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Christopher Kalberg - One of the best experts on this subject based on the ideXlab platform.
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effect of fluticasone propionate Salmeterol 250 50 μg or Salmeterol 50 μg on copd exacerbations
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:Summary Objectives COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50μg twice daily on moderate to severe exacerbations. Methods Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. Results In 782 patients with COPD (mean FEV 1 =0.94±0.36L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p p =0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% ( p Conclusions We conclude that fluticasone propionate/Salmeterol 250/50 is more effective than Salmeterol at reducing the rate of moderate to severe exacerbations over 1year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/Salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.
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effect of fluticasone propionate Salmeterol 250 50 microg or Salmeterol 50 microg on copd exacerbations
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:OBJECTIVES COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50 microg twice daily on moderate to severe exacerbations. METHODS Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. RESULTS In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p<0.001), (2) the risk of time to first exacerbation by 25% (hazard ratio=0.750, p=0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% (p<0.001). Clinical improvements observed during run-in treatment with fluticasone propionate/Salmeterol 250/50 were better maintained over 12 months with fluticasone propionate/Salmeterol 250/50 than Salmeterol. Adverse events were reported for a similar percentage of subjects across groups. A higher reporting of pneumonia was observed with fluticasone propionate/Salmeterol 250/50 than Salmeterol (7% vs. 4%). CONCLUSIONS We conclude that fluticasone propionate/Salmeterol 250/50 is more effective than Salmeterol at reducing the rate of moderate to severe exacerbations over 1 year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/Salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.
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Effect of fluticasone propionate/Salmeterol (250/50 microg) or Salmeterol (50 microg) on COPD exacerbations.
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:OBJECTIVES COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50 microg twice daily on moderate to severe exacerbations. METHODS Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. RESULTS In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p
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addition of Salmeterol to low dose fluticasone versus higher dose fluticasone an analysis of asthma exacerbations
The Journal of Allergy and Clinical Immunology, 2001Co-Authors: Jonathan Matz, Amanda Emmett, Kathleen Rickard, Christopher KalbergAbstract:Abstract Background: Adding Salmeterol to low-dose fluticasone propionate (FP) produces greater improvements in pulmonary function and symptom control than increasing the dose of FP in patients who remain symptomatic with low-dose FP. Objective: We sought to compare the rates and characteristics of asthma exacerbations in patients after adding Salmeterol to low-dose FP with the rates and characteristics of exacerbations in patients receiving higher dose FP. Methods: In 2 multicenter, double-blind studies, 925 patients 12 years of age and older receiving 88μg twice daily FP randomly received either 42 μg of Salmeterol and 88 μg of FP or an increased dose of FP (220μg) twice daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening were assessed for all patients who experienced an asthma exacerbation. Results: The addition of Salmeterol resulted in a significantly lower rate and number of exacerbations compared with higher dose FP. A total of 41 (8.8%) patients experienced 47 exacerbations with the addition of Salmeterol compared with 63 (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP ( P = .017). Salmeterol plus low-dose FP was significantly more protective than increased-dose FP in preventing asthma exacerbations, as assessed by the time to first exacerbation ( P Conclusion: Salmeterol plus low-dose FP was more effective than higher dose FP alone in reducing asthma exacerbations in patients with persistent asthma. The ability to detect deteriorating asthma and the severity of exacerbation was similar between groups. (J Allergy Clin Immunol 2001;107:783-9.)
Amanda Emmett - One of the best experts on this subject based on the ideXlab platform.
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effect of fluticasone propionate Salmeterol 250 50 μg or Salmeterol 50 μg on copd exacerbations
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:Summary Objectives COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50μg twice daily on moderate to severe exacerbations. Methods Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. Results In 782 patients with COPD (mean FEV 1 =0.94±0.36L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p p =0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% ( p Conclusions We conclude that fluticasone propionate/Salmeterol 250/50 is more effective than Salmeterol at reducing the rate of moderate to severe exacerbations over 1year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/Salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.
