[Long-term prognosis of asthmatic patients treated with low-dose beclomethasone dipropionate]. Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a five-month multicentre Canadian study. Proof of concept study to evaluate step-down therapy with inhaled corticosteroid alone or additive therapy on surrogate inflammatory markers in asthma. A proof of concept study to evaluate stepping down the dose of fluticasone in combination with salmeterol and tiotropium in severe persistent asthma. Comparison of the efficacy of ciclesonide with that of budesonide in mild to moderate asthma patients after step-down therapy: a randomised parallel-group study The CONCEPT trial: a 1-year, multicenter, randomized,double-blind, double-dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing regimen of formoterol/budesonide in adults with persistent asthma. Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics. Salmeterol/fluticasone stable-dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health-related quality of life High or standard initial dose of budesonide to control mild-to-moderate asthma? Stepping down inhaled corticosteroids in asthma: randomised controlled trial Economic assessment of adjustable maintenance treatment with budesonide/formoterol in a single inhaler versus fixed treatment in asthma [Treatment of bronchial asthma using a new adjustable combination treatment plan: Asthma Control Plan (ATACO)]. Step-Down and Step-Up Therapy in Moderate Persistent Asthma Initial loading (400 micrograms twice daily) versus static (400 micrograms nocte) dose budesonide for asthma management. PLAN Research Group. Step-down of budesonide/formoterol in early stages of asthma treatment leads to insufficient anti-inflammatory effect Tolerance to reduction of oral steroid dosage in severely asthmatic patients receiving nedocromil sodium. Maintaining asthma control in persistent asthma: comparison of three strategies in a 6-month double-blind randomised study. Equivalent asthma control after dose reduction with HFA-134a beclomethasone solution aerosol. Comparative Inhaled Steroid Investigation Group (CISIG). Asthma control can be maintained when fluticasone propionate/salmeterol in a single inhaler is stepped down. Reduction of budesonide after a year of increased use: a randomized controlled trial to evaluate whether improvements in airway responsiveness and clinical asthma are maintained. Predictors of loss of asthma control induced by corticosteroid withdrawal. Serum Eosinophil Cationic Protein for Predicting the Prognosis of a Step-Down in Inhaled Corticosteroid Therapy in Adult Chronic Asthmatics Steroid-dependent asthma treated with inhaled beclomethasone dipropionate. A long-term study. Randomized comparison of strategies for reducing treatment in mild persistent asthma. Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma Budesonide/formoterol adjustable maintenance dosing reduces asthma exacerbations versus fixed dosing. Budesonide Turbuhaler delivered once daily improves health-related quality of life and maintains improvements with a stepped-down dose in adults with mild to moderate asthma. Comparison of a step-down dose of once-daily ciclesonide with a continued dose of twice-daily fluticasone propionate in maintaining control of asthma*
To clarify the prognosis of asthmatics treated with low-dose of inhaled beclomethasone dipropionate ( BDP ) , we retrospectively assessed 43 patients treated with initial dose of 200 or 400 micrograms/day for 5 years , and obtained the following results . 1 ) 15 patients achieved step-down therapy ( group A ) , 17 patients maintained initial dose of BDP ( group B ) , and 11 patients required step-up therapy of BDP or daily use of oral prednisolone ( group C ) . 2 ) There was no significant difference in age , sex , duration of disease , severity of disease , peripheral eosinophil counts , % FEV1 and histamine PC20 before BDP treatment among three groups . The percentage of atopic asthmatics was significantly higher in group C than in group A. 3 ) There was no significant difference in symptom and histamine PC20 between after 1 year state and after 5 years state in three groups . 4 ) After 1 year from the start of BDP treatment , only 18 % patients got symptom free and neither patients exceeded 20,000 micrograms/ml of histamine PC20 in group C. Long-term treatment of low-dose BDP inhalation was effective on mild/moderate asthmatics . Patients requiring step-up therapy had not got sufficient improvement in bronchial hyperresponsiveness after one-year treatment BACKGROUND Adjustable maintenance dosing with budesonide/formoterol in a single inhaler ( Symbicort , AstraZeneca , Lund , Sweden ) may provide a convenient means of maintaining asthma control with the minimum effective medication level . OBJECTIVES To compare adjustable and fixed maintenance dosing regimens of budesonide/formoterol in asthma . METHODS This was an open-label , r and omized , parallel-group , multicentre , Canadian study of asthma patients ( aged 12 years or older , postbronchodilator forced expiratory volume in 1 s 70 % or greater of predicted normal ) . Following a one-month run-in on budesonide/formoterol ( 100/6 µg or 200/6 µg metered doses , two inhalations twice daily ) , 995 patients were r and omly assigned either to continue on this fixed dosing regimen or to receive budesonide/formoterol adjustable dosing ( step down to one inhalation twice daily if symptoms were controlled or temporarily step up to four inhalations twice daily for seven or 14 days if asthma worsened ) . The primary efficacy variable was the occurrence of exacerbations ( requiring oral or inhaled corticosteroids , emergency department treatment , serious adverse events or added maintenance therapy because of asthma ) . RESULTS With adjustable dosing , significantly fewer patients experienced exacerbations compared with fixed dosing ( 4.0 % versus 8.9 % , P=0.002 ; number needed to treat=21 [ 95 % CI 13 to 59 ] ) . Patients required 36 % fewer overall doses of budesonide/formoterol  ( 2.5 versus 3.9 inhalations/day , P<0.001 ) , and total costs per patient were lower ( difference over five months -141 Canadian dollars [ 95 % CI -162 Canadian dollars to -116 Canadian dollars ] ) . Asthma symptom severity ( modified National Heart , Lung , and Blood Institute stage ) was maintained or improved in 97 % or greater of patients in both groups ( pre-run-in to end of