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: 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 BACKGROUND The greatest prevalence of asthma is in preschool children ; however , the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index , long-term tolerability , and frequency and /or difficulty of administration .  Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma , although very young patients may have difficulty using inhalers , and dose delivery can be variable . Moreover , reduced compliance with inhaled therapy relative to orally administered therapy has been reported . One potential advantage of montelukast is the ease of administering a once-daily chewable tablet ; additionally , no tachyphylaxis or change in the safety profile has been evidence d after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years , respectively . To our knowledge , this represents the first large , multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma , as well as one of the few asthma studies that incorporated end points vali date d for use in preschool children . OBJECTIVE Our primary objective was to determine the safety profile of montelukast , an oral leukotriene receptor antagonist , in preschool children with persistent asthma . Secondarily , the effect of montelukast on exploratory measures of asthma control was also studied . DESIGN AND STATISTICAL ANALYSIS : We conducted a double-blind , multicenter , multinational study at 93 centers worldwide : including 56 in the United States , and 21 in countries in Africa , Australia , Europe , North America , and South America . In this study , we r and omly assigned 689 patients ( aged 2 - 5 years ) to 12 weeks of treatment with placebo ( 228 patients ) or 4 mg of montelukast as a chewable tablet ( 461 patients ) after a 2-week placebo baseline period . Patients had a history of physician-diagnosed asthma requiring use of beta-agonist and a predefined level of daytime asthma symptoms . Caregivers answered questions twice daily on a vali date d , asthma-specific diary card and , at specified times during the study , completed a vali date d asthma-specific quality -of-life question naire . Physicians and caregivers completed a global evaluation of asthma control at the end of the study . Efficacy end points included : daytime and overnight asthma symptoms , daily use of beta-agonist , days without asthma , frequency of asthma attacks , number of patients discontinued because of asthma , need for rescue medication , physician and caregiver global evaluations of change , asthma-specific caregiver quality of life , and peripheral blood eosinophil counts . Although exploratory , the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding . At screening and at study completion , a complete physical examination was performed . Routine laboratory tests were drawn at screening and weeks 6 and 12 , and su bmi tted to a central laboratory for analysis . Adverse effects were collected from caregivers at each clinic visit . An intention-to-treat approach , including all patients with a baseline measurement and at least 1 postr and omization measurement , was performed for all efficacy end points . An analysis -of-variance model with terms for treatment , study center and stratum ( inhaled/nebulized corticosteroid use , cromolyn use , or none ) was used to estimate treatment group means and between-group differences and to construct 95 % confidence intervals . Treatment-by-age , -sex , -race , -radioallergosorbent test , -stratum , and - study center interactions were evaluated by including each term separately . Fisher 's exact test was used for between-group comparisons of the frequency of asthma attacks , discontinuations from the study because of worsening asthma , need for rescue medication , and the frequencies of adverse effects . Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups , an analysis of covariance was performed on the eosinophil change from baseline with the patient 's baseline as covariate . STUDY PARTICIPANTS Of the 689 patients enrolled , approximately 60 % were boys and 60 % were white . Patients were relatively evenly divided by age : 21 % , 24 % , 30 % , and 23 % were aged 2 , 3 , 4 , and 5 years , respectively . For 77 % of the patients , asthma symptoms first developed during the first 3 years of life . During the placebo baseline period , patients had asthma symptoms on 6.1 days/week and used beta-agonist on 6.0 days/week . RESULTS In over 12 weeks of treatment of patients aged 2 to 5 years , montelukast administered as a 4-mg chewable tablet produced significant improvements compared with placebo in multiple parameters of asthma control including : daytime asthma symptoms ( cough , wheeze , trouble breathing , and activity limitation ) ; overnight asthma symptoms ( cough ) ; the percentage of days with asthma symptoms ; the percentage of days without asthma ; the need for beta-agonist or oral corticosteroids ; physician global evaluations ; and peripheral blood eosinophils . The clinical benefit of montelukast was evident within 1 day of starting therapy . Improvements in asthma control were consistent across age , sex , race , and study center , and whether or not patients had a positive radioallergosorbent test . Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy . Caregiver global evaluations , the percentage of patients experiencing asthma attacks , and improvements in quality -of-life scores favored montelukast , but were not significantly different from placebo . There were no clinical ly meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects , with the exception of asthma , which occurred significantly more frequently in the placebo group . There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels .  Approximately 90 % of the patients completed the study . CONCLUSIONS Oral montelukast ( 4-mg chewable tablet ) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinical ly important adverse effects . Similarly , in adults and children aged 6 to 14 years , montelukast improves multiple parameters of asthma control . Thus , this study confirms and extends the benefit of montelukast to younger children with persistent asthma 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 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 
    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: 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 BACKGROUND The greatest prevalence of asthma is in preschool children ; however , the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index , long-term tolerability , and frequency and /or difficulty of administration .  Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma , although very young patients may have difficulty using inhalers , and dose delivery can be variable . Moreover , reduced compliance with inhaled therapy relative to orally administered therapy has been reported . One potential advantage of montelukast is the ease of administering a once-daily chewable tablet ; additionally , no tachyphylaxis or change in the safety profile has been evidence d after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years , respectively . To our knowledge , this represents the first large , multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma , as well as one of the few asthma studies that incorporated end points vali date d for use in preschool children . OBJECTIVE Our primary objective was to determine the safety profile of montelukast , an oral leukotriene receptor antagonist , in preschool children with persistent asthma . Secondarily , the effect of montelukast on exploratory measures of asthma control was also studied . DESIGN AND STATISTICAL ANALYSIS : We conducted a double-blind , multicenter , multinational study at 93 centers worldwide : including 56 in the United States , and 21 in countries in Africa , Australia , Europe , North America , and South America . In this study , we r and omly assigned 689 patients ( aged 2 - 5 years ) to 12 weeks of treatment with placebo ( 228 patients ) or 4 mg of montelukast as a chewable tablet ( 461 patients ) after a 2-week placebo baseline period . Patients had a history of physician-diagnosed asthma requiring use of beta-agonist and a predefined level of daytime asthma symptoms . Caregivers answered questions twice daily on a vali date d , asthma-specific diary card and , at specified times during the study , completed a vali date d asthma-specific quality -of-life question naire . Physicians and caregivers completed a global evaluation of asthma control at the end of the study . Efficacy end points included : daytime and overnight asthma symptoms , daily use of beta-agonist , days without asthma , frequency of asthma attacks , number of patients discontinued because of asthma , need for rescue medication , physician and caregiver global evaluations of change , asthma-specific caregiver quality of life , and peripheral blood eosinophil counts . Although exploratory , the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding . At screening and at study completion , a complete physical examination was performed . Routine laboratory tests were drawn at screening and weeks 6 and 12 , and su bmi tted to a central laboratory for analysis . Adverse effects were collected from caregivers at each clinic visit . An intention-to-treat approach , including all patients with a baseline measurement and at least 1 postr and omization measurement , was performed for all efficacy end points . An analysis -of-variance model with terms for treatment , study center and stratum ( inhaled/nebulized corticosteroid use , cromolyn use , or none ) was used to estimate treatment group means and between-group differences and to construct 95 % confidence intervals . Treatment-by-age , -sex , -race , -radioallergosorbent test , -stratum , and - study center interactions were evaluated by including each term separately . Fisher 's exact test was used for between-group comparisons of the frequency of asthma attacks , discontinuations from the study because of worsening asthma , need for rescue medication , and the frequencies of adverse effects . Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups , an analysis of covariance was performed on the eosinophil change from baseline with the patient 's baseline as covariate . STUDY PARTICIPANTS Of the 689 patients enrolled , approximately 60 % were boys and 60 % were white . Patients were relatively evenly divided by age : 21 % , 24 % , 30 % , and 23 % were aged 2 , 3 , 4 , and 5 years , respectively . For 77 % of the patients , asthma symptoms first developed during the first 3 years of life . During the placebo baseline period , patients had asthma symptoms on 6.1 days/week and used beta-agonist on 6.0 days/week . RESULTS In over 12 weeks of treatment of patients aged 2 to 5 years , montelukast administered as a 4-mg chewable tablet produced significant improvements compared with placebo in multiple parameters of asthma control including : daytime asthma symptoms ( cough , wheeze , trouble breathing , and activity limitation ) ; overnight asthma symptoms ( cough ) ; the percentage of days with asthma symptoms ; the percentage of days without asthma ; the need for beta-agonist or oral corticosteroids ; physician global evaluations ; and peripheral blood eosinophils . The clinical benefit of montelukast was evident within 1 day of starting therapy . Improvements in asthma control were consistent across age , sex , race , and study center , and whether or not patients had a positive radioallergosorbent test . Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy . Caregiver global evaluations , the percentage of patients experiencing asthma attacks , and improvements in quality -of-life scores favored montelukast , but were not significantly different from placebo . There were no clinical ly meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects , with the exception of asthma , which occurred significantly more frequently in the placebo group . There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels .  Approximately 90 % of the patients completed the study . CONCLUSIONS Oral montelukast ( 4-mg chewable tablet ) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinical ly important adverse effects . Similarly , in adults and children aged 6 to 14 years , montelukast improves multiple parameters of asthma control . Thus , this study confirms and extends the benefit of montelukast to younger children with persistent asthma 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 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 
    Output:
    