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effect of fluticasone propionate Salmeterol 250 50 microg or Salmeterol 50 microg on copd exacerbations
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:OBJECTIVES COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50 microg twice daily on moderate to severe exacerbations. METHODS Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. RESULTS In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p<0.001), (2) the risk of time to first exacerbation by 25% (hazard ratio=0.750, p=0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% (p<0.001). Clinical improvements observed during run-in treatment with fluticasone propionate/Salmeterol 250/50 were better maintained over 12 months with fluticasone propionate/Salmeterol 250/50 than Salmeterol. Adverse events were reported for a similar percentage of subjects across groups. A higher reporting of pneumonia was observed with fluticasone propionate/Salmeterol 250/50 than Salmeterol (7% vs. 4%). CONCLUSIONS We conclude that fluticasone propionate/Salmeterol 250/50 is more effective than Salmeterol at reducing the rate of moderate to severe exacerbations over 1 year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/Salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.
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Effect of fluticasone propionate/Salmeterol (250/50 microg) or Salmeterol (50 microg) on COPD exacerbations.
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:OBJECTIVES COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50 microg twice daily on moderate to severe exacerbations. METHODS Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. RESULTS In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p
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addition of Salmeterol to low dose fluticasone versus higher dose fluticasone an analysis of asthma exacerbations
The Journal of Allergy and Clinical Immunology, 2001Co-Authors: Jonathan Matz, Amanda Emmett, Kathleen Rickard, Christopher KalbergAbstract:Abstract Background: Adding Salmeterol to low-dose fluticasone propionate (FP) produces greater improvements in pulmonary function and symptom control than increasing the dose of FP in patients who remain symptomatic with low-dose FP. Objective: We sought to compare the rates and characteristics of asthma exacerbations in patients after adding Salmeterol to low-dose FP with the rates and characteristics of exacerbations in patients receiving higher dose FP. Methods: In 2 multicenter, double-blind studies, 925 patients 12 years of age and older receiving 88μg twice daily FP randomly received either 42 μg of Salmeterol and 88 μg of FP or an increased dose of FP (220μg) twice daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening were assessed for all patients who experienced an asthma exacerbation. Results: The addition of Salmeterol resulted in a significantly lower rate and number of exacerbations compared with higher dose FP. A total of 41 (8.8%) patients experienced 47 exacerbations with the addition of Salmeterol compared with 63 (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP ( P = .017). Salmeterol plus low-dose FP was significantly more protective than increased-dose FP in preventing asthma exacerbations, as assessed by the time to first exacerbation ( P Conclusion: Salmeterol plus low-dose FP was more effective than higher dose FP alone in reducing asthma exacerbations in patients with persistent asthma. The ability to detect deteriorating asthma and the severity of exacerbation was similar between groups. (J Allergy Clin Immunol 2001;107:783-9.)
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Salmeterol Plus Theophylline Combination Therapy in the Treatment of COPD
Chest, 2001Co-Authors: Richard Zuwallack, Amanda Emmett, Donald A. Mahler, Donna Reilly, Nina L. Church, Kathleen A. Rickard, Katharine KnobilAbstract:Background Patients with COPD often require multiple therapies to improve lung function and decrease symptoms and exacerbations. Salmeterol and theophylline are indicated for the treatment of COPD, but the use of these agents in combination has not been extensively studied. Objectives To compare the efficacy and safety of Salmeterol plus theophylline vs either agent alone in COPD. Methods Randomized, double-blind, double-dummy, parallel-group trial in 943 patients with COPD. After an open-label theophylline titration period (serum levels, 10 to 20μ g/mL), patients were randomly assigned to receive Salmeterol (42μ g bid) plus theophylline, Salmeterol (42 μg bid), or theophylline for 12 weeks. Serial pulmonary function tests were completed on day 1 and treatment week 12. Patients kept diary cards and noted their peak flow rates, symptom scores, and albuterol use, and periodically completed quality-of-life and dyspnea questionnaires. Results All three groups significantly improved compared with baseline. Combination treatment with Salmeterol plus theophylline provided significantly (p ≤ 0.045) greater improvements in pulmonary function; significantly (p ≤ 0.048) greater decreases in symptoms, dyspnea, and albuterol use; and significantly fewer COPD exacerbations (p = 0.023 vs theophylline). In general, treatment with Salmeterol provided greater improvement in lung function and satisfaction with treatment compared with theophylline. Salmeterol treatment was also associated with significantly fewer drug-related adverse events (p ≤ 0.042) than either treatment that included theophylline. The safety profile (adverse events, vital signs, and ECG findings) of the two treatments that included theophylline were similar. Conclusion Patients with COPD may benefit from combination treatment with Salmeterol plus theophylline, without a resulting increase in adverse events or other adverse sequelae.