treatment ) . Both treatments were well tolerated . CONCLUSIONS Budesonide/formoterol adjustable maintenance dosing provided more effective asthma control than fixed dosing , with a lower overall drug dose and reduced total cost WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Much of the focus of inflammatory surrogates and airway challenges in asthma has been directed towards success of therapy and diagnosis . Few have considered them in the context of guiding dose reduction once sufficient control has been achieved . WHAT THIS STUDY ADDS Adenosine monophosphate ( AMP ) as an indirect bronchial airway challenge , together with non invasive inflammatory surrogate measures were not found to be clinical ly useful when guiding therapy in a group of asthmatic patients through step 3 - 4 in British Thoracic Society asthma guidelines . However , they may still play a role in predicting failure of individual step-down . AIM The aim of the study was to evaluate the usefulness of inflammatory surrogates in determining step-down therapy in asthma . METHODS AMP challenge , serum eosinophil cationic protein ( ECP ) , exhaled nitric oxide ( eNO ) and pulmonary function tests were recorded . Subjects were divided into two groups following high dose inhaled corticosteroids ( ICS ) : Group A fixed dose ICS vs. Group B ICS alone and in combination with add on therapies . RESULTS No differences were seen in inflammatory measures between fixed dose ICS and reduced dose ICS alone or with combination therapies . CONCLUSIONS AMP challenge conferred no additional benefit in guiding step-down therapy . The role of inflammatory surrogates may still play a role in predicting failed step-down on an individual basis We conducted a double blind , r and omised , placebo-controlled , crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol , or salmeterol and tiotropium .  Eighteen life-long non-smoking severe asthmatics [ mean FEV(1 ) 1.49 l ( 51 % ) ] were run-in for 4 weeks on HFA-fluticasone propionate 1000 microg daily , and were subsequently r and omised to 4 weeks of either ( a ) HFA-fluticasone propionate 500 microg BD/salmeterol 100 microg BD/HFA-tiotropium bromide18 microg od ; or ( b ) fluticasone propionate 500 microg BD/salmeterol 100 microg BD matched placebo . Measurements of spirometry and body plethysmography were made . Adding salmeterol to half the dose of fluticasone led to a mean improvement ( 95 % CI ) vs. baseline in morning PEF of 41.5 (14.0 - 69.0)l/min [ p<0.05 ] ; and RAW of 0.98 (0.14 - 1.8)cm H(2)O/l/s [ p<0.05 ] . Adding salmeterol/tiotropium produced similar improvements in PEF and RAW , but also improved FEV(1 ) by 0.17 (0.01 - 0.32)l [ p<0.05 ] ; FVC 0.24 (0.05 - 0.43)l [ p<0.05 ] and reduced exhaled NO by 2.86 (0.12 - 5.6)ppb [ p<0.05 ] . RV and TLC were not altered by either treatment ; there were no significant changes in symptoms or quality of life compared with baseline . Addition of salmeterol/tiotropium to half the dose of fluticasone afforded small , but significant improvements in pulmonary function . These effects were not associated with commensurate changes in subjective symptoms or quality of life Background : Inhaled corticosteroids ( ICSs ) are widely used in asthma control . Ciclesonide ( CIC ) is an ICS with on-site lung activation for potent anti-inflammatory activity . Aims : This study aim ed to compare the clinical benefit of CIC with budesonide ( BUD ) in step-down therapy . Methods : A total of 150 patients with mild-to-moderate asthma well controlled by a combination of ICS and long-acting β2-agonist were r and omised to receive either CIC 320 μg ( n=75 ) once daily or 2 inhalations of BUD 200 μg ( n=75 ) twice daily for 12 weeks . The forced expiratory volume in 1s ( FEV1 ) , maximum mid-expiratory flow ( MMEF ) and asthma control test ( ACT ) scores were measured . Ranked stratification of patients and physicians was assessed . Results : Drug adherence was significantly higher in the CIC group than in the BUD group ( 76.0 % vs. 58.7 % , P=0.03 ) . The FEV1 and MMEF remained stable throughout the 12-week CIC treatment . In the BUD group , FEV1 significantly decreased at weeks 4 and 12 . MMEF had a higher value in the CIC group than in the BUD group . Both patients and physicians ranked CIC over BUD . Conclusions : CIC is more effective and has better drug adherence than BUD as step-down treatment when asthma is well controlled by combination therapy BACKGROUND A patient-driven , adjustable maintenance dosing ( AMD ) approach to asthma therapy , in which the dose is adjusted by patients according to the severity of their symptoms , has recently been compared with fixed-dose therapy in open-label studies . OBJECTIVE This study used a double-blind , double-dummy design to compare the efficacy of 2 treatment approaches : stable dosing of salmeterol/fluticasone propionate ( SAL/FP ) and AMD of formoterol/budesonide ( FOR/BUD ) . METHODS This was a 1-year , multicenter , r and omized , double-blind , double-dummy study in adult patients with symptomatic asthma that was not controlled by therapy with 200 to 500 microg/d inhaled corticosteroid ( ICS ) plus a long-acting beta2 agonist , or with > 500 to 1000 microg/d ICS alone . Patients were r and omized to receive 1 inhalation of SAL/FP 50/250 microg BID or 2 inhalations of FOR/BUD 6/200 microg BID , both delivered via dry powder inhaler devices . After 4 weeks of stable dosing in both groups , eligible patients continued the study for an additional 48 weeks , receiving either a stable dose of SAL/FP or AMD of FOR/BUD . According to the AMD treatment plan , patients initially halved their dose and subsequently stepped up or down as indicated by the presence or absence of nocturnal awakenings due to asthma , frequency of rescue medication use , and changes in morning peak expiratory flow ( PEF ) . The primary end point was the percentage of symptom-free days . Other parameters included daily asthma symptom scores , morning PEF , percentage of days free of rescue medication use , daily rescue medication use , percentage of nighttime awakenings due to asthma , percentage of weeks with well-controlled asthma , and number of exacerbations requiring oral corticosteroids or emergency department ( ED ) visits/hospitalizations . Tolerability was assessed in terms of adverse events spontaneously reported or elicited at clinic visits . RESULTS The intent-to-treat population