human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 exacerb 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 exacerb 
    Output:
    