Gary T Ferguson - One of the best experts on this subject based on the ideXlab platform.
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effect of fluticasone propionate Salmeterol 250 50 μg or Salmeterol 50 μg on copd exacerbations
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:Summary Objectives COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50μg twice daily on moderate to severe exacerbations. Methods Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. Results In 782 patients with COPD (mean FEV 1 =0.94±0.36L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p p =0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% ( p Conclusions We conclude that fluticasone propionate/Salmeterol 250/50 is more effective than Salmeterol at reducing the rate of moderate to severe exacerbations over 1year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/Salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.
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effect of fluticasone propionate Salmeterol 250 50 microg or Salmeterol 50 microg on copd exacerbations
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:OBJECTIVES COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50 microg twice daily on moderate to severe exacerbations. METHODS Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. RESULTS In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p<0.001), (2) the risk of time to first exacerbation by 25% (hazard ratio=0.750, p=0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% (p<0.001). Clinical improvements observed during run-in treatment with fluticasone propionate/Salmeterol 250/50 were better maintained over 12 months with fluticasone propionate/Salmeterol 250/50 than Salmeterol. Adverse events were reported for a similar percentage of subjects across groups. A higher reporting of pneumonia was observed with fluticasone propionate/Salmeterol 250/50 than Salmeterol (7% vs. 4%). CONCLUSIONS We conclude that fluticasone propionate/Salmeterol 250/50 is more effective than Salmeterol at reducing the rate of moderate to severe exacerbations over 1 year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/Salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.
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Effect of fluticasone propionate/Salmeterol (250/50 microg) or Salmeterol (50 microg) on COPD exacerbations.
Respiratory Medicine, 2008Co-Authors: Gary T Ferguson, Antonio Anzueto, Richard Fei, Amanda Emmett, Katharine Knobil, Christopher KalbergAbstract:OBJECTIVES COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/Salmeterol 250/50 and Salmeterol 50 microg twice daily on moderate to severe exacerbations. METHODS Patients received standardized treatment with fluticasone propionate/Salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/Salmeterol 250/50 or Salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. RESULTS In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/Salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with Salmeterol (1.06 and 1.53 per subject per year, respectively, p
Brian J Lipworth - One of the best experts on this subject based on the ideXlab platform.
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a proof of concept study to evaluate stepping down the dose of fluticasone in combination with Salmeterol and tiotropium in severe persistent asthma
Respiratory Medicine, 2007Co-Authors: Thomas C Fardon, K Haggart, Brian J LipworthAbstract:Summary We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus Salmeterol, or Salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV 1 1.49l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000μg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500μg BD/Salmeterol 100μg BD/HFA-tiotropium bromide18μg od; or (b) fluticasone propionate 500μg BD/Salmeterol 100μg BD matched placebo. Measurements of spirometry and body plethysmography were made. Adding Salmeterol to half the dose of fluticasone led to a mean improvement (95% CI) vs. baseline in morning PEF of 41.5 (14.0–69.0)l/min [ p 2 O/l/s [ p 1 by 0.17 (0.01–0.32)l [ p p p
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a proof of concept study to evaluate stepping down the dose of fluticasone in combination with Salmeterol and tiotropium in severe persistent asthma
Respiratory Medicine, 2007Co-Authors: Thomas C Fardon, K Haggart, Daniel K C Lee, Brian J LipworthAbstract:We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus Salmeterol, or Salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV(1) 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 microg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 microg BD/Salmeterol 100 microg BD/HFA-tiotropium bromide18 microg od; or (b) fluticasone propionate 500 microg BD/Salmeterol 100 microg BD matched placebo. Measurements of spirometry and body plethysmography were made. Adding Salmeterol to half the dose of fluticasone led to a mean improvement (95% CI) vs. baseline in morning PEF of 41.5 (14.0-69.0)l/min [p<0.05]; and RAW of 0.98 (0.14-1.8)cm H(2)O/l/s [p<0.05]. Adding Salmeterol/tiotropium produced similar improvements in PEF and RAW, but also improved FEV(1) by 0.17 (0.01-0.32)l [p<0.05]; FVC 0.24 (0.05-0.43)l [p<0.05] and reduced exhaled NO by 2.86 (0.12-5.6)ppb [p<0.05]. RV and TLC were not altered by either treatment; there were no significant changes in symptoms or quality of life compared with baseline. Addition of Salmeterol/tiotropium to half the dose of fluticasone afforded small, but significant improvements in pulmonary function. These effects were not associated with commensurate changes in subjective symptoms or quality of life.
