler in patients with chronic obstructive pulmonary disease results from a 1 year randomized controlled clinical trial
Drugs, 2009Co-Authors: Stephen I. Rennard, Donald P. Tashkin, Sulabha Ramachandran, Ubaldo J. Martin, Mitchell Goldman, Jennifer Mcelhattan, Philip E. SilkoffAbstract:Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. The efficacy and tolerability of the combination of budesonide/Formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study. Objective: This study assessed the long-term efficacy and tolerability of budesonide/Formoterol HFA pMDI in patients with moderate to very severe COPD. Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico. After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/Formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/Formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); Formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo. Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1. Results: Budesonide/Formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus Formoterol (p = 0.008), and both budesonide/Formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001). The rate of COPD exacerbations was lower in both budesonide/Formoterol groups compared with Formoterol and placebo (p ≤ 0.004). Both budesonide/Formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire). All treatments were generally well tolerated. The incidence of pneumonia was not different for active (3.4–4.0%) and placebo (5.0%) groups. Conclusions: Budesonide/Formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD. Only budesonide/Formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with Formoterol DPI 9 μg. Both budesonide/Formoterol pMDI dosages were well tolerated relative to Formoterol and placebo.
