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: BACKGROUND For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid ( ICS ) therapy , the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose . OBJECTIVE To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma . METHODS A r and omized , multicenter , double-blind , active-controlled , parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy . Patients received fluticasone propionate-salmeterol ( 100/50 microg ) or fluticasone propionate ( 100 microg ) alone twice daily for 12 weeks . RESULTS The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone . The overall incidence of adverse events was 59 % for fluticasone propionate-salmeterol and 57 % for fluticasone propionate . Both treatments were well tolerated . Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma . Changes in heart rate , blood pressure , and laboratory variables were infrequent and were similar between treatments . No patients had clinical ly significant abnormal electrocardiographic findings during treatment . Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups ; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment . The incidence of withdrawals due to asthma exacerbations was 2 % in the fluticasone propionate-salmeterol group and 5 % in the fluticasone propionate group . CONCLUSIONS In pediatric patients with persistent asthma , fluticasone propionate-salmeterol twice daily was well tolerated , with a safety profile similar to that of fluticasone propionate used alone The aim of the study was to investigate the effect of addition of montelukast to inhaled fluticasone propionate ( FP ) therapy , compared with FP therapy alone ( 100 microg twice a day ) on airway immunopathology in individuals with mild asthma . Twenty-eight subjects received FP ( 100 microg twice a day ) or FP ( 100 microg twice a day ) plus montelukast ( 10 mg at night ) for 8 weeks and were then crossed over to the alternate treatment for a further 8 weeks . Physiological measurements and bronchial biopsies were obtained at + /- 2 days before treatment and + /- 2 days at the end of each treatment period . A two-period crossover analysis was performed and the mean and SE were calculated . There was no significant difference in percent predicted FEV1 ( p = 0.51 ) or PC20 mg/ml ( p = 0.81 ) between the two treatment regimes after 8 weeks of therapy . There was no difference in the efficacy of either treatment in decreasing T cell ( p = 0.97 ) , CD45RO+ ( p = 0.37 ) , mast cell ( p = 0.37 ) , or activated eosinophils ( p = 0.55 ) numbers in bronchial biopsies . There was no significant difference in the percentage area stained for IFN-gamma ( p = 0.76 ) or interleukin-4 ( p = 0.61 ) between treatments . Reduction of inflammatory cell numbers in the bronchial mucosa achieved with FP plus montelukast was not significantly different from the reduction observed with FP alone in individuals with mild asthma Abstract Objectives To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone . Design and setting A 52 week , two period , double blind , multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were r and omised to add montelukast or salmeterol .  Participants Patients ( 15 - 72 years ; n = 1490 ) had a clinical history of chronic asthma for ≥ 1 year , a baseline forced expiratory volume in one second ( FEV 1 ) value 50 - 90 % predicted , and a β agonist improvement of ≥ 12 % in FEV 1 . Main outcome measures The primary end point was the percentage of patients with at least one asthma exacerbation . Results 20.1 % of the patients in the group receiving montelukast and fluticasone  had an asthma exacerbation compared with 19.1 % in the group receiving salmeterol and fluticasone ; the difference was 1 % ( 95 % confidence interval -3.1 % to 5.0 % ) . With a risk ratio ( montelukast-fluticasone/salmeterol-fluticasone ) of 1.05 ( 0.86 to 1.29 ) , treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone . Salmeterol and fluticasone  significantly increased FEV 1 before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone ( P ≤ 0.001 ) , whereas FEV 1 after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups . Montelukast and fluticasone significantly ( P = 0.011 ) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone . Both treatments were generally well tolerated . Conclusion The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids  represent a management challenge . Leukotrienes play a key role in asthma pathophysiology , and since pro-inflammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add a leukotriene receptor antagonist ( LTRA ) when a low to moderate dose of inhaled corticosteroids does not provide sufficient disease control . Long acting beta2-agonist ( LABA ) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment . To compare the relative clinical benefits of adding either a LTRA or a LABA to asthma patients inadequately controlled by inhaled corticosteroids , a r and omized , double-blind , multi-centre , 48-week study will be initiated at approximately 120 centres throughout Europe , Latin America , Middle East , Africa and the Asia-Pacific region in early 2000 . The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol , each administered on a background of inhaled fluticasone , on asthma attacks , quality of life , lung function , eosinophil levels , healthcare utilization , and safety , in approximately 1200 adult asthmatic patients . The requirements for study enrollment include a history of asthma , FEV1 or PEFR values between 50 % and 90 % of the predicted value together with > or = 12 % improvement in FEV1 after beta-agonist administration , a minimum pre-determined level of asthma symptoms and daily beta-agonist medication . The study will include a 4-week run-in period , during which patients previously taking inhaled corticosteroids are switched to open-label fluticasone ( 200 microg daily ) , followed by a 48-week double-blind , treatment period in which patients continuing to experience abnormal pulmonary function and daytime symptoms are r and omized to receive montelukast ( 10 mg once daily ) and salmeterol placebo , or inhaled salmeterol ( 100 microg daily ) and montelukast placebo . All patients will continue with inhaled fluticasone ( 200 microg daily ) . During the study , asthma attacks , overnight asthma symptoms , and morning peak expiratory flow rate will be assessed using patient diary cards ; quality of life will also be assessed using an asthma-specific quality -of life question naire . The results of this study are expected to provide physicians with important clinical evidence to help them make a rational and logical treatment choice for asthmatic patients experiencing breakthrough symptoms on inhaled corticosteroids The aim of this study was to verify FeNO usefulness , as a marker of bronchial inflammation , in the assessment of therapeutic management of childhood asthma . We performed a prospect i ve 1-year r and omized clinical trial evaluating two groups of 32 children with allergic asthma : “ GINA group ” , in which therapy was assessed only by GINA guidelines and “ FeNO group ” , who followed a therapeutic program assessed also on FeNO measurements .  Asthma Severity score ( ASs ) , Asthma Exacerbation Frequency ( AEf ) , and Asthma Therapy score ( ATs ) were evaluated at the start of the study ( T1 ) , 6 months ( T2 ) , and 1 year after ( T3 ) . ASs and AEf significantly decreased only in the FeNO group at times T2 and T3 ( p[T1-T2 ] = 0.0001 , and p[T1-T3 ] = 0.01 ; p[T1-T2 ] = 0.0001 ; and p[T1-T3 ] < 0.0001 , resp . ) . After six months of follow-up , we found a significant increase of patients under inhaled corticosteroid and /or antileukotrienes  in the GINA group compared to the FeNO group ( P = .02 ) . Our data show that FeNO measurements , might be a very useful additional parameter for management of asthma , which is able to avoid unnecessary inhaled corticosteroid and antileukotrienes therapies , however , mantaining a treatment sufficient to obtain a meaningful improvement of asthma Background : The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids . Objectives : The study aim ed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids  improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone . Methods : Ninety patients with incompletely controlled asthma were allocated , in a r and omised , double-blind fashion , to one of three treatment groups : group A : double dose of inhaled budesonide ( 400 µg b.i.d . ) , group B : 400 mg oral sustained-release theophylline plus budesonide ( 200 µg b.i.d . ) and group C : 10 mg montelukast plus budesonide ( 200 µg b.i.d . ) . The primary endpoints were forced expiratory volume in 1 s ( FEV1 ) and mean morning peak expiratory flow rate ( PEFR ) . Results : All three groups had improved FEV1 and PEFR at 8 weeks ( p < 0.001 ) . Group C increased their PEFR by 18.7 l/min ( 95 % confidence interval , CI , 12.4–25.1 ) more than group A and by 19.8 l/min ( 95 % CI 13.4–26.1 ) more than group B ( both p = 0.001 ) . Similarly , group C had a 114 ml ( 95 % CI 45–183 ml ) greater improvement in FEV1 than group A and a 95 ml ( 95 % CI 26–164 ml ) greater improvement than group B ( both p = 0.01 ) . Conclusions : Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters  than high-dose budesonide treatment or addition of theophylline BACKGROUND For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids , addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines . OBJECTIVE To compare montelukast , a once-daily leukotriene receptor antagonist , and salmeterol , a twice-daily , long-acting beta-agonist , concomitantly administered with inhaled fluticasone , according to the percentage of patients without an asthma attack for 1 year . METHODS A r and omized , double-blind , double-dummy , multicenter study was conducted . Adult patients with moderate-to-severe persistent asthma ( ages 14 - 73 years ) receiving inhaled fluticasone ( 220 microg/d ) who remained symptomatic during a 4-week run-in period were r and omized to the addition of salmeterol ( 84 microg/d ) or montelukast ( 10 mg/d ) for 48 weeks . RESULTS Of the 1,473 r and omized patients , 743 were r and omized to montelukast and 730 to salmeterol ; 1,059 patients completed the study . Eighty percent of patients in the montelukast group and 83.3 % of patients in the salmeterol group remained attack free during the 48 weeks of treatment ( relative risk , 1 
    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: BACKGROUND For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid ( ICS ) therapy , the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose . OBJECTIVE To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma . METHODS A r and omized , multicenter , double-blind , active-controlled , parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy . Patients received fluticasone propionate-salmeterol ( 100/50 microg ) or fluticasone propionate ( 100 microg ) alone twice daily for 12 weeks . RESULTS The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone . The overall incidence of adverse events was 59 % for fluticasone propionate-salmeterol and 57 % for fluticasone propionate . Both treatments were well tolerated . Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma . Changes in heart rate , blood pressure , and laboratory variables were infrequent and were similar between treatments . No patients had clinical ly significant abnormal electrocardiographic findings during treatment . Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups ; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment . The incidence of withdrawals due to asthma exacerbations was 2 % in the fluticasone propionate-salmeterol group and 5 % in the fluticasone propionate group . CONCLUSIONS In pediatric patients with persistent asthma , fluticasone propionate-salmeterol twice daily was well tolerated , with a safety profile similar to that of fluticasone propionate used alone The aim of the study was to investigate the effect of addition of montelukast to inhaled fluticasone propionate ( FP ) therapy , compared with FP therapy alone ( 100 microg twice a day ) on airway immunopathology in individuals with mild asthma . Twenty-eight subjects received FP ( 100 microg twice a day ) or FP ( 100 microg twice a day ) plus montelukast ( 10 mg at night ) for 8 weeks and were then crossed over to the alternate treatment for a further 8 weeks . Physiological measurements and bronchial biopsies were obtained at + /- 2 days before treatment and + /- 2 days at the end of each treatment period . A two-period crossover analysis was performed and the mean and SE were calculated . There was no significant difference in percent predicted FEV1 ( p = 0.51 ) or PC20 mg/ml ( p = 0.81 ) between the two treatment regimes after 8 weeks of therapy . There was no difference in the efficacy of either treatment in decreasing T cell ( p = 0.97 ) , CD45RO+ ( p = 0.37 ) , mast cell ( p = 0.37 ) , or activated eosinophils ( p = 0.55 ) numbers in bronchial biopsies . There was no significant difference in the percentage area stained for IFN-gamma ( p = 0.76 ) or interleukin-4 ( p = 0.61 ) between treatments . Reduction of inflammatory cell numbers in the bronchial mucosa achieved with FP plus montelukast was not significantly different from the reduction observed with FP alone in individuals with mild asthma Abstract Objectives To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone . Design and setting A 52 week , two period , double blind , multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were r and omised to add montelukast or salmeterol .  Participants Patients ( 15 - 72 years ; n = 1490 ) had a clinical history of chronic asthma for ≥ 1 year , a baseline forced expiratory volume in one second ( FEV 1 ) value 50 - 90 % predicted , and a β agonist improvement of ≥ 12 % in FEV 1 . Main outcome measures The primary end point was the percentage of patients with at least one asthma exacerbation . Results 20.1 % of the patients in the group receiving montelukast and fluticasone  had an asthma exacerbation compared with 19.1 % in the group receiving salmeterol and fluticasone ; the difference was 1 % ( 95 % confidence interval -3.1 % to 5.0 % ) . With a risk ratio ( montelukast-fluticasone/salmeterol-fluticasone ) of 1.05 ( 0.86 to 1.29 ) , treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone . Salmeterol and fluticasone  significantly increased FEV 1 before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone ( P ≤ 0.001 ) , whereas FEV 1 after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups . Montelukast and fluticasone significantly ( P = 0.011 ) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone . Both treatments were generally well tolerated . Conclusion The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids  represent a management challenge . Leukotrienes play a key role in asthma pathophysiology , and since pro-inflammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add a leukotriene receptor antagonist ( LTRA ) when a low to moderate dose of inhaled corticosteroids does not provide sufficient disease control . Long acting beta2-agonist ( LABA ) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment . To compare the relative clinical benefits of adding either a LTRA or a LABA to asthma patients inadequately controlled by inhaled corticosteroids , a r and omized , double-blind , multi-centre , 48-week study will be initiated at approximately 120 centres throughout Europe , Latin America , Middle East , Africa and the Asia-Pacific region in early 2000 . The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol , each administered on a background of inhaled fluticasone , on asthma attacks , quality of life , lung function , eosinophil levels , healthcare utilization , and safety , in approximately 1200 adult asthmatic patients . The requirements for study enrollment include a history of asthma , FEV1 or PEFR values between 50 % and 90 % of the predicted value together with > or = 12 % improvement in FEV1 after beta-agonist administration , a minimum pre-determined level of asthma symptoms and daily beta-agonist medication . The study will include a 4-week run-in period , during which patients previously taking inhaled corticosteroids are switched to open-label fluticasone ( 200 microg daily ) , followed by a 48-week double-blind , treatment period in which patients continuing to experience abnormal pulmonary function and daytime symptoms are r and omized to receive montelukast ( 10 mg once daily ) and salmeterol placebo , or inhaled salmeterol ( 100 microg daily ) and montelukast placebo . All patients will continue with inhaled fluticasone ( 200 microg daily ) . During the study , asthma attacks , overnight asthma symptoms , and morning peak expiratory flow rate will be assessed using patient diary cards ; quality of life will also be assessed using an asthma-specific quality -of life question naire . The results of this study are expected to provide physicians with important clinical evidence to help them make a rational and logical treatment choice for asthmatic patients experiencing breakthrough symptoms on inhaled corticosteroids The aim of this study was to verify FeNO usefulness , as a marker of bronchial inflammation , in the assessment of therapeutic management of childhood asthma . We performed a prospect i ve 1-year r and omized clinical trial evaluating two groups of 32 children with allergic asthma : “ GINA group ” , in which therapy was assessed only by GINA guidelines and “ FeNO group ” , who followed a therapeutic program assessed also on FeNO measurements .  Asthma Severity score ( ASs ) , Asthma Exacerbation Frequency ( AEf ) , and Asthma Therapy score ( ATs ) were evaluated at the start of the study ( T1 ) , 6 months ( T2 ) , and 1 year after ( T3 ) . ASs and AEf significantly decreased only in the FeNO group at times T2 and T3 ( p[T1-T2 ] = 0.0001 , and p[T1-T3 ] = 0.01 ; p[T1-T2 ] = 0.0001 ; and p[T1-T3 ] < 0.0001 , resp . ) . After six months of follow-up , we found a significant increase of patients under inhaled corticosteroid and /or antileukotrienes  in the GINA group compared to the FeNO group ( P = .02 ) . Our data show that FeNO measurements , might be a very useful additional parameter for management of asthma , which is able to avoid unnecessary inhaled corticosteroid and antileukotrienes therapies , however , mantaining a treatment sufficient to obtain a meaningful improvement of asthma Background : The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids . Objectives : The study aim ed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids  improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone . Methods : Ninety patients with incompletely controlled asthma were allocated , in a r and omised , double-blind fashion , to one of three treatment groups : group A : double dose of inhaled budesonide ( 400 µg b.i.d . ) , group B : 400 mg oral sustained-release theophylline plus budesonide ( 200 µg b.i.d . ) and group C : 10 mg montelukast plus budesonide ( 200 µg b.i.d . ) . The primary endpoints were forced expiratory volume in 1 s ( FEV1 ) and mean morning peak expiratory flow rate ( PEFR ) . Results : All three groups had improved FEV1 and PEFR at 8 weeks ( p < 0.001 ) . Group C increased their PEFR by 18.7 l/min ( 95 % confidence interval , CI , 12.4–25.1 ) more than group A and by 19.8 l/min ( 95 % CI 13.4–26.1 ) more than group B ( both p = 0.001 ) . Similarly , group C had a 114 ml ( 95 % CI 45–183 ml ) greater improvement in FEV1 than group A and a 95 ml ( 95 % CI 26–164 ml ) greater improvement than group B ( both p = 0.01 ) . Conclusions : Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters  than high-dose budesonide treatment or addition of theophylline BACKGROUND For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids , addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines . OBJECTIVE To compare montelukast , a once-daily leukotriene receptor antagonist , and salmeterol , a twice-daily , long-acting beta-agonist , concomitantly administered with inhaled fluticasone , according to the percentage of patients without an asthma attack for 1 year . METHODS A r and omized , double-blind , double-dummy , multicenter study was conducted . Adult patients with moderate-to-severe persistent asthma ( ages 14 - 73 years ) receiving inhaled fluticasone ( 220 microg/d ) who remained symptomatic during a 4-week run-in period were r and omized to the addition of salmeterol ( 84 microg/d ) or montelukast ( 10 mg/d ) for 48 weeks . RESULTS Of the 1,473 r and omized patients , 743 were r and omized to montelukast and 730 to salmeterol ; 1,059 patients completed the study . Eighty percent of patients in the montelukast group and 83.3 % of patients in the salmeterol group remained attack free during the 48 weeks of treatment ( relative risk , 1 
    Output:
    