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 This study assessed the long-term safety and efficacy of tiotropium Respimat , a long-acting inhaled anticholinergic bronchodilator , in asthma , added on to inhaled corticosteroids ( ICS ) with or without long-acting β2-agonist ( LABA ) . Methods 285 patients with symptomatic asthma , despite treatment with ICS±LABA  , were r and omised 2:2:1 to once-daily tiotropium 5 μg , tiotropium 2.5 μg or placebo for 52 weeks ( via the Respimat SoftMist inhaler ) added on to ICS±LABA , in a double-blind , placebo-controlled , parallel-group study ( NCT01340209 ) . Primary objective : to describe the long-term safety profile  of tiotropium . Secondary end points included : trough forced expiratory volume in 1 second ( FEV1 ) response ; peak expiratory flow rate ( PEFR ) response ; seven- question Asthma Control Question naire ( ACQ-7 ) score . Results At Week 52 , adverse-event ( AE ) rates  with tiotropium 5 μg , 2.5 μg and placebo were 88.6 % , 86.8 % and 89.5 % , respectively . Commonly reported AEs with tiotropium 5 μg , 2.5 μg and placebo were nasopharyngitis ( 48.2 % , 44.7 % , 42.1 % ) , asthma ( 28.9 % , 29.8 % , 38.6 % ) , decreased PEFR ( 15.8 % , 7.9 % , 21.1 % ) , bronchitis ( 9.6 % , 13.2 % , 7.0 % ) , pharyngitis ( 7.9 % , 13.2 % , 3.5 % ) and gastroenteritis ( 10.5 % , 3.5 % , 5.3 % ) . In the tiotropium 5 μg , 2.5 μg and placebo groups , 8.8 % , 5.3 % and 5.3 % of patients reported drug-related AEs ; 3.5 % , 3.5 % and 15.8 % reported serious AEs . Asthma worsening was the only serious AE reported in more than one patient . At Week 52 , adjusted mean trough FEV1 and trough PEFR responses were significantly higher with tiotropium 5 μg ( but not 2.5 μg ) versus placebo . ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24 . Conclusions The long-term tiotropium Respimat  safety profile was comparable with that of placebo Respimat , and associated with mild to moderate , non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy . Compared with placebo , tiotropium 5 μg , but not 2.5 μg , significantly improved lung function and symptoms , supporting the long-term efficacy of the 5 μg dose . Trial Registration Clinical Trials.gov BACKGROUND We evaluated the dose-response of umeclidinium ( UMEC ; a long-acting muscarinic antagonist ) combined with fluticasone furoate ( FF ; an inhaled corticosteroid [ ICS ] ) in patients with asthma . METHODS In a double-blind , three-period crossover study , 421 subjects ( symptomatic on ICS ) , were r and omized to a sequence of three of seven treatments : FF 100 mcg alone , FF 100 mcg combined with UMEC ( 15.6 , 31.25 , 62.5 , 125 , or 250 mcg ) , or vilanterol 25 mcg ( a long-acting β-agonist ) , inhaled once-daily for 14 days ( 12 - 14-day washout ) . Trough forced expiratory volume in one second ( FEV1 ) , peak expiratory flow ( PEF ) , and safety were assessed . RESULTS Period baseline was a significant covariate , indicating a potential carryover effect between treatment periods . Across all treatment periods , trough FEV1 improved with FF/UMEC 125 and 250 versus FF ( treatment difference 0.055 L [ both doses ] ; p = 0.018 ) . FF/UMEC increased morning ( 15.9 - 22.9 L/min ) and evening ( 16.2 - 28.8 L/min ) PEF versus FF . As intended assessment s were confounded , post hoc Period 1 data analyses were performed , demonstrating significant increases in trough FEV1 with FF/UMEC 31.25 , 62.5 , and 250 versus FF . Trough FEV1 improvements with FF/UMEC were greater in subjects with fixed ( 0.095 - 0.304 L ) versus non-fixed ( -0.084 to 0.041 L ) obstruction . The incidence of on-treatment adverse events was 13 - 25 % across groups . No treatment-related effects on laboratory parameters were reported . CONCLUSION FF/UMEC may be a viable treatment for patients with asthma symptomatic on ICS ; benefit may be most prominent in those with fixed obstruction . The carryover effect suggests future UMEC studies should use an alternative design . Clinical Trials.gov : NCT01573624 We present results from the first phase III trial of once-daily tiotropium add-on to inhaled corticosteroids ( ICS ) plus one or more controller therapies in adolescents with severe symptomatic asthma . In this double-blind , parallel-group trial ( NCT01277523 ) , 392 patients aged 12–17 years were r and omised to receive once-daily tiotropium 5 µg or 2.5 µg , or placebo , as an add-on to ICS plus other controller therapies over 12 