comprised 688 patients ( 344 per treatment arm ) with a mean age of 45 years and a mean baseline forced expiratory volume in 1 second 81 % of the predicted normal value . After 4 weeks ' stable dosing , 581 patients ( 295 SAL/FP , 286 FOR/BUD ) continued beyond visit 3 into the remaining 48-week treatment period . Over weeks 1 through 52 , patients receiving stable dosing of SAL/FP had a significantly greater percentage of symptom-free days compared with those receiving AMD of FOR/BUD ( median , 58.8 % vs 52.1 % , respectively ; P = 0.034 ) . The incidence of asthma exacerbations requiring oral steroids or an ED visit/hospitalization was 47 % lower with SAL/FP compared with FOR/BUD ( adjusted annual mean rate , 0.18 vs 0.33 ; P = 0.008 ) . During weeks 5 through 52 , patients in the FOR/BUD AMD group used a mean of 1.8 inhalations/d ( equivalent to BUD 360 microg/d ) , and 235 ( 82.2 % ) patients stepped down to 1 inhalation/d . Mean ( SD ) daily ICS exposure over 52 weeks was 463 ( 81 ) microg FP and 480 ( 238 ) microg BUD in the respective treatment arms . CONCLUSIONS In this adult population with persistent asthma , stable dosing of SAL/FP 50/250 microg BID result ed in significantly greater increases in symptom-free days , days free of rescue medication , and morning PEE , as well as almost halving the exacerbation rate , compared with AMD of FOR/BUD 6/200 microg . The results suggest that there is a minimum daily amount of maintenance therapy necessary to prevent exacerbations in adults with persistent asthma Budesonide 400 micrograms daily , in nonsteroid-dependent asthma , can produce improvements in airway responsiveness and clinical asthma severity , with some patients returning to normal responsiveness and becoming asymptomatic . This study examined whether similar improvements occur when asthmatics , who are dependent upon inhaled steroids , take either a regular maintenance dose of inhaled steroid or twice that amount for a year . Thirty two asthmatics were each stabilized on the minimum amount of inhaled steroid that would keep symptoms non-troublesome . In a double-blind , r and omized manner , half were assigned to remain on a maintenance dose ( MD ) and the rest received twice that dose ( MDx2 ) for one year . Before and monthly throughout the study , airway responsiveness to methacholine was measured and clinical asthma severity assessed by question naire , inhaled bronchodilator use and number of asthma exacerbations . There was a significant improvement in airway responsiveness and clinical asthma severity in both treatment groups . Those on MDx2 showed the greatest improvement but the difference between the two groups did not reach significance . This study provides strong evidence that prolonged use of inhaled steroids is associated with improvement in airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthma with a suggestion that the improvements are dose related Background Improving patients ' health-related quality of life ( HRQoL ) is recognized as a fundamental part of asthma management . The aims of this study were to evaluate the long-term efficacy ( including symptom-free days and exacerbations ) and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate ( SAL/FP ) and an adjustable maintenance dosing ( AMD ) regimen of formoterol/budesonide ( FOR/BUD ) where treatment is adjusted based on symptoms [ SAM40056 ] . Methods A total of 688 out patients with asthma receiving regular low-dose inhaled corticosteroids ( ICS ) plus a long-acting β2-agonist , or medium dose ICS alone participated in this r and omized , double-blind , double-dummy , parallel-group , 1-year trial , which was conducted in 91 centers in 15 countries . Patients were r and omized to receive 1 inhalation of SAL/FP 50/250 μg BID or 2 inhalations of FOR/BUD 6/200 μg BID during Weeks 1–4 . For Weeks 5–52 , patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP . Results The percentage of symptom-free days was significantly greater ( 58.8 % vs 52.1 % ; p = 0.034 ) and the annual exacerbation rate was significantly lower ( 47 % ; p = 0.008 ) with stable-dose SAL/FP compared with FOR/BUD AMD . A total of 568 patients completed the Asthma Quality of Life Question naire ( AQLQ ) at least once during the study . The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52 , but did not reach statistical significance ( p = 0.121 at Week 52 ) . However , in a post hoc logistic regression analyses for any AQLQ improvement , significant benefits with SAL/FP were seen at both time points ( p = 0.038 and p = 0.009 , respectively ) . The minimally important difference of ≥ 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 ( 68 % vs 60 % ; p = 0.049 ) ; a trend for this difference remained at Week 52 ( 71 % vs 65 % ) ( p = 0.205 ) . Conclusion In this population of patients with persistent asthma , stable-dose SAL/FP result ed in significantly greater increases in symptom-free days , a reduction in exacerbation rates , and provided greater HRQoL benefits compared with FOR/BUD AMD.Trial registration Clinical Trials registration number Guidelines on the use of inhaled steroids in asthma advocate that the daily dose should be chosen according to the severity of the disease . However , the question of the optimal starting dose remains to be properly addressed , as does the issue of the adjustment in dose required for a given patient . Whether a high initial dose of budesonide ( 800 microg b.i.d ) was more efficacious than a st and ard dose ( 200 microg b.i.d ) in controlling mild-to-moderate asthma was investigated , and whether the dose could be decreased , based on peak expiratory flow ( PEF ) , symptom-score , beta2-agonist use in a double-blind , r and omized , parallel-group 18-week study . One-hundred and sixty-nine patients ( mean age 38 yrs , mean forced expiratory volume in one second 74 % predicted ) were enrolled . No difference was detected between the two groups in improvement in morning PEF ( + 61 L x min(-1 ) in the high-dose group , + 60 L x min(-1 ) in the st and ard-dose group by 16 weeks ) . Morning and evening PEF values stabilized before the end of the first 4 weeks . No difference between groups was observed in symptom score , beta2-agonist use , number of exacerbation per interval and the best forced expiratory volume in one second achieved . The proportion of subjects being able to decrease the doses of budesonide was similar in