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effects of regular Salmeterol on lung function and exercise capacity in patients with chronic obstructive airways disease
Thorax, 1996Co-Authors: Alison Grove, L Ramage, Brian J Lipworth, C G Ingram, P Reid, R P Smith, R J Jenkins, J H Winter, D P DhillonAbstract:BACKGROUND: The aim of this study was to evaluate the effects of single and chronic dosing with Salmeterol on exercise capacity and lung function in patients with chronic obstructive pulmonary disease. METHODS: Twenty nine patients of mean (SE) age 64 (1.5) years, forced expiratory volume in one second (FEV1) 42(3)% of predicted, and 5-15% reversibility to salbutamol 200 micrograms were randomised to receive four weeks treatment with Salmeterol 50 micrograms twice daily or placebo in a double blind crossover fashion with a one week washout period in between. Measurements of spirometric parameters, static lung volumes, and exercise capacity were made one and six hours after a single dose, and six hours after the final dose of Salmeterol or placebo. RESULTS: Salmeterol produced a small increase in FEV1 at one and six hours after a single dose, and this was maintained after chronic dosing (mean difference and 95% CI versus placebo): single dosing at one hour 0.07 (95% CI 0.02 to 0.11) 1, single dosing at six hours 0.16 (95% CI 0.09 to 0.22) 1, chronic dosing at six hours 0.11 (95% CI 0.03 to 0.19) 1. The increase in forced vital capacity (FVC) was greater with Salmeterol than with placebo six hours after single but not chronic dosing: single dosing at six hours 0.17 (95% CI 0.04 to 0.29) 1, chronic dosing at six hours 0.02 (95% CI -0.18 to 0.22) 1. Slow vital capacity was increased after treatment with Salmeterol compared with placebo one and six hours after single but not after chronic dosing. There were no significant differences in static lung volumes or exercise capacity after single or chronic dosing with Salmeterol compared with placebo. Patients reported a significantly lower Borg score for perceived exertion following the six minute walk after chronic treatment with Salmeterol compared with placebo. CONCLUSIONS: Salmeterol produced a small improvement in spirometric values compared with placebo consistent with the degree of reversibility originally shown by the subjects to salbutamol 200 micrograms. This was not associated with improvements in static lung volumes or exercise capacity, but there was some symptomatic benefit in that patients were able to walk the same distance in six minutes with less perceived exertion.
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reduced protection against exercise induced bronchoconstriction after chronic dosing with Salmeterol
Respiratory Medicine, 1994Co-Authors: L Ramage, Brian J Lipworth, C G Ingram, Ian A Cree, D P DhillonAbstract:Abstract The purpose of the present study was to assess the degree of protection of inhaled Salmeterol against exercise-induced bronchoconstriction (EIB) after chronic compared with single dosing in patients with asthma. Twelve patients with exercise-induced asthma took part in a randomized double-blind crossover study to compare the duration of action of inhaled Salmeterol 50 μg twice daily for 4 weeks with that of placebo. A standardized exercise test was performed at 6 h and 12 h after dosing on the first and last day of each treatment period. Salmeterol produced significant protection against EIB at 6 and 12 h after the first dose in comparison with placebo, whereas there was no significant attenuation of EIB after 4 weeks of chronic treatment with Salmeterol. The percentage fall in FEV 1 after exercise challenge at 6 h was (first dose): placebo 34·8 ± 4·9% vs. Salmeterol 11·9 ± 2·8% ( P vs. Salmeterol 24·0 ± 4·4% (ns). These results suggest that tachyphylaxis may develop to the functional antagonism of Salmeterol against EIB.
