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Graeme P. Currie - One of the best experts on this subject based on the ideXlab platform.

  • effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper responsiveness in mild to Moderate Persistent Asthma
    British Journal of Clinical Pharmacology, 2004
    Co-Authors: Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Aims There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-Moderate Persistent Asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods Nineteen mild-to-Moderate Asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusions There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

  • Effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper‐responsiveness in mild‐to‐Moderate Persistent Asthma
    British journal of clinical pharmacology, 2004
    Co-Authors: Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Aims There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-Moderate Persistent Asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods Nineteen mild-to-Moderate Asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusions There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

  • Effects of hydrofluoroalkane formulations of ciclesonide 320μg once daily versus fluticasone propionate 220μg twice daily on methacholine hyperresponsiveness in mild-to-Moderate Persistent Asthma
    Journal of Allergy and Clinical Immunology, 2004
    Co-Authors: Thomas C. Fardon, Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Rob Gray, Brian J. Lipworth
    Abstract:

    Abstract Rationale We evaluated the comparative efficacy of HFA formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods 19 mild-to-Moderate Asthmatics completed the study in randomized, double-blind, double-dummy, cross-over fashion. Patients stopped their inhaled corticosteroids during the study and were commenced instead on salmeterol (SM) 50μg 1puff bid + montelukast (ML) 10mg qd for 2-week washout periods prior to each randomized treatment. Patients received 4 weeks of either CIC 200μg ex-valve (160μg ex-actuator ) 2puffs qd (8am) + CIC-placebo (PL) 2puffs qd (8pm) + FP-PL 2puffs bid (8am/8pm), or FP 125μg ex-valve (110μg ex-actuator ) 2puffs bid (8am/8pm) + CIC-PL 2puffs bid (8am/8pm). SM+ML were withheld for 72hours prior to post-washout visits and CIC or FP was withheld for 24hours prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC 20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4dd (95%CI −0.4–1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs. FP second; mean difference: 0.2dd (95%CI −1.3–1.7) or FP first vs. CIC second; mean difference: 0.9dd (95%CI −0.1–1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusion There were no differences between 4 weeks of CIC 320μg qd and FP 220μg bid on methacholine hyperresponsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

  • comparison of combination inhalers vs inhaled corticosteroids alone in Moderate Persistent Asthma
    British Journal of Clinical Pharmacology, 2003
    Co-Authors: Daniel K. C. Lee, Catherine M. Jackson, Graeme P. Currie, Wendy J. Cockburn, Brian J. Lipworth
    Abstract:

    Aims  Inhalers combining long acting β2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current Asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with Moderate Persistent Asthma. Methods  Twenty-nine patients with mean FEV1 (± SEM) of 78 ± 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 µg + formoterol 12 µg (BUD + FM) combination twice daily followed by 1 week of BUD 400 µg alone twice daily, or 4 weeks of fluticasone propionate 250 µg + salmeterol 50 µg (FP + SM) combination twice daily followed by 1 week of FP 250 µg alone twice daily. Measurements were made at baseline and following each randomized treatment. Results  FEV1 increase from pretreatment baseline as mean (± SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 ± 1%) vs BUD (2 ± 1%), and for FP + SM (8 ± 1%) vs FP (2 ± 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 ± 1%), BUD (24 ± 1%), FP + SM (23 ± 1%) and FP (23 ± 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 ± 35.5) vs BUD (281.1 ± 52.8), and with FP + SM (553.1 ± 34.1) vs FP (368.3 ± 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments. Conclusions  Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction.