both treatment strategies . It is concluded that both high and st and ard initial doses are equally effective in controlling symptoms and improving lung function in mild-to-moderate asthma 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 Abstract Objectives : To compare the costs and effectiveness of adjustable maintenance dosing with budesonide/formoterol in a single inhaler versus fixed dosing in adults with asthma . Methods : In this prospect i ve , r and omised , open-label , parallel-group , multicentre trial conducted in Germany , patients with asthma received budesonide/formoterol 160µg/4.5 µg in a single inhaler ( Symbicort ® Turbuhaler ® ) with two inhalations twice daily for a 4-week run-in period . Patients were then r and omised to either adjustable maintenance dosing ( one inhalation twice daily , stepping up to four inhalations twice daily for 1 week if asthma worsened ; n = 1679 ) or fixed dosing ( two inhalations twice daily ; n = 1618 ) for 12 weeks . The primary efficacy variable was the change in health-related quality of life ( HR-QOL ) , measured using the Asthma Quality of Life Question naire ( st and ardised ) during the r and omised treatment period . Re source utilisation data were collected in parallel and combined with German unit costs to estimate direct and indirect costs ( year 2001 values ) . Results : Both treatment regimens were equally effective in maintaining HR-QOL and asthma control during the r and omised treatment period . However , overall , patients in the adjustable maintenance dosing group took fewer daily inhalations of budesonide/formoterol  than those in the fixed-dosing group ( mean : 2.63 vs 3.82 inhalations ; p < 0.001 ) . Adjustable maintenance dosing was associated with significantly lower asthma-related direct costs  compared with fixed dosing ( mean : € 221 vs € 292 ; p < 0.001 ) . This pattern was maintained when patients were stratified into those with peak expiratory flow ( PEF ) of 60 % to < 80 % predicted normal and those with PEF of ≥80 % predicted normal and when total costs were considered . Conclusion : Adjustable maintenance dosing with budesonide/formoterol in a single inhaler maintained HR-QOL in adult patients with asthma at a significantly lower cost than fixed dosing The current guideline of the German Respiratory League ( Deutsche Atemwegsliga ) recommends the synergistic combination therapy with long acting beta 2-agonists and inhalative corticosteroids only for patients suffering from moderate to severe persistent asthma ( step 3 and 4 of the asthma severity scale ) . Now convenient fixed combinations of these substances are available , which could enhance patient 's compliance . A large , r and omised , parallel-group study in 8000 mild to moderate asthmatics was design ed to compare a flexible asthma control plan with the conventional fixed-dose management with respect to quality of life , symptom control and treatment costs . The fixed combination of 6 micrograms Formoterol and 200 micrograms Budesonide per puff in a new dry powder device was applied either due to a novel flexible asthma control plan " ATACO " ( group A ) or as a st and ardised conventional dosing regimen ( group B ) inhaling two puffs b.i.d . In group A ( ATACO ) patients reduce the run-in dose after four weeks from two puffs b.i.d . to one puff b.i.d . with the option of doubling the dose immediately , if ( pre-defined ) asthma deterioration occurs . One week later the dose can be either doubled again or reduced due to the actual asthma symptoms of the patient . After run-in , group B patients continue to take two inhalations b.i.d . In this group , asthma exacerbations will be managed as usual by the physician . In contrast , the ATACO group flexible management plan allows the self-medication : an immediate increase in the dose of the fixed combination will lead to both a fast relief of bronchospasm and an automatically higher dosed corticosteroid treatment for the underlying asthmatic inflammation . Conversely , if later asthma symptoms improve , less reliever and controller medication will be needed and used . The immediate treatment of new onset bronchospasm and asthmatic inflammation by the patient himself could maintain at least the same grade of asthma control , as the conventional group B treatment , improve asthma-related quality of life and decrease treatment costs . If the concept works , fixed combinations of long-acting beta 2 agonists and inhalative corticosteroids could have an impact on future asthma guidelines Background : A step-down therapy may be more beneficial for the management of asthma than a step-up therapy . Methods : Eighty-two asthmatic patients with moderate persistent asthma were enrolled in the study and r and omized into three groups . One group of patients received 400 µg/day of beclomethasone dipropionate ( BDP ) for 4 weeks and then 800 µg/day for another 4 weeks ( step-up group ) . The other two groups of patients received 1,200 µg/day of BDP for 4 weeks with or without short-term oral steroid ( prednisolone , 0.5 mg/day for 1 week ) and then 800 µg/day for another 4 weeks ( step-down group ) . Severe exacerbation of asthma , asthma symptoms , respiratory function and rescue use of inhaled β2-agonists were monitored . If asthma was well controlled , the dose of BDP was decreased every 3 months and if asthma was exacerbated , the dose of BDP was increased until 8 months after the initial treatment . Results : Twenty-two patients during the run-in period , 4 patients in the step-up group , 2 patients in the step-down group treated with a high dose of BDP and no patients in the step-down group with oral steroids during first 4 weeks dropped out because of severe exacerbation of asthma . Although asthma symptoms and respiratory function significantly improved 8 weeks after the therapy in all groups , more significant and prompt improvements of these parameters were observed in patients of the step-down group than in patients of the step-up group after the first 2 weeks of treatment . Furthermore , step-down therapy with short-term oral steroid result ed in the lowest maintenance doses of BDP at 8 months of the three groups . Conclusions : These results suggest that step-down therapy starting with a high dose of inhaled steroid and short-term oral steroid is more effective in gaining prompt control of asthma and reducing the severe exacerbation of asthma and the maintenance dose of inhaled steroids than a step-up therapy starting with a low dose of inhaled steroids in patients with moderate persistent asthma This double-blind study aim ed to determine whether superior asthma control is achieved with budesonide ( Pulmicort Turbohaler ) at a loading dose ( LD ) ( 400 micrograms b.d . ) for 6 weeks , followed by step down to 400 micrograms nocte for 12 weeks , compared with a static dose ( SD ) ( 400 micrograms nocte ) for 18 weeks . A total of 682 patients ( mean peak expiratory flow rate ( PEFR ) 413 l/min ) , who demonstrated > or = 15 % reversibility in PEFR , were r and omised into the study . After 18 weeks , patients experienced improvements in morning PEFR ( + 45 l/min , both groups ) , symptom score ( LD -0.57 , SD -0.49 , on a scale of 0 - 3 ) , sleep disturbance ( LD -1.21 nights/week , SD -1.06 nights/week ) and beta 2-agonist use ( LD -1.36 puffs/day , SD -1.06 puffs/day ) , within both groups ( each p = 0.0001 ) . At 18 weeks , 82 % ( LD ) and 84 % ( SD ) of patients benefited from no nocturnal wakening in the previous 7 days . Overall , at 18 weeks , asthma control was not significantly different between the groups . After 6 weeks , improvements in morning PEFR ( LD + 36 l/min , SD + 26 l/min ) and beta 2-agonist use ( LD -1.10 puffs/day , SD -0.94 puffs/day ) were greater in the loading dose than in the static dose group ( each p < 0.05 ) . The greater improvement in morning PEFR in the loading dose group was significant by day 7 ( p < 0.05 ) . While both regimens are equally effective in achieving asthma control at 18 weeks , early clinical advantage is gained with initial loading dose budesonide ( 400 micrograms b.d . ) Abstract Objective : Administration of the combination of an inhaled corticosteroid ( ICS ) and a long-acting beta agonist ( LABA ) is the main treatment strategy for bronchial asthma . The ICS/LABA dosage can be reduced ( stepped down ) when the patient ’s symptoms and lung functions are well-controlled . In this study , we obtained fractional exhaled nitric oxide ( FeNO ) measurements to clarify whether the anti-inflammatory effect of budesonide/formoterol is shortened by step-down . Methods : Fifty-four patients who visited the Kawasaki Medical School Hospital with newly diagnosed asthma from November 2008 to July 2010 received budesonide/formoterol for 8 weeks or more . In 29 patients , the forced expiratory volume in 1 s% predicted increased to 80 % or more , and the Asthma Control Question naire ( ACQ ) score decreased to 0.5 or less within 12 weeks . These 29 patients were r and omly divided into two groups : the dosage-continued group ( n = 14 ) and the step-down group ( n = 15 ) . Then , the impact of budesonide/formoterol step-down on ACQ score , pulmonary function and FeNO level was compared between the groups . Results : In the step-down group , the dosage was stepped down from 538 mcg/day to 331 mcg/day . In both groups , pulmonary function indicators and symptoms did not change . However , the mean FeNO level decreased significantly in the dosage-continued group ( from 50.9 ppb to 45.0 ppb ) , and increased significantly in the step-down group ( from 51.0 ppb to 65.7 ppb ) . Conclusions : Clinicians should be more careful when stepping down budesonide/formoterol based solely on patients ’ symptoms and /or pulmonary function We examined the efficacy of nedocromil sodium as an oral steroid sparing agent in a group of 37 severe , oral steroid-dependent asthmatics . All were receiving daily or alternate-day prednisone .  These patients had taken part in an earlier , 12-week double-blind trial of nedocromil sodium 16 mg daily by inhalation or matching placebo . They continued with test treatment ( 26 patients on nedocromil sodium and 11 on placebo ) on a double-blind basis for a further 12 weeks . During this time , patients visited the clinic every 2 weeks , when asthma severity and symptoms were assessed . On the basis of these assessment s , the dose of oral steroid was either decreased , or maintained at the same level , or the patient was withdrawn if the asthma had deteriorated to a clinical ly unacceptable level . The nedocromil sodium group was able to achieve a greater percentage reduction in oral steroid dose ( P less than 0.05 ) . The rate of withdrawal due to worsening asthma was 31 % from active and 55 % from placebo treatment . Trends in other variables ( time before withdrawal and numbers of patients able to withst and complete removal of oral steroids ) favoured nedocromil sodium but the differences between the groups were not statistically significant UNLABELLED In patients controlled with SFC250 Diskus bd , this double-blind , r and omised 6-month study compared continuing SFC250 to stepping down to either SFC100 bd or FP250 bd .  Six hundred and three patients previously using 1,000 microg BDP ( or equivalent ) daily + LABA and controlled according to investigator 's judgement were recruited . Patients received SFC250 bd during an 8-week open run-in period . Four hundred and seventy six patients ( mean age=43 years , mean FEV(1)=2.9+/-1.0 ) who fulfilled the r and omisation criterion ( ' Well-controlled ' asthma according to the GOAL weekly definition for the last 2 weeks of the run-in period ) entered a 24-week treatment period . The statistical hypothesis was based on a non-inferiority of SFC100 or FP250 compared to SFC250 . The main criterion was the change from baseline in morning PEF over weeks 1 - 12 in the per- protocol population . The non-inferiority limit was -15 L/min . At inclusion , the three treatment groups were well balanced . Mean morning PEF was 476 , 470 and 465 L/min in the SFC250 , SFC100 and FP250 groups , respectively . The adjusted mean change in morning PEF over weeks 1 - 12 was + 1.76+/-2.43 L/min for SFC250 , -3.07+/-2.32 L/min for SFC100 and -16.51+/-2.46 L/min for FP250 . SFC100 was at least as effective as SFC250 ( treatment difference -4.83 [ -12.39 ; 2.72 ] , p=0.151 ) whereas FP250 was not ( treatment difference -18.27 [ -26.05 ; -10.49 ] , p<0.001 ) . Similar results were observed over weeks 13 - 24 in morning PEF ( SFC100-SFC250=-4.54+/-3.84 , p=0.238 ; FP250-SFC250=-20.11+/-3.92 , p<0.0001 ) . Secondary endpoints showed a similar pattern . Over weeks 1 - 12 , SFC250 was significantly more effective than FP250 on evening PEF , daily symptoms and bronchodilator use . There was no difference between