Therapeutic ratio of hydrofluoroalkane and chlorofluorocarbon formulations of fluticasone propionate. A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation Adrenal function and high dose inhaled corticosteroids for asthma Significant variability in response to inhaled corticosteroids for persistent asthma. Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients. A Comparison of the Efficacy and Safety of a Half Dose of Fluticasone Propionate with Beclamethasone Dipropionate and Budesonide in Childhood Asthma A randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial of the minimal effective doses of budesonide and fluticasone dry-powder inhalers in adults with mild to moderate asthma. 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A dose-range comparison between fluticasone propionate and budesonide, measuring their effect on bronchial hyperresponsiveness and adrenal cortex function. Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma. An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers Effects of fluticasone propionate and beclomethasone dipropionate on parameters of inflammation in peripheral blood of patients with asthma Cost Effectiveness of Fluticasone and Budesonide in Patients with Moderate Asthma A randomized, double-blind comparison of beclomethasone dipropionate extrafine aerosol and fluticasone propionate. 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Knemometry, Urine Cortisol Excretion, and Measures of the Insulin-Like Growth Factor Axis and Collagen Turnover in Children Treated with Inhaled Glucocorticosteroids
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 of FP , and the subjects were followed for another 6 weeks . Blood sample s were obtained for osteocalcin and plasma cortisol levels after each treatment period . In the second part of the study , 50 patients continued to take FP at the half dose of BUD or BD for another 30 weeks . Clinic visits , including lung function and PEF measurements , were conducted every 10 weeks . After 6 weeks of FP treatment , there was a small but statistically significant decrease in FEV1 and FEF25–75 in both groups ( BUD and BD ) without any significant obstruction . These mild changes in lung function measurements continued during long-term follow-up . However , there was no statistically significant further decrease in any lung function parameters while receiving FP ( visits 3–8 ) ( coefficient = −0.00751 L/day , p = 0.39 for FEF25–75 and coefficient = −0.00910 L/sec/day , p = 0.055 for FEV1 ) . There were no significant changes in the morning and evening PEF measurements and diurnal PEF variations after 6 weeks of treatment with FP compared with BUD and BD treatments . There were no significant changes in basal cortisol and osteocalcin levels before or after 6 weeks of FP treatment ( p > 0.05 ) . The present study concluded that , although FP at the half dose of BUD or BD seems to maintain reasonable control of the disease symptoms , a mild but significant and persistent decrease in lung function parameters may indicate that FP may not be twice as potent as BUD or BD in childhood asthma by evaluation of lung functions . This conclusion must be further verified with long-term studies BACKGROUND Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma . Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses , they typically induce a near-maximal response in asthma patients . OBJECTIVE The aim of the present dose-response study was to estimate the minimal effective doses ( MEDs ) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma . METHODS This was a r and omized , double-blind , double-dummy , parallel-group , multicenter , dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids . After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d , patients fulfilling defined criteria for asthma control were r and omly allocated to treatment with budesonide or fluticasone , both administered BID at a total of 800 pg/d . At 5-week intervals , the dose was reduced to 400 and then 200 pg/d ( 200 and 100 pg BID ) if asthma control was maintained according to further defined criteria . The MED was defined as the last dose level before deterioration of asthma control . RESULTS Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group . In both groups , baseline mean forced expiratory volume in 1 second ( FEV(1 ) ) was 79.4 % of the predicted normal volume and baseline mean FEV(1 ) reversibility was 22.3 % . The median MED for both groups was 400 microg/d , with no detectable difference in dis-tributions . The budesonide-to-fluticasone ratio for the geometric mean MED was 123 % ( 95 % CI , 99 - 153 [ not significant ] ) . No statistically significant differences regarding lung function , symptom scores , or rescue medication usage were found between the treatment groups during the first treatment period . Adverse-event profiles were similar in both groups , and no unexpected adverse events were considered to be caused by the study drugs . CONCLUSION This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma Background : With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers , it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids . We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate ( FLU-HFA ) and beclomethasone dipropionate ( BEC-HFA ) at recommended labelled doses . Methods : Twenty mild to moderate asthmatics were r and omised in crossover fashion to receive 6 weeks of 500 μg/day followed by 1000 μg/day FLU-HFA and BEC-HFA . Measurements were made at baseline after placebo run in and washout , and after each r and omised treatment . The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second ( FEV1 ) of 20 % or more ( methacholine PD20 ) and for systemic adverse effects was overnight urinary cortisol/creatinine ( OUCC ) . Results : For mean responses , both doses of BEC-HFA and FLU-HFA produced significant improvements in PD20 compared with baseline . The improvement was not significantly greater with 1000 μg/day FLU-HFA versus BEC-HFA , a 1.69 fold difference ( 95 % CI 0.94 to 3.04 ) . Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline , with significantly ( p<0.05 ) lower values at 1000 μg/day for BEC-HFA versus FLU-HFA ( 1.97 fold difference ( 95 % CI 1.28 to 3.02 ) ) . Conclusion : There was no difference in the airway and systemic effects in patients with mild to moderate asthma  between FLU-HFA and BEC-HFA at a dose of 500 μg/day . At 1000 μg/day there was increased systemic bioactivity  with BEC-HFA compared with FLU-HFA , without any gain in airway efficacy Abstract Objective : The aim of this study was to evaluate the steady-state effects of once-daily inhaled fluticasone propionate ( FP ) and budesonide ( BUD ) on adrenocortical activity in asthmatic patients . Methods : Ten asthmatic patients with a mean age of 31.2 years , a mean forced expiratory volume in 1 s ( FEV1 ) of 91 % predicted and a forced mid-expiratory flow ( FEF25–75 ) of 62.3 % predicted were studied in a single-blind r and omised crossover design comparing placebo ( PL ) , FP ( 375 μg per day and 750 μg per day ) and BUD ( 400 μg per day and 800 μg per day ) all given once daily for 4 days at each dose via a pressurised metered dose inhaler ( pMDI ) at 0800 hours . After 4 days of treatment , plasma cortisol was measured at 0800 hours ( 24 h after the last dose ) and a 10-h overnight urine collection was taken , 14 h after the last dose ( 2200–0800 hours ) for analysis of cortisol and creatinine excretion . Results : Plasma cortisol levels ( nmol · l−1 , as geometric mean ) at 0800 hours demonstrated a significant difference between the highest doses of FP and BUD ( 424.1 vs 510.3 nmol · l−1 , respectively ) but not between the low doses ( 506.8 vs 514.9 nmol · l−1 ; PL 532.2 nmol · l−1 ) . For the highest dose FP ( 750 μg ) this equated to 20 % suppression of 0800 hours plasma cortisol . Likewise , for overnight urinary cortisol output ( nmol · 10 h−1 , as geometric mean ) , there was a significant difference at the high doses of FP and BUD ( 25.5 vs 38.2 nmol · 10 h−1 ) , but not at the low doses 31.3 vs 34.8 nmol · 10 h−1 ; PL 32.0 nmol · 10 h−1 . For the overnight urinary cortisol/creatinine ratio ( nmol · mmol−1 , as geometric mean ) there was a similar trend ; 4.5 vs 6.1 nmol · mmol−1 for high dose and 5.6 vs 6.3 nmol · mmol−1 for low dose ; PL 5.9 nmol · mmol−1 . Conclusion : Repeated doses of FP 750 μg once daily caused greater adrenal suppression than BUD 800 μg once daily , when comparing effects on plasma cortisol levels at 0800 hours , 24 h after the last dose , as well as effects on overnight urinary cortisol output . Neither FP 375 μg once daily nor BUD 400 μg once daily produced detectable adrenal suppression Qvar Autohaler efficacy on asthma control , assessed with E. Juniper asthma control question naire ( ACQ ) , was compared with fluticasone and budesonide . An open r and omized study , stratified ( 2:1 ) on the intake of long-acting beta2-mimetics ( LAbeta2 ) , was performed in patients with moderate to severe poorly controlled asthma ( defined by at least one nocturnal discomfort in the last 5 days or a mean of 2 puffs of short-acting beta2-mimetics in the last 7 days or exercise dyspnea ) despite treatment with beclomethasone < or = 1000 microg/day ( or equivalent ) . 