  • Comparison of combination inhalers vs inhaled corticosteroids alone in Moderate Persistent Asthma
    British journal of clinical pharmacology, 2003
    Co-Authors: Daniel K. C. Lee, Catherine M. Jackson, Graeme P. Currie, Wendy J. Cockburn, Brian J. Lipworth
    Abstract:

    Aims  Inhalers combining long acting β2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current Asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with Moderate Persistent Asthma. Methods  Twenty-nine patients with mean FEV1 (± SEM) of 78 ± 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 µg + formoterol 12 µg (BUD + FM) combination twice daily followed by 1 week of BUD 400 µg alone twice daily, or 4 weeks of fluticasone propionate 250 µg + salmeterol 50 µg (FP + SM) combination twice daily followed by 1 week of FP 250 µg alone twice daily. Measurements were made at baseline and following each randomized treatment. Results  FEV1 increase from pretreatment baseline as mean (± SEM) % predicted was significantly higher (P 

Brian J. Lipworth - One of the best experts on this subject based on the ideXlab platform.

  • effect of ciclesonide and fluticasone on hypothalamicpituitary adrenal axis function in adults with mild to Moderate Persistent Asthma
    Annals of Allergy Asthma & Immunology, 2005
    Co-Authors: Brian J. Lipworth, Craig Laforce, Michael A Kaliner, James W Baker, Harold B Kaiser, Dilip Amin, S Kundu, James Williams, Renate Engelstaetter, Donald Banerji
    Abstract:

    Background Despite their proven efficacy in the treatment and prevention of Asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events. Objective To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-Moderate Persistent Asthma. Methods This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-Moderate Asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 μg of ciclesonide once daily, 320 μg of ciclesonide twice daily, and 440 μg of fluticasone propionate twice daily, all doses ex-actuator. Results For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-μg/d ciclesonide, 2.4% for 640-μg/d ciclesonide, and 22.0% for 880-μg/d fluticasone propionate. Conclusions These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 μg/d, the drug does not affect sensitive markers of adrenal function.

  • Airway and Systemic Effects of Hydrofluoroalkane Formulations of High-Dose Ciclesonide and Fluticasone in Moderate Persistent Asthma
    Chest, 2005
    Co-Authors: Daniel K. C. Lee, Lesley C. Mcfarlane, Thomas C. Fardon, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Background There are no data comparing the relative effects of high-dose ciclesonide (CIC) and fluticasone propionate (FP) on airway and systemic outcomes in patients with Moderate Persistent Asthma Objective We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor (hCRF) and bronchial hyperresponsiveness to methacholine as the primary outcome variables, in addition to secondary outcomes of overnight 10-h urinary cortisol (OUC) levels, exhaled nitric oxide levels, lung function, symptoms, and quality of life Methods Fourteen patients with Moderate Persistent Asthma (mean FEV 1 , 67% predicted [prior to each randomized treatment]) completed the study, which had a randomized, double-blind, double-dummy, crossover design, per protocol. Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol, 50 μg twice daily, and montelukast, 10 mg once daily, for the 2-week washout periods prior to each randomized treatment, in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy. Patients received 4 weeks of either CIC, 200 μg ex-valve (160 μg ex-actuator) four puffs twice daily, plus FP-placebo, four puffs twice daily, or FP, 250 μg ex-valve (220 μg ex-actuator) four puffs twice daily, plus CIC-placebo, four puffs twice daily. Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit, and CIC or FP was withheld for 12 h prior to each posttreatment visit Results FP, but not CIC, when compared to respective baseline values, significantly suppressed (p 1 , as follows: CIC: doubling dilution difference, 0.8; 95% CI, 0.1 to 1.6; FP: doubling dilution difference, 1.0; 95% CI, 0.1 to 2.0. It also significantly reduced (p Conclusion FP, 2,000 μg daily, but not CIC, 1,600 μg daily, significantly suppressed hypothalamic-pituitary-adrenal axis outcomes, with OUC levels being lower after FP administration than after CIC administration. Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels. The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses

  • effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper responsiveness in mild to Moderate Persistent Asthma
    British Journal of Clinical Pharmacology, 2004
    Co-Authors: Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Aims There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-Moderate Persistent Asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods Nineteen mild-to-Moderate Asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusions There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

  • Effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper‐responsiveness in mild‐to‐Moderate Persistent Asthma
    British journal of clinical pharmacology, 2004
    Co-Authors: Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Aims There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-Moderate Persistent Asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods Nineteen mild-to-Moderate Asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusions There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