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reduced protection against exercise induced bronchoconstriction after chronic dosing with Salmeterol
Respiratory Medicine, 1994Co-Authors: L Ramage, Brian J Lipworth, C G Ingram, Ian A Cree, D P DhillonAbstract:Abstract The purpose of the present study was to assess the degree of protection of inhaled Salmeterol against exercise-induced bronchoconstriction (EIB) after chronic compared with single dosing in patients with asthma. Twelve patients with exercise-induced asthma took part in a randomized double-blind crossover study to compare the duration of action of inhaled Salmeterol 50 μg twice daily for 4 weeks with that of placebo. A standardized exercise test was performed at 6 h and 12 h after dosing on the first and last day of each treatment period. Salmeterol produced significant protection against EIB at 6 and 12 h after the first dose in comparison with placebo, whereas there was no significant attenuation of EIB after 4 weeks of chronic treatment with Salmeterol. The percentage fall in FEV 1 after exercise challenge at 6 h was (first dose): placebo 34·8 ± 4·9% vs. Salmeterol 11·9 ± 2·8% ( P vs. Salmeterol 24·0 ± 4·4% (ns). These results suggest that tachyphylaxis may develop to the functional antagonism of Salmeterol against EIB.
Mario Cazzola - One of the best experts on this subject based on the ideXlab platform.
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the functional impact of adding Salmeterol and tiotropium in patients with stable copd
Respiratory Medicine, 2004Co-Authors: Mario Cazzola, Pierachille Santus, Michele Mondoni, F Di Marco, Massimo Verga, Stefano Centanni, Maria Gabriella MateraAbstract:Abstract The aim of this double-blind, double-dummy, crossover, randomised, pilot study was to explore the acute effects of adding Salmeterol and tiotropium in patients with stable COPD. A total of 20 outpatients with stable COPD were enrolled. Single doses of 18-μg tiotropium, 50-μg Salmeterol, and 18-μg tiotropium+50-μg Salmeterol were given. Serial measurements of forced expiratory volume in 1s (FEV 1 ) were performed over 24h. The mean maximum increases in FEV 1 from pre-dosing value on each of the dosing days were 0.165l (95% CI: 0.098–0.232) for tiotropium, 0.241l (95% CI: 0.151–0.332) for Salmeterol, and 0.290l (95% CI: 0.228–0.353) for the combination and occurred 4h after inhalation of tiotropium or Salmeterol and 3h after the combination. At 12h, the mean increases in FEV 1 from pre-dosing value were 0.071l (95% CI: 0.001–0.141; P =0.047) for tiotropium, 0.069l (95% CI: 0.018-0.120; P =0.010) for Salmeterol, and 0.108l (95% CI: 0.047–0.170; P =0.001) for the tiotropium+Salmeterol combination. Only the difference between Salmeterol and tiotropium+Salmeterol was statistically significant ( P =0.009). At 24h, the mean FEV 1 value was still higher than the mean pre-dosing value for tiotropium (0.042l; 95% CI: −0.012–0.097; P =0.119) and the tiotropium+Salmeterol combination (0.051l; 95% CI: 0.015–0.087; P =0.007), but not for Salmeterol alone (−0.013l; 95% CI: −0.041–0.014; P =0.324). The FEV 1 area under the curve (AUCs 0−12h ) were 1.657l (95% CI: 1.152–2.162) for tiotropium, 2.068l (95% CI: 1.385–2.752) for Salmeterol, and 2.541l (95% CI: 1.954–3.129) for tiotropium+Salmeterol. Only the difference between tiotropium and the tiotropium+Salmeterol combination was statistically significant ( P =0.01). The FEV 1 AUCs 0−24h were 2.854l (95% CI: 1.928–3.780) for tiotropium, 2.786l (95% CI: 1.913–3.660) for Salmeterol, and 3.640l (95% CI: 2.674–4.605) for tiotropium+Salmeterol. All differences between treatments were not statistically significant ( P >0.05). These results seem to indicate that the use of the tiotropium+Salmeterol combination is more efficacious than the single agents alone, but the once-daily administration of the two drugs is inadvisable due to the broncholytic profile of Salmeterol.