460 patients received Qvar Autohaler 800 microg/day ( n = 149 ) , fluticasone Diskus 1000 microg/day ( n = 149 ) or budesonide Turbuhaler 1600 microg/day ( n = 162 ) during 12 weeks . Asthma control improved in all groups , with no difference between groups . For patients treated with LAbeta2 ( n = 286 ) a significantly greater improvement of the ACQ score was obtained with Qvar Autohaler versus fluticasone ( 1.0 + /- 1.0 vs. 0.6 + /- 0.9 ; P = 0.019 ) , but not versus budesonide ( 0.9 + /- 0.9 ) . Pulmonary function test improvements were similar in the 3 groups . The significant improvement in asthma control in patients receiving LAbeta2 suggests potential advantages for extrafine aerosols as part of anti-inflammatory treatment optimization BACKGROUND --High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma . Although effective , they may cause systemic side effects .  Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses . METHODS --Fluticasone propionate , 1.5 mg per day , was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma ; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate .  The study was multicentre , double blind and of a parallel design . For the first three months patients attended the clinic every four weeks and completed daily diary cards . For the next nine months they were only seen at three monthly intervals in the clinic . RESULTS --During the first three months diary card peak expiratory flow ( PEF ) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate ( difference in morning PEF 15 l/min ( 95 % CI 6 to 25 ) ) , and these differences were apparent at the end of the first week . The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8 % compared with those receiving beclomethasone dipropionate . No significant differences between the two groups were observed in morning plasma cortisol levels , urinary free cortisol levels , or response to synthetic ACTH stimulation . In addition , both the rates of withdrawal and of adverse events were low , and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate . CONCLUSIONS --This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate , with no increase in systemic or other side effects BACKGROUND : In a previous single dosing comparison between fluticasone propionate and budesonide differences in cortisol levels measured at 08.00 hours were observed at doses in excess of 1000 micrograms . The aim of this study was to compare the adrenal suppression caused by chronic twice daily dosing with inhaled fluticasone propionate ( FP ) and budesonide ( B ) given on a microgram equivalent basis by metered dose inhaler to asthmatic patients . METHODS : Twelve stable asthmatic patients of mean age 29.7 years with forced expiratory volume in one second ( FEV1 ) 89.0 % predicted and mid forced expiratory flow ( FEF25 - 75 ) 58.9 % predicted , on 400 micrograms/day or less of inhaled corticosteroid , were studied in a double blind , placebo controlled , crossover design comparing inhaled budesonide and fluticasone propionate in doses of 250 micrograms , 500 micrograms , and 1000 micrograms twice daily . Each dose was given at 08.00 hours and 22.00 hours for four days by metered dose inhaler with mouth rinsing . Measurements were made of overnight urinary cortisol excretion and plasma cortisol levels at 08.00 hours , 10 hours after the eighth dose . RESULTS : The plasma cortisol levels ( nmol/ l ) at 08.00 hours showed that fluticasone propionate produced lower cortisol levels than budesonide at all three dose levels : F500 333.8 , B500 415.2 ( 95 % CI 28.9 to 134.0 ) ; F1000 308.3 , B1000 380.3 ( 95 % CI 10.5 to 133.5 ) ; F2000 207.3 , B2000 318.5 ( 95 % CI 5.8 to 216.7 ) ; placebo 399.9 . Fluticasone produced greater effects than budesonide on the overnight urinary cortisol/creatinine ratio ( nmol/mmol ) at all three dose levels : F500 3.12 , B500 5.55 ( 95 % CI 0.16 to 3.79 ) ; F1000 2.54 , B1000 6.12 ( 95 % CI 1.25 to 5.91 ) ; F2000 2.07 , B2000 6.09 ( 95 % CI 0.88 to 7.18 ) ; placebo 5.23 . CONCLUSIONS : With repeated dosing across a dose range of 250 - 1000 micrograms twice daily , fluticasone propionate produced significantly greater adrenal suppression than budesonide for both plasma and urinary cortisol . It was therefore possible to demonstrate differences between fluticasone and budesonide at lower doses with chronic dosing from those previously found with single dosing when given on a microgram equivalent basis in asthmatic patients . Factors contributing to the systemic adverse activity profile of fluticasone comprise enhanced receptor potency , prolonged receptor residency time , greater tissue retention , and a longer elimination half life OBJECTIVE To compare the long-term effect of treatment with fluticasone propionate or beclomethasone dipropionate on growth in asthmatic children . DESIGN Prospect i ve , multicenter , r and omized , double-blind , parallel-group study . SETTING Children requiring regular treatment with inhaled corticosteroids and with a sexual maturity rating of Tanner stage 1 ( prepubertal ) . PATIENTS Three hundred forty-three children aged 4 to 11 years with asthma . The growth population ( excluding patients with protocol violations likely to affect growth measurements ) included 277 patients . INTERVENTIONS Fluticasone propionate or beclomethasone dipropionate , both at a dosage of 200 microg administered twice daily via a dry powder inhaler ( Diskhaler ) for 12 months . MAIN OUTCOME MEASURES Growth velocity , lung function , and serum and urinary cortisol levels . RESULTS The adjusted mean growth velocity in the fluticasone group was significantly greater than that in the beclomethasone group ( 5.01 [ SE , 0.14 ] vs 4.10 [ SE , 0.15 ] cm/y ; difference , 0.91 cm ; 95 % confidence interval , 0.63 - 1.20 cm ; P<.001 ) . Both treatments improved lung function , with significant differences in favor of fluticasone .  Adverse events were similar in both groups , and there were no significant differences in effect on serum and urinary cortisol levels . CONCLUSIONS The more favorable risk-benefit ratio of fluticasone indicates that this agent is preferable to beclomethasone for the long-term treatment of children with asthma , especially if moderate doses are required We wanted to evaluate the improvement in efficacy when increasing the daily dose of inhaled steroids and to compare the efficacy , safety , and tolerance of 1.6 mg beclomethasone dipropionate ( BDP ) with that of 2.0 mg fluticasone propionate ( FP ) . The study was a r and omized , double-blind , 3 month , multicentre study . One hundred and thirty four asthmatics currently using inhaled steroids ( 0.4 - 1.6 mg BDP or budesonide ( BUD ) )  were stratified according to pretrial daily steroid use . Within each stratum they were r and omized to either 1.6 mg BDP or 2.0 mg FP . A significant increase in the primary efficacy variables , i.e. mean morning and evening peak expiratory flow ( PEF ) ( approximately 20 l.min-1 ) during the treatment period , was found for both treatments . No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables ( use of beta 2-agonists , symptom scores , and PEF , forced vital capacity ( FVC ) , forced expiratory volume in one second ( FEV1 ) recorded at the clinical visits ) . However , significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone . We conclude that , although both treatments gave statistically significant increases in efficacy parameters when compared with baseline , the increases were so small that they can be regarded as being clinical ly unimportant . Daily doses of BDP , 1.6 mg , and FP , 2.0 mg , had comparable effects on lung function . A suppression of the hypothalamic pituitary adrenal ( HPA ) axis was only found with a daily dose of 2 mg FP Inhaled steroids are frequently used in childhood asthma , but concerns based on limited objective evidence remain , regarding long-term side-effects . In this study the systemic effects of st and ard doses of inhaled steroids in childhood asthma were assessed , comparing beclomethasone dipropionate ( BDP ) with fluticasone propionate ( FP ) . The study was prospect i ve , r and omized and double-blind . Twenty-three steroid-naive children with moderately severe asthma , aged 5 - 10 yrs , were allocated either BDP ( 400 microg x day(-1 ) or FP ( 200 microg x day(-1 ) ) using a metered-dose inhaler with a spacer . Asthma control was assessed at regular intervals over 20 months . Fasting morning blood and overnight urine sample s were collected for estimation of serum cortisol , serum 1-carboxyterminal telopeptide ( ICTP ) , serum osteocalcin and urine deoxypyridinoline ( DPD ) . Bone mineral density ( BMD ) was measured at each visit . None of the markers of bone turnover showed any change during the study period . BMD increased at normal rates with age . Serum cortisol significantly decreased on BDP , but not on FP . A significant difference in growth rates was found between the groups , with a slower rate of growth towards the end of the observation period in the BDP group . In conclusion when taken in a relatively modest dose over a period of time , beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma . These systemic effects were not seen with an equipotent dose of fluticasone propionate BACKGROUND The potential for long term adverse effects from inhaled corticosteroids relates to their systemic absorption , usually assessed from proxy markers in short term studies . When fluticasone propionate and budesonide have been compared in this way the results have been inconsistent . To determine whether this is because of the subjects studied or the sensitivity of the systemic marker used , we have compared the effects of fluticasone propionate and budesonide in healthy and asthmatic subjects and investigated the effect of treatment on three systemic markers . METHODS Forty six healthy subjects were r and omised to receive inhaled fluticasone propionate 1500 μg/day ( via an Accuhaler ) , budesonide 1600 μg/day ( via a Turbuhaler ) , or placebo ;  31 subjects with moderately severe asthma were r and omised to receive the same doses of fluticasone propionate or budesonide but not placebo . Systemic effects in healthy and asthmatic subjects were compared after 7 days . Treatment was continued for another 21 days in the subjects with asthma when systemic effects and asthma control were assessed . RESULTS At baseline healthy subjects had higher urinary levels of total cortisol metabolites ( TCM ) than subjects with asthma . After 7 days of treatment with fluticasone propionate urinary TCM levels in the healthy subjects were significantly lower than in the subjects with asthma ( mean difference between groups 1663 μg/day , 95 % CI 328 to 2938 ) . This was not the case with budesonide , however , where urinary TCM levels in the healthy subjects remained above those in the asthmatic subjects ( mean difference between groups 1210 μg/day , 95 % CI –484 to 2904 ) . Urinary TCM levels were considerably more sensitive to the effects of inhaled corticosteroids than morning serum cortisol or osteocalcin concentrations .  