SFC100 and SFC250 . The mean annual rate of moderate exacerbations was 0.16 in both SFC 250 and SFC 100 groups , and 0.21 in FP 250 group ( ns , Poisson analysis ) . All treatments were well tolerated . CONCLUSION In patients achieving asthma control with SFC250 , stepping treatment down with SFC100 was at least as effective on lung function and symptoms as continuing SFC250 , whereas FP250 was not AIM The replacement of chlorofluorocarbon ( CFC ) by hydrofluoroalkane has the potential to improve airway deposition of BDP . We investigated whether HFA-BDP extra-fine solution aerosol 400 microg day(-1 ) is as effective as CFC-BDP 1000 micro day(-1 ) in patients with stable , moderate asthma , having persistent bronchial hyperresponsiveness . PATIENTS AND METHODS One hundred and fifty patients with moderate asthma from 20 centres , on inhaled steroids for < or = 3 months , entered a 4-week run-in period with 1000 microg day(-1 ) CFC-BDP . Patients were then allocated to a 10-week study phase , receiving CFC-BDP 1000 microg day(-1 ) or HFA-BDP 400 microg day(-1 ) . Symptom score and PEF were measured daily and recorded as biweekly means . Spirometry , PC20FEV1 , blood eosinophils and serum ECP were determined on days 15 , 29 , 43 and 71 , and compared to the last visit of the run-in period . All group members were trained in a quality control centre . RESULTS Treating the population of the HFA-BDP group ( n = 72 ) and the CFC-BDP group ( n = 78 ) did not show significant differences in terms of symptoms , lung function , airway hyperresponsiveness and serum markers of inflammation at the end of the run-in period and the end of the study phase . CONCLUSION Using HFA instead of a CFC metered dose inhaler , containing less than half the daily dose of BDP , allows control of symptoms and lung function parameters , without changes in bronchial hyperresponsiveness BACKGROUND Asthma control is the goal of treatment , but little data exist to support treatment strategies for stepping down treatment once control has been achieved . OBJECTIVE We assessed whether either the long-acting beta2-agonist or corticosteroid could be reduced without loss of asthma control once control had been attained with fluticasone propionate/salmeterol ( FSC ) . METHODS After 12 weeks of open-label treatment with FSC 250/50 microg twice daily , patients whose asthma was well controlled were r and omized to FSC 100/50 microg twice daily or fluticasone propionate ( FP ) 250 microg twice daily . for 12 weeks . The primary endpoint was mean morning peak expiratory flow over the r and omized study period . Secondary endpoints included symptom scores , rescue albuterol use , and asthma control . RESULTS During open-label treatment , improvements from baseline were seen , and 435 of 641 patients ( 68 % ) achieved well controlled status during each of the last 4 weeks of this period . A total of 246 patients received FSC 100/50 microg twice daily and 238 FP 250 microg twice daily . The adjusted mean change in morning peak expiratory flow from the end of open-label treatment was -0.3 L/min for FSC and -13.2 L/min for FP ( treatment difference , 12.9 L/min ; 95 % CI , 8.1 - 17.6 ; P<.001 ) . Secondary efficacy endpoints also showed FSC 100/50 microg twice daily to be more effective than FP 250 microg twice daily alone . The majority of patients remained well controlled , but the proportion was higher with FSC . CONCLUSION In patients achieving asthma control with FSC 250/50 microg twice daily , stepping treatment down to a lower dose of FSC 100/50 microg twice daily is more effective than switching to an inhaled corticosteroid alone We have demonstrated recently that 1 year of regular inhaled budesonide use can produce substantial improvements in airway responsiveness accompanied by significant improvements in clinical asthma severity . The present study was design ed to evaluate whether these improvements are maintained when the dose of budesonide is reduced . At the end of the original study , 28 subjects with asthma , who had been in the active-treatment arm of the study were r and omized either to continue taking the dose of budesonide taken in the original study or to have the dose reduced . Airway responsiveness to  methacholine , bronchodilator requirements , symptoms , and spirometry were assessed after 6 weeks and 3 months . During the 3 months , no subject experienced an asthma exacerbation , and there was no evidence of change in airway responsiveness in subjects who had their steroids reduced ( provocative concentration causing a 20 % drop in FEV1 ; initial , 2.03 mg/ml ; final , 1.91 mg/ml ) , and this change was not different from change in subjects maintained with a higher dose ( initial , 3.02 mg/ml ; final , 3.12 mg/ml ) ( p = 0.39 ) . Similarly , there was no evidence of any change in bronchodilator requirements ( p = 0.89 ) . However , after 3 months of reduced steroid use , there was a small decline in spirometry ( FEV1 percent predicted : initial , 84.4 % ; final , 81.5 % ) , and this change was significantly different from change in subjects in whom steroids were not reduced ( initial , 90.2 % ; final , 90.2 % ) ( p = 0.002 ) . At 3 months , symptoms ( predominantly sputum production ) were also beginning to redevelop in the reduced budesonide group ( p = 0.056 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Asthma guidelines recommend reducing the dose of inhaled corticosteroids after establishing control . OBJECTIVE To identify predictors of loss of control and the kinetics of symptoms , and inflammatory and physiological measurements when inhaled corticosteroids are reduced in patients with stable asthma . PATIENTS AND METHODS In a single-blind study , the daily dose of inhaled corticosteroid was reduced by one-half at intervals of 20+/-2 days in 17 adults with controlled asthma until loss of asthma control occurred or until the corticosteroid was replaced with placebo for 20 days . The patients recorded symptoms and peak expiratory flow each day , and forced expiratory volume in 1 s ( FEV1 ) , the provocative concentration of methacholine causing a 20 % fall in FEV1 ( PC20 ) , exhaled nitric oxide , and eosinophils in sputum and blood were measured every 10 days . A loss of asthma control was defined as a worsening of the symptoms score of at least 20 % , and either a decrease in FEV1 of at least 15 % or a decrease in PC20 of at least fourfold . RESULTS Two patients had a respiratory infection and were withdrawn from the study . In eight patients , asthma became uncontrolled after a mean of 33 days ( range 13 to 48 days ) . This was accurately reflected by a worsening of all parameters . The first parameter to change was the sputum eosinophil percentage ( 20 days before the loss of asthma control ) . Significant changes in exhaled nitric oxide , FEV1 and methacholine PC20 were observed only when the symptoms became uncontrolled . A high blood eosinophil count at baseline ( risk ratio of 2.5 , 95 % CI 1.0 to 6.5 ) and an increase in sputum eosinophil count after the reduction of corticosteroids were predictors of loss of asthma control . CONCLUSION In patients whose asthma is controlled on inhaled corticosteroid , it is prudent not to reduce the dose further if the blood eosinophils are increased or if the sputum eosinophils increase by as little as 1 % after the reduction of corticosteroids We investigated whether the serum concentration of eosinophil cationic protein ( s-ECP ) can be used to determine when a step-down in inhaled corticosteroid therapy is indicated for patients with chronic asthma . A total of 24 adult patients , whose symptoms were well controlled with inhaled beclomethasone dipropionate ( iBDP ) , were studied . The dosage of iBDP was reduced by half once a month until the dose reached one-quarter of the original level .  s-ECP and blood eosinophil counts were determined once a month before and during the 6-month period after the step-down . In 12 patients , moderate and frequent exacerbation occurred , thus requiring a return to the initial or twice the initial dose of iBDP . Thus , the step-down here was defined as unsuccessful . In the remaining 12 patients , the symptoms were stable over the course of the 6 months , and the step-down was defined as successful . s-ECP correlated with eosinophil counts in peripheral blood ( EOS ) in both the successful and the unsuccessful groups . Although EOS before the step-down did not differ significantly between the two groups , s-ECP  was significantly higher in the unsuccessful group ( mean 35.7 μg/L ) than in the successful group ( mean 17.0 μg/L , p < 0.03 ) . Thus , s-ECP appears to be a useful marker for determining when a step-down in iBDP therapy is indicated , and thus may contribute to successful long-term management of chronic asthma The efficacy of inhaled beclomethasone dipropionate has been examined in 44 steroid-dependent asthmatics observed for 9 months to 2 years . A 3-month double-blind trial found that subjects treated with beclomethasone had a significant diminution in symptoms , were able to reduce their use of medication , and had improved maximum expiratory flow rates . Approximately one half were able to discontinue the use of oral prednisone within 9 months after starting beclomethasone , and a further one third reduced their dose by at least 50 % . No characteristics could be defined to predict responsiveness to beclomethasone . The effectiveness of beclomethasone was sustained for as long as 2 years and was not associated with any abnormal urine , blood , or serum values or chest X-ray findings . C and idiasis of the palate appeared in approximately one third of the subjects and was usually transient . The chronic use of beclomethasone did not result in endocrine suppression BACKGROUND Treatment guidelines recommend the use of inhaled corticosteroids in patients with asthma who have persistent symptoms and the " stepping down " of therapy to the minimum needed to maintain control of asthma . Whether patients with asthma that is well controlled with the use of inhaled corticosteroids twice daily can receive a step-down treatment with once-daily montelukast ( our primary hypothesis ) or once-daily fluticasone propionate plus salmeterol ( our secondary hypothesis ) has not yet been determined . METHODS We r and omly assigned 500 patients with asthma that was well controlled by inhaled fluticasone ( 100 microg twice daily ) to receive continued  fluticasone ( 100 microg twice daily ) ( 169 patients ) , montelukast ( 5 or 10 mg each night ) ( 166 patients ) , or fluticasone ( 100 microg ) plus salmeterol ( 50 microg ) each night ( 165 patients ) . Treatment was administered for 16 weeks in a double-blind manner . The primary outcome was the time to treatment failure . RESULTS Approximately 20 % of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure , as compared with 30.3 % of subjects switched to montelukast . The hazard ratio for both comparisons was 1.6 ( 95 % confidence interval , 1.1 to 2.6 ; P=0.03 ) . The percentage of days on which patients were free of asthma symptoms ( 78.7 to 85.8 % ) was similar across the three groups . CONCLUSIONS Patients with asthma that is well controlled with the use of twice-daily inhaled fluticasone can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure . A switch to montelukast results in an increased rate of treatment failure and decreased asthma control ; however , patients taking montelukast remained free of symptoms on 78.7 % of treatment days . ( Clinical Trials.gov number , NCT00156819 [ Clinical Trials.gov ] . ) SUMMARY Background : Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans . However , many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms . Objectives : This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol ( Symbicort Turbuhaler * 160/4.5 |ig ) according to asthma severity compared with traditional fixed dosing ( FD ) regimens . * Symbicort and Turbuhaler are registered trademarks owned by the AstraZeneca group , t Seretide and Diskus are trademarks of GlaxoSmithKline . Methods : Symptomatic patients with asthma ( n = 658 , mean symptom score 1.5 , mean inhaled corticosteroids 735|ig/day , mean forced expiratory volume in 1 second [ FEV1 ] 84 % predicted ) were r and omised after 2 weeks ' run-in to either : budesonide/formoterol adjustable maintenance dosing ( AMD ) , budesonide/formoterol FD or salmeterol/fluticasone ( Seretide Diskust 50/250 |ig ) FD . In a 4-week double-blind period , both budesonide/formoterol AMD and FD groups received two inhalations twice daily ( bid ) and salmeterol/fluticasone FD patients received one inhalation bid . In the following 6-month open extension , both FD groups continued with the same treatment . Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid ; others continued with two inhalations bid . All AMD patients could increase to four inhalations bid for 7 - 14 days if symptoms worsened . All patients used terbutaline or salbutamol for symptom relief throughout . The primary variable was the odds of achieving a well-controlled asthma week ( WCAW ) . Results : The odds ratio for achieving a WCAW did not differ between the FD regimens ; however , during the open period , budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD ( odds ratio 1.335 ; 95 % CI : 1.001,1.783 ; p = 0.049 ) despite a 15 % reduction in average study drug use . Budesonide/formoterol AMD patients had a lower exacerbation rate over the study : 40 % lower vs. salmeterol/fluticasone FD ( p = 0.018 ) ; 32 % lower vs. budesonide/formoterol FD ( NS ) . During the double-blind period , there were no clinical ly relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups . Budesonide/formoterol AMD patients used less reliever medication in the open extension : 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD ( p = 0.001 ) and 0.80 occasions/day for salmeterol/fluticasone FD ( p = 0.011 ) . Conclusions : Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone A guided , adjustable-dosing regimen with budesonide/formoterol was investigated in asthma patients . In a r and omised , open , multicentre study , 1034 patients received budesonide/ formoterol ( Symbicort , Turbuhaler , ) 80/4.5 microg or 160/4.5 microg ( depending on pre- study inhaled corticosteroid dose ) two inhalations twice daily for four weeks , followed by adjustable or fixed maintenance dosing for six months . Patients receiving adjustable dosing stepped down to one inhalation twice daily if symptoms were controlled and could , if symptoms worsened , step up to four inhalations twice daily for one or two weeks according to a self-guided management plan . The primary efficacy variable was occurrence of exacerbations . Compared with fixed dosing , adjustable dosing was associated with fewer patients experiencing exacerbations ( 6.2 % vs 9.5 % , NNT 30 , p<0.05 ) , fewer daily inhalations of budesonide/formoterol ( 2.35 vs 3.95 , p<0.001 ) , lower costs ( six-month saving Euros 98 , p<0.001 ) and was similarly well tolerated . Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control than fixed dosing , and reduces costs BACKGROUND Budesonide inhalation powder administered via Turbuhaler ( budesonide Turbuhaler , AstraZeneca LP , Wilmington , DE ) is proven efficacious and safe in the treatment of mild to severe asthma . OBJECTIVE To evaluate the effect of once-daily budesonide Turbuhaler on health-related quality of life ( HRQL ) in adults with mild to moderate asthma . METHODS In this double-blind , parallel-group study , 309 asthmatic patients between 18 and 70 years of age were r and omized to receive once-daily treatment with budesonide 200 or 400 microg or placebo for 6 weeks . Patients initially receiving 400 microg budesonide had their dose reduced to 200 microg ( 400/200-microg group ) , and patients receiving 200 microg ( 200/200-microg group ) or placebo continued to receive their assigned doses for a 12-week maintenance phase . HRQL was evaluated using the Asthma Quality of Life Question naire at r and omization , week 6 , and week 18 . RESULTS Compared with placebo , patients initially receiving 400 and 200 microg budesonide Turbuhaler demonstrated significantly greater HRQL scores at week 6 ( P < or = 0.001 and P < or = 0.010 , respectively ) that were maintained at week 18 ( P < or = 0.001 ) . Clinical ly important ( > or = 0.5 unit ) improvement in Asthma Quality of Life Question naire overall at week 18 was demonstrated by 55 % and 43 % of patients in the 400/200-microg and 200/200-microg budesonide Turbuhaler groups , respectively . CONCLUSIONS In patients with mild to moderate asthma , once-daily budesonide Turbuhaler 200 and 400 microg demonstrates statistically significant and clinical ly important improvements in HRQL that can be maintained with a low dose of 200 microg ABSTRACT Objective : To compare a step-down approach in well-controlled asthma patients , as recommended by treatment guidelines , from fluticasone propionate 250 μg twice daily ( FP250 BID ) , or equivalent , to ciclesonide 160 μg once daily ( CIC160 OD ) with continued FP250 BID treatment . Research design and methods : Patients with well-controlled asthma prior to study entry were included in two identical , r and omized , double-blind , double-dummy , parallel-group studies . After a 2-week run-in period with FP250 BID , patients were r and omized to CIC160 OD ( n = 58 ) or FP250 BID ( n = 53 ) for 12 weeks . Primary endpoints were percentage of days with asthma control , asthma symptom-free days , rescue medication-free days and nocturnal awakening-free days . Secondary endpoints included lung function variables , asthma symptom scores , rescue medication use and asthma exacerbations . Safety variables were also recorded . Results : Patients had ≥ 97 % of days with asthma control , 98 % asthma symptom-free days and 100 % of days free from rescue medication use and nocturnal awakenings in both treatment groups ( median values ) . There were no significant between-treatment differences for any of the primary or secondary efficacy variables . Overall , 42 treatment-emergent adverse events ( TEAEs ) were reported in the CIC160 OD group and 49 TEAEs were reported in the FP250 BID group . There were no clinical ly relevant changes from baseline in the safety variables in either treatment group . Conclusions : Patients well controlled on FP250 BID , or equivalent , who were stepped down to CIC160 OD , maintained similar asthma control compared with patients who received continued treatment st and ardized to FP250 BID
BACKGROUND Asthma is a condition of the airways affecting more than 300 million adults and children worldwide .
National and international guidelines recommend titrating up the dose of inhaled corticosteroids ( ICS ) to gain symptom control at the lowest possible dose because long-term use of higher doses of ICS carries a risk of systemic adverse events .
For patients whose asthma symptoms are controlled on moderate or higher doses of ICS , it may be possible to reduce the dose of ICS without compromising symptom control .
OBJECTIVES To evaluate the evidence for stepping down ICS treatment in adults with well-controlled asthma who are already receiving a moderate or high dose of ICS .