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: We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium , tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) . This was a multicentre , r and omised , double-blind , placebo- and active-controlled , 26-week trial . Patients ( n = 2144 ) were r and omised ( 2:2:2:2:1 ) to receive once-daily QVA149 ( indacaterol 110 & mgr;g/glycopyrronium 50 & mgr;g ) , indacaterol 150 & mgr;g , glycopyrronium 50 & mgr;g , open-label tiotropium 18 & mgr;g or placebo . The primary end-point was trough forced expiratory volume in 1 s ( FEV1 ) at week 26 for QVA149 versus its monocomponents . Secondary end-points included dyspnoea , health status , rescue medication use and safety . Trough FEV1 at week 26 was significantly improved ( p<0.001 ) with QVA149 compared with indacaterol and glycopyrronium ( least squares mean ( LSM ) differences 0.07 L and 0.09 L , respectively ) , tiotropium and placebo ( LSM differences 0.08 L and 0.20 L , respectively ) ; these beneficial effects were sustained throughout the 26-week study . QVA149 significantly improved dyspnoea and health status versus placebo ( p<0.001 and p = 0.002 , respectively ) and tiotropium ( p = 0.007 and p = 0.009 , respectively ) at week 26 . All treatments were well tolerated . Dual bronchodilation with once-daily QVA149 demonstrated superior and clinical ly meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator , with a safety and tolerability profile similar to placebo , supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting & bgr;2-agonist combinations for the treatment of COPD . Dual indacaterol/glycopyrronium therapy was safe and more efficacious than monotherapy in moderate-to-severe COPD NVA237 ( glycopyrronium bromide ) is a once-daily long-acting muscarinic antagonist ( LAMA ) in development for chronic obstructive pulmonary disease ( COPD ) . The GLycopyrronium bromide in COPD airWays clinical Study 2 ( GLOW2 ) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks . Patients were r and omised 2:1:1 to NVA237 50 μg , placebo or open-label tiotropium 18 μg for 52 weeks . Primary end-point was trough forced expiratory volume in 1 s ( FEV1 ) at 12 weeks . 1,066 patients were r and omised , 810 completed the study . At week 12 , trough FEV1 increased significantly by 97 mL with NVA237 ( 95 % CI 64.6–130.2 ; p<0.001 ) and 83 mL with tiotropium ( 95 % CI 45.6–121.4 ; p<0.001 ) . Compared with placebo , NVA237 produced significant improvements in dyspnoea ( Transition Dyspnoea Index at week 26 ; p=0.002 ) and health status ( St George 's Respiratory Question naire at week 52 ; p<0.001 ) . NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34 % ( p=0.001 ) and the use of rescue medication ( p=0.039 ) , versus  placebo  . NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes . Safety profiles were similar across groups . NVA237 50 μg provided significant improvements in lung function , dyspnoea , health status , exacerbations and rescue medication use , versus placebo , and was comparable to tiotropium . NVA237 can potentially be an alternative choice of LAMA for COPD patients Background QVA149 is a once-daily ( o.d . ) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD . The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol ( TIO+FOR ) in improving health-related quality of life ( HRQoL ) of patients with COPD . Methods This multicentre , blinded , triple-dummy , parallel-group , non-inferiority study r and omised patients aged ≥40 years with moderate-to-severe COPD ( post-bronchodilator forced expiratory volume in 1 s ( FEV1 ) ≥30 % to < 80 % predicted ) to QVA149 110/50 µg o.d . or TIO 18 µg o.d.+ FOR 12 µg twice daily ( 1:1 ) for 26 weeks . The primary endpoint was to demonstrate non-inferiority in HRQoL assessed using St George 's Respiratory Question naire- COPD ( SGRQ-C ) . The prespecified non-inferiority margin was 4 units . Secondary endpoints included Transition Dyspnoea Index ( TDI ) score , pre-dose FEV1 , forced vital capacity ( FVC ) and safety . Results Of the 934 patients r and omised ( QVA149=476 and TIO+FOR=458 ) , 87.9 % completed the study . At week 26 , non-inferiority was met for SGRQ-C ( QVA149 vs TIO+FOR ; difference : –0.69 units ; 95 % CI −2.31 to 0.92 ; p=0.399 ) . A significantly higher percentage of patients achieved a clinical ly relevant ≥1 point improvement in TDI total score with QVA149 ( 49.6 % ) versus TIO+FOR ( 42.4 % ; p=0.033 ) . QVA149 significantly increased pre-dose FEV1 ( + 68 mL , 95 % CI 37 mL to 100 mL ; p<0.001 ) and FVC ( + 74 mL , 95 % CI 24 mL to 125 mL ; p=0.004 ) compared with TIO+FOR at week 26 . The incidence of adverse events was comparable between both treatments ( QVA149=43.7 % and TIO+FOR=42.6 % ) . Conclusions QVA149 is non-inferior to TIO+FOR in improving HRQoL , with clinical ly meaningful and significant improvements in breathlessness and lung function in patients with COPD . Trial registration number NCT01120717 BACKGROUND Fluticasone furoate/vilanterol ( FF/VI ) is an inhaled corticosteroid/long-acting beta2-agonist ( ICS/LABA ) , recently approved as once-daily maintenance therapy for COPD . We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol ( FP/SAL ) . METHODS Three 12 week studies comparing FF/VI and FP/SAL were conducted . Patients aged ≥40 years with moderate-to-very severe COPD were r and omized to receive double-blind , double-dummy FF/VI 100/25 mcg once-daily , or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period . The primary endpoint of each study was change from baseline trough in 0 - 24 h weighted mean FEV(1 ) ( wmFEV(1 ) ) on Day 84 . Safety was also assessed . RESULTS In Study 1 ( HZC113109 ) ( intent-to-treat n : FF/VI = 260 ; FP/SAL = 259 ) , the increase from baseline in 0 - 24 h wmFEV(1 ) was significantly greater with FF/VI than FP/SAL ( Δ80 mL , P < 0.001 ) . In Study 2 ( HZC112352 ) ( intent-to-treat n : FF/VI = 259 ; FP/SAL = 252 ) and Study 3 ( RLV116974 ) ( intent-to-treat n : FF/VI = 412 ; FP/SAL = 416 ) , the increase from baseline in 0 - 24 h wmFEV(1 ) was not significantly greater with FF/VI than FP/SAL ( Δ29 mL , P = 0.267 ; Δ25 mL , P = 0.137 ) . The treatment difference was statistically but not clinical ly significant in a pooled analysis ( Δ41 mL , P < 0.001 ) . Pooled adverse events ( FF/VI 27 % ; FP/SAL 28 % ) and serious adverse events ( FF/VI 2 % ; FP/SAL 3 % ) were similar between treatments . CONCLUSIONS Our data suggest that once-daily FF/VI 100/25 mcg provides FEV(1 ) improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg , although interpretation is limited by differences in individual study outcomes . The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar . CLINICAL TRIAL REGISTRATION clinical trials.gov : NCT01323634 ; NCT01323621 ; NCT01706328 . GlaxoSmithKline study codes : HZC113109 ; HZC112352 ; RLV116974 Background The current Global initiative for chronic Obstructive Lung Disease ( GOLD ) treatment strategy recommends the use of one or more bronchodilators according to the patient ’s airflow limitation , their history of exacerbations , and symptoms . The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist ( LAMA ) dual bronchodilator , QVA149 ( indacaterol/glycopyrronium ) , as compared with the LABA/inhaled corticosteroid , salmeterol/fluticasone ( SFC ) , in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year . Methods In this double-blind , double-dummy , parallel-group study , 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were r and omized ( 1:1 ) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks . The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second ( FEV1 ) at week 26 . Results Overall , 676 patients completed the study . The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met . QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 ( treatment difference [Δ]=75 mL ; P<0.001 ) . QVA149 demonstrated a statistically significant improvement in st and ardized area under the curve ( AUC ) from 0 hours to 4 hours for FEV1 ( FEV1 AUC0–4h ) at week 26 versus SFC ( Δ=122 mL ; P<0.001 ) . QVA149 and SFC had similar improvements in transition dyspnea index focal score , St George Respiratory Question naire total score , and rescue medication use . However , QVA149 significantly reduced the rate of moderate or severe exacerbations by 31 % ( P=0.048 ) over SFC . Overall , the incidence of adverse events was comparable between QVA149 ( 40.1 % ) and SFC ( 47.4 % ) . The incidence of pneumonia was threefold lower with QVA149 ( 0.8 % ) versus SFC ( 2.7 % ) . Conclusion These findings support the use of the LABA/LAMA , QVA149 as an alternative treatment , over LABA/inhaled corticosteroid , in the management of moderate-to-severe COPD patients ( GOLD B and GOLD D ) with a history of ≤1 exacerbation in the previous year Introduction Chronic obstructive pulmonary disease ( COPD ) is associated with exercise limitation and physical inactivity , which are believed to have significant long-term negative health consequences for patients . While a number of COPD treatments and exercise training programmes increase exercise capacity , there is limited evidence for their effects on physical activity levels , with no clear association between exercise capacity and physical activity in clinical trials . Physical activity depends on a number of behaviour , environmental and physiological factors . 
    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: We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium , tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) . This was a multicentre , r and omised , double-blind , placebo- and active-controlled , 26-week trial . Patients ( n = 2144 ) were r and omised ( 2:2:2:2:1 ) to receive once-daily QVA149 ( indacaterol 110 & mgr;g/glycopyrronium 50 & mgr;g ) , indacaterol 150 & mgr;g , glycopyrronium 50 & mgr;g , open-label tiotropium 18 & mgr;g or placebo . The primary end-point was trough forced expiratory volume in 1 s ( FEV1 ) at week 26 for QVA149 versus its monocomponents . Secondary end-points included dyspnoea , health status , rescue medication use and safety . Trough FEV1 at week 26 was significantly improved ( p<0.001 ) with QVA149 compared with indacaterol and glycopyrronium ( least squares mean ( LSM ) differences 0.07 L and 0.09 L , respectively ) , tiotropium and placebo ( LSM differences 0.08 L and 0.20 L , respectively ) ; these beneficial effects were sustained throughout the 26-week study . QVA149 significantly improved dyspnoea and health status versus placebo ( p<0.001 and p = 0.002 , respectively ) and tiotropium ( p = 0.007 and p = 0.009 , respectively ) at week 26 . All treatments were well tolerated . Dual bronchodilation with once-daily QVA149 demonstrated superior and clinical ly meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator , with a safety and tolerability profile similar to placebo , supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting & bgr;2-agonist combinations for the treatment of COPD . Dual indacaterol/glycopyrronium therapy was safe and more efficacious than monotherapy in moderate-to-severe COPD NVA237 ( glycopyrronium bromide ) is a once-daily long-acting muscarinic antagonist ( LAMA ) in development for chronic obstructive pulmonary disease ( COPD ) . The GLycopyrronium bromide in COPD airWays clinical Study 2 ( GLOW2 ) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks . Patients were r and omised 2:1:1 to NVA237 50 μg , placebo or open-label tiotropium 18 μg for 52 weeks . Primary end-point was trough forced expiratory volume in 1 s ( FEV1 ) at 12 weeks . 1,066 patients were r and omised , 810 completed the study . At week 12 , trough FEV1 increased significantly by 97 mL with NVA237 ( 95 % CI 64.6–130.2 ; p<0.001 ) and 83 mL with tiotropium ( 95 % CI 45.6–121.4 ; p<0.001 ) . Compared with placebo , NVA237 produced significant improvements in dyspnoea ( Transition Dyspnoea Index at week 26 ; p=0.002 ) and health status ( St George 's Respiratory Question naire at week 52 ; p<0.001 ) . NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34 % ( p=0.001 ) and the use of rescue medication ( p=0.039 ) , versus  placebo  . NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes . Safety profiles were similar across groups . NVA237 50 μg provided significant improvements in lung function , dyspnoea , health status , exacerbations and rescue medication use , versus placebo , and was comparable to tiotropium . NVA237 can potentially be an alternative choice of LAMA for COPD patients Background QVA149 is a once-daily ( o.d . ) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD . The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol ( TIO+FOR ) in improving health-related quality of life ( HRQoL ) of patients with COPD . Methods This multicentre , blinded , triple-dummy , parallel-group , non-inferiority study r and omised patients aged ≥40 years with moderate-to-severe COPD ( post-bronchodilator forced expiratory volume in 1 s ( FEV1 ) ≥30 % to < 80 % predicted ) to QVA149 110/50 µg o.d . or TIO 18 µg o.d.+ FOR 12 µg twice daily ( 1:1 ) for 26 weeks . The primary endpoint was to demonstrate non-inferiority in HRQoL assessed using St George 's Respiratory Question naire- COPD ( SGRQ-C ) . The prespecified non-inferiority margin was 4 units . Secondary endpoints included Transition Dyspnoea Index ( TDI ) score , pre-dose FEV1 , forced vital capacity ( FVC ) and safety . Results Of the 934 patients r and omised ( QVA149=476 and TIO+FOR=458 ) , 87.9 % completed the study . At week 26 , non-inferiority was met for SGRQ-C ( QVA149 vs TIO+FOR ; difference : –0.69 units ; 95 % CI −2.31 to 0.92 ; p=0.399 ) . A significantly higher percentage of patients achieved a clinical ly relevant ≥1 point improvement in TDI total score with QVA149 ( 49.6 % ) versus TIO+FOR ( 42.4 % ; p=0.033 ) . QVA149 significantly increased pre-dose FEV1 ( + 68 mL , 95 % CI 37 mL to 100 mL ; p<0.001 ) and FVC ( + 74 mL , 95 % CI 24 mL to 125 mL ; p=0.004 ) compared with TIO+FOR at week 26 . The incidence of adverse events was comparable between both treatments ( QVA149=43.7 % and TIO+FOR=42.6 % ) . Conclusions QVA149 is non-inferior to TIO+FOR in improving HRQoL , with clinical ly meaningful and significant improvements in breathlessness and lung function in patients with COPD . Trial registration number NCT01120717 BACKGROUND Fluticasone furoate/vilanterol ( FF/VI ) is an inhaled corticosteroid/long-acting beta2-agonist ( ICS/LABA ) , recently approved as once-daily maintenance therapy for COPD . We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol ( FP/SAL ) . METHODS Three 12 week studies comparing FF/VI and FP/SAL were conducted . Patients aged ≥40 years with moderate-to-very severe COPD were r and omized to receive double-blind , double-dummy FF/VI 100/25 mcg once-daily , or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period . The primary endpoint of each study was change from baseline trough in 0 - 24 h weighted mean FEV(1 ) ( wmFEV(1 ) ) on Day 84 . Safety was also assessed . RESULTS In Study 1 ( HZC113109 ) ( intent-to-treat n : FF/VI = 260 ; FP/SAL = 259 ) , the increase from baseline in 0 - 24 h wmFEV(1 ) was significantly greater with FF/VI than FP/SAL ( Δ80 mL , P < 0.001 ) . In Study 2 ( HZC112352 ) ( intent-to-treat n : FF/VI = 259 ; FP/SAL = 252 ) and Study 3 ( RLV116974 ) ( intent-to-treat n : FF/VI = 412 ; FP/SAL = 416 ) , the increase from baseline in 0 - 24 h wmFEV(1 ) was not significantly greater with FF/VI than FP/SAL ( Δ29 mL , P = 0.267 ; Δ25 mL , P = 0.137 ) . The treatment difference was statistically but not clinical ly significant in a pooled analysis ( Δ41 mL , P < 0.001 ) . Pooled adverse events ( FF/VI 27 % ; FP/SAL 28 % ) and serious adverse events ( FF/VI 2 % ; FP/SAL 3 % ) were similar between treatments . CONCLUSIONS Our data suggest that once-daily FF/VI 100/25 mcg provides FEV(1 ) improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg , although interpretation is limited by differences in individual study outcomes . The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar . CLINICAL TRIAL REGISTRATION clinical trials.gov : NCT01323634 ; NCT01323621 ; NCT01706328 . GlaxoSmithKline study codes : HZC113109 ; HZC112352 ; RLV116974 Background The current Global initiative for chronic Obstructive Lung Disease ( GOLD ) treatment strategy recommends the use of one or more bronchodilators according to the patient ’s airflow limitation , their history of exacerbations , and symptoms . The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist ( LAMA ) dual bronchodilator , QVA149 ( indacaterol/glycopyrronium ) , as compared with the LABA/inhaled corticosteroid , salmeterol/fluticasone ( SFC ) , in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year . Methods In this double-blind , double-dummy , parallel-group study , 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were r and omized ( 1:1 ) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks . The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second ( FEV1 ) at week 26 . Results Overall , 676 patients completed the study . The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met . QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 ( treatment difference [Δ]=75 mL ; P<0.001 ) . QVA149 demonstrated a statistically significant improvement in st and ardized area under the curve ( AUC ) from 0 hours to 4 hours for FEV1 ( FEV1 AUC0–4h ) at week 26 versus SFC ( Δ=122 mL ; P<0.001 ) . QVA149 and SFC had similar improvements in transition dyspnea index focal score , St George Respiratory Question naire total score , and rescue medication use . However , QVA149 significantly reduced the rate of moderate or severe exacerbations by 31 % ( P=0.048 ) over SFC . Overall , the incidence of adverse events was comparable between QVA149 ( 40.1 % ) and SFC ( 47.4 % ) . The incidence of pneumonia was threefold lower with QVA149 ( 0.8 % ) versus SFC ( 2.7 % ) . Conclusion These findings support the use of the LABA/LAMA , QVA149 as an alternative treatment , over LABA/inhaled corticosteroid , in the management of moderate-to-severe COPD patients ( GOLD B and GOLD D ) with a history of ≤1 exacerbation in the previous year Introduction Chronic obstructive pulmonary disease ( COPD ) is associated with exercise limitation and physical inactivity , which are believed to have significant long-term negative health consequences for patients . While a number of COPD treatments and exercise training programmes increase exercise capacity , there is limited evidence for their effects on physical activity levels , with no clear association between exercise capacity and physical activity in clinical trials . Physical activity depends on a number of behaviour , environmental and physiological factors . 
    Output:
    