Only budesonide reduced the serum level of osteocalcin . CONCLUSIONS When given by dry powder inhaler for 7 days , fluticasone propionate 1500 μg/day has a greater effect on the hypothalamic-pituitary-adrenal axis in healthy subjects than in subjects with asthma , but this is not the case for budesonide 1600 μg/day . These findings , together with the differences in sensitivity between systemic markers , explain many of the discrepancies in the literature Few thorough comparisons of the systemic effects of inhaled corticosteroids in children are available . The aim of this study was to compare the effect of budesonide and fluticasone propionate on short-term lower leg growth .  Fluticasone propionate , budesonide and placebo were administered for 2 weeks in a r and omized , double-blind , double-dummy , cross-over design . Twenty four children aged 6 - 12 yrs received 200 microg x day(-1 ) of each drug , or placebo .  Another 24 children aged 6 - 12 years received 400 microg x day(-1 ) of each drug , or placebo . Dry powder inhalers were used . Lower leg length was measured by knemometry twice a week during all three treatment periods , and 24 h cortisol excretion in the urine was measured at the end of each period . In the low-dose group , lower leg growth rate was the same during treatment with placebo ( 0.35 mm x week(-1 ) ) , fluticasone propionate ( 0.38 mm x week(-1 ) ) or budesonide ( 0.26 mm x week(-1 ) ) . No significant difference ( p=0.39 ) in lower leg growth rate was found between treatment with 400 microg x day(-1 ) budesonide ( 0.30 mm x week(-1 ) ) and 400 microg fluticasone propionate treatment ( 0.37 mm x week(-1 ) ) . Growth rate during treatment with budesonide , 400 microg x day(-1 ) , was significantly lower than during placebo treatment ( 0.52 mm x week(-1 ) ) . Cortisol excretion in the urine during treatment with 200 microg x day(-1 ) fluticasone propionate was significantly reduced as compared with placebo ( p=0.006 ) , but not when compared with 200 microg x day(-1 ) budesonide ( p=0.07 ) . Budesonide 200 microg x day(-1 ) was not significantly different from placebo . Fluticasone propionate and budesonide , both at 400 microg x day(-1 ) , result ed in a significant reduction in cortisol excretion in the urine as compared with placebo ( p=0.001 ) . It is concluded that , dose-for-dose , budesonide Turbuhaler and fluticasone propionate Diskhaler have similar systemic effects The aim of this study was to compare fluticasone propionate ( FP ) with budesonide ( BUD ) at a dose of 400 microg x day(-1 ) in the treatment of children with asthma . Two hundred and twenty nine children with mild-to-moderate asthma , currently receiving 200 - 400 microg x day(-1 ) of inhaled corticosteroid  , were r and omized to receive either 400 microg x day(-1 ) of FP from the Diskhaler ( registered trade mark of the Glaxo Group of Companies ) or 400 microg x day(-1 ) of BUD from the Turbuhaler ( registered trade mark of Astra Pharmaceuticals Ltd ) for 8 weeks , in a parallel-group , double-blind , double-dummy study . Primary efficacy was assessed by measurement of daily peak expiratory flow ( PEF ) . In addition , pulmonary function tests were performed at each clinic visit and a self-administered patient-centred question naire was completed by one parent of each patient at the start and end of study treatment . Mean morning PEF increased following treatment both with FP and BUD , but was significantly higher following treatment with FP during Weeks 1 - 4 ( p=0.015 ) and Weeks 1 - 8 ( p=0.019 ) . Similar results were found for mean evening PEF and percentage predicted morning and evening PEF . Children receiving FP experienced significantly less disruption in their physical activities ( i.e. sports , games ) because of their asthma compared to children treated with BUD ( p=0.03 ) . Mean cortisol levels increased in both groups , but the increase was significantly higher in the FP group at 4 weeks ( p=0.022 ) . Serum and urine markers of bone formation and resorption changed very little and showed no consistent pattern of change . Fluticasone propionate at a dosage of 400 microg x day(-1 ) from the Diskhaler provided a more rapid and greater improvement in lung function in children with mild-to-moderate asthma than BUD 400 microg day(-1 ) from the Turbuhaler . Both treatments were well-tolerated , with a similar safety profile Background : It is important to be able to compare the efficacy and systemic effects of inhaled corticosteroids but their slow onset of action makes it difficult to measure the maximum response to a given dose . Submaximal responses could be compared if the time course of action of the inhaled corticosteroids being compared was similar . We have compared the time course of action of fluticasone and budesonide , measuring response as change in the provocative dose of adenosine monophosphate causing a 20 % fall in forced expiratory volume in 1 second ( PD20AMP ) . Methods : Eighteen subjects with mild asthma , aged 18–65 , took part in a three way r and omised crossover study . Subjects took fluticasone ( 1500 μg/day ) , budesonide ( 1600 μg/day ) , and placebo each for 4 weeks with a washout period of at least 2 weeks between treatments ; PD20AMP and forced expiratory volume in 1 second ( FEV1 ) were measured during and after treatment . The time taken to achieve 50 % of the maximum response ( T50 % ) was compared as a measure of onset of action . Results : There was a progressive increase in PD20AMP during the 4 weeks of treatment with both fluticasone and budesonide but not placebo ; the increase after 1 and 4 weeks was 2.28 and 4.50 doubling doses ( DD ) for fluticasone and 2.49 and 3.65 DD for budesonide . T50 % was 9.3 days for fluticasone and 7.5 days for budesonide with a median difference between fluticasone and budesonide of 0.1 days ( 95 % CI −1.4 to 2.65 ) . There was a wide range of response to both inhaled corticosteroids but good correlation between the response to fluticasone and budesonide within subjects . FEV1 and morning peak expiratory flow rate ( PEFR ) increased during the first week of both active treatments and were stable thereafter . There was a small progressive improvement in nocturnal symptoms with both active treatments . Conclusion : PD20AMP was a more sensitive marker of response to inhaled corticosteroid therapy than FEV1 and PEFR . The time course of action of fluticasone and budesonide on PD20AMP is similar , suggesting that comparative studies of their efficacy using 1 or 2 week treatment periods are valid . When a new inhaled corticosteroid becomes available , a pilot study comparing its time course of action with that of an established corticosteroid should allow comparative studies to be performed more efficiently Abstract Objectives To determine whether the dose of inhaled corticosteroids can be stepped down in patients with chronic stable asthma while maintaining control . Design One year , r and omised controlled , double blind , parallel group trial . Setting General practice s throughout western and central Scotl and . Participants 259 adult patients with asthma receiving regular treatment with inhaled corticosteroids at high dose ( mean dose 1430 μg beclomethasone dipropionate ) . Interventions Participants were allocated to receive either no alteration to their dose of inhaled corticosteroid ( control ) or a 50 % reduction in their dose if they met criteria for stable asthma ( stepdown ) . Main outcome measures Comparison of asthma exacerbation rates , asthma related visits to general practice and hospital , health status measures , and corticosteroid dosage between the two groups . Results The proportions of subjects with asthma exacerbations were not significantly different ( stepdown 31 % , control 26 % , P=0.354 ) . Similarly , the numbers of visits to general practice or hospital and the disease specific and generic measures of health status over the one year period were not significantly different . On average the stepdown group received 348 μg ( 95 % confidence interval 202 μgto494 μg ) of beclomethasone dipropionate less per day than the controls ( a difference of 25 % ) , with no difference in the annual dose of oral corticosteroids between the two treatment regimens . Conclusions