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Clinical Pharmacokinetics of Salmeterol
Clinical Pharmacokinetics, 2002Co-Authors: Mario Cazzola, Renato Testi, Maria Gabriella MateraAbstract:Salmeterol is an inhaled long-acting selective β2-adrenoceptor agonist that is commercially available as the xinafoate (1-hydroxy-2-naphthoic acid) salt of the racemic mixture of the two optical isomers, ( R )- and ( S )-, of Salmeterol. It acts locally in the lung through action on β_2 receptors. Limited data have been published on the pharmacokinetics of Salmeterol. Moreover, there are no data on the extent to which inhaled Salmeterol undergoes first-pass metabolism. This lack of information is most likely due to the very low plasma concentrations reached after inhalation of therapeutic doses of Salmeterol and the problems in developing an analytical method that is sensitive enough to determine these concentrations. When Salmeterol is inhaled, plasma concentrations of the drug often cannot be detected, even at 30 minutes after administration of therapeutic doses. Larger inhaled doses give approximately proportionally increased blood concentrations. Plasma Salmeterol concentrations of 0.1 to 0.2 and 1 to 2 µg/L have been attained in healthy volunteers about 5 to 15 minutes after inhalation of a single dose of 50 and 400 µg, respectively. In patients who inhaled Salmeterol 50µg twice daily for 10 months, a second peak concentration of 0.07 to 0.2 µg/L occurred 45 to 90 minutes after inhalation, probably because of the gastrointestinal absorption of the swallowed drug. Salmeterol xinafoate dissociates in solution to Salmeterol and 1-hydroxy-2-naphthoic acid. These two compounds are then absorbed, distributed, metabolised and excreted independently. The xinafoate moiety has no apparent pharmacological activity, is highly protein bound (>99%), largely to albumin, and has a long elimination half-life of about 12 to 15 days in healthy individuals. For this reason, it accumulates in plasma during repeated administration, with steady-state concentrations reaching about 80 to 90 µg/L in patients treated with Salmeterol 50µg twice daily for several months. The cytochrome P450 (CYP) isoform 3A4 is responsible for aliphatic oxidation of Salmeterol base, which is extensively metabolised by hydroxylation with the major metabolite being α-hydroxySalmeterol, with subsequent elimination predominantly in the faeces. It has been demonstrated that 57.4% of administered radioactivity is recovered in the faeces and 23% in the urine; most is recovered between 24 and 72 hours after administration. Unchanged Salmeterol accounts for
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Addition of an extra dose of Salmeterol Diskus to conventional dose of Salmeterol Diskus in patients with COPD.
Respiratory Medicine, 2002Co-Authors: Mario Cazzola, Pierachille Santus, F Di Marco, Maria Gabriella Matera, F. Castagna, Claudio Terzano, Stefano CentanniAbstract:Patients experiencing dyspnoea can request an additional dose of Salmeterol during the dose interval for the control of their symptoms, although under treatment with Salmeterol. In this study we have explored the effects on respiratory function of an additive dose of Salmeterol Diskus® in 15 chronic obstructive pulmonary disease (COPD) patients in regular treatment with a conventional dose of 50 μ g Salmeterol. On two different days, patients inhaled 50μ g Diskus®. After 240 min, they inhaled additional 50 μ g Salmeterol Diskus® (Salmeterol arm) or placebo Diskus® (placebo arm). Lung function was controlled before first drug administration and 0·5, 1, 2, 3, 4, 4·5, 6, 8, 10, and 12 h thereafter. The mean (95% Cl) peak increase in FEV1 from baseline was reached after 4 h in the Salmeterol arm (0·174 L; 0·144–0204) and after 5 h (0·141 L; 0·115–0·168) in the placebo arm; after 12 h, the mean (95% Cl) increase in FEV1 from basal values was still 0·149 L (0·119–0·179) in Salmeterol arm, but only 0·041 L (0·017–0·064) in placebo arm. The mean (95% Cl) FEV1 AUC0–12h for all patients were 2·01 (1·72–2·30) L when Salmeterol was added and 1·30 (1·03–1·58) L when placebo was inhaled. The difference (mean; 95% Cl) between the FEV1 AUC0–12h of the two arms (0·71 L; 0·47–0·95) was statistically significant (P