weeks . The primary and key secondary end-points were change from baseline ( response ) in peak forced expiratory volume in 1 s ( FEV1 ) within 3 h post-dosing ( FEV1(0–3h ) ) and trough FEV1 , respectively , after 12 weeks of treatment  . Tiotropium 5 µg provided numerical improvements in peak FEV1(0–3h ) response , compared with placebo ( 90 mL ; p=0.104 ) , and significant improvements were observed with tiotropium 2.5 µg ( 111 mL ; p=0.046 ) . Numerical improvements in trough FEV1 response and asthma control were observed with both tiotropium doses , compared  with placebo . The safety and tolerability  of tiotropium were comparable with those of  placebo . Once-daily tiotropium Respimat add-on to ICS plus one or more controller therapies in adolescents with severe symptomatic asthma  was well tolerated . The primary end-point of efficacy was not met , although positive trends for improvements in lung function and asthma control were observed  . Tiotropium add-on therapy provided numerical improvements in outcomes in adolescents with asthma BACKGROUND Tiotropium , a once-daily long-acting anticholinergic bronchodilator , has demonstrated efficacy in patients with asthma who were symptomatic despite treatment with medium- to high-dose inhaled corticosteroids ( ICS ) . OBJECTIVE The objective of this study was to evaluate the efficacy and safety of once-daily tiotropium Respimat ( 5 μg or 2.5 μg ) , compared with placebo Respimat , as add-on therapy to low- to medium-dose ICS for adults with symptomatic asthma . METHODS A phase III , double-blind , placebo-controlled trial was conducted ( NCT01316380 ) . Adults with symptomatic asthma receiving low- to medium-dose ICS ( 200 - 400 μg budesonide or equivalent dose ) and a pre-bronchodilator forced expiratory volume in 1 second ( FEV1 ) ≥60 % and ≤90 % of predicted normal were r and omized to 12 weeks of treatment with once-daily tiotropium Respimat 5 μg or 2.5 μg , or placebo Respimat , as add-on therapy to ICS . The primary endpoint was peak FEV1(0 - 3h ) response . RESULTS In total , 464 patients were r and omized ( 61 % female ; mean age 43 years ; mean baseline FEV1 78 % of predicted normal ) . After 12 weeks , both tiotropium Respimat doses were superior to placebo ( adjusted mean difference from placebo : 5 μg , 128 mL ; 2.5 μg , 159 mL ; both P < .001 ) . Both doses of tiotropium Respimat were also superior to placebo with regard to the secondary endpoints of adjusted mean trough FEV1 and FEV1 area under the curve(0 - 3h ) responses , and the other endpoints of morning and evening peak expiratory flow . Adverse events were comparable across the treatment groups . CONCLUSIONS Once-daily tiotropium Respimat add-on therapy to low- to medium-dose ICS in adults with symptomatic asthma is an efficacious bronchodilator , and its safety and tolerability are comparable with those of placebo Respimat Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background To date , there is limited psychometric evidence on the Asthma Quality of Life Question naire ( AQLQ12 + ) among population s that include adolescents and adults . Objective To provide evidence of the psychometric properties of the AQLQ12 + as a measure of asthma-specific quality of life ( QOL ) in patients with persistent asthma treated with a combination of inhaled glucocorticoid and long-acting beta2-agonist  , as well as explore the predictors of at least a minimally important AQLQ12 + improvement . Methods The psychometric properties of the AQLQ12 + were assessed through post hoc analysis of two large ( n = 740 and 778 ) Phase III , r and omized , double-blinded , placebo-controlled efficacy studies of mometasone furoate/formoterol fumarate ( MF/F ) combination compared with monotherapy in subjects with persistent asthma previously treated with either low-dose or medium-dose inhaled glucocorticoids .  