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: 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 One of the characteristics of asthma is the variability of inflammation . Thus , it is important to monitor inflammation serially in asthma , e.g. by the use of peripheral blood markers . To evaluate the effect of treatment on allergic inflammation , we measured serum levels of sIL-2R , sICAM-1  and clinical parameters before and after 4 weeks treatment with triamcinolon , montelukast , nedocromil and formoterol . It was 8 week , placebo-controlled and r and omized , double blind trial of 158 children with moderate atopic asthma . Patients were r and omly allocated to received 400 micrograms triamcinolon ( n = 28 ) , 5 or 10 mg ( according to age ) montelukast ( n = 27 ) , 16 mg nedocromil ( n = 30 ) , 24 micrograms formoterol ( n = 29 ) or placebo ( n = 44 ) . 140 children completed the study . After treatment with triamcinolon , montelukast and nedocromil sIL-2R and sICAM-1 serum level significantly decreased , and all clinical parameters improved ; treatment with triamcinolon had the strongest effect on most parameters ( except of FEV1 ) . Mean sIL-2R before and after treatment with triamcinolon were 724.1 pg/ml and 486.1 pg/ml respectively ( p < 0.001 ) ; with nedocromil were 760.2 pg/ml and 596.7 pg/ml respectively ( p < 0.001 ) ; with montelukast were 617.9 pg/ml and 491.2 pg/ml respectively ( p < 0.001 ) ; with formoterol were 705.4 pg/ml and 698.9 pg/ml respectively ( p = 0.8 ) . Mean sICAM-1 serum levels before and after treatment with triamcinolon were 262.4 ng/ml and 210.4 ng/ml respectively ( p < 0.001 ) ; with nedocromil were 292.9 ng/ml and 258.4 ng/ml respectively ( p < 0.001 ) ; with montelukast were 277.7 ng/ml and 242.9 ng/ml respectively ( p < 0.001 ) ; with formoterol were 262.6 ng/ml and 260.0 ng/ml ( p = 0.6 ) . We found significant correlation between : sIL-2R and hyperresponsiveness , sICAM-1 and hyper responsiveness , FEV1 and sICAM-1 , FEV1 and sIL-2R , sIL-2R and sICAM-1 after treatment . This study shows that triamcinolon , montelukast and nedocromil contribute to inhibition of allergic inflammation by decreasing sIL-2R and sICAM-1 serum levels . The serum level of sIL-2R and sICAM-1 seem to be a good clinical marker of monitoring the disease ; their levels decrease after treatment together with improvement in hyperresponsiveness and clinical parameters Background : Addition of the long acting β2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids . However , little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process , control of which is considered important for the long term outcome of asthma . Methods : After a 4 week fluticasone run-in period , 54 patients with allergic asthma were r and omised to receive twice daily treatment with fluticasone 250 μg with or without salmeterol 50 μg for 1 year in a double blind , parallel group design ( total daily dose of fluticasone 500 μg in both treatment groups ) . Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations . Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker . The effects on allergen induced changes were determined before and at the end of the treatment period . Results : Adding salmeterol to fluticasone result ed in improved peak expiratory flow , symptom scores , rescue medication usage , and bronchial hyperresponsiveness ( p<0.05 for all ) . There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment ( p>0.05 ) . However , adding salmeterol significantly reduced sputum ratios of α2-macroglobulin and albumin during the treatment period ( p = 0.001 ) . Conclusions : The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane . This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting β2 agonist is combined with inhaled corticosteroids BACKGROUND In addition to their bronchodilating effect , long-acting inhaled beta-agonists have recently been shown to have some anti-inflammatory properties . OBJECTIVE The purpose of this study was to evaluate the effect of formoterol on inflammatory mediators in children . METHODS In this double-blind , r and omized , placebo-controlled trial , 34 children , aged 6 to 18 years , with moderate atopic asthma , were r and omly allocated to receive formoterol or matching placebo for 4 weeks . The primary endpoint of this study was to determine changes in serum levels of inflammatory markers after treatment with formoterol ; secondary endpoints included clinical efficacy and bronchial hyperreactivity . The following parameters were measured : symptom score , forced expiratory volume in 1 second ( FEV1 ) , provocative concentration of histamine causing a 20 % fall in FEV1 ( PC20 ) for histamine and peripheral blood eosinophil count , serum levels of eosinophil cationic protein ( ECP ) , soluble receptor of interleukin-2 ( sIL-2R ) , level of interleukin-4 ( IL-4 ) , level of soluble intercellular adhesion molecule-1 ( ICAM-1 ) , and immunoglobulin E ( IgE ) level before and after treatment . RESULTS Compared with placebo , treatment with formoterol significantly improved lung function . The mean value of FEV1 changed from 74 % of predicted value before treatment to 80 % of predicted value after treatment ( P < 0.001 ) . The mean concentration of eosinophil blood count before and after treatment was 379 and 310 cells/mm3 ( P = 0.035 ) ; ECP was 93 and 83 mcg/L ; and serum IL-4 was 0.13 and 0.11 pg/mL ( P = 0.001 ) . There was no significant difference between formoterol and placebo recipients in PC20H , and serum concentration of sIL-2R , sICAM-1 , or IgE after treatment . The group that received formoterol showed improvement in pulmonary function as measured by FEV1 ( P < 0.001 ) , and PC20H ( P = 0.04 ) after 4 weeks of treatment . These patients also showed improvement of clinical symptoms ( P < 0.001 ) . Serum marker measurements in the formoterol group showed decreased concentrations of eosinophil blood count , ECP , and IL-4 , but there was no difference in before and after measurements of sIL-2R , sICAM-1 , and IgE. CONCLUSIONS These results indicate that formoterol has measurable anti-inflammatory properties and can diminish asthma symptoms and bronchial hyperreactivity Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma . Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease . To assess this directly , the effects of 6 weeks ' treatment with salmeterol on indices of clinical activity , airway dysfunction and inflammation in subjects with stable atopic asthma were investigated . In a double blind study , asthmatic patients were r and omized to 6 weeks ' treatment with either salmeterol 50 microg twice daily ( n=14 ) or placebo ( n=12 ) . They underwent bronchoscopy with bronchoalveolar lavage ( BAL ) and bronchial biopsy immediately before starting treatment and again after 6 weeks . Treatment with salmeterol improved clinical indices of asthma activity , but there were no changes in BAL differential cell counts or mediator levels , and no change in T-cell numbers or activation status . In the biopsy specimens there were no changes in numbers of inflammatory cells , sub-basement membrane collagen deposition or mast cell degranulation . Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process . These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication STUDY OBJECTIVE To determine the efficacy of salmeterol alone in a group of patients with moderate asthma with nocturnal worsening of symptoms .  DESIGN Double-blind , r and omized , placebo-controlled crossover study . SETTING Tertiary care hospital specializing in respiratory diseases . PARTICIPANTS Ten patients with nocturnal asthma . INTERVENTIONS Subjects were r and omized to salmeterol , 100 micrograms twice daily , or placebo for 6 weeks with a 1-week washout between treatment periods . Symptoms , nocturnal awakenings , and beta 2-agonist use were recorded daily .  Spirometry  was performed at weeks 1 and 6 of each period at bedtime and at 4 AM , and methacholine challenge was performed at 4 AM followed by bronchoscopy with BAL . BAL fluid analysis included cell count and differential count , eosinophil cationic protein , Charcot-Leyden crystal protein , leukotriene B4 , and thromboxane B2 . RESULTS The percentage of nights with awakenings decreased significantly with salmeterol ( 69.8 + /- 8.7 % vs 30.6 + /- 10.8 % for placebo and salmeterol , respectively ; p = 0.02 ) . The percentage of 24-h days with supplemental inhaled beta 2-agonist use significantly decreased with salmeterol ( 85.9 + /- 9.4 % vs 70.4 + /- 10.1 % for placebo and salmeterol , respectively ; p = 0.04 ) . There were no significant differences in bronchial reactivity , 4 AM FEV1 , overnight percentage change in FEV1 , or indexes of airway inflammation . CONCLUSIONS Salmeterol alone improves the number of nocturnal awakenings and supplemental 24-h beta 2-agonist use in nocturnal asthma without significantly altering lung function and airway inflammation BACKGROUND Treatment decisions in asthma are based on assessment s of symptoms and simple measures of lung function , which do not relate closely to underlying eosinophilic airway inflammation . We aim ed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a st and ard management strategy . METHODS We recruited 74 patients with moderate to severe asthma from hospital clinics and r and omly allocated them to 
    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: 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 One of the characteristics of asthma is the variability of inflammation . Thus , it is important to monitor inflammation serially in asthma , e.g. by the use of peripheral blood markers . To evaluate the effect of treatment on allergic inflammation , we measured serum levels of sIL-2R , sICAM-1  and clinical parameters before and after 4 weeks treatment with triamcinolon , montelukast , nedocromil and formoterol . It was 8 week , placebo-controlled and r and omized , double blind trial of 158 children with moderate atopic asthma . Patients were r and omly allocated to received 400 micrograms triamcinolon ( n = 28 ) , 5 or 10 mg ( according to age ) montelukast ( n = 27 ) , 16 mg nedocromil ( n = 30 ) , 24 micrograms formoterol ( n = 29 ) or placebo ( n = 44 ) . 140 children completed the study . After treatment with triamcinolon , montelukast and nedocromil sIL-2R and sICAM-1 serum level significantly decreased , and all clinical parameters improved ; treatment with triamcinolon had the strongest effect on most parameters ( except of FEV1 ) . Mean sIL-2R before and after treatment with triamcinolon were 724.1 pg/ml and 486.1 pg/ml respectively ( p < 0.001 ) ; with nedocromil were 760.2 pg/ml and 596.7 pg/ml respectively ( p < 0.001 ) ; with montelukast were 617.9 pg/ml and 491.2 pg/ml respectively ( p < 0.001 ) ; with formoterol were 705.4 pg/ml and 698.9 pg/ml respectively ( p = 0.8 ) . Mean sICAM-1 serum levels before and after treatment with triamcinolon were 262.4 ng/ml and 210.4 ng/ml respectively ( p < 0.001 ) ; with nedocromil were 292.9 ng/ml and 258.4 ng/ml respectively ( p < 0.001 ) ; with montelukast were 277.7 ng/ml and 242.9 ng/ml respectively ( p < 0.001 ) ; with formoterol were 262.6 ng/ml and 260.0 ng/ml ( p = 0.6 ) . We found significant correlation between : sIL-2R and hyperresponsiveness , sICAM-1 and hyper responsiveness , FEV1 and sICAM-1 , FEV1 and sIL-2R , sIL-2R and sICAM-1 after treatment . This study shows that triamcinolon , montelukast and nedocromil contribute to inhibition of allergic inflammation by decreasing sIL-2R and sICAM-1 serum levels . The serum level of sIL-2R and sICAM-1 seem to be a good clinical marker of monitoring the disease ; their levels decrease after treatment together with improvement in hyperresponsiveness and clinical parameters Background : Addition of the long acting β2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids . However , little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process , control of which is considered important for the long term outcome of asthma . Methods : After a 4 week fluticasone run-in period , 54 patients with allergic asthma were r and omised to receive twice daily treatment with fluticasone 250 μg with or without salmeterol 50 μg for 1 year in a double blind , parallel group design ( total daily dose of fluticasone 500 μg in both treatment groups ) . Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations . Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker . The effects on allergen induced changes were determined before and at the end of the treatment period . Results : Adding salmeterol to fluticasone result ed in improved peak expiratory flow , symptom scores , rescue medication usage , and bronchial hyperresponsiveness ( p<0.05 for all ) . There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment ( p>0.05 ) . However , adding salmeterol significantly reduced sputum ratios of α2-macroglobulin and albumin during the treatment period ( p = 0.001 ) . Conclusions : The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane . This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting β2 agonist is combined with inhaled corticosteroids BACKGROUND In addition to their bronchodilating effect , long-acting inhaled beta-agonists have recently been shown to have some anti-inflammatory properties . OBJECTIVE The purpose of this study was to evaluate the effect of formoterol on inflammatory mediators in children . METHODS In this double-blind , r and omized , placebo-controlled trial , 34 children , aged 6 to 18 years , with moderate atopic asthma , were r and omly allocated to receive formoterol or matching placebo for 4 weeks . The primary endpoint of this study was to determine changes in serum levels of inflammatory markers after treatment with formoterol ; secondary endpoints included clinical efficacy and bronchial hyperreactivity . The following parameters were measured : symptom score , forced expiratory volume in 1 second ( FEV1 ) , provocative concentration of histamine causing a 20 % fall in FEV1 ( PC20 ) for histamine