By adopting a stepdown approach to the use of inhaled steroids at high doses in asthma a reduction in the dose can be achieved without compromising asthma control BACKGROUND Inhaled corticosteroids are recognised as the most effective agents in the treatment of asthma . However , concerns have been expressed about the effects of high doses of inhaled corticosteroids on safety in relation to bone resorption and formation . This study measures the effects of two inhaled corticosteroids on bone markers and bone mineral density ( BMD ) over one year . METHODS A one year r and omised , prospect i ve , open parallel study comparing inhaled fluticasone propionate ( FP ) , 500 μg twice daily in 30 patients , and budesonide ( BUD ) , 800 μg twice daily in 29 patients , delivered by metered dose inhaler and large volume spacers was performed in adults with moderate to severe asthma . Biochemical markers of bone turnover ( osteocalcin , procollagen type 1 C-terminal propeptide ( PICP ) , immunoreactive free deoxypyridinoline ( iFDpd ) , N-terminal crosslinked telopeptides of type I collagen ( NTx ) ) , BMD at the spine and femoral neck , and serum cortisol concentrations were measured at baseline and 12 months later . RESULTS There were no significant differences between the inhaled steroids on bone markers of bone resorption and formation or bone mineral density . Bone mineral density of the spine increased slightly in both groups over the 12 month period . Serum osteocalcin levels increased from baseline in both treatment groups ( FP 16.9 % , p = 0.02 ; BUD 14.3 % , p = 0.04 ) . PICP did not differ significantly from baseline . Both markers of bone resorption ( iFDpd , NTx ) varied considerably with no significant changes after one year . There was a significant correlation in percentage change from baseline between BMD of the spine and osteocalcin at 12 months ( r = 0.4 , p = 0.017 ) . Mean serum cortisol levels remained within the normal range in both groups following treatment . CONCLUSION There was no evidence of a decrease in BMD during 12 months of treatment with high doses of either FP or BUD . The change in spine BMD correlated with the increase in osteocalcin . Studies extending over several years are needed to establish whether these findings persist OBJECTIVE High-dose inhaled corticosteroids ( ICS ) have been associated with the same side-effects as oral corticosteroids . Beclomethasone dipropionate ( BDP ) and budesonide ( BUD ) in doses greater than 2000 microg/day are used regularly in severe asthma , despite the fact that safety and efficacy data at such high doses are limited . Fluticasone propionate ( FP ) has been promoted as being twice as potent clinical ly as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile . The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD . METHODOLOGY Patients fulfilling the entry criteria were r and omized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open , parallel group study . The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards , while determination of safety was based on a number of endpoints including changes in bone turnover indices , the incidence of topical side-effects and assessment s of quality of life . RESULTS It was shown that patients who were switched to FP , but not those continuing with BDP or BUD , had significant increases in levels of morning serum cortisol and the urine cortisol : creatinine ratio while maintaining asthma control . Serum osteocalcin and the pyridinoline : creatinine ratio , as well as the deoxypyridinoline : creatinine ratio , were also shown to increase only in the FP group . Subjective assessment s such as quality of life score , the incidence and ease of bruising , and reports of hoarseness also favoured the FP group . CONCLUSIONS It is concluded that , at the doses studied and with the delivery devices used clinical ly , FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects Abstract : There is a dearth of data on long-term effects of inhaled corticosteroids ( ICS ) on bone architecture in childhood asthma . This study was design ed to assess the possible effects of two different inhaled steroids on bone mineral density ( BMD ) in steroid-native , prepubertal children . Twenty-three children were r and omized to receive equipotent doses of either fluticasone propionate ( 100 mg twice daily ) or beclomethasone dipropionate ( 200 mg twice daily ) . They were followed up over a period of 20 months with regular dual-energy X-ray absorptiometry scans for BMD . Densitometry of lumbar spine and total body showed a significant increase over time , which followed the normal patterns for growth . No difference was observed between the two subgroups . There was no change in fat distribution over time and no increase in percentage total body fat . As expected , girls had significantly higher total body fat . This absence of deleterious effects suggests that in the st and ard doses used neither beclomethasone nor fluticasone has any significant effect on bone density over a moderate period of time . Further studies should continue monitoring BMD through the critical years of bone mass accumulation during adolescence This r and omized , double-blind , double-dummy , multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal ( HPA ) axis of fluticasone propionate ( 750 microg twice daily given via the Diskus ) and budesonide ( 800 microg twice daily given via the Turbuhaler ) . Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period . During run-in and washout , patients received beclomethasone dipropionate ( BDP ) or budesonide at a constant dose of 1500 - 1600 microg day(-1 ) . Sixty patients aged 18 - 75 years with moderate to severe asthma not fully controlled by treatment with 1500 - 1600 microg day(-1 ) budesonide or BDP  entered run-in and 45 completed the study . HPA axis suppression was assessed by morning serum cortisol ( area under the curve from 08.00 to 10.30 hours ) and 12-h nocturnal urinary cortisol excretion , measured at the end of run-in ( baseline 1 ) , at the end of washout ( baseline 2 ) , and at the end of each treatment period . Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines . Only a few patients had serum-cortisol and urinary cortisol values below the normal range , before and after treatment . This shows that the patients did not have adrenal suppression before entering the study . The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 ( 95 % CI 0.92 - 1.06 ) , indicating equivalent effects on the HPA axis . This result was achieved after having omitted two patients ' results , due to their very sensitive reaction to budesonide , but not to fluticasone . Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment . Both treatments were well tolerated . In conclusion , budesonide 1600 microg day(-1 ) via Turbuhaler and fluticasone propionate 1500 microg day(-1 ) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma In the treatment of asthma , inhaled steroids are more effective than cromolyn , whereas the latter offers extreme safety . The aim of the present pilot study was to evaluate , contemporarily , efficacy and safety aspects of different asthma treatment modalities . In 75 school-age children ( mean age 9.5 years ; range 5.5 - 14.7 years ) , treatment of asthma was started with budesonide ( BUD , n = 30 ) , fluticasone propionate ( FP , n = 30 ) or cromones ( CROM , n = 15 ) . BUD was used at a dose of 800 microg/day during the first 2 months and at 400 microg/day thereafter . The respective FP doses were 500 and 200 microg/day . Efficacy of the treatment was assessed by measuring forced expiratory volume in 1 second ( FEV1 ) and by evaluating the use of bronchodilators . Side-effects of the treatment were evaluated by following growth of the children and by performing low-dose adrenocorticotropin ( ACTH ) testing . At 4 months FEV1 had improved by a mean of 8.2 % in the BUD group and by 5.4 % in the FP group ( p < 0.01 vs. baseline in both groups ; NS between BUD and FP groups ) . The use of bronchodilators had decreased from five doses/week to one dose/week in the BUD group ( p < 0.05 ) , and from three doses/week to one dose/week in the FP group ( p < 0.01 ) ( NS between the groups ) . In the CROM group , the FEV1 value and the use of bronchodilators did not change . The treatment was unsuccessful on the basis of FEV1 decrease and increased bronchodilator use in , respectively , 30 and 15 % of the BUD- , 20 and 7 % of the FP- , and 50 and 47 % of the CROM-treated children . Therefore , to prevent one treatment failure in the CROM group , between three and five children would need to move to treatment with steroids . The treatment had measurable systemic effects on the basis of height st and ard deviation ( SD ) score decrease and minor adrenocortical suppression in , respectively , 60 and 30 % of the BUD- , 27 and 17 % of the FP- , and 20 and 0 % of the CROM-treated children . Therefore , to avoid systemic effects in one steroid-treated child , three BUD- and six to 14 FP-treated children would need to move to treatment with CROM . In conclusion , in school-age children asthma should be treated first with inhaled steroids . It is probable that the best combination of efficacy and safety can be achieved by using low steroid doses Short-term lower leg growth was investigated with twice weekly knemometry measurements in 19 schoolchildren with mild asthma during treatment with daily doses of 200 micrograms fluticasone propionate  , 400 micrograms , and 800 micrograms beclomethasone dipropionate