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Additive effects of Salmeterol and fluticasone or theophylline in COPD
Chest, 2000Co-Authors: Mario Cazzola, Gabriele Di Lorenzo, Felice Di Perna, F. Calderaro, R Testi, Stefano CentanniAbstract:Background: β 2 -Agonists andcorticosteroids or theophylline can interact to produce beneficialeffects on airway function in asthma, but this has not been establishedin COPD. Methods: Eighty patients with well-controlledCOPD were randomized to receive 3 months of treatment in one of fourtreatment groups: (1) Salmeterol, 50 μg bid; (2) Salmeterol, 50 μg, plus fluticasone propionate, 250 μg bid; (3) Salmeterol, 50 μg, plus fluticasone propionate, 500 μg bid; and (4) Salmeterol, 50 μg, plus titrated theophylline bid. At each visit, a dose-response curve toinhaled salbutamol was constructed using a total cumulative dose of 800μg. Results: A gradual increase in FEV 1 was observed with each of the four treatments. Maximum significantincreases in FEV 1 over baseline values that were observedafter 3 months of treatment were as follows: Salmeterol, 50 μg bid,0.163 L (95% confidence interval [CI], 0.080 to 0.245 L);Salmeterol, 50 μg, plus fluticasone propionate, 250 μg bid, 0.188 L(95% CI, 0.089 to 0.287 L); Salmeterol, 50 μg, plus fluticasonepropionate, 500 μg bid, 0.239 L (95% CI, 0.183 to 0.296 L); andSalmeterol, 50 μg, plus titrated theophylline bid, 0.157 L (95% CI,0.027 to 0.288 L). Salbutamol always caused a significantdose-dependent increase in FEV 1 (p 1 after Salmeterol, 50 μg, plusfluticasone propionate, 500 μg bid, and that after Salmeterol, 50μg, plus titrated theophylline bid or Salmeterol, 50 μg bid, werestatistically significant(p Conclusion: These data show thatboth long-acting β 2 -agonists and inhaled corticosteroidshave a role in COPD. The data also show that fluticasone propionate andSalmeterol given together are more effective than Salmeterol alone. Moreover, it suggests that the addition of fluticasone propionate toSalmeterol allows a greater improvement in lung function aftersalbutamol, although regular Salmeterol is able to improve lungfunction in COPD patients without development of a true subsensitivityto its bronchodilator effect. In any case, patients must be treated forat least 3 months before a real improvement in lung function isachieved.
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Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease a dose response study
Respiratory Medicine, 1995Co-Authors: Mario Cazzola, Maria Gabriella Matera, Gabriella Santangelo, A Vinciguerra, Francesca Manes Rossi, Gennaro DamatoAbstract:When testing the response to beta 2-agonist drugs in severe chronic obstructive pulmonary disease (COPD), a dose-response assessment should be undertaken. This study compares the time course of inhaled Salmeterol (25, 50 and 75 micrograms) and formoterol (12, 24 and 36 micrograms) at different doses in a group of 12 patients with partially reversible, but severe COPD (FEV1 of 12-32% of predicted values after beta 2-agonist drugs had been withheld for 24 h). All doses of Salmeterol and formoterol induced a significant (P < 0.01) spirometric improvement over the 12-h monitoring period, when compared to the spirometric improvement after placebo, but while formoterol induced a dose-dependent increase of the FVC, FEV1 and FEF50, this was not the case for Salmeterol. In fact, 75 micrograms Salmeterol did not produce a further improvement of these parameters. Mean peak bronchodilation, expressed as the increase in FEV1 over baseline values, occurred 2 h after inhalation of the three doses of Salmeterol, and 1 h after inhalation of the three doses of formoterol. A comparison of 50 micrograms Salmeterol with 12 micrograms or 24 micrograms formoterol (clinically recommended doses), showed that improvement of FEV1 after Salmeterol was statistically (P < 0.05) higher than that after the two doses of formoterol, although the mean peak bronchodilations were similar. This was because Salmeterol has a longer duration of action than formoterol. These data demonstrate that Salmeterol is equally effective as, but longer-acting than, formoterol at clinically recommended doses in patients suffering from COPD, with severe airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)