and peripheral blood eosinophil count , serum levels of eosinophil cationic protein ( ECP ) , soluble receptor of interleukin-2 ( sIL-2R ) , level of interleukin-4 ( IL-4 ) , level of soluble intercellular adhesion molecule-1 ( ICAM-1 ) , and immunoglobulin E ( IgE ) level before and after treatment . RESULTS Compared with placebo , treatment with formoterol significantly improved lung function . The mean value of FEV1 changed from 74 % of predicted value before treatment to 80 % of predicted value after treatment ( P < 0.001 ) . The mean concentration of eosinophil blood count before and after treatment was 379 and 310 cells/mm3 ( P = 0.035 ) ; ECP was 93 and 83 mcg/L ; and serum IL-4 was 0.13 and 0.11 pg/mL ( P = 0.001 ) . There was no significant difference between formoterol and placebo recipients in PC20H , and serum concentration of sIL-2R , sICAM-1 , or IgE after treatment . The group that received formoterol showed improvement in pulmonary function as measured by FEV1 ( P < 0.001 ) , and PC20H ( P = 0.04 ) after 4 weeks of treatment . These patients also showed improvement of clinical symptoms ( P < 0.001 ) . Serum marker measurements in the formoterol group showed decreased concentrations of eosinophil blood count , ECP , and IL-4 , but there was no difference in before and after measurements of sIL-2R , sICAM-1 , and IgE. CONCLUSIONS These results indicate that formoterol has measurable anti-inflammatory properties and can diminish asthma symptoms and bronchial hyperreactivity Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma . Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease . To assess this directly , the effects of 6 weeks ' treatment with salmeterol on indices of clinical activity , airway dysfunction and inflammation in subjects with stable atopic asthma were investigated . In a double blind study , asthmatic patients were r and omized to 6 weeks ' treatment with either salmeterol 50 microg twice daily ( n=14 ) or placebo ( n=12 ) . They underwent bronchoscopy with bronchoalveolar lavage ( BAL ) and bronchial biopsy immediately before starting treatment and again after 6 weeks . Treatment with salmeterol improved clinical indices of asthma activity , but there were no changes in BAL differential cell counts or mediator levels , and no change in T-cell numbers or activation status . In the biopsy specimens there were no changes in numbers of inflammatory cells , sub-basement membrane collagen deposition or mast cell degranulation . Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process . These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication STUDY OBJECTIVE To determine the efficacy of salmeterol alone in a group of patients with moderate asthma with nocturnal worsening of symptoms .  DESIGN Double-blind , r and omized , placebo-controlled crossover study . SETTING Tertiary care hospital specializing in respiratory diseases . PARTICIPANTS Ten patients with nocturnal asthma . INTERVENTIONS Subjects were r and omized to salmeterol , 100 micrograms twice daily , or placebo for 6 weeks with a 1-week washout between treatment periods . Symptoms , nocturnal awakenings , and beta 2-agonist use were recorded daily .  Spirometry  was performed at weeks 1 and 6 of each period at bedtime and at 4 AM , and methacholine challenge was performed at 4 AM followed by bronchoscopy with BAL . BAL fluid analysis included cell count and differential count , eosinophil cationic protein , Charcot-Leyden crystal protein , leukotriene B4 , and thromboxane B2 . RESULTS The percentage of nights with awakenings decreased significantly with salmeterol ( 69.8 + /- 8.7 % vs 30.6 + /- 10.8 % for placebo and salmeterol , respectively ; p = 0.02 ) . The percentage of 24-h days with supplemental inhaled beta 2-agonist use significantly decreased with salmeterol ( 85.9 + /- 9.4 % vs 70.4 + /- 10.1 % for placebo and salmeterol , respectively ; p = 0.04 ) . There were no significant differences in bronchial reactivity , 4 AM FEV1 , overnight percentage change in FEV1 , or indexes of airway inflammation . CONCLUSIONS Salmeterol alone improves the number of nocturnal awakenings and supplemental 24-h beta 2-agonist use in nocturnal asthma without significantly altering lung function and airway inflammation BACKGROUND Treatment decisions in asthma are based on assessment s of symptoms and simple measures of lung function , which do not relate closely to underlying eosinophilic airway inflammation . We aim ed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a st and ard management strategy . METHODS We recruited 74 patients with moderate to severe asthma from hospital clinics and r and omly allocated them to 
    Output:
    