Results With 15 % and 8 % participation from 12- to 17-year olds , blinded trial data demonstrated excellent reproducibility ( ICC range : 0.76–0.85 ) and moderate-to-strong construct validity with other measures of asthma health at baseline and over time for the AQLQ12 + . A greater percentage of the MF/F treatment group ( 44 % ) achieved an important change at 26 weeks on the AQLQ12 +  compared with formoterol fumarate ( F , 23 % ) and placebo ( 18 % ) treatment groups in the low-dose study ( P < 0.001 ) and the medium-dose study ( 50 % ( MF/F ) versus 34 % ( F ) and 23 % ( placebo ) ; P < 0.001 ) . Pre-r and omization nighttime awakenings and rescue medications use were significant predictors of AQLQ12 + improvement . Conclusions These findings provide strong support for the measurement properties of the AQLQ12 + among patients with persistent asthma and confidence in the AQLQ12 + improvements demonstrated by the MF/F treatment group AIM To evaluate the best second-line treatments for patients with uncontrolled moderate asthma . METHODS A single-center , r and om study was conducted in adult patients with uncontrolled moderate asthma to evaluate the effects of add-on treatments . After add-on treatments for 4 and 12 weeks , the concentration of exhaled nitric oxide ( FeNO ) , average daily durnal peak expiratory flow ( PEF ) variability and asthma control test ( ACT ) score were measured . RESULTS 94 patients have been divided into three groups to take different add-on treatments , in tiotropium bromide group , montelukast sodium group and double-dose inhaled corticosteroid ( ICS ) group . After four weeks , most patients improved their symptoms and ACT scores , with lower concentration of FeNO and small PEF variability . In double-dose ICS group , almost all patients took the complete controls of asthma , compared to those in other two groups . After additional 12 weeks ' therapy , patients in all three groups nearly achieved complete controls of asthma . There were two patients with pneumonia in double-dose ICS group . Patients in double-dose ICS group had higher ACT scores , lower concentrations of FeNO and smaller PEF variabilities , but a higher risk of pneumonia , compared to those in other two groups . The differences of PEF variabilities and ACT scores between tiotropium group and double-dose ICS group were not significant . CONCLUSION Tiotropium in combination with ICS plus LABA showed the similar effects with double-dose ICS plus LABA , without adverse effects , which might be the best option for optimal control of asthma Background The age limit for some adult asthma clinical trials has recently been lowered to 12 years . In this study we have made minor modifications to the st and ardised version of the adult Asthma Quality of Life Question naire ( 
    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 This study assessed the long-term safety and efficacy of tiotropium Respimat , a long-acting inhaled anticholinergic bronchodilator , in asthma , added on to inhaled corticosteroids ( ICS ) with or without long-acting β2-agonist ( LABA ) . Methods 285 patients with symptomatic asthma , despite treatment with ICS±LABA  , were r and omised 2:2:1 to once-daily tiotropium 5 μg , tiotropium 2.5 μg or placebo for 52 weeks ( via the Respimat SoftMist inhaler ) added on to ICS±LABA , in a double-blind , placebo-controlled , parallel-group study ( NCT01340209 ) . Primary objective : to describe the long-term safety profile  of tiotropium . Secondary end points included : trough forced expiratory volume in 1 second ( FEV1 ) response ; peak expiratory flow rate ( PEFR ) response ; seven- question Asthma Control Question naire ( ACQ-7 ) score . Results At Week 52 , adverse-event ( AE ) rates  with tiotropium 5 μg , 2.5 μg and placebo were 88.6 % , 86.8 % and 89.5 % , respectively . Commonly reported AEs with tiotropium 5 μg , 2.5 μg and placebo were nasopharyngitis ( 48.2 % , 44.7 % , 42.1 % ) , asthma ( 28.9 % , 29.8 % , 38.6 % ) , decreased PEFR ( 15.8 % , 7.9 % , 21.1 % ) , bronchitis ( 9.6 % , 13.2 % , 7.0 % ) , pharyngitis ( 7.9 % , 13.2 % , 3.5 % ) and gastroenteritis ( 10.5 % , 3.5 % , 5.3 % ) . In the tiotropium 5 μg , 2.5 μg and placebo groups , 8.8 % , 5.3 % and 5.3 % of patients reported drug-related AEs ; 3.5 % , 3.5 % and 15.8 % reported serious AEs . Asthma worsening was the only serious AE reported in more than one patient . At Week 52 , adjusted mean trough FEV1 and trough PEFR responses were significantly higher with tiotropium 5 μg ( but not 2.5 μg ) versus placebo . ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24 . Conclusions The long-term tiotropium Respimat  safety profile was comparable with that of placebo Respimat , and associated with mild to moderate , non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy . Compared with placebo , tiotropium 5 μg , but not 2.5 μg , significantly improved lung function and symptoms , supporting the long-term efficacy of the 5 μg dose . Trial Registration Clinical Trials.gov BACKGROUND We evaluated the dose-response of umeclidinium ( UMEC ; a long-acting muscarinic antagonist ) combined with fluticasone furoate ( FF ; an inhaled corticosteroid [ ICS ] ) in patients with asthma . METHODS In a double-blind , three-period crossover study , 421 subjects ( symptomatic on ICS ) , were r and omized to a sequence of three of seven treatments : FF 100 mcg alone , FF 100 mcg combined with UMEC ( 15.6 , 31.25 , 62.5 , 125 , or 250 mcg ) , or vilanterol 25 mcg ( a long-acting β-agonist ) , inhaled once-daily for 14 days ( 12 - 14-day washout ) . Trough forced expiratory volume in one second ( FEV1 ) , peak expiratory flow ( PEF ) , and safety were assessed . RESULTS Period baseline was a significant covariate , indicating a potential carryover effect between treatment periods . Across all treatment periods , trough FEV1 improved with FF/UMEC 125 and 250 versus FF ( treatment difference 0.055 L [ both doses ] ; p = 0.018 ) . FF/UMEC increased morning ( 15.9 - 22.9 L/min ) and evening ( 16.2 - 28.8 L/min ) PEF versus FF . As intended assessment s were confounded , post hoc Period 1 data analyses were performed , demonstrating significant increases in trough FEV1 with FF/UMEC 31.25 , 62.5 , and 250 versus FF . Trough FEV1 improvements with FF/UMEC were greater in subjects with fixed ( 0.095 - 0.304 L ) versus non-fixed ( -0.084 to 0.041 L ) obstruction . The incidence of on-treatment adverse events was 13 - 25 % across groups . No treatment-related effects on laboratory parameters were reported . CONCLUSION FF/UMEC may be a viable treatment for patients with asthma symptomatic on ICS ; benefit may be most prominent in those with fixed obstruction . The carryover effect suggests future UMEC studies should use an alternative design . Clinical Trials.gov : NCT01573624 We present results from the first phase III trial of once-daily tiotropium add-on to inhaled corticosteroids ( ICS ) plus one or more controller therapies in adolescents with severe symptomatic asthma . In this double-blind , parallel-group trial ( NCT01277523 ) , 392 patients aged 12–17 years were r and omised to receive once-daily tiotropium 5 µg or 2.5 µg , or placebo , as an add-on to ICS plus other controller therapies over 12 weeks . The primary and key secondary end-points were change from baseline ( response ) in peak forced expiratory volume in 1 s ( FEV1 ) within 3 h post-dosing ( FEV1(0–3h ) ) and trough FEV1 , respectively , after 12 weeks of treatment  . Tiotropium 5 µg provided numerical improvements in peak FEV1(0–3h ) response , compared with placebo ( 90 mL ; p=0.104 ) , and significant improvements were observed with tiotropium 2.5 µg ( 111 mL ; p=0.046 ) . Numerical improvements in trough FEV1 response and asthma control were observed with both tiotropium doses , compared  with placebo . The safety and tolerability  of tiotropium were comparable with those of  placebo . Once-daily tiotropium Respimat add-on to ICS plus one or more controller therapies in adolescents with severe symptomatic asthma  was well tolerated . The primary end-point of efficacy was not met , although positive trends for improvements in lung function and asthma control were observed  . Tiotropium add-on therapy provided numerical improvements in outcomes in adolescents with asthma BACKGROUND Tiotropium , a once-daily long-acting anticholinergic bronchodilator , has demonstrated efficacy in patients with asthma who were symptomatic despite treatment with medium- to high-dose inhaled corticosteroids ( ICS ) . OBJECTIVE The objective of this study was to evaluate the efficacy and safety of once-daily tiotropium Respimat ( 5 μg or 2.5 μg ) , compared with placebo Respimat , as add-on therapy to low- to medium-dose ICS for adults with symptomatic asthma . METHODS A phase III , double-blind , placebo-controlled trial was conducted ( NCT01316380 ) . Adults with symptomatic asthma receiving low- to medium-dose ICS ( 200 - 400 μg budesonide or equivalent dose ) and a pre-bronchodilator forced expiratory volume in 1 second ( FEV1 ) ≥60 % and ≤90 % of predicted normal were r and omized to 12 weeks of treatment with once-daily tiotropium Respimat 5 μg or 2.5 μg , or placebo Respimat , as add-on therapy to ICS . The primary endpoint was peak FEV1(0 - 3h ) response . RESULTS In total , 464 patients were r and omized ( 61 % female ; mean age 43 years ; mean baseline FEV1 78 % of predicted normal ) . After 12 weeks , both tiotropium Respimat doses were superior to placebo ( adjusted mean difference from placebo : 5 μg , 128 mL ; 2.5 μg , 159 mL ; both P < .001 ) . Both doses of tiotropium Respimat were also superior to placebo with regard to the secondary endpoints of adjusted mean trough FEV1 and FEV1 area under the curve(0 - 3h ) responses , and the other endpoints of morning and evening peak expiratory flow . Adverse events were comparable across the treatment groups . CONCLUSIONS Once-daily tiotropium Respimat add-on therapy to low- to medium-dose ICS in adults with symptomatic asthma is an efficacious bronchodilator , and its safety and tolerability are comparable with those of placebo Respimat Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background To date , there is limited psychometric evidence on the Asthma Quality of Life Question naire ( AQLQ12 + ) among population s that include adolescents and adults . Objective To provide evidence of the psychometric properties of the AQLQ12 + as a measure of asthma-specific quality of life ( QOL ) in patients with persistent asthma treated with a combination of inhaled glucocorticoid and long-acting beta2-agonist  , as well as explore the predictors of at least a minimally important AQLQ12 + improvement . Methods The psychometric properties of the AQLQ12 + were assessed through post hoc analysis of two large ( n = 740 and 778 ) Phase III , r and omized , double-blinded , placebo-controlled efficacy studies of mometasone furoate/formoterol fumarate ( MF/F ) combination compared with monotherapy in subjects with persistent asthma previously treated with either low-dose or medium-dose inhaled glucocorticoids .  Results With 15 % and 8 % participation from 12- to 17-year olds , blinded trial data demonstrated excellent reproducibility ( ICC range : 0.76–0.85 ) and moderate-to-strong construct validity with other measures of asthma health at baseline and over time for the AQLQ12 + . A greater percentage of the MF/F treatment group ( 44 % ) achieved an important change at 26 weeks on the AQLQ12 +  compared with formoterol fumarate ( F , 23 % ) and placebo ( 18 % ) treatment groups in the low-dose study ( P < 0.001 ) and the medium-dose study ( 50 % ( MF/F ) versus 34 % ( F ) and 23 % ( placebo ) ; P < 0.001 ) . Pre-r and omization nighttime awakenings and rescue medications use were significant predictors of AQLQ12 + improvement . Conclusions These findings provide strong support for the measurement properties of the AQLQ12 + among patients with persistent asthma and confidence in the AQLQ12 + improvements demonstrated by the MF/F treatment group AIM To evaluate the best second-line treatments for patients with uncontrolled moderate asthma . METHODS A single-center , r and om study was conducted in adult patients with uncontrolled moderate asthma to evaluate the effects of add-on treatments . After add-on treatments for 4 and 12 weeks , the concentration of exhaled nitric oxide ( FeNO ) , average daily durnal peak expiratory flow ( PEF ) variability and asthma control test ( ACT ) score were measured . RESULTS 94 patients have been divided into three groups to take different add-on treatments , in tiotropium bromide group , montelukast sodium group and double-dose inhaled corticosteroid ( ICS ) group . After four weeks , most patients improved their symptoms and ACT scores , with lower concentration of FeNO and small PEF variability . In double-dose ICS group , almost all patients took the complete controls of asthma , compared to those in other two groups . After additional 12 weeks ' therapy , patients in all three groups nearly achieved complete controls of asthma . There were two patients with pneumonia in double-dose ICS group . Patients in double-dose ICS group had higher ACT scores , lower concentrations of FeNO and smaller PEF variabilities , but a higher risk of pneumonia , compared to those in other two groups . The differences of PEF variabilities and ACT scores between tiotropium group and double-dose ICS group were not significant . CONCLUSION Tiotropium in combination with ICS plus LABA showed the similar effects with double-dose ICS plus LABA , without adverse effects , which might be the best option for optimal control of asthma Background The age limit for some adult asthma clinical trials has recently been lowered to 12 years . In this study we have made minor modifications to the st and ardised version of the adult Asthma Quality of Life Question naire ( 
    Output:
    