from a dry powder inhaler . The design was a r and omised , double blind , crossover trial . After a run in period of four days ( period 1 ) the children were allocated to a sequence of active treatments in periods 2 , 4 , and 6 . In periods 3 and 5 ( wash out ) placebo was given . All periods except the run in were two weeks long . The mean lower leg growth velocities during the wash out periods were 0.61 and 0.80 mm/week . Mean growth velocities during treatment with fluticasone propionate and low and high doses of beclomethasone dipropionate were 0.34 , 0.09 , and 0.06 mm/week respectively . Compared with fluticasone propionate , treatment with beclomethasone dipropionate 400 and 800 micrograms/day was associated with a statistically significant reduction in growth velocity Inhaled corticosteroids have become the mainstay treatment of bronchial asthma . However , simultaneous evaluations of efficacy and side effects are few . This study aim ed to compare the relative effect of fluticasone propionate ( FP ) and budesonide ( BUD ) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma . The study was double-blind and included 66 adults with asthma , who were r and omized to FP ( n = 33 ) or BUD ( n = 33 ) . Pre study , all participants were clinical ly stable , using inhaled corticosteroids and hyperresponsive to methacholine . Eligible patients were r and omized to three consecutive 2-wk periods with either FP 250 microg twice daily , FP 500 microg twice daily , and FP 1,000 microg twice daily , or BUD 400 microg twice daily , BUD 800 microg twice daily , and BUD 1,600 microg twice daily , delivered by Diskhaler and Turbuhaler , respectively . Before r and omization and at the end of each treatment , bronchial methacholine PD(20 ) , 24-h urinary cortisol excretion ( 24-h UC ) , plasma cortisol , serum osteocalcin , and blood eosinophils were determined . The relative PD(20 ) potency between FP and BUD was 2.51 ( 95 % CI , 1.05 - 5.99 ; p < 0 . 05 ) , while the relative 24-h UC potency was 0.60 ( 95 % CI , 0.44 - 0.83 ; p < 0.01 ) . The differential therapeutic ratio ( FP/BUD ) based on PD(20 ) potency and 24-h UC was 4.18 ( 95 % CI , 1.16 - 15.03 ; p < 0.05 ) . The difference in systemic potency was also seen for plasma cortisol , serum osteocalcin , and blood eosinophils . Therapeutic ratio over a wide dose range , determined by impact on bronchial responsiveness and endogenous corticosteroid production , seems to favor FP This study was design ed to compare the efficacy and safety of a new inhaled corticosteroid , fluticasone propionate at a total daily dose of 200 micrograms , with beclomethasone dipropionate 400 micrograms/day in childhood asthma . A total of 398 asthmatic children ( aged 4 - 19 years ) were r and omised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler . During the study the patients recorded morning and evening peak expiratory flow rate ( PEFR ) , symptom scores , and use of beta 2 agonist rescue medication . In addition , clinic visit PEFR and forced expiratory volume in one second were measured . Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment . For the purpose s of analysis the diary card data were grouped into three periods : week 3 ( days 15 - 21 ) , week 6 ( days 36 - 42 ) , and weeks 1 - 6 ( days 1 - 42 ) . The results showed no significant difference between treatments on most efficacy parameters . However , there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 ( fluticasone propionate 6.1 % , beclomethasone dipropionate 3.9 % ) and at week 6 ( fluticasone propionate 8.3 % , beclomethasone dipropionate 5 . 9 % ) and % predicted evening PEFR at week 6 ( fluticasone propionate 7.3 % , beclomethasone dipropionate 4.9 % and over weeks 1 - 6 ( fluticasone propionate 5.5 % , beclomethasone dipropionate 3.6 % . Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 ( fluticasone propionate 87 % , beclomethasone dipropionate 81 % ) and % days without rescue medication at week 6 ( fluticasone propionate 87 % , beclomethasone dipropionate 80 % ) and over weeks 1 - 6 ( fluticasone propionate 80 % , beclomethasone dipropionate 73 % ) . Except for a higher incidence of sore throat in the fluticasone propionate group , the two treatments did not differ with regard to safety . There was no evidence of adrenal suppression with either treatment . In conclusion , fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma The systemic effects of single and multiple doses of inhaled fluticasone propionate ( FP ) and budesonide were examined in 24 healthy male volunteers ( age range 18–29 years ) . The study was of an open , placebo-controlled , r and omized , three-way crossover design . On each study day , multiple blood sample s were taken over a 20 h period after drug administration ( after a single dose and after the last of seven doses ) and area under the curve ( AUC0–20 ) for plasma cortisol and white blood cell ( WBC ) counts was calculated . Results : The present study shows that multiple dosing with FP 1.0 mg b.i.d . for 3.5 days ( seven doses ) result ed in a marked cortisol suppression from placebo which , at 55 % , was more than double that seen with a single dose ( 25 % suppression ) . Multiple dosing with budesonide 0.8 mg b.i.d . result ed in a 34 % suppression in plasma cortisol compared with a suppression of 26 % with a single dose . The increase in systemic activity of  FP  after multiple dosing is confirmed by both the number of subjects with 0800 hours plasma cortisol values below normal limits and by the changes in WBC and differential counts . Conclusion : The results of the present study confirm previous findings with regard to the more marked systemic effect of  FP  following multiple dosing as compared with a single dose . This increase in systemic effect from single dosing to multiple dosing is significantly greater for FP than for budesonide Bronchial inflammation plays a central role in asthma . We investigated whether parameters of inflammation were increased in peripheral blood . Furthermore , we tested whether fluticasone propionate ( FP ) , a new inhaled corticosteroid ( ICS ) , and beclomethasone dipropionate ( BDP ) affected these parameters . FP 750 μg/day and BDP 1500 μg/day were compared in a r and omized , crossover study consisting of two 6‐week treatment periods , each preceded by a 3‐week placebo period . Twenty‐one patients with symptomatic asthma completed the study . The results were compared with those of six normal subjects ( controls ) . Immunophenotyping of inflammatory cells was performed in whole blood , and serum eosinophil cationic protein ( ECP ) was measured . With regard to clinical efficacy , ICS increased PCjo histamine by more than 1.9 doubling doses and FEV , by more than 0.34 1 . The number of CD3/HLA‐DR+ lymphocytes was significantly increased in asthmatics compared to the normal subjects , both after placebo ( P<0.01 ) and after therapy ( P<0.05 ) . The CD3/HLA‐DR‐H lymphocytes decreased significantly after treatment with FP ( P<0.05 ) . Serum ECP was elevated in patients without ICS and decreased after treatment with BDP ( P<0.001 ) . In conclusion , the number of CD3/HLA‐DR‐I‐ lymphocytes and serum ECP levels were raised in the peripheral blood of symptomatic asthmatics , and decreased by clinical ly effective doses of ICS . In this respect , FP 750 ng/day was at least as effective as BDP 1500 μg/day Abstract Objective : The objective of this study was to assess the relative cost effectiveness of fluticasone via metered dose inhaler and budesonide via Turbuhaler ® in corticosteroid-naive patients with moderate asthma from a third-party payer perspective ( German Sickness Funds ) . Patients and Methods : A retrospective economic assessment of direct medication costs of treatment was performed on data from a prospect i ve , r and omised , parallel group , 6-week clinical trial . 457 corticosteroid-naive patients between the ages of 18 and 70 years with moderate asthma were included in the intention-to-treat analysis . Results : The fluticasone group had a higher proportion of successfully treated patients ( those with a peak expiratory flow rate improvement of ≥10 % ) [ 47 vs 42 % ] , a higher average proportion of symptom-free days ( 40 vs 34 % ) and lower direct healthcare costs [ 1997 Deutschmarks ( DM ) ] per day ( DM4.23 vs DM5.19 ) than the budesonide group . Therefore , the daily costs per successfully treated patient ( DM9.00 vs DM12.36 ) and the cost per symptom-free day ( DM10.58 vs DM15.26 ) were both lower with fluticasone than with budesonide . Sensitivity analysis demonstrated that these results were relatively robust over a wide range of plausible assumptions . Conclusion : These results showed that from the perspective of a third-party payer , fluticasone was more cost effective  than budesonide over the 6-week study period BACKGROUND Inhaled corticosteroids provide first-line treatment for asthma . An advance to improve potency was to produce new molecules with increased glucocorticoid receptor affinity ( eg , fluticasone propionate [ FP ] ) . An alternative is to deliver more medication to both the large and small airway inflammation of asthma by using an extrafine aerosol ( eg , beclomethasone dipropionate extrafine aerosol [ BDP-extrafinel ) . OBJECTIVE To demonstrate clinical equivalence of BDP-extrafine ( 400 microg daily ) and FP ( 400 microg daily ) in symptomatic asthmatic patients over the course of 6 weeks . METHODS This was a double-blind , double-dummy , parallel-group , multicenter , 6-week study in adults with