  • Effects of hydrofluoroalkane formulations of ciclesonide 320μg once daily versus fluticasone propionate 220μg twice daily on methacholine hyperresponsiveness in mild-to-Moderate Persistent Asthma
    Journal of Allergy and Clinical Immunology, 2004
    Co-Authors: Thomas C. Fardon, Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Rob Gray, Brian J. Lipworth
    Abstract:

    Abstract Rationale We evaluated the comparative efficacy of HFA formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods 19 mild-to-Moderate Asthmatics completed the study in randomized, double-blind, double-dummy, cross-over fashion. Patients stopped their inhaled corticosteroids during the study and were commenced instead on salmeterol (SM) 50μg 1puff bid + montelukast (ML) 10mg qd for 2-week washout periods prior to each randomized treatment. Patients received 4 weeks of either CIC 200μg ex-valve (160μg ex-actuator ) 2puffs qd (8am) + CIC-placebo (PL) 2puffs qd (8pm) + FP-PL 2puffs bid (8am/8pm), or FP 125μg ex-valve (110μg ex-actuator ) 2puffs bid (8am/8pm) + CIC-PL 2puffs bid (8am/8pm). SM+ML were withheld for 72hours prior to post-washout visits and CIC or FP was withheld for 24hours prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC 20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4dd (95%CI −0.4–1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs. FP second; mean difference: 0.2dd (95%CI −1.3–1.7) or FP first vs. CIC second; mean difference: 0.9dd (95%CI −0.1–1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusion There were no differences between 4 weeks of CIC 320μg qd and FP 220μg bid on methacholine hyperresponsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

B. J. Lipworth - One of the best experts on this subject based on the ideXlab platform.

  • effects of low dose fluticasone salmeterol combination on surrogate inflammatory markers in Moderate Persistent Asthma
    Allergy, 2003
    Co-Authors: Graeme P. Currie, Lesley C. Mcfarlane, Frank A. Carey, N J Symegrant, B. J. Lipworth
    Abstract:

    Background: Noninvasive surrogate markers provide valuable information on the Asthmatic inflammatory process. We wished to examine the effects of low dose fluticasone/salmeterol combination on different commonly used inflammatory markers in Moderate Persistent Asthma. Methods: Twenty-five Moderate Persistent atopic Asthmatics were enrolled of whom 20 completed an open label study. Following an initial 4 week steroid washout period in which patients took salmeterol 50 μg dry powder inhaler 1 puff BD, they received the addition of fluticasone as fluticasone 100 μg/salmeterol 50 μg combination dry powder inhaler 1 puff BD for the next 2 weeks. Exhaled nitric oxide, spirometry, methacholine PD20, sputum/blood eosinophils and sputum/serum eosinophil cationic protein (ECP) were measured following the salmeterol only and fluticasone/salmeterol combination treatment periods. Results: Compared to salmeterol alone (i.e. after the steroid washout), the use of fluticasone/salmeterol combination conferred significant improvements (P < 0.05) in all surrogate markers of inflammation apart from serum ECP. Geometric mean fold changes were 4.3-fold/1.3-fold for sputum/blood eosinophils, 2.2-fold/1.2-fold for sputum/serum ECP, 2.3-fold for methacholine PD20 and 1.8-fold for exhaled nitric oxide. Conclusions: Surrogate markers apart from serum ECP may be used as a guide to evaluate the anti-inflammatory effects of low dose inhaled corticosteroids. Sputum markers tend to be more sensitive than blood when assessing the anti-inflammatory response.

