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 Chronic obstructive pulmonary disease is associated with significant morbidity and mortality . Trials of maintenance chronic obstructive pulmonary disease treatments focus on improvement in lung function and reductions in exacerbations , while patients are much more concerned about symptoms and health status . Our aim was to investigate the effects of tiotropium + olo date rol on  patient-reported health outcomes , breathlessness and night-time rescue medication use in patients with chronic obstructive pulmonary disease , compared to placebo , tiotropium or olo date rol monotherapy . Two pairs of replicate , phase III studies of 12 ( OTEMTO 1 + 2 ) and 52 weeks ’ ( TONADO 1 + 2 ) duration were evaluated , in which patients received either tiotropium + olo date rol 2.5/5 or 5/5 μg , tiotropium 2.5 or 5 μg , olo date rol 5 μg or placebo , all delivered once daily via Respimat inhaler . Patient-reported outcomes included breathlessness assessed by transition dyspnoea index focal score , health status assessed by St George ’s Respiratory Question naire total score and night-time rescue medication use at 12 or 24 weeks . Outcomes from the pooled study data are reported . Overall , 1621 and 5162 patients were treated in the OTEMTO and TONADO trials , respectively . Significantly larger improvements in St George ’s Respiratory Question naire and transition dyspnoea index focal scores were observed and a greater proportion of patients were responders to therapy ( based on minimum clinical ly important differences in St George ’s Respiratory Question naire and transition dyspnoea index ) with tiotropium + olo date rol compared to either monotherapy or to placebo . Tiotropium + olo date rol 5/5 µg significantly reduced night-time rescue medication usage . Chronic obstructive pulmonary disease : Combined inhaler proves effective Results from four in-depth studies show that a combined inhaler is very effective for treatment of moderate to severe chronic lung disease . Alleviating the symptoms of chronic obstructive pulmonary disease ( COPD ) , particularly sleep disturbance , is crucial to enhancing patients ’ quality of life . Gary Ferguson at the Pulmonary Research Institute of Southeast Michigan , together with other scientists across the USA and Germany , analysed data from four large-scale studies to evaluate the efficacy of STIOLTO Respimat , a combination of two bronchodilators — tiotropium , and olo date rol , which tackle airway obstruction and breathlessness , improving long-term lung function . They found that the new drug combination triggered significant improvements in patients ’ quality of life and levels of breathlessness . Use of night-time rescue medication in patients on STIOLTO  Respimat was considerably reduced . A greater number of patients responded positively to the combined inhaler than to monotherapy Background : The objective of the FLIGHT3 study was to evaluate the long-term safety and efficacy of indacaterol/glycopyrrolate * ( IND/GLY ) versus an active comparator , IND , in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) over 52 weeks . Method : FLIGHT3 was a multicenter , r and omized , double-blind , parallel-group , 52-week study . Patients were r and omized ( 1:1:1 ) to IND/GLY ( 27.5/15.6 or 27.5/31.2 µg twice daily [ b.i.d . ] ) or IND ( 75 µg once daily [ o.d . ] ) , delivered via the Neohaler ® device . The primary objective was to evaluate the long-term safety and tolerability of IND/GLY versus IND in terms of adverse event (AE)-reporting rates in patients with moderate-to-severe COPD over 52 weeks . The secondary objective was to evaluate the long-term efficacy of IND/GLY versus IND in terms of pre-dose trough forced expiratory volume in 1 second ( FEV1 ) and post-dose 1-h FEV1 over 52 weeks . Results : A total of 85.2 % patients completed the study treatment .  The overall incidence of AEs ( and SAEs ) was similar between treatments . Major adverse cardiovascular events ( MACE ) and /or cardiovascular ( CV ) events were comparable between treatment groups . The rate of discontinuation of the study treatment due to AEs was lower for IND/GLY than IND . Improvements in pre-dose trough FEV1 and post-dose 1-h FEV1 were consistently superior with IND/GLY than with IND over 52 weeks , demonstrating long-term maintenance of lung function . Conclusions : IND/GLY demonstrated a favorable long-term safety and tolerability profile and provided effective bronchodilation , with maintenance of lung function over 52 weeks in patients with moderate-to-severe COPD . These data support the safety and efficacy of IND/GLY as a treatment option for COPD . Trial registration : ClinTrials.gov identifier NCT01682863 * Glycopyrrolate 15.6 µg ( excluding the bromide salt ) is equivalent to 12.5 µg glycopyrronium INTRODUCTION Aclidinium bromide/formoterol fumarate ( AB/FF ) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies ( AUGMENT and ACLIFORM ) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . This Phase III , double-blind , placebo-controlled , 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg ( NCT01572792 ) . METHODS Patients were r and omised in AUGMENT  ( 1:1:1:1:1 ) to twice-daily AB/FF 400/12 μg , AB/FF 400/6 μg , AB 400 μg , FF 12 μg or placebo . Patients completing AUGMENT were invited to continue the same treatment in the extension . Adverse events ( AEs ) , major adverse cardiovascular events ( MACE ) , laboratory tests , electrocardiograms and vital signs were recorded . Efficacy was assessed . RESULTS Of 1322 patients completing AUGMENT , 921 enrolled and 780 completed the extension .  AE incidence was low and comparable across treatment groups ; most common were nasopharyngitis ( range 4.8%-9.3 % ) , urinary tract infection ( range 4.1%-8.8 % ) and upper respiratory tract infection ( range 2.7%-5.5 % ) . Serious AEs ( SAEs ) and MACE were low ( ranges 6.8%-7.7 % and 0.5%-1.5 % , respectively ) . Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo . Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies . AB/FF combinations increased the time to first exacerbation by approximately 30 % versus placebo ( p < 0.05 ) . CONCLUSION AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs , SAEs and MACE that were comparable across treatment groups . Improvements in bronchodilation , symptoms and health status were maintained across 52 weeks BACKGROUND Evidence is scarce on the relative risk-benefit of inhaled triple therapy , consisting of inhaled corticosteroid , long-acting muscarinic antagonist , and long-acting β2-agonist , versus dual bronchodilation for chronic obstructive pulmonary disease ( COPD ) . We aim ed to compare a single-inhaler triple combination of beclometasone dipropionate , formoterol fumarate , and glycopyrronium ( BDP/FF/G ) versus a single-inhaler dual bronchodilator combination of indacaterol plus glycopyrronium ( IND/GLY ) in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks of treatment . METHODS This r and omised , parallel-group , double-blind , double-dummy study was done at 187 sites across 17 countries . Eligible patients had symptomatic COPD , severe or very severe airflow limitation , at least one moderate or severe exacerbation in the previous year , and were receiving inhaled maintenance medication . After a 2 week run-in period with one inhalation per 
    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 Chronic obstructive pulmonary disease is associated with significant morbidity and mortality . Trials of maintenance chronic obstructive pulmonary disease treatments focus on improvement in lung function and reductions in exacerbations , while patients are much more concerned about symptoms and health status . Our aim was to investigate the effects of tiotropium + olo date rol on  patient-reported health outcomes , breathlessness and night-time rescue medication use in patients with chronic obstructive pulmonary disease , compared to placebo , tiotropium or olo date rol monotherapy . Two pairs of replicate , phase III studies of 12 ( OTEMTO 1 + 2 ) and 52 weeks ’ ( TONADO 1 + 2 ) duration were evaluated , in which patients received either tiotropium + olo date rol 2.5/5 or 5/5 μg , tiotropium 2.5 or 5 μg , olo date rol 5 μg or placebo , all delivered once daily via Respimat inhaler . Patient-reported outcomes included breathlessness assessed by transition dyspnoea index focal score , health status assessed by St George ’s Respiratory Question naire total score and night-time rescue medication use at 12 or 24 weeks . Outcomes from the pooled study data are reported . Overall , 1621 and 5162 patients were treated in the OTEMTO and TONADO trials , respectively . Significantly larger improvements in St George ’s Respiratory Question naire and transition dyspnoea index focal scores were observed and a greater proportion of patients were responders to therapy ( based on minimum clinical ly important differences in St George ’s Respiratory Question naire and transition dyspnoea index ) with tiotropium + olo date rol compared to either monotherapy or to placebo . Tiotropium + olo date rol 5/5 µg significantly reduced night-time rescue medication usage . Chronic obstructive pulmonary disease : Combined inhaler proves effective Results from four in-depth studies show that a combined inhaler is very effective for treatment of moderate to severe chronic lung disease . Alleviating the symptoms of chronic obstructive pulmonary disease ( COPD ) , particularly sleep disturbance , is crucial to enhancing patients ’ quality of life . Gary Ferguson at the Pulmonary Research Institute of Southeast Michigan , together with other scientists across the USA and Germany , analysed data from four large-scale studies to evaluate the efficacy of STIOLTO Respimat , a combination of two bronchodilators — tiotropium , and olo date rol , which tackle airway obstruction and breathlessness , improving long-term lung function . They found that the new drug combination triggered significant improvements in patients ’ quality of life and levels of breathlessness . Use of night-time rescue medication in patients on STIOLTO  Respimat was considerably reduced . A greater number of patients responded positively to the combined inhaler than to monotherapy Background : The objective of the FLIGHT3 study was to evaluate the long-term safety and efficacy of indacaterol/glycopyrrolate * ( IND/GLY ) versus an active comparator , IND , in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) over 52 weeks . Method : FLIGHT3 was a multicenter , r and omized , double-blind , parallel-group , 52-week study . Patients were r and omized ( 1:1:1 ) to IND/GLY ( 27.5/15.6 or 27.5/31.2 µg twice daily [ b.i.d . ] ) or IND ( 75 µg once daily [ o.d . ] ) , delivered via the Neohaler ® device . The primary objective was to evaluate the long-term safety and tolerability of IND/GLY versus IND in terms of adverse event (AE)-reporting rates in patients with moderate-to-severe COPD over 52 weeks . The secondary objective was to evaluate the long-term efficacy of IND/GLY versus IND in terms of pre-dose trough forced expiratory volume in 1 second ( FEV1 ) and post-dose 1-h FEV1 over 52 weeks . Results : A total of 85.2 % patients completed the study treatment .  The overall incidence of AEs ( and SAEs ) was similar between treatments . Major adverse cardiovascular events ( MACE ) and /or cardiovascular ( CV ) events were comparable between treatment groups . The rate of discontinuation of the study treatment due to AEs was lower for IND/GLY than IND . Improvements in pre-dose trough FEV1 and post-dose 1-h FEV1 were consistently superior with IND/GLY than with IND over 52 weeks , demonstrating long-term maintenance of lung function . Conclusions : IND/GLY demonstrated a favorable long-term safety and tolerability profile and provided effective bronchodilation , with maintenance of lung function over 52 weeks in patients with moderate-to-severe COPD . These data support the safety and efficacy of IND/GLY as a treatment option for COPD . Trial registration : ClinTrials.gov identifier NCT01682863 * Glycopyrrolate 15.6 µg ( excluding the bromide salt ) is equivalent to 12.5 µg glycopyrronium INTRODUCTION Aclidinium bromide/formoterol fumarate ( AB/FF ) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies ( AUGMENT and ACLIFORM ) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . This Phase III , double-blind , placebo-controlled , 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg ( NCT01572792 ) . METHODS Patients were r and omised in AUGMENT  ( 1:1:1:1:1 ) to twice-daily AB/FF 400/12 μg , AB/FF 400/6 μg , AB 400 μg , FF 12 μg or placebo . Patients completing AUGMENT were invited to continue the same treatment in the extension . Adverse events ( AEs ) , major adverse cardiovascular events ( MACE ) , laboratory tests , electrocardiograms and vital signs were recorded . Efficacy was assessed . RESULTS Of 1322 patients completing AUGMENT , 921 enrolled and 780 completed the extension .  AE incidence was low and comparable across treatment groups ; most common were nasopharyngitis ( range 4.8%-9.3 % ) , urinary tract infection ( range 4.1%-8.8 % ) and upper respiratory tract infection ( range 2.7%-5.5 % ) . Serious AEs ( SAEs ) and MACE were low ( ranges 6.8%-7.7 % and 0.5%-1.5 % , respectively ) . Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo . Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies . AB/FF combinations increased the time to first exacerbation by approximately 30 % versus placebo ( p < 0.05 ) . CONCLUSION AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs , SAEs and MACE that were comparable across treatment groups . Improvements in bronchodilation , symptoms and health status were maintained across 52 weeks BACKGROUND Evidence is scarce on the relative risk-benefit of inhaled triple therapy , consisting of inhaled corticosteroid , long-acting muscarinic antagonist , and long-acting β2-agonist , versus dual bronchodilation for chronic obstructive pulmonary disease ( COPD ) . We aim ed to compare a single-inhaler triple combination of beclometasone dipropionate , formoterol fumarate , and glycopyrronium ( BDP/FF/G ) versus a single-inhaler dual bronchodilator combination of indacaterol plus glycopyrronium ( IND/GLY ) in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks of treatment . METHODS This r and omised , parallel-group , double-blind , double-dummy study was done at 187 sites across 17 countries . Eligible patients had symptomatic COPD , severe or very severe airflow limitation , at least one moderate or severe exacerbation in the previous year , and were receiving inhaled maintenance medication . After a 2 week run-in period with one inhalation per 
    Output:
    