asthma taking conventional FP 100 to 250 microg daily or equivalent , and displaying signs/symptoms of active disease requiring additional therapy . RESULTS Eighty-eight patients were r and omized to BDP-extrafine ( and FP-placebo ) and 84 to FP ( and BDP-placebo ) . There were no significant differences between treatments with respect to symptom control , as evidence d by mean change from baseline in percentage days without asthma symptoms/nights without sleep disturbance observed at weeks 1 to 2 , 3 to 4 , or 5 to 6 . Mean changes from baseline in AM PEFR at weeks 5 to 6 for BDP-extrafine ( 19.0 ) and FP ( 30.5 ) were equivalent ( P = 0.022 for equivalence ) . There were significant ( P < 0.001 ) within-treatment-group differences in mean change from baseline in AM PEFR at weeks 1 to 2 for both treatments . There was no difference in the incidence of patients reporting at least one adverse event during the study ( BDP-extrafine 41 % ; FP 37 % ) . Mean percentage change from baseline for AM plasma cortisol at week 6 was + 17.7 % for BDP-extrafine and + 4.2 % for FP ( P = 0.066 for difference ) . CONCLUSIONS BDP-extrafine and FP at doses of 400 microg daily provided equivalent asthma control in patients with symptomatic asthma and exhibited similar safety profiles A total of 261 patients with symptomatic , mild to moderate asthma were r and omized to treatment in this 4‐week , double‐blind , parallel‐group comparison of fluticasone propionate 200 μg/d with beclomethasone dipropionate 400 μg/d . Improvements from both treatments were seen in diary card data . Morning peak expiratory flow rate ( PEFR ) improved from 375 to 390 and 371 to 382 1/min with fluticasone propionate and beclomethasone dipropionate , respectively . Symptom scores , percentage of symptom‐free days and nights , and use of rescue ( β2‐agonist medication also improved , as did clinical lung function . With the exception of percentage of rescue‐free days , which was greater for beclomethasone dipropionate , none of the differences between the groups were statistically significant . There was a significant difference between treatments in the number of rescue‐free days over days 1–28 ; however , there was no difference between treatments in the number of rescue‐free days over days 1‐14 , nor was there any difference in the number of inhalations of rescue medication used throughout the study . Very few adverse effects were reported . Although all mean plasma cortisol values were within the normal range , they were significantly different between treatments , rising from 402 to 429 nmol/1 with fluticasone propionate , and falling from 435 to 394 nmol/1 with beclomethasone dipropionate  ( P= 0.006 ) . Mean stimulated cortisol levels 30 min after tetracosactin injection were also significantly greater with fluticasone propionate ( P = 0.024 ) . In conclusion , fluticasone propionate 200 μg/d is as effective as beclomethasone dipropionate 400 μg/d with less effect on plasma cortisol levels BACKGROUND --Fluticasone propionate is a new inhaled corticosteroid with a 2:1 efficacy ratio compared with beclomethasone dipropionate with regard to lung function and symptom scores , without increased systemic activity . The aim of this study was to investigate whether this was also the case for bronchial hyperresponsiveness , assessed by both a direct ( histamine ) and an indirect ( ultrasonically nebulised distilled water ( UNDW ) ) provocation test . METHODS --Fluticasone propionate , 750 micrograms/day , and beclomethasone dipropionate , 1500 micrograms/day , were compared in a r and omised , double blind , crossover study consisting of two six week treatment periods , each preceded by a three week single blind placebo period . Twenty one non-smoking asthmatics ( mean forced expiratory volume in one second ( FEV1 ) 74.7 % predicted , mean PC20histamine 0.36 mg/ml ) completed the study . RESULTS --Fluticasone propionate and beclomethasone dipropionate improved FEV1 , peak flow rates , asthma symptoms , and bronchial hyperresponsiveness to the same extent . Both fluticasone propionate and beclomethasone dipropionate caused an increase in PC20histamine ( mean 2.29 [ 95 % confidence interval 1.45 to 3.13 ] and 1.95 [ 1.07 to 2.84 ] doubling doses , respectively ) and in PD20UNDW ( 1.12 [ 0.55 to 1.70 ] and 1.28 [ 0.88 to 1.70 ] doubling doses , respectively ) . Neither treatment changed morning serum cortisol levels , but fluticasone propionate decreased the number of peripheral blood eosinophils less than beclomethasone dipropionate , indicating smaller systemic effects of fluticasone propionate . CONCLUSIONS --These findings show that fluticasone propionate is as effective as twice the dose of beclomethasone dipropionate on bronchial hyperresponsiveness , assessed by provocation with both histamine and UNDW , without increased systemic activity BACKGROUND New inhaled glucocorticosteroids and inhalers are being developed . Their clinical equipotency is difficult to assess and is often discussed . OBJECTIVE This study was carried out to compare the effect of budesonide Turbuhaler and fluticasone propionate ( FP ) Diskhaler in a dose reduction study in children ( ages 5 to 16 years ) with asthma . METHODS Children treated with budesonide administered through a pressurized metered-dose inhaler with a large volume spacer had their budesonide dose gradually reduced to define the minimal effective dose with this delivery system . After this period , 217 children were r and omly allocated to treatment with half the dose of either budesonide Turbukaler or FP Diskhaler for 5 weeks in a double-blind trial . If no deterioration in asthma control was seen , the dose was further reduced by 50 % at 5-week intervals until deterioration in asthma control was seen . Throughout the study , morning and evening peak expiratory flow , symptoms , and use of rescue beta 2-agonist were recorded in diaries . Lung function tests and a st and ardized exercise test were performed at the clinic at the end of each treatment period . Urine cortisol excretion ( 24 hours ) was measured before and after the first 5-week treatment period . St and ardized criteria for deterioration in asthma control , based on diary card variables and exercise testing , were used to determine the minimal effective dose for each patient ; and from this , the number of dose reduction steps was calculated . RESULTS No statistically significant difference was seen in number of dose reduction steps from baseline or in minimal effective dose between the two treatments ; mean reduction was 1.59 dose steps for budesonide Turbuhaler and 1.65 dose steps for FP Diskhaler ( p = 0.52 ) , and minimal effective dose was 188 micrograms for budesonide Turbuhaler and 180 micrograms for FP Diskhaler . After these dose reductions , the same level of asthma control was observed in the budesonide Turbuhaler and FP Diskhaler groups . Furthermore , no statistically significant differences between the two inhaler-drug combinations were seen in daytime or nighttime symptoms , morning and evening peak expiratory flow , use of rescue beta 2-agonist , lung functions at the clinic , exercise-induced fall in lung function , or 24-hour urinary cortisol excretion during the first 5-week period . CONCLUSION Microgram for microgram , budesonide Turbuhaler and FP Diskhaler are equally effective in treatment of children with moderate asthma BACKGROUND : The aim of this study was to compare the systemic bioactivity of inhaled budesonide ( B ) and fluticasone propionate ( F ) , each given by large volume spacer , on a microgram equivalent basis in asthmatic children . METHODS : Ten stable asthmatic children of mean age 11 years and forced expiratory volume in one second ( FEV1 ) 81.6 % predicted , who were receiving treatment with < or = 400 micrograms/day of inhaled corticosteroid  , were studied in a placebo controlled single blind ( investigator blind ) r and omised crossover design comparing single doses of inhaled budesonide and fluticasone propionate 400 micrograms , 800 micrograms , and 1250 micrograms . Doses were given at 20.00 hours with mouth rinsing and an overnight 12 hour urine sample was collected for estimation of free cortisol and creatinine excretion . RESULTS : The results of overnight 12 hour urinary cortisol output ( nmol/12 hours ) showed suppression with all doses of fluticasone propionate ( as geometric means ) : F400 micrograms ( 11.99 ) , F800 micrograms ( 6.49 ) , F1250 micrograms ( 7.00 ) compared with placebo ( 24.43 ) , whereas budesonide caused no suppression at any dose . A comparison of the drugs showed that there were differences at 800 micrograms and 1250 micrograms levels for urinary cortisol : B800 micrograms versus F800 micrograms ( 2.65-fold , 95 % CI 1.26 to 5.58 ) , B1250 micrograms versus F1250 micrograms ( 2.94-fold , 95 % CI 1.67 to 5.15 ) . The results for the cortisol/creatinine ratio were similar to that of urinary cortisol , with fluticasone causing suppression at all doses and with differences between the drugs at 800 micrograms and 1250 micrograms . CONCLUSIONS : Single doses of inhaled fluticasone produce greater systemic bioactivity than budesonide when given by large volume spacer on a microgram equivalent basis in asthmatic children . The systemic bioactivity of fluticasone , like budesonide , is due mainly to lung bioavailability The purpose of this study was to investigate the comparative efficacy and safety of equal doses of inhaled fluticasone propionate ( FP ) and inhaled budesonide ( BUD ) using their respective dry