  • Effects of low dose fluticasone/salmeterol combination on surrogate inflammatory markers in Moderate Persistent Asthma.
    Allergy, 2003
    Co-Authors: Graeme P. Currie, N. J. Syme-grant, Lesley C. Mcfarlane, Frank A. Carey, B. J. Lipworth
    Abstract:

    Background: Noninvasive surrogate markers provide valuable information on the Asthmatic inflammatory process. We wished to examine the effects of low dose fluticasone/salmeterol combination on different commonly used inflammatory markers in Moderate Persistent Asthma. Methods: Twenty-five Moderate Persistent atopic Asthmatics were enrolled of whom 20 completed an open label study. Following an initial 4 week steroid washout period in which patients took salmeterol 50 μg dry powder inhaler 1 puff BD, they received the addition of fluticasone as fluticasone 100 μg/salmeterol 50 μg combination dry powder inhaler 1 puff BD for the next 2 weeks. Exhaled nitric oxide, spirometry, methacholine PD20, sputum/blood eosinophils and sputum/serum eosinophil cationic protein (ECP) were measured following the salmeterol only and fluticasone/salmeterol combination treatment periods. Results: Compared to salmeterol alone (i.e. after the steroid washout), the use of fluticasone/salmeterol combination conferred significant improvements (P 

Lesley C. Mcfarlane - One of the best experts on this subject based on the ideXlab platform.

  • Airway and Systemic Effects of Hydrofluoroalkane Formulations of High-Dose Ciclesonide and Fluticasone in Moderate Persistent Asthma
    Chest, 2005
    Co-Authors: Daniel K. C. Lee, Lesley C. Mcfarlane, Thomas C. Fardon, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Background There are no data comparing the relative effects of high-dose ciclesonide (CIC) and fluticasone propionate (FP) on airway and systemic outcomes in patients with Moderate Persistent Asthma Objective We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor (hCRF) and bronchial hyperresponsiveness to methacholine as the primary outcome variables, in addition to secondary outcomes of overnight 10-h urinary cortisol (OUC) levels, exhaled nitric oxide levels, lung function, symptoms, and quality of life Methods Fourteen patients with Moderate Persistent Asthma (mean FEV 1 , 67% predicted [prior to each randomized treatment]) completed the study, which had a randomized, double-blind, double-dummy, crossover design, per protocol. Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol, 50 μg twice daily, and montelukast, 10 mg once daily, for the 2-week washout periods prior to each randomized treatment, in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy. Patients received 4 weeks of either CIC, 200 μg ex-valve (160 μg ex-actuator) four puffs twice daily, plus FP-placebo, four puffs twice daily, or FP, 250 μg ex-valve (220 μg ex-actuator) four puffs twice daily, plus CIC-placebo, four puffs twice daily. Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit, and CIC or FP was withheld for 12 h prior to each posttreatment visit Results FP, but not CIC, when compared to respective baseline values, significantly suppressed (p 1 , as follows: CIC: doubling dilution difference, 0.8; 95% CI, 0.1 to 1.6; FP: doubling dilution difference, 1.0; 95% CI, 0.1 to 2.0. It also significantly reduced (p Conclusion FP, 2,000 μg daily, but not CIC, 1,600 μg daily, significantly suppressed hypothalamic-pituitary-adrenal axis outcomes, with OUC levels being lower after FP administration than after CIC administration. Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels. The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses

  • effects of low dose fluticasone salmeterol combination on surrogate inflammatory markers in Moderate Persistent Asthma
    Allergy, 2003
    Co-Authors: Graeme P. Currie, Lesley C. Mcfarlane, Frank A. Carey, N J Symegrant, B. J. Lipworth
    Abstract:

    Background: Noninvasive surrogate markers provide valuable information on the Asthmatic inflammatory process. We wished to examine the effects of low dose fluticasone/salmeterol combination on different commonly used inflammatory markers in Moderate Persistent Asthma. Methods: Twenty-five Moderate Persistent atopic Asthmatics were enrolled of whom 20 completed an open label study. Following an initial 4 week steroid washout period in which patients took salmeterol 50 μg dry powder inhaler 1 puff BD, they received the addition of fluticasone as fluticasone 100 μg/salmeterol 50 μg combination dry powder inhaler 1 puff BD for the next 2 weeks. Exhaled nitric oxide, spirometry, methacholine PD20, sputum/blood eosinophils and sputum/serum eosinophil cationic protein (ECP) were measured following the salmeterol only and fluticasone/salmeterol combination treatment periods. Results: Compared to salmeterol alone (i.e. after the steroid washout), the use of fluticasone/salmeterol combination conferred significant improvements (P < 0.05) in all surrogate markers of inflammation apart from serum ECP. Geometric mean fold changes were 4.3-fold/1.3-fold for sputum/blood eosinophils, 2.2-fold/1.2-fold for sputum/serum ECP, 2.3-fold for methacholine PD20 and 1.8-fold for exhaled nitric oxide. Conclusions: Surrogate markers apart from serum ECP may be used as a guide to evaluate the anti-inflammatory effects of low dose inhaled corticosteroids. Sputum markers tend to be more sensitive than blood when assessing the anti-inflammatory response.

  • Effects of low dose fluticasone/salmeterol combination on surrogate inflammatory markers in Moderate Persistent Asthma.
    Allergy, 2003
    Co-Authors: Graeme P. Currie, N. J. Syme-grant, Lesley C. Mcfarlane, Frank A. Carey, B. J. Lipworth
    Abstract:

    Background: Noninvasive surrogate markers provide valuable information on the Asthmatic inflammatory process. We wished to examine the effects of low dose fluticasone/salmeterol combination on different commonly used inflammatory markers in Moderate Persistent Asthma. Methods: Twenty-five Moderate Persistent atopic Asthmatics were enrolled of whom 20 completed an open label study. Following an initial 4 week steroid washout period in which patients took salmeterol 50 μg dry powder inhaler 1 puff BD, they received the addition of fluticasone as fluticasone 100 μg/salmeterol 50 μg combination dry powder inhaler 1 puff BD for the next 2 weeks. Exhaled nitric oxide, spirometry, methacholine PD20, sputum/blood eosinophils and sputum/serum eosinophil cationic protein (ECP) were measured following the salmeterol only and fluticasone/salmeterol combination treatment periods. Results: Compared to salmeterol alone (i.e. after the steroid washout), the use of fluticasone/salmeterol combination conferred significant improvements (P 

Daniel K. C. Lee - One of the best experts on this subject based on the ideXlab platform.

  • Airway and Systemic Effects of Hydrofluoroalkane Formulations of High-Dose Ciclesonide and Fluticasone in Moderate Persistent Asthma
    Chest, 2005
    Co-Authors: Daniel K. C. Lee, Lesley C. Mcfarlane, Thomas C. Fardon, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Background There are no data comparing the relative effects of high-dose ciclesonide (CIC) and fluticasone propionate (FP) on airway and systemic outcomes in patients with Moderate Persistent Asthma Objective We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor (hCRF) and bronchial hyperresponsiveness to methacholine as the primary outcome variables, in addition to secondary outcomes of overnight 10-h urinary cortisol (OUC) levels, exhaled nitric oxide levels, lung function, symptoms, and quality of life Methods Fourteen patients with Moderate Persistent Asthma (mean FEV 1 , 67% predicted [prior to each randomized treatment]) completed the study, which had a randomized, double-blind, double-dummy, crossover design, per protocol. Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol, 50 μg twice daily, and montelukast, 10 mg once daily, for the 2-week washout periods prior to each randomized treatment, in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy. Patients received 4 weeks of either CIC, 200 μg ex-valve (160 μg ex-actuator) four puffs twice daily, plus FP-placebo, four puffs twice daily, or FP, 250 μg ex-valve (220 μg ex-actuator) four puffs twice daily, plus CIC-placebo, four puffs twice daily. Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit, and CIC or FP was withheld for 12 h prior to each posttreatment visit Results FP, but not CIC, when compared to respective baseline values, significantly suppressed (p 1 , as follows: CIC: doubling dilution difference, 0.8; 95% CI, 0.1 to 1.6; FP: doubling dilution difference, 1.0; 95% CI, 0.1 to 2.0. It also significantly reduced (p Conclusion FP, 2,000 μg daily, but not CIC, 1,600 μg daily, significantly suppressed hypothalamic-pituitary-adrenal axis outcomes, with OUC levels being lower after FP administration than after CIC administration. Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels. The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses

  • effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper responsiveness in mild to Moderate Persistent Asthma
    British Journal of Clinical Pharmacology, 2004
    Co-Authors: Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Aims There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-Moderate Persistent Asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods Nineteen mild-to-Moderate Asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusions There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

  • Effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper‐responsiveness in mild‐to‐Moderate Persistent Asthma
    British journal of clinical pharmacology, 2004
    Co-Authors: Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Brian J. Lipworth
    Abstract:

    Aims There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-Moderate Persistent Asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods Nineteen mild-to-Moderate Asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusions There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

  • Effects of hydrofluoroalkane formulations of ciclesonide 320μg once daily versus fluticasone propionate 220μg twice daily on methacholine hyperresponsiveness in mild-to-Moderate Persistent Asthma
    Journal of Allergy and Clinical Immunology, 2004
    Co-Authors: Thomas C. Fardon, Daniel K. C. Lee, Graeme P. Currie, Caroline E. Bates, K. Haggart, Rob Gray, Brian J. Lipworth
    Abstract:

    Abstract Rationale We evaluated the comparative efficacy of HFA formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Methods 19 mild-to-Moderate Asthmatics completed the study in randomized, double-blind, double-dummy, cross-over fashion. Patients stopped their inhaled corticosteroids during the study and were commenced instead on salmeterol (SM) 50μg 1puff bid + montelukast (ML) 10mg qd for 2-week washout periods prior to each randomized treatment. Patients received 4 weeks of either CIC 200μg ex-valve (160μg ex-actuator ) 2puffs qd (8am) + CIC-placebo (PL) 2puffs qd (8pm) + FP-PL 2puffs bid (8am/8pm), or FP 125μg ex-valve (110μg ex-actuator ) 2puffs bid (8am/8pm) + CIC-PL 2puffs bid (8am/8pm). SM+ML were withheld for 72hours prior to post-washout visits and CIC or FP was withheld for 24hours prior to study visits. Results There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC 20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4dd (95%CI −0.4–1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs. FP second; mean difference: 0.2dd (95%CI −1.3–1.7) or FP first vs. CIC second; mean difference: 0.9dd (95%CI −0.1–1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. Conclusion There were no differences between 4 weeks of CIC 320μg qd and FP 220μg bid on methacholine hyperresponsiveness in mild-to-Moderate Persistent Asthma. Longer-term studies are indicated to evaluate their relative efficacy on Asthma exacerbations.

  • comparison of combination inhalers vs inhaled corticosteroids alone in Moderate Persistent Asthma
    British Journal of Clinical Pharmacology, 2003
    Co-Authors: Daniel K. C. Lee, Catherine M. Jackson, Graeme P. Currie, Wendy J. Cockburn, Brian J. Lipworth
    Abstract:

    Aims  Inhalers combining long acting β2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current Asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with Moderate Persistent Asthma. Methods  Twenty-nine patients with mean FEV1 (± SEM) of 78 ± 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 µg + formoterol 12 µg (BUD + FM) combination twice daily followed by 1 week of BUD 400 µg alone twice daily, or 4 weeks of fluticasone propionate 250 µg + salmeterol 50 µg (FP + SM) combination twice daily followed by 1 week of FP 250 µg alone twice daily. Measurements were made at baseline and following each randomized treatment. Results  FEV1 increase from pretreatment baseline as mean (± SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 ± 1%) vs BUD (2 ± 1%), and for FP + SM (8 ± 1%) vs FP (2 ± 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 ± 1%), BUD (24 ± 1%), FP + SM (23 ± 1%) and FP (23 ± 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 ± 35.5) vs BUD (281.1 ± 52.8), and with FP + SM (553.1 ± 34.1) vs FP (368.3 ± 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments. Conclusions  Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction.