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 : TORCH ( Towards a Revolution in COPD Health ) is an international multicentre , r and omised , placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease ( COPD ) . The primary outcome is all-cause mortality . Cause-specific mortality and deaths related to COPD are additional outcome measures , but systematic methods for ascertainment of these outcomes have not previously been described . Methods : A Clinical Endpoint Committee ( CEC ) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic , unbiased and independent manner . The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD -relatedness ; the independent review of cases by all members with development of a consensus opinion ; and a substantial infrastructure to collect medical information . Results : 911 deaths were review ed and consensus was reached in all . Cause-specific mortality was : cardiovascular 27 % , respiratory 35 % , cancer 21 % , other 10 % and unknown 8 % . 40 % of deaths were definitely or probably related to COPD . Adjudications were identical in 83 % of blindly re-adjudicated cases ( κ = 0.80 ) . COPD -relatedness was reproduced 84 % of the time ( κ = 0.73 ) . The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52 % of cases . Conclusion : A CEC can provide st and ardised , reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators Background : Airway inflammation in chronic obstructive pulmonary disease ( COPD ) is characterised by infiltration of CD8 + T cells and CD68 + macrophages and an increased number of neutrophils , whereas few studies have described the presence of eosinophils . Although the anti-inflammatory effects of corticosteroids in stable COPD are unclear , recent studies suggest that combination therapy could be beneficial . A study was therefore undertaken to evaluate combined salmeterol/fluticasone propionate ( SFC ) and fluticasone propionate ( FP ) alone on inflammatory cells in the airways of patients with COPD . Methods : Patients were treated in a r and omised , double blind , parallel group , placebo-controlled trial with either a combination of 50 µg salmeterol and 500 µg FP twice daily  ( SFC , n = 19 , 19 men , mean age 62 years ) , 500 µg FP twice daily ( n = 20 , 15 men , mean age 64 years ) or placebo  ( n = 21 , 17 men , mean age 66 years ) for 3 months . At the start and end of treatment bronchoscopy with bronchial biopsies was performed and the numbers of CD8 + T lymphocytes , CD68 + macrophages , neutrophils and eosinophils were measured . Results : CD8 + cells were significantly reduced by SFC compared with placebo ( difference −98.05 cells/mm2 ; 95 % CI −143.14 to −52.9 ; p<0.001 ) . Such a marked effect was not seen with FP alone ( −44.67 cells/mm2 ; 95 % CI −90.92 to 1.57 ; p = 0.06 ) . CD68 + macrophages were also reduced by SFC compared with placebo ( difference −31.68 cells/mm2 ; 95 % CI −61.07 to −2.29 ; p = 0.03 ) but not by FP . SFC did not significantly change neutrophils and eosinophils compared with placebo . Conclusions : SFC has airway anti-inflammatory effects not seen with inhaled corticosteroids alone BACKGROUND Previous studies showing that tiotropium improves multiple end points in patients with chronic obstructive pulmonary disease ( COPD ) led us to examine the long-term effects of tiotropium therapy . METHODS In this r and omized , double-blind trial , we compared 4 years of therapy with either tiotropium or placebo in patients with COPD who were permitted to use all respiratory medications except inhaled anticholinergic drugs . The patients were at least 40 years of age , with a forced expiratory volume in 1 second ( FEV(1 ) ) of 70 % or less after bronchodilation and a ratio of FEV(1 ) to forced vital capacity ( FVC ) of 70 % or less . Co primary end points were the rate of decline in the mean FEV(1 ) before and after bronchodilation beginning on day 30 . Secondary end points included measures of FVC , changes in response on St. George 's Respiratory Question naire ( SGRQ ) , exacerbations of COPD , and mortality . RESULTS Of a total of 5993 patients ( mean age , 65+/-8 years ) with a mean FEV(1 ) of 1.32+/-0.44 liters after bronchodilation ( 48 % of predicted value ) , we r and omly assigned 2987 to the tiotropium group and 3006 to the placebo group . Mean absolute improvements in FEV(1 ) in the tiotropium group were maintained throughout the trial ( ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation ) , as compared with the placebo group ( P<0.001 ) . After day 30 , the differences between the two groups in the rate of decline in the mean FEV(1 ) before and after bronchodilation were not significant . The mean absolute total score on the SGRQ was improved ( lower ) in the tiotropium group , as compared with the placebo group , at each time point throughout the 4-year period ( ranging from 2.3 to 3.3 units , P<0.001 ) . At 4 years and 30 days , tiotropium was associated with a reduction in the risks of exacerbations , related hospitalizations , and respiratory failure . CONCLUSIONS In patients with COPD , therapy with tiotropium was associated with improvements in lung function , quality of life , and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV(1 ) . ( Clinical Trials.gov number , NCT00144339 . BACKGROUND AND OBJECTIVES Data on the onset of action of COPD medications are lacking . This study compared the onset of bronchodilation following different inhaled therapies in patients with moderate-to-severe COPD and reversible airway obstruction . METHODS In this double-blind , double-dummy , crossover study , 90 patients ( aged > or=40 years ; FEV(1 ) 30 - 70 % predicted ) were r and omized to a single dose ( two inhalations ) of budesonide/formoterol 160/4.5 microg , salmeterol/fluticasone 25/250 microg , salbutamol 100 microg or placebo ( via pressurized metered-dose inhalers ) on four visits . The primary end-point was change in FEV(1 ) 5 min after drug inhalation ; secondary end-points included inspiratory capacity ( IC ) and perception of onset of effect . RESULTS Budesonide/formoterol significantly improved FEV(1 ) at 5 min compared with placebo ( P < 0.0001 ) and salmeterol/fluticasone ( P = 0.0001 ) . Significant differences were first observed at 3 min . Onset of effect was similar with budesonide/formoterol and salbutamol . Improvements in FEV(1 ) following active treatments were superior to placebo after 180 min ( all P < 0.0001 ) ; both combinations were better than salbutamol at maintaining FEV(1 ) improvements ( P < or= 0.0001 ) at 180 min . Active treatments improved IC at 15 and 185 min compared with placebo ( P < 0.0001 ) . Maximal IC was greater with budesonide/formoterol than salmeterol/fluticasone ( P = 0.0184 ) at 65 min . Patients reported a positive response to the perceptions of the onset of effect question shortly after receiving active treatments ( median time to onset 5 min for active treatments vs 20 min for placebo ) , with no significant difference between active treatments . CONCLUSION Budesonide/formoterol has an onset of bronchodilatory effect in patients with COPD and reversible airway obstruction that is faster than salmeterol/fluticasone and similar to salbutamol Background : Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid ( ICS ) is recommended in patients with chronic obstructive pulmonary disease ( COPD ) who have frequent exacerbations . The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler ( DPI ) in a 1-year study and when administered via the hydrofluoroalkane ( HFA ) pressurized metered-dose inhaler ( pMDI ) in a 6-month study . Objective : This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD . Methods : This was a 12-month , r and omized , double-blind , double-dummy , parallel-group , active- and placebo-controlled , multicentre study ( NCT00206167 ) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US , Europe and Mexico . After 2 weeks of treatment based on previous therapy ( ICSs , short-acting bronchodilators allowed ) , patients received one of the following treatments twice daily : budesonide/formoterol pMDI 160/4.5 μg × two inhalations ( 320/9 μg ) ; budesonide/formoterol pMDI 80/4.5 μg × two inhalations ( 160/9 μg ) ; formoterol DPI 4.5 μg × two inhalations ( 9 μg ) ; or placebo . Main outcome measures : The co- primary efficacy variables were pre-dose forced expiratory volume in 1 second ( FEV1 ) and 1-hour post-dose FEV1 . Results : Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1  versus formoterol ( p = 0.008 ) , and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1  versus placebo ( p < 0.001 ) . The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo ( p ≤ 0.004 ) . Both budesonide/formoterol doses were more effective  than placebo ( p ≤ 0.006 ) for controlling dyspnoea and improving health status ( St George ’s Respiratory Question naire ) . All treatments were generally well tolerated . The incidence of pneumonia was not different for active ( 3.4–4.0 % ) and placebo ( 5.0 % ) groups . Conclusions : Budesonide/formoterol pMDI ( 320/9 μg and 160/9 μg ) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD .  Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co- primary variables compared with formoterol DPI 9 μg . Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo BACKGROUND The combination of tiotropium and fluticasone propionate/salmeterol ( FSC ) is commonly used to treat chronic obstructive pulmonary disease ( COPD ) , but no study had evaluated the effectiveness of tiotropium plus FSC with 250 μg of fluticasone propionate . Our aim was to assess whether tiotropium ( 18 μg once daily ) plus FSC ( 250/50 μg twice daily ) provides better clinical outcomes compared to tiotropium monotherapy . METHODS In this 24-week , r and omized , open label , multicenter two-arm parallel study , 479 patients received tiotropium plus FSC ( n = 237 ) or tiotropium alone ( n = 242 ) . RESULTS After 24 weeks of treatment , the triple-inhaled treatment group had a significant improvement in pre-bronchodilator FEV(1 ) ( L ) compared to the tiotropium-only group ( 0.090 L vs. 0.038 L ; P = 0.005 ) . Regarding health-related quality of life , the mean change in total score on the St. George 's Respiratory Question naire for COPD patients ( SGRQ-C ) was -6.6 points in the tiotropium plus FSC group , but -1.5 points in the tiotropium-only group ( P = 0.001 ) . In the subgroup of GOLD stage II patients with COPD , treatment with tiotropium plus FSC also improved FEV(1 ) compared to tiotropium alone ( 0.088 L vs. 0.030 L ; 
    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 : TORCH ( Towards a Revolution in COPD Health ) is an international multicentre , r and omised , placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease ( COPD ) . The primary outcome is all-cause mortality . Cause-specific mortality and deaths related to COPD are additional outcome measures , but systematic methods for ascertainment of these outcomes have not previously been described . Methods : A Clinical Endpoint Committee ( CEC ) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic , unbiased and independent manner . The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD -relatedness ; the independent review of cases by all members with development of a consensus opinion ; and a substantial infrastructure to collect medical information . Results : 911 deaths were review ed and consensus was reached in all . Cause-specific mortality was : cardiovascular 27 % , respiratory 35 % , cancer 21 % , other 10 % and unknown 8 % . 40 % of deaths were definitely or probably related to COPD . Adjudications were identical in 83 % of blindly re-adjudicated cases ( κ = 0.80 ) . COPD -relatedness was reproduced 84 % of the time ( κ = 0.73 ) . The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52 % of cases . Conclusion : A CEC can provide st and ardised , reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators Background : Airway inflammation in chronic obstructive pulmonary disease ( COPD ) is characterised by infiltration of CD8 + T cells and CD68 + macrophages and an increased number of neutrophils , whereas few studies have described the presence of eosinophils . Although the anti-inflammatory effects of corticosteroids in stable COPD are unclear , recent studies suggest that combination therapy could be beneficial . A study was therefore undertaken to evaluate combined salmeterol/fluticasone propionate ( SFC ) and fluticasone propionate ( FP ) alone on inflammatory cells in the airways of patients with COPD . Methods : Patients were treated in a r and omised , double blind , parallel group , placebo-controlled trial with either a combination of 50 µg salmeterol and 500 µg FP twice daily  ( SFC , n = 19 , 19 men , mean age 62 years ) , 500 µg FP twice daily ( n = 20 , 15 men , mean age 64 years ) or placebo  ( n = 21 , 17 men , mean age 66 years ) for 3 months . At the start and end of treatment bronchoscopy with bronchial biopsies was performed and the numbers of CD8 + T lymphocytes , CD68 + macrophages , neutrophils and eosinophils were measured . Results : CD8 + cells were significantly reduced by SFC compared with placebo ( difference −98.05 cells/mm2 ; 95 % CI −143.14 to −52.9 ; p<0.001 ) . Such a marked effect was not seen with FP alone ( −44.67 cells/mm2 ; 95 % CI −90.92 to 1.57 ; p = 0.06 ) . CD68 + macrophages were also reduced by SFC compared with placebo ( difference −31.68 cells/mm2 ; 95 % CI −61.07 to −2.29 ; p = 0.03 ) but not by FP . SFC did not significantly change neutrophils and eosinophils compared with placebo . Conclusions : SFC has airway anti-inflammatory effects not seen with inhaled corticosteroids alone BACKGROUND Previous studies showing that tiotropium improves multiple end points in patients with chronic obstructive pulmonary disease ( COPD ) led us to examine the long-term effects of tiotropium therapy . METHODS In this r and omized , double-blind trial , we compared 4 years of therapy with either tiotropium or placebo in patients with COPD who were permitted to use all respiratory medications except inhaled anticholinergic drugs . The patients were at least 40 years of age , with a forced expiratory volume in 1 second ( FEV(1 ) ) of 70 % or less after bronchodilation and a ratio of FEV(1 ) to forced vital capacity ( FVC ) of 70 % or less . Co primary end points were the rate of decline in the mean FEV(1 ) before and after bronchodilation beginning on day 30 . Secondary end points included measures of FVC , changes in response on St. George 's Respiratory Question naire ( SGRQ ) , exacerbations of COPD , and mortality . RESULTS Of a total of 5993 patients ( mean age , 65+/-8 years ) with a mean FEV(1 ) of 1.32+/-0.44 liters after bronchodilation ( 48 % of predicted value ) , we r and omly assigned 2987 to the tiotropium group and 3006 to the placebo group . Mean absolute improvements in FEV(1 ) in the tiotropium group were maintained throughout the trial ( ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation ) , as compared with the placebo group ( P<0.001 ) . After day 30 , the differences between the two groups in the rate of decline in the mean FEV(1 ) before and after bronchodilation were not significant . The mean absolute total score on the SGRQ was improved ( lower ) in the tiotropium group , as compared with the placebo group , at each time point throughout the 4-year period ( ranging from 2.3 to 3.3 units , P<0.001 ) . At 4 years and 30 days , tiotropium was associated with a reduction in the risks of exacerbations , related hospitalizations , and respiratory failure . CONCLUSIONS In patients with COPD , therapy with tiotropium was associated with improvements in lung function , quality of life , and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV(1 ) . ( Clinical Trials.gov number , NCT00144339 . BACKGROUND AND OBJECTIVES Data on the onset of action of COPD medications are lacking . This study compared the onset of bronchodilation following different inhaled therapies in patients with moderate-to-severe COPD and reversible airway obstruction . METHODS In this double-blind , double-dummy , crossover study , 90 patients ( aged > or=40 years ; FEV(1 ) 30 - 70 % predicted ) were r and omized to a single dose ( two inhalations ) of budesonide/formoterol 160/4.5 microg , salmeterol/fluticasone 25/250 microg , salbutamol 100 microg or placebo ( via pressurized metered-dose inhalers ) on four visits . The primary end-point was change in FEV(1 ) 5 min after drug inhalation ; secondary end-points included inspiratory capacity ( IC ) and perception of onset of effect . RESULTS Budesonide/formoterol significantly improved FEV(1 ) at 5 min compared with placebo ( P < 0.0001 ) and salmeterol/fluticasone ( P = 0.0001 ) . Significant differences were first observed at 3 min . Onset of effect was similar with budesonide/formoterol and salbutamol . Improvements in FEV(1 ) following active treatments were superior to placebo after 180 min ( all P < 0.0001 ) ; both combinations were better than salbutamol at maintaining FEV(1 ) improvements ( P < or= 0.0001 ) at 180 min . Active treatments improved IC at 15 and 185 min compared with placebo ( P < 0.0001 ) . Maximal IC was greater with budesonide/formoterol than salmeterol/fluticasone ( P = 0.0184 ) at 65 min . Patients reported a positive response to the perceptions of the onset of effect question shortly after receiving active treatments ( median time to onset 5 min for active treatments vs 20 min for placebo ) , with no significant difference between active treatments . CONCLUSION Budesonide/formoterol has an onset of bronchodilatory effect in patients with COPD and reversible airway obstruction that is faster than salmeterol/fluticasone and similar to salbutamol Background : Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid ( ICS ) is recommended in patients with chronic obstructive pulmonary disease ( COPD ) who have frequent exacerbations . The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler ( DPI ) in a 1-year study and when administered via the hydrofluoroalkane ( HFA ) pressurized metered-dose inhaler ( pMDI ) in a 6-month study . Objective : This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD . Methods : This was a 12-month , r and omized , double-blind , double-dummy , parallel-group , active- and placebo-controlled , multicentre study ( NCT00206167 ) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US , Europe and Mexico . After 2 weeks of treatment based on previous therapy ( ICSs , short-acting bronchodilators allowed ) , patients received one of the following treatments twice daily : budesonide/formoterol pMDI 160/4.5 μg × two inhalations ( 320/9 μg ) ; budesonide/formoterol pMDI 80/4.5 μg × two inhalations ( 160/9 μg ) ; formoterol DPI 4.5 μg × two inhalations ( 9 μg ) ; or placebo . Main outcome measures : The co- primary efficacy variables were pre-dose forced expiratory volume in 1 second ( FEV1 ) and 1-hour post-dose FEV1 . Results : Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1  versus formoterol ( p = 0.008 ) , and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1  versus placebo ( p < 0.001 ) . The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo ( p ≤ 0.004 ) . Both budesonide/formoterol doses were more effective  than placebo ( p ≤ 0.006 ) for controlling dyspnoea and improving health status ( St George ’s Respiratory Question naire ) . All treatments were generally well tolerated . The incidence of pneumonia was not different for active ( 3.4–4.0 % ) and placebo ( 5.0 % ) groups . Conclusions : Budesonide/formoterol pMDI ( 320/9 μg and 160/9 μg ) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD .  Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co- primary variables compared with formoterol DPI 9 μg . Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo BACKGROUND The combination of tiotropium and fluticasone propionate/salmeterol ( FSC ) is commonly used to treat chronic obstructive pulmonary disease ( COPD ) , but no study had evaluated the effectiveness of tiotropium plus FSC with 250 μg of fluticasone propionate . Our aim was to assess whether tiotropium ( 18 μg once daily ) plus FSC ( 250/50 μg twice daily ) provides better clinical outcomes compared to tiotropium monotherapy . METHODS In this 24-week , r and omized , open label , multicenter two-arm parallel study , 479 patients received tiotropium plus FSC ( n = 237 ) or tiotropium alone ( n = 242 ) . RESULTS After 24 weeks of treatment , the triple-inhaled treatment group had a significant improvement in pre-bronchodilator FEV(1 ) ( L ) compared to the tiotropium-only group ( 0.090 L vs. 0.038 L ; P = 0.005 ) . Regarding health-related quality of life , the mean change in total score on the St. George 's Respiratory Question naire for COPD patients ( SGRQ-C ) was -6.6 points in the tiotropium plus FSC group , but -1.5 points in the tiotropium-only group ( P = 0.001 ) . In the subgroup of GOLD stage II patients with COPD , treatment with tiotropium plus FSC also improved FEV(1 ) compared to tiotropium alone ( 0.088 L vs. 0.030 L ; 
    Output:
    