human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES To compare the therapeutic ratio of chlorofluorocarbon ( CFC ) and hydrofluoroalkane-134a ( HFA ) formulations of fluticasone propionate ( FP ) . METHODS We performed a r and omized , placebo-controlled , crossover study comparing 6 weeks of treatment with FP using 500 micro g/d and 1,000 microg/d formulations of CFC and HFA . The primary end points were provocative dose of methacholine causing a 20 % fall in FEV1 ( PD20 ) and overnight urinary cortisol/creatinine excretion . RESULTS Eighteen patients with mild-to-moderate asthma and geometric mean ( SEM ) PD20 of 82.3 micro g ( 19.2 micro g ) completed the study . All treatments significantly improved PD20 values and morning peak expiratory flow vs placebo , while 1,000 microg/d was significantly better than 500 microg/d for the CFC formulation of FP ( CFC-FP ) but not the HFA formulation of FP ( HFA-FP ) . Only 1,000 microg/d of CFC-FP caused significant suppression of overnight urinary cortisol/creatinine compared to placebo . There were no differences between formulations at either dose . CONCLUSIONS The increased airway benefit with CFC-FP > 500 microg/d was offset by greater systemic effects . Although HFA-FP had fewer systemic effects than CFC-FP at 1,000 microg/d , there was no benefit to increasing HFA-FP to > 500 microg/d In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma . However , controversy still remains as to whether these differences translate into clinical benefits . This 12-week , international , r and omized , doubleblind , parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate ( FP ) 800 μg daily , administered as a powder via the Diskhaler ® , and budesonide ( BUD ) 1600 μg daily , administered using the Turbuhaler ® , in adult patients with moderate-tosevere asthma . A total of 518 patients participated in the study , 256 of whom received FP and 262 BUD .  Assessment of mean morning peak expiratory flow ( PEF ) over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 μg daily and BUD 1600 μg daily in favour of FP ( p = 0.003 ) , with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD . Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF ( p = 0.04 ) , diurnal PEF variation ( p = 0.03 ) and percentage predicted PEF ( p = 0.003 ) , as well as forced expiratory volume ( p = 0.008 ) , forced vital capacity ( p = 0.02 ) and PEF ( p = 0.005 ) measured at clinic visits . The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups , with similar changes seen for the median percentage of days with symptom score < 2 , rescue medication use and exacerbations of asthma . The incidence of adverse events was found to be comparable in the two treatment groups . The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP , indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline , and 0.93 for BUD ( p = 0.0002 compared with FP ) . In summary , FP 800 μg daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 μg daily OBJECTIVE To investigate effects on adrenal function of fluticasone , a recently released inhaled steroid preparation with lower systemic bioavailability than beclomethasone dipropionate . METHODS 34 children on high doses ( 400 - 909 μg/m2/d ) of inhaled beclomethasone dipropionate or budesonide  were recruited into a double blind , crossover study investigating the effects on adrenal function of beclomethasone and fluticasone propionate , given using a st and ard spacer ( Volumatic ) . The 24 hour excretion rates of total cortisol and cortisol metabolites were determined at baseline ( after a two week run in ) , after six weeks treatment with an equal dose of beclomethasone , and after six weeks of treatment with half the dose of fluticasone , both given through a spacer device . RESULTS The comparison of effects between fluticasone and beclomethasone during treatment periods , although favouring fluticasone in all measured variables , reached significance only after correction for urinary creatinine excretion ( tetrahydrocortisol and 5α-tetrahydrocortisol geometric means : 424 v 341 μg/m2/d ) . The baseline data showed adrenal suppression in the children taking beclomethasone ( total cortisol geometric means : 975 v 1542 μg/d ) and a dose related suppression in the children taking budesonide . Suppressed adrenal function in the children who were taking beclomethasone at baseline subsequently improved with fluticasone and beclomethasone during treatment periods . CONCLUSIONS Fluticasone is less likely to suppress adrenal function than beclomethasone at therapeutically equivalent doses . The baseline data also support the cl aim that spacer devices should be used for the administration of high doses of inhaled topical steroids BACKGROUND A clinical model is needed to compare inhaled corticosteroids ( ICSs ) with respect to efficacy . OBJECTIVE The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs . METHODS A 24-week , parallel , open-label , multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma . Benefit was assessed by improvements in FEV(1 ) and PC(20 ) ; risk was assessed by overnight plasma cortisol suppression .  Thirty subjects were r and omized to either beclomethasone dipropionate ( BDP ) 168 , 672 , and 1344 microg/day ( n = 15 ) or fluticasone propionate ( FP ) 88 , 352 , and 704 microg/day ( n = 15 ) , both administered by means of a metered dose inhaler ( MDI ) with chlorofluorocarbon propellant via a spacer , in 3 consecutive 6-week intervals ; this was followed by 3 weeks of FP dry powder inhaler ( DPI ) 2000 microg/day . RESULTS Maximum FEV(1 ) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI . Near-maximum methacholine PC(20 ) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI . Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression . Responsiveness to ICS treatment was found to vary markedly among subjects . Good ( > 15 % ) FEV(1 ) response , in contrast to poor ( < 5 % ) response , was found to be associated with high exhaled nitric oxide ( median , 17.6 vs 11.1 ppb ) , high bronchodilator reversibility ( 25.2 % vs 8.8 % ) , and a low FEV(1)/forced vital capacity ratio ( 0.63 vs 0.73 ) before treatment . Excellent ( > 3 doubling dilutions ) improvement in PC(20 ) , in contrast to poor ( < 1 doubling dilution ) improvement , was found to be associated with high sputum eosinophil levels ( 3.4 % vs 0.1 % ) and older age at onset of asthma ( age , 20 - 29 years vs < 10 years ) . CONCLUSIONS Near-maximal FEV(1 ) and PC(20 ) effects occurred with low-medium dose for both ICSs in the subjects studied . High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated , but it did increase the systemic effect measure , overnight cortisol secretion . Significant intersubject variability in response occurred with both ICSs . It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study , such as prevention of asthma exacerbations BACKGROUND : A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis , each given by metered dose inhaler to asthmatic patients . METHODS : Twelve asthmatic patients of mean age 29.9 years , with a forced expiratory volume in one second ( FEV1 ) 92.9 % predicted and forced expiratory flow 25 - 75 % ( FEF25 - 75 ) 69.5 % predicted , on less than or equal to 400 micrograms/day inhaled corticosteroid , were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400 , 1000 , 1600 , 2000 micrograms and fluticasone propionate 500 , 1000 , 1500 , 2000 micrograms . Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later . RESULTS : Serum cortisol levels compared with placebo ( mean 325.2 nmol/l ) were suppressed by fluticasone at doses of 1500 micrograms ( 211.6 nmol/l ) and 2000 micrograms ( 112.3 nmol/l ) and by budesonide at 2000 micrograms ( 243.4 nmol/l ) . Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms ( 95 % CI for difference 42.9 to 219.2 ) . The dose ratio ( geometric mean ) for the relative potency was 2.89 fold ( 95 % CI 1.19 to 7.07 ) . In terms of percentage suppression versus placebo , fluticasone propionate also produced greater effects ( means and 95 % CI for difference ) : budesonide 1600 micrograms ( 16.0 ) versus fluticasone propionate 1500 micrograms ( 40.9 ) ( 95 % CI -0.6 to 50.6 ) , budesonide 2000 micrograms ( 26.0 ) versus fluticasone 2000 micrograms ( 65.2 ) ( 95 % CI 10.5 to 67.8 ) . Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range ( 150 nmol/l ) for fluticasone and five of 24 for budesonide . Fluticasone propionate also caused greater ACTH suppression than budesonide ( as % versus placebo ) : budesonide 1600 micrograms ( 12.0 ) versus fluticasone propionate 1500 micrograms ( 31.9 ) ( 95 % CI 7.6 to 32.1 ) , budesonide 2000 micrograms ( 13.5 ) versus fluticasone propionate 2000 micrograms ( 44.4 ) ( 95 % CI 13.2 to 48.7 ) . For overnight 10 hour urinary cortisol ( nmol/10 hours ) there was a difference between the lowest doses of the two drugs : budesonide 400 micrograms ( 37.2 ) versus fluticasone propionate 500 micrograms ( 19.9 ) ( 95 % CI 6.9 to 27.8 ) . CONCLUSIONS : Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption . Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients This study was carried out in an attempt to compare the efficacy and safety of fluticasone propionate ( FP ) at the half dose of budesonide ( BUD ) and beclamethasone dipropionate ( BD ) in childhood asthma . Ninety-six children with moderate to severe asthma ( 9.6 ± 2.17 years ) whose asthma was already controlled on BUD ( n = 52 ) or BD ( n = 44 ) were recruited into the study . In the first part of the study ( the first 12 weeks ) each group was followed with three weekly lung function measurements , daily diary records , and peak expiratory flow ( PEF ) measurements on the initial medication . At the end of 6 weeks , drugs were switched to a half dose 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES To compare the therapeutic ratio of chlorofluorocarbon ( CFC ) and hydrofluoroalkane-134a ( HFA ) formulations of fluticasone propionate ( FP ) . METHODS We performed a r and omized , placebo-controlled , crossover study comparing 6 weeks of treatment with FP using 500 micro g/d and 1,000 microg/d formulations of CFC and HFA . The primary end points were provocative dose of methacholine causing a 20 % fall in FEV1 ( PD20 ) and overnight urinary cortisol/creatinine excretion . RESULTS Eighteen patients with mild-to-moderate asthma and geometric mean ( SEM ) PD20 of 82.3 micro g ( 19.2 micro g ) completed the study . All treatments significantly improved PD20 values and morning peak expiratory flow vs placebo , while 1,000 microg/d was significantly better than 500 microg/d for the CFC formulation of FP ( CFC-FP ) but not the HFA formulation of FP ( HFA-FP ) . Only 1,000 microg/d of CFC-FP caused significant suppression of overnight urinary cortisol/creatinine compared to placebo . There were no differences between formulations at either dose . CONCLUSIONS The increased airway benefit with CFC-FP > 500 microg/d was offset by greater systemic effects . Although HFA-FP had fewer systemic effects than CFC-FP at 1,000 microg/d , there was no benefit to increasing HFA-FP to > 500 microg/d In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma . However , controversy still remains as to whether these differences translate into clinical benefits . This 12-week , international , r and omized , doubleblind , parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate ( FP ) 800 μg daily , administered as a powder via the Diskhaler ® , and budesonide ( BUD ) 1600 μg daily , administered using the Turbuhaler ® , in adult patients with moderate-tosevere asthma . A total of 518 patients participated in the study , 256 of whom received FP and 262 BUD .  Assessment of mean morning peak expiratory flow ( PEF ) over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 μg daily and BUD 1600 μg daily in favour of FP ( p = 0.003 ) , with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD . Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF ( p = 0.04 ) , diurnal PEF variation ( p = 0.03 ) and percentage predicted PEF ( p = 0.003 ) , as well as forced expiratory volume ( p = 0.008 ) , forced vital capacity ( p = 0.02 ) and PEF ( p = 0.005 ) measured at clinic visits . The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups , with similar changes seen for the median percentage of days with symptom score < 2 , rescue medication use and exacerbations of asthma . The incidence of adverse events was found to be comparable in the two treatment groups . The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP , indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline , and 0.93 for BUD ( p = 0.0002 compared with FP ) . In summary , FP 800 μg daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 μg daily OBJECTIVE To investigate effects on adrenal function of fluticasone , a recently released inhaled steroid preparation with lower systemic bioavailability than beclomethasone dipropionate . METHODS 34 children on high doses ( 400 - 909 μg/m2/d ) of inhaled beclomethasone dipropionate or budesonide  were recruited into a double blind , crossover study investigating the effects on adrenal function of beclomethasone and fluticasone propionate , given using a st and ard spacer ( Volumatic ) . The 24 hour excretion rates of total cortisol and cortisol metabolites were determined at baseline ( after a two week run in ) , after six weeks treatment with an equal dose of beclomethasone , and after six weeks of treatment with half the dose of fluticasone , both given through a spacer device . RESULTS The comparison of effects between fluticasone and beclomethasone during treatment periods , although favouring fluticasone in all measured variables , reached significance only after correction for urinary creatinine excretion ( tetrahydrocortisol and 5α-tetrahydrocortisol geometric means : 424 v 341 μg/m2/d ) . The baseline data showed adrenal suppression in the children taking beclomethasone ( total cortisol geometric means : 975 v 1542 μg/d ) and a dose related suppression in the children taking budesonide . Suppressed adrenal function in the children who were taking beclomethasone at baseline subsequently improved with fluticasone and beclomethasone during treatment periods . CONCLUSIONS Fluticasone is less likely to suppress adrenal function than beclomethasone at therapeutically equivalent doses . The baseline data also support the cl aim that spacer devices should be used for the administration of high doses of inhaled topical steroids BACKGROUND A clinical model is needed to compare inhaled corticosteroids ( ICSs ) with respect to efficacy . OBJECTIVE The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs . METHODS A 24-week , parallel , open-label , multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma . Benefit was assessed by improvements in FEV(1 ) and PC(20 ) ; risk was assessed by overnight plasma cortisol suppression .  Thirty subjects were r and omized to either beclomethasone dipropionate ( BDP ) 168 , 672 , and 1344 microg/day ( n = 15 ) or fluticasone propionate ( FP ) 88 , 352 , and 704 microg/day ( n = 15 ) , both administered by means of a metered dose inhaler ( MDI ) with chlorofluorocarbon propellant via a spacer , in 3 consecutive 6-week intervals ; this was followed by 3 weeks of FP dry powder inhaler ( DPI ) 2000 microg/day . RESULTS Maximum FEV(1 ) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI . Near-maximum methacholine PC(20 ) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI . Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression . Responsiveness to ICS treatment was found to vary markedly among subjects . Good ( > 15 % ) FEV(1 ) response , in contrast to poor ( < 5 % ) response , was found to be associated with high exhaled nitric oxide ( median , 17.6 vs 11.1 ppb ) , high bronchodilator reversibility ( 25.2 % vs 8.8 % ) , and a low FEV(1)/forced vital capacity ratio ( 0.63 vs 0.73 ) before treatment . Excellent ( > 3 doubling dilutions ) improvement in PC(20 ) , in contrast to poor ( < 1 doubling dilution ) improvement , was found to be associated with high sputum eosinophil levels ( 3.4 % vs 0.1 % ) and older age at onset of asthma ( age , 20 - 29 years vs < 10 years ) . CONCLUSIONS Near-maximal FEV(1 ) and PC(20 ) effects occurred with low-medium dose for both ICSs in the subjects studied . High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated , but it did increase the systemic effect measure , overnight cortisol secretion . Significant intersubject variability in response occurred with both ICSs . It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study , such as prevention of asthma exacerbations BACKGROUND : A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis , each given by metered dose inhaler to asthmatic patients . METHODS : Twelve asthmatic patients of mean age 29.9 years , with a forced expiratory volume in one second ( FEV1 ) 92.9 % predicted and forced expiratory flow 25 - 75 % ( FEF25 - 75 ) 69.5 % predicted , on less than or equal to 400 micrograms/day inhaled corticosteroid , were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400 , 1000 , 1600 , 2000 micrograms and fluticasone propionate 500 , 1000 , 1500 , 2000 micrograms . Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later . RESULTS : Serum cortisol levels compared with placebo ( mean 325.2 nmol/l ) were suppressed by fluticasone at doses of 1500 micrograms ( 211.6 nmol/l ) and 2000 micrograms ( 112.3 nmol/l ) and by budesonide at 2000 micrograms ( 243.4 nmol/l ) . Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms ( 95 % CI for difference 42.9 to 219.2 ) . The dose ratio ( geometric mean ) for the relative potency was 2.89 fold ( 95 % CI 1.19 to 7.07 ) . In terms of percentage suppression versus placebo , fluticasone propionate also produced greater effects ( means and 95 % CI for difference ) : budesonide 1600 micrograms ( 16.0 ) versus fluticasone propionate 1500 micrograms ( 40.9 ) ( 95 % CI -0.6 to 50.6 ) , budesonide 2000 micrograms ( 26.0 ) versus fluticasone 2000 micrograms ( 65.2 ) ( 95 % CI 10.5 to 67.8 ) . Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range ( 150 nmol/l ) for fluticasone and five of 24 for budesonide . Fluticasone propionate also caused greater ACTH suppression than budesonide ( as % versus placebo ) : budesonide 1600 micrograms ( 12.0 ) versus fluticasone propionate 1500 micrograms ( 31.9 ) ( 95 % CI 7.6 to 32.1 ) , budesonide 2000 micrograms ( 13.5 ) versus fluticasone propionate 2000 micrograms ( 44.4 ) ( 95 % CI 13.2 to 48.7 ) . For overnight 10 hour urinary cortisol ( nmol/10 hours ) there was a difference between the lowest doses of the two drugs : budesonide 400 micrograms ( 37.2 ) versus fluticasone propionate 500 micrograms ( 19.9 ) ( 95 % CI 6.9 to 27.8 ) . CONCLUSIONS : Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption . Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients This study was carried out in an attempt to compare the efficacy and safety of fluticasone propionate ( FP ) at the half dose of budesonide ( BUD ) and beclamethasone dipropionate ( BD ) in childhood asthma . Ninety-six children with moderate to severe asthma ( 9.6 ± 2.17 years ) whose asthma was already controlled on BUD ( n = 52 ) or BD ( n = 44 ) were recruited into the study . In the first part of the study ( the first 12 weeks ) each group was followed with three weekly lung function measurements , daily diary records , and peak expiratory flow ( PEF ) measurements on the initial medication . At the end of 6 weeks , drugs were switched to a half dose 
    Output:
    