powder inhalers in a population of severe asthmatics requiring high doses of inhaled corticosteroid . This double-blind double-dummy parallel-group study compared the effects of 24 weeks of treatment with FP ( 2000 micrograms daily via a Diskhaler inhaler ; Glaxo Wellcome , Evreux , France ) and BUD ( 2000 micrograms daily via a Turbuhaler inhaler ; Astra Pharmaceuticals , Rijswijka , Netherl and s ) on lung function and asthma exacerbations in 395 patients with asthma . FP was statistically significantly superior to BUD with respect to the percentage of symptom-free days ( P = 0.02 ) , the incidence of days free from rescue bronchodilator usage ( P = 0.02 ) and the distribution of change in peak expiratory flow ( PEF ) expressed as a percentage of the predicted PEF ( P = 0.04 ) . During the treatment period FP was statistically significantly superior to BUD for change in forced expiratory volume in 1 sec ( FEV1 ) at 8 , 16 and 24 weeks , change in the median daytime symptom score during weeks 5 - 16 , for incidence of symptom-free days and incidence of days free from rescue bronchodilator usage during weeks 17 - 24 . There was no significant difference between FP and BUD with respect to the number of patients experiencing one or more asthma exacerbation ( 33.8 and 28.4 % of patients , respectively ) . There was , however , evidence that the exacerbations were clinical ly less severe in patients treated with FP , in that the time to resolution was quicker ( 11.0 vs. 14.7 days ; P = 0.035 ) , mean duration of all exacerbations ( for an individual patient ) tended to be shorter ( 18.5 vs. 23.6 days ; P = 0.12 ) , the time off work was reduced ( 4.2 vs. 7.6 days ; P = 0.012 ) and the lowest PEF recorded during the exacerbation was higher ( 301 vs. 263 l min-1 ; P = 0.07 ) . There were no clinical ly relevant differences in the safety ( serum cortisol levels , markers of bone turnover , adverse events ) of FP and BUD at these microgram equivalent doses . The patients recruited into this study , in retrospect , probably had no need for such high doses of inhaled corticosteroid but , irrespective of this , FP at microgram equivalent doses showed evidence of superior efficacy to BUD with respect to lung function and severity of asthma exacerbations without producing any greater adverse systemic effect BACKGROUND In a previous single dosing study in asthmatic school children  fluticasone propionate produced significantly greater suppression of overnight urinary cortisol excretion than budesonide at high doses of 800 micrograms/day or greater . The aim of this study was to assess whether conventional lower doses of both drugs cause adrenal suppression when given at steady state twice daily by large volume spacer on a microgram equivalent basis in asthmatic school children . METHODS Eight school children of mean age 12.1 years with stable asthma of mild to moderate severity ( forced expiratory volume in one second ( FEV1 ) 78.6 % predicted , mid forced expiratory flow rate ( FEF25 - 75 ) 72.5 % predicted ) , on 400 micrograms/day or less of inhaled corticosteroid , were studied in a single blind ( investigator blind ) , placebo controlled , crossover design comparing inhaled budesonide and fluticasone propionate 100 micrograms bid and 200 micrograms bid . Each dose was given at 08.00 hours and 20.00 hours for four days by metered dose inhaler via their respective large volume spacers with mouth rinsing . Measurements were made of overnight urinary cortisol and creatinine excretion after the eighth dose . RESULTS Neither drug produced significant suppression of overnight urinary cortisol or cortisol/creatinine excretion compared with pooled placebo and there were no differences between the drugs . Only one subject with each drug at 200 micrograms twice daily had abnormally low urinary cortisol excretion of < 10 nmol/12 hours . Ratios for the fold difference between active treatment versus placebo for urinary cortisol excretion were ( as means and 95 % confidence intervals for difference ) : budesonide 100 micrograms b.i.d 1.03 ( 95 % CI 0.46 to 1.61 ) , budesonide 200 micrograms b.i.d 1.04 ( 95 % CI 0.62 to 1.46 ) ; fluticasone 100 micrograms b.i.d 1.11 ( 0.45 to 1.77 ) , fluticasone 200 micrograms b.i.d 1.12 ( 0.78 to 1.47 ) . Likewise , there were no significant differences in overnight urinary cortisol/creatinine excretion . CONCLUSIONS With repeated twice daily administration at steady state across a dose range of 200 - 400 micrograms/day no evidence of significant adrenal suppression was found using the sensitive marker of overnight urinary cortisol excretion for either fluticasone propionate or budesonide given via a large volume spacer . These results emphasise the good safety profile in children of these inhaled steroids at conventional dose levels , which have proven antiasthmatic efficacy The inhaled corticosteroid fluticasone propionate ( FP ) was introduced into the Thorpewood General Practice , Norwich , U.K. in 1993 -initially in treating relatively severe asthmatics . Observed beneficial effects led to exp and ed use particularly for poorly controlled asthma not responsive to increased inhaled anti-inflammatories . However , an early review suggested little advantage over existing agents ( l ) , and FP was marketed at a price premium . The aims of this study were to investigate whether continued and exp and ing use of FP was justified in terms of improved clinical outcomes , and if such improvements were associated with reduced NHS costs ( off setting more expensive prescriptions ) . A controlled , retrospective , nonr and omized primary care audit compared clinical outcomes and asthma management costs 1 year prior to and 1 year into FP therapy We assessed the systemic effects of budesonide ( BUD ) and fluticasone propionate ( FP ) in 23 patients with asthma , using a double-blind , placebo-controlled , double-dummy , and cross-over design . The following five treatments were given in a r and omized order for 1 wk with a washout period in between of 2 wk : ( 1 ) placebo ; ( 2 ) FP , 200 micrograms twice a day , inhaled from a Diskhaler ; ( 3 ) FP , 1,000 micrograms twice a day , inhaled from a Diskhaler ; ( 4 ) BUD , 200 micrograms twice a day , inhaled from a Turbuhaler ; and ( 5 ) BUD , 800 micrograms twice a day , inhaled from a Turbuhaler . The primary variable was the area under the curve of serum cortisol versus time ( AUC0 - 20 ) , derived from serum sample s taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression . Compared with placebo , however , FP ( 1 , 000 micrograms , twice daily and BUD ( 800 micrograms , twice daily ) decreased the AUC0 - 20 by 34 and 16 % , respectively . Fluticasone ( 1,000 micrograms , twice daily ) was more suppressive than BUD ( 800 micrograms , twice daily ) ( p = 0.0006 ) . The FEV1 , measured the morning after the last inhalation , was significantly higher after the active treatments , compared with placebo ( p < 0.02 ) , but did not differ between all active treatments . We conclude that high doses of BUD and FP ( in particular the latter ) , inhaled via their respective dry powder inhalers for 1 wk , result in a measurable systemic activity in patients with asthma This study was design ed primarily to assess the safety and tolerability of fluticasone propionate ( FP ) 1 mg day-1 by comparison with beclomethasone dipropionate ( BDP ) 2 mg day-1 over a 12-month study period . Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term . Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were r and omized to treatment in a ratio of 3:1 for FP : BDP  ( 159 patients FP ; 54 patients BDP ) , both via metered dose inhalers . Both treatments were well tolerated with a similar adverse event profile . No unexpected adverse events were recorded . Most adverse events were related to the patients ' asthma , an intercurrent infection or underlying atopy . The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect . Mean serum cortisol levels remained within the normal range at all visits for both treatments . At 12 months , however , the mean cortisol levels for the FP group had risen 4 % above the baseline value but had dropped 15 % below for the BDP group , giving a ratio of FP : BDP of 1.22 ; P = 0.01 ; 95 % confidence limits ( CL ) 1.05 - 1.43 . Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function ( PEF , FEV1 and FVC ) over this period . Moreover , the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group ( P = 0.04 ; difference = 0.12 1 ; 95 % CL = 0.01 , 0.24 1 ) . The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months ( difference in treatments = -3 % ; 95 % CL = - 7 - 0 % ; P = 0.044 ) . This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma BACKGROUND Inhaled corticosteroids are recommended for the treatment of persistent asthma . Comparative clinical studies evaluating 2 or more doses of these agents are few . OBJECTIVE We sought to compare the efficacy and safety of 2 doses of fluticasone propionate ( 88 micrograms twice daily and 220 micrograms twice daily ) with 2 doses of beclomethasone dipropionate ( 168 micrograms twice daily and 336 micrograms twice daily ) in subjects with persistent asthma . METHODS Three hundred ninety-nine subjects participated in this r and omized , double-blind , parallel-group clinical trial . Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45 % to 80 % of predicted value . Clinic visits , including spirometry , were conducted every 1 to 2 weeks . Subjects recorded symptoms , use of albuterol , and peak expiratory flows on daily diary cards . RESULTS Fluticasone propionate treatment result ed in significantly ( P < /=.034 ) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use ( P < /=.010 ) and asthma symptoms ( P < /=.027 ) . Both low-dose ( 88 micrograms twice daily ) and medium-dose ( 220 micrograms twice daily ) fluticasone propionate significantly increased FEV1 compared with higher doses of beclomethasone dipropionate ( P = . 006 ) . Low-dose and medium-dose fluticasone propionate improved FEV1 by 0.31 L ( 14 % ) and 0.36 L ( 15 % ) , respectively , compared with improvements of 0.18 L ( 8 % ) and 0.21 L ( 9 % ) with low-dose and medium-dose beclomethasone dipropionate . The adverse event profiles were similar for both medications . CONCLUSION Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate , with a comparable adverse event profile OBJECTIVE To compare the efficacy and adverse effects of inhaled fluticasone propionate ( FP ) , 400 microgram/d , with those of budesonide ( BUD ) , 800 microgram/d , in children with moderate to severe asthma . METHODS Three hundred thirty-three children , ages 4 to 12 years , receiving inhaled corticosteroids  were enrolled in a double-blind , double-dummy , r and omized , parallel-group study . After a 2-week run-in phase , 166 children received FP and 167 received BUD for 20 weeks . The primary outcome variable was mean morning peak expiratory flow ; the 2 treatments were to be regarded as equivalent if the 90 % CI for the treatment difference was within + /- 15 L/min . Pulmonary function , height , and diary cards were assessed at each visit ; and morning serum cortisol levels were determined before and after treatment . RESULTS Baseline peak expiratory flow was similar , FP 236 + /- 72 ( SD ) L/min and BUD 229 + /- 74 , increasing after treatment to 277 + /- 41 and 257 + /- 28 , a difference between treatments of 12 L/min ( 90 % CI 6 - 19 L/min ; P = .002 ) . Symptom control and use of rescue medication were the same . Cortisol levels after treatment were 199 nmol/L ( FP ) and 183 nmol/L ( BUD ) ( treatment ratio = 1.09 ; 90 % CI 0.98 - 1.21 ; P = .172 ) . Linear growth was less in those receiving BUD ( mean difference , 6.2 mm ; 95 % CI 2.9 - 9.6 ; P = .0003 ) . CONCLUSION FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms . Growth was reduced with BUD compared with FP , but there was no difference in serum cortisol suppression or hepatic or renal function The efficacy and tolerability of fluticasone propionate ( FP ) 2 mg daily via a metered-dose inhaler and Volumatic ( Glaxo Wellcome ) spacer device was compared with nebulized budesonide ( nBUD ) , 2 and 4 mg daily , in a multi-centre , open-label , cross-over study of adult asthmatics . Patients received , in r and om order , either 4 weeks of treatment with FP followed by 4 weeks of treatment with nBUD , or vice versa , with an intervening 4 week ' wash-out ' period between treatments . Thirty patients completed the study , of whom 24 were evaluable . In terms of the primary efficacy parameter , change in mean morning peak expiratory flow ( PEF ) ( l min-1 ) from baseline to the fourth week of each treatment period , FP was more effective than nBUD [ mean difference ( FP-nBUD ) 21.1 l min-1 , P = 0.007 , 95 % CI ( 6.5 , 35.7 ) ] . Sub-group analysis demonstrated FP to be superior to the 4 mg nBUD [ mean treatment difference ( FP-nBUD ) 42.9 l min-1 , P = 0.026 , 95 % CI ( 7.1 , 78.8 ) ] and at least as efficacious as the 2 mg nBUD sub-group [ mean treatment difference ( FP-nBUD ) 10.2 l min-1 , P = 0.211 , 95 % CI ( -6.5 , 26.9 ) ] . Furthermore , larger reductions in diurnal variation were observed during FP treatment [ mean treatment difference ( FP-nBUD ) -4.4 percentage points , P = 0.028 , 95 % CI ( -8.4 , -0.5 ) ] . There was no significant difference between the treatments for the proportion of symptom-free 24 h periods . Of those expressing a preference , significantly more patients found FP via a metered-dose inhaler and spacer device both easier to administer ( 78 % , P = 0.007 ) and more convenient to take ( 76 % , P = 0.008 ) than nebulized budesonide . In addition , cost per patient analysis showed that nebulized budesonide was from 1.7 to 3.5 times more expensive than FP AIMS The present study was undertaken to see whether the difference in plasma cortisol suppression between single and repeated dosing of fluticasone propionate ( FP ) can be explained by systemic accumulation . METHODS Twelve healthy subjects ( six women ) were given , in a crossover fashion , a single dose inhalation ( 1000 micrograms ) of FP via Diskhaler and repeated inhalations ( 1000 micrograms twice daily ) every 12 h during 7 days . There was a washout period of 2 weeks between the treatments . An intravenous dose of 20 micrograms FP was given as a reference . Plasma concentrations of  FP  for each treatment were determined by liquid chromatography plus t and em mass spectrometry . Plasma cortisol after the inhaled doses was determined using an immunoassay and was compared with baseline values . RESULTS The average plasma concentration of FP  was about 1.7 times higher after multiple inhalations than after a single dose . Systemic availability , mainly attributable to pulmonary deposition , was 15.6 [13.6 - 18.0]% of the nominal dose . Daytime plasma cortisol suppression vs baseline was 47 [20 - 65]% and 95 [93 - 97]% for the single and repeated doses , respectivley . CONCLUSIONS To conclude , a slow elimination of FP leads to accumulation during repeated dosing . This accumulation may explain the marked decrease in plasma cortisol seen during treatment with fluticasone propionate within the clinical dose range OBJECTIVE Changes in health-related quality of life ( HRQoL ) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide ( BDP/BUD )  and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD . METHODOLOGY HRQoL was assessed as part of an open , multicentre , r and omized , parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate ( FP ) 1000 - 2000 micro g/day ( n = 67 ) compared with remaining on BDP/BUD > /=1750 micro g/day ( n = 66 ) for 6 months . Patients completed two HRQoL question naires , the Asthma Quality of Life Question naire ( AQLQ ) and the Medical Outcomes Study Short Form-36 ( SF-36 ) , at baseline and at weeks 12 and 24 . A change in AQLQ score of > /=0.5 was considered to be clinical ly meaningful . RESULTS There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 ( i.e. physical functioning , general health , role-emotional , and mental health ) , while there were no significant improvements in HRQoL in the BDP/BUD group . Overall , patients in the FP group experienced significantly greater improvement ( P < 0.001 ) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group . On the individual domains of the AQLQ , there were significant treatment differences ( P < 0.01 ) in favour of FP in three of the four domains ( activity limitations [ 0.92 ] , symptoms [ 0.73 ] , and emotional function [ 1.02 ] ) . Mean differences between groups for overall score and these three domains were also clinical ly meaningful . CONCLUSION Patients with severe asthma who received FP ( at approximately half the dose of BDP/BUD ) experienced statistically significant , as well as clinical ly meaningful , improvements in their Correlations between knemometric ( lower leg length ) growth rates and urine free cortisol excretion , respectively , and serum concentrations of IGF-I , IGF binding protein-3 , osteocalcin , carboxy terminal propeptide of type I collagen(PICP ) , carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen ( ICTP ) , and amino terminal propeptide of type III procollagen(PIIINP ) were investigated in 17 asthmatic children aged 7 - 14 y during treatment with fluticasone propionate , 200 μg , and beclomethasone dipropionate , 400 and 800 μg/d , taken from dry powder inhalers . The study was a double blind , crossover trial with three active treatment periods and two wash-out periods . All periods were 15 d long . Overnight urine free cortisol/creatinine × 106 did not correlate with knemometric growth rates or any of the serum markers . Significant correlations ( Pearson 's correlation coefficient , P ) between knemometric growth rates and IGF-I ( 0.41 ; 0.006 ) , IGFBP-3 ( 0.35 ; 0.02 ) , PICP ( 0.44 ; 0.003 ) , ICTP ( 0.35 ; 0.001 ) , and PIIINP ( 0.46 ; 0.002 ) were found . Compared with fluticasone propionate , 200 μg , beclomethasone dipropionate , 400 and 800 μg , caused significant suppression of lower leg growth rate ( F = 12.41;p = 0.002 , and F = 23.30 ; p = 0.0001 , respectively ) and of urine free cortisol/creatinine × 106(F = 10.52 ; p = 0.003 , and F = 13.74;p = 0.001 ) . Beclomethasone , 800 μg , caused suppression of PICP compared with fluticasone propionate , 200 μg ( F = 8.31;p = 0.008 ) , and beclomethasone , 400 μg ( F = 7.53;p = 0.01 ) . Both low ( F = 6.82 ; p = 0.02 ) and high ( F = 23.35 ; p = 0.0001 ) doses of beclomethasone were associated with reduced concentrations of ICTP , the high dose being the most suppressive ( F = 4.42 ; p = 0.05 ) . Beclomethasone 400(F = 9.75 ; p = 0.004 ) and 800 μg ( F = 23.61;p = 0.0001 ) result ed in reduced levels of PIIINP . Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover
BACKGROUND Beclomethasone dipropionate ( BDP ) and budesonide ( BUD ) are commonly prescribed inhaled corticosteroids for the treatment of asthma .
Fluticasone propionate ( FP ) is newer agent with greater potency in in-vitro assays .
OBJECTIVES To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma .