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 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 BACKGROUND Whether the combination of a once-daily inhaled corticosteroid with a once-daily longacting β(2 ) agonist is more protective than a once-daily longacting β(2 ) agonist alone against exacerbations of chronic obstructive pulmonary disease ( COPD ) is unknown . We hypothesised that fluticasone furoate and vilanterol would prevent more exacerbations than would vilanterol alone . METHODS We did two replicate double-blind parallel-group 1 year trials . Both studies began on Sept 25 , 2009 . Study 1 ended on Oct 31 , 2011 , and study 2 on Oct 17 , 2011 . Eligible patients were aged 40 years or older , had a history of COPD , a smoking history of 10 or more pack-years , a ratio of forced expiratory volume in 1 s ( FEV(1 ) ) to forced vital capacity of 0·70 or less after bronchodilators ( and an FEV(1 ) of 70 % or less of predicted ) , and a documented history of one or more moderate or severe disease exacerbations in the year before screening . Patients were r and omly assigned ( 1:1:1:1 ) on the basis of the Registration and Medication Ordering System to 25 μg vilanterol alone or 25 μg vilanterol combined with either 50 μg , 100 μg , or 200 μg fluticasone furoate once daily . Our primary endpoint was the yearly rate of moderate and severe exacerbations . The trials were analysed separately and a pooled analysis was also done . These trials are registered with Clinical Trials.gov ( NCT01009463 and NCT01017952 ) . FINDINGS 1622 patients in study 1 and 1633 patients in study 2 were r and omly assigned . In study 1 , no significant difference in exacerbation rate was noted between the 200/25 μg fluticasone furoate/vilanterol group and the vilanterol only group ( mean 0·90 events vs 1·05 events per year ; ratio 0·9 [ 95 % CI 0·7 - 1·0 ] ) . Because of the statistical hierarchy used , we could not infer significance for the 50 μg and 100 μg groups . In study 2 , significantly fewer moderate and severe exacerbations were noted in all fluticasone furoate/vilanterol groups than in the vilanterol only group ( p=0·0398 for the 50 μg group , 0·0244 for the 100 μg group , and 0·0004 for the 200 μg group ) . In the pooled analysis , significantly fewer moderate and severe exacerbations were noted in all fluticasone furoate/vilanterol groups than in the vilanterol only group ( 0·0141 for the 50 μg group , < 0·0001 for the 100 μg group , and 0·0003 for the 200 μg group ) . Nasopharyngitis was the most frequently reported adverse event in both studies . Pneumonia and fractures were reported more frequently with fluticasone furoate and vilanterol than with vilanterol alone . Eight deaths from pneumonia were noted in the fluticasone furoate/vilanterol groups compared with none in the vilanterol only group . INTERPRETATION Addition of fluticasone furoate to vilanterol was associated with a decreased rate of moderate and severe exacerbations of COPD  in patients with a history of exacerbation , but was also associated with an increased pneumonia risk . FUNDING GlaxoSmithKline BACKGROUND To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium ( QVA149 ) and its monocomponents ; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety data bases . METHODS Data from 11,404 patients with chronic obstructive pulmonary disease ( COPD ) were pooled from 14 clinical studies of QVA149 , indacaterol and glycopyrronium of ≥3 month 's duration with at least two of the treatment groups :  QVA149 110/50 μg , glycopyrronium 50 μg , indacaterol 150 μg , placebo or tiotropium 18 μg . Overall hazard ratio ( HR ) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction , inhaled corticosteroid use , cardiovascular risk factors , sex , age and body mass index for death , serious cases of cardio- and cerebrovascular ( CCV ) events , major adverse cardiovascular events ( MACEs ) , pneumonia , COPD exacerbations requiring hospitalisation or atrial flutter/fibrillation ( AF/F ) . RESULTS The HR for QVA149 versus placebo showed no significant increase in the overall risk for death ( HR [ 95 % confidence interval ] : 0.93 [ 0.34 - 2.54 ] ) ; CCV events ( 0.60 [ 0.29 - 1.24 ] ) ; MACE ( 1.04 [ 0.45 - 2.42 ] ) ; pneumonia ( 1.10 [ 0.54 - 2.25 ] ) ; COPD exacerbations ( 0.60 [ 0.40 - 0.91 ] ) ; and AF/F ( 1.03 [ 0.49 - 2.18 ] ) . Similar results were observed for indacaterol , glycopyrronium and tiotropium versus placebo for overall risk and in analysed subgroups . CONCLUSIONS There was no increase in the risk for the investigated safety endpoints for the fixed-dose combination QVA149 , and it had a comparable safety profile as its monocomponents and tiotropium versus placebo Background Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease ( COPD ) that are greater than those derived from either treatment alone . The efficacy and safety of a fixed-dose combination ( FDC ) of aclidinium bromide , a long-acting muscarinic antagonist , and formoterol fumarate , a long-acting β2-agonist , in patients with moderate to severe COPD are presented . Methods In this 24-week double-blind study , 1692 patients with stable COPD were equally r and omized to twice-daily treatment with FDC aclidinium 400μg/formoterol 12μg ( ACL400/FOR12 FDC ) , FDC aclidinium 400μg/formoterol 6μg ( ACL400/FOR6 FDC ) , aclidinium 400μg , formoterol 12μg , or placebo administered by a multidose dry powder inhaler (Genuair ® /Pressair ® )*. Co primary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 ( FDCs versus aclidinium ) and change from baseline to week 24 in morning predose ( trough ) FEV1 ( FDCs versus formoterol ) . Secondary endpoints were change from baseline in St. George ’s Respiratory Question naire ( SGRQ ) total score and improvement in Transition Dyspnea Index ( TDI ) focal score at week 24 . Safety and tolerability were also assessed . Results At study end , improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium ( 108 mL and 87 mL , respectively ; p < 0.0001 ) . Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol ( 45 mL ; p = 0.0102 ) , a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC . Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study 
    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 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 BACKGROUND Whether the combination of a once-daily inhaled corticosteroid with a once-daily longacting β(2 ) agonist is more protective than a once-daily longacting β(2 ) agonist alone against exacerbations of chronic obstructive pulmonary disease ( COPD ) is unknown . We hypothesised that fluticasone furoate and vilanterol would prevent more exacerbations than would vilanterol alone . METHODS We did two replicate double-blind parallel-group 1 year trials . Both studies began on Sept 25 , 2009 . Study 1 ended on Oct 31 , 2011 , and study 2 on Oct 17 , 2011 . Eligible patients were aged 40 years or older , had a history of COPD , a smoking history of 10 or more pack-years , a ratio of forced expiratory volume in 1 s ( FEV(1 ) ) to forced vital capacity of 0·70 or less after bronchodilators ( and an FEV(1 ) of 70 % or less of predicted ) , and a documented history of one or more moderate or severe disease exacerbations in the year before screening . Patients were r and omly assigned ( 1:1:1:1 ) on the basis of the Registration and Medication Ordering System to 25 μg vilanterol alone or 25 μg vilanterol combined with either 50 μg , 100 μg , or 200 μg fluticasone furoate once daily . Our primary endpoint was the yearly rate of moderate and severe exacerbations . The trials were analysed separately and a pooled analysis was also done . These trials are registered with Clinical Trials.gov ( NCT01009463 and NCT01017952 ) . FINDINGS 1622 patients in study 1 and 1633 patients in study 2 were r and omly assigned . In study 1 , no significant difference in exacerbation rate was noted between the 200/25 μg fluticasone furoate/vilanterol group and the vilanterol only group ( mean 0·90 events vs 1·05 events per year ; ratio 0·9 [ 95 % CI 0·7 - 1·0 ] ) . Because of the statistical hierarchy used , we could not infer significance for the 50 μg and 100 μg groups . In study 2 , significantly fewer moderate and severe exacerbations were noted in all fluticasone furoate/vilanterol groups than in the vilanterol only group ( p=0·0398 for the 50 μg group , 0·0244 for the 100 μg group , and 0·0004 for the 200 μg group ) . In the pooled analysis , significantly fewer moderate and severe exacerbations were noted in all fluticasone furoate/vilanterol groups than in the vilanterol only group ( 0·0141 for the 50 μg group , < 0·0001 for the 100 μg group , and 0·0003 for the 200 μg group ) . Nasopharyngitis was the most frequently reported adverse event in both studies . Pneumonia and fractures were reported more frequently with fluticasone furoate and vilanterol than with vilanterol alone . Eight deaths from pneumonia were noted in the fluticasone furoate/vilanterol groups compared with none in the vilanterol only group . INTERPRETATION Addition of fluticasone furoate to vilanterol was associated with a decreased rate of moderate and severe exacerbations of COPD  in patients with a history of exacerbation , but was also associated with an increased pneumonia risk . FUNDING GlaxoSmithKline BACKGROUND To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium ( QVA149 ) and its monocomponents ; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety data bases . METHODS Data from 11,404 patients with chronic obstructive pulmonary disease ( COPD ) were pooled from 14 clinical studies of QVA149 , indacaterol and glycopyrronium of ≥3 month 's duration with at least two of the treatment groups :  QVA149 110/50 μg , glycopyrronium 50 μg , indacaterol 150 μg , placebo or tiotropium 18 μg . Overall hazard ratio ( HR ) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction , inhaled corticosteroid use , cardiovascular risk factors , sex , age and body mass index for death , serious cases of cardio- and cerebrovascular ( CCV ) events , major adverse cardiovascular events ( MACEs ) , pneumonia , COPD exacerbations requiring hospitalisation or atrial flutter/fibrillation ( AF/F ) . RESULTS The HR for QVA149 versus placebo showed no significant increase in the overall risk for death ( HR [ 95 % confidence interval ] : 0.93 [ 0.34 - 2.54 ] ) ; CCV events ( 0.60 [ 0.29 - 1.24 ] ) ; MACE ( 1.04 [ 0.45 - 2.42 ] ) ; pneumonia ( 1.10 [ 0.54 - 2.25 ] ) ; COPD exacerbations ( 0.60 [ 0.40 - 0.91 ] ) ; and AF/F ( 1.03 [ 0.49 - 2.18 ] ) . Similar results were observed for indacaterol , glycopyrronium and tiotropium versus placebo for overall risk and in analysed subgroups . CONCLUSIONS There was no increase in the risk for the investigated safety endpoints for the fixed-dose combination QVA149 , and it had a comparable safety profile as its monocomponents and tiotropium versus placebo Background Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease ( COPD ) that are greater than those derived from either treatment alone . The efficacy and safety of a fixed-dose combination ( FDC ) of aclidinium bromide , a long-acting muscarinic antagonist , and formoterol fumarate , a long-acting β2-agonist , in patients with moderate to severe COPD are presented . Methods In this 24-week double-blind study , 1692 patients with stable COPD were equally r and omized to twice-daily treatment with FDC aclidinium 400μg/formoterol 12μg ( ACL400/FOR12 FDC ) , FDC aclidinium 400μg/formoterol 6μg ( ACL400/FOR6 FDC ) , aclidinium 400μg , formoterol 12μg , or placebo administered by a multidose dry powder inhaler (Genuair ® /Pressair ® )*. Co primary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 ( FDCs versus aclidinium ) and change from baseline to week 24 in morning predose ( trough ) FEV1 ( FDCs versus formoterol ) . Secondary endpoints were change from baseline in St. George ’s Respiratory Question naire ( SGRQ ) total score and improvement in Transition Dyspnea Index ( TDI ) focal score at week 24 . Safety and tolerability were also assessed . Results At study end , improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium ( 108 mL and 87 mL , respectively ; p < 0.0001 ) . Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol ( 45 mL ; p = 0.0102 ) , a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC . Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study 
    Output:
    