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 To investigate the effects of inhaled beta-agonists on sub-maximal and maximal exercise capacity , breathing pattern , dyspnoea , leg-discomfort and spirometry in patients with cystic fibrosis ( CF ) . OBJECTIVES Eight patients performed two maximal incremental cycle-ergometry tests on separate days with inhaled placebo or salbutamol ( 600 microg ) administered before each test in a r and omized , double-blind , placebo-controlled crossover trial . Primary outcomes were exercise duration ( Exdur ) in seconds ( s ) and maximal oxygen uptake ( VO2max ) in litres/minute ( L/min ) . Forced expiratory volume in 1 s ( FEV1 ) was measured immediately pre-inhaler , post-inhaler and post-exercise . Dyspnoea and leg-discomfort were assessed post-exercise . RESULTS Within-day FEV1 comparisons demonstrated that the placebo test day FEV1 improved significantly post-exercise ( 0.11 L , p<0.05 ) and the salbutamol test day FEV1 improved significantly post-inhaler ( 0.22 L , p<0.001 ) and post-exercise ( 0.07 L , p<0.01 ) . Between-day FEV1 comparisons demonstrated significant improvements in post-inhaler ( 0.17 L , p<0.05 ) and post-exercise ( 0.13 L , p<0.05 ) FEV1 following salbutamol . Sub-maximal and maximal exercise showed no significant difference as shown by Exdur ( 547+/-154 s vs. 529+/-127 s ) and VO2max ( 1.9+/-0.5 L/min vs. 1.9+/-0.6 L/min ) . No significant change in breathing pattern , dyspnoea or leg-discomfort was detected . The study had a power of 92 % to detect a 10 % improvement in Exdur . CONCLUSIONS In adults with CF , salbutamol improves post-exercise FEV1 and is safe when administered immediately before exercise but does not improve exercise capacity , exercise-induced dyspnoea or leg-discomfort BACKGROUND Inhaled , short-acting beta-adrenergic agonists ( SAbetaAs ) are widely prescribed in cystic fibrosis ( CF ) subjects , despite a lack of convincing data for efficacy and the potential for these agents to result in airway instability . We tested the hypothesis that inhaled albuterol would improve maximal exercise performance in CF subjects with airflow obstruction , as a result of acute bronchodilation . METHODS R and omized , double-blind , placebo-controlled crossover study of the effect of inhaled albuterol on maximal exercise performance in 20 stable adult CF patients ( mean + /- SD age , 23.3 + /- 6.1 years ; FEV(1 ) , 57.65 + /- 17.13 % of predicted ) . RESULTS Ventilatory limitation to exercise was demonstrated in 16 subjects ( 80 % ) . Significant bronchodilation occurred with exercise alone ( end-exercise FEV(1 ) , 2.24 + /- 0.8 L ; vs preexercise FEV(1 ) , 2.09 + /- 0.77 L ; p < 0.0001 ) , but albuterol result ed in significantly greater exercise-induced bronchodilation than placebo ( change in FEV(1 ) , 0.3 + /- 0.15 L vs 0.15 + /- 0.11 L ; 95 % confidence interval [ CI ] , + 0.07 to + 0.23 ; p < 0.001 ) . However , there was no difference in maximal workload achieved  ( albuterol , 158 + /- 46 W ; vs placebo , 158 + /- 45 W ; 95 % CI , - 4.41 to + 4.71 ; p = 0.95 ) , nor any other measure of exercise performance including maximal oxygen uptake . CONCLUSIONS Despite causing significant acute bronchodilation , inhaled albuterol did not improve maximal exercise performance in ventilatory-limited CF adults , adding to the body of literature that fails to show any clinical benefit of SAbetaAs in CF subjects . The current results provide further evidence to question the widespread use of these agents , although the potential for adrenergic beta-agonists to instead improve submaximal exercise performance merits further investigation The efficacy of inhaled sympathomimetic and anticholinergic agents on airway obstruction in cystic fibrosis ( CF ) has been proven in several studies . However , studies comparing combined therapy with monotherapy led to divergent results , probably due to different study design s , different dosages , and the small numbers of patients investigated . Therefore , we wanted to answer the question which inhalation has the best short term effect : a sympathomimetic or an anticholinergic agent , or the combination of both . We investigated 17 patients with CF on 4 successive days in the morning , using pulmonary function testing before and 30 min after inhalation . Each patient received aerosolized salbutamol ( SB , maximum dose ( max . ) 2.5 mg ) , ipratropium bromide ( IB , max . 0.5 mg ) , the combination of both , or placebo ( normal saline ) in a r and omized , double-blind crossover design . The mean forced expiratory volume in the first second improved significantly ( adjusted P-value < 0.017 ) after each treatment compared to placebo . Analysis of variance showed that SB and combination therapy with SB and IB were superior to IB alone , without significant difference between SB and combination therapy . Response of a patient to combined therapy was usually associated with response to SB . Long-term efficacy and side effects of treatment with bronchodilators still remain to be investigated after this short term study . We conclude that in CF patients bronchodilator therapy with sympathomimetic agents is usually sufficient . Only in cases with proven additional benefit from inhalation by anticholinergics should combination therapy be recommended BACKGROUND Tiotropium Respimat improved lung function in a phase 2 trial in patients with cystic fibrosis ( CF ) . We investigated its efficacy and safety in a phase 3 trial , including a pre-specified pooled analysis of the phase 2 and 3 trials . METHODS 12-week , r and omized , double-blind , placebo-controlled trial of tiotropium Respimat 5 μg once daily in patients with CF ( N=463 ) . RESULTS Co- primary efficacy endpoints showed no statistical difference between tiotropium and placebo : percent-predicted forced expiratory volume in 1s ( FEV1 ) area under the curve from 0 - 4h ( AUC0 - 4h ) ( 95 % CI ) : 1.64 % ( 0.27,3.55 ; p=0.092 ) ; percent-predicted trough FEV1 ( 95 % CI ) 1.40 % ( 0.50,3.30 ; p=0.15 ) . Adverse events were similar between groups . Pooled phase 2/3 trial results showed a treatment difference in favor of tiotropium : percent-predicted FEV1 AUC0 - 4h ( 95 % CI ) : 2.62 % ( 1.34,3.90 ) . CONCLUSION Tiotropium was well tolerated in patients with CF ; lung function improvements compared with placebo were not statistically significant in the phase 3 trial . CLINICAL TRIALS These studies are registered with clinical trial identifier numbers NCT00737100 and NCT01179347 NCT00737100 NCT01179347 . These studies are also registered with the EudraCT number : 2008 - 001156 - 43 and 2010 - 019802 - 17 The efficacy and tolerability of high-dose salmeterol ( 100 mcg , BID ) and albuterol ( 2.5 mg , BID ) were compared with those of albuterol ( 2.5 mg , BID ) in out patients with cystic fibrosis in a r and omized , double-blind , double-dummy , placebo-controlled , crossover study with both short- ( 4 weeks of each ) and long-term ( 24 weeks of each ) treatment periods . The primary outcome measure was the difference in mean change in forced expired volume in 1 sec ( FEV(1 ) ) from baseline to the end of each treatment , and secondary measures included changes in forced vital capacity ( FVC ) , forced expiratory flow between 25 - 75 % of FVC ( FEF(25 - 75 ) ) , patient-rated weekly symptom scores , number of extra ( rescue ) albuterol treatments , and number of antibiotic treatments . Tolerability was evaluated by changes in vital signs and adverse events .  Thirty-six out of 44 patients enrolled finished the short-term treatment period , and 19 out of 23 who continued the study also finished the long-term treatment period . There was no significant difference in the mean % change in FEV(1 ) from baseline to completion of 4 weeks with each drug in the short-term treatment period ( 0.1 % vs. 0.06 % , albuterol vs. salmeterol ; respectively ) . In the long-term treatment period , there was a significant decrease from baseline in FEV(1 ) with albuterol vs. salmeterol , as measured after both 12 and 24 weeks of each treatment ( -6.2 % vs. 1.8 % , P = 0.013 after 12 weeks , and -6.5 % vs. 1.7 % , P = 0.002 , after 24 weeks , respectively ) . In both treatment periods , salmeterol was well-tolerated . While there were more rescue treatments per patient per week with albuterol than with salmeterol treatment in both the short- and long-term periods ( 0.67 vs. 0.40 and 1.76 vs. 0.74 , respectively ) , rescue treatments were needed significantly more often for only the long-term period with albuterol compared to salmeterol ( P = 0.022 ) . Also , there were more antibiotic interventions with albuterol than with salmeterol treatment in both the short- and long-term periods ( 25 vs. 10 and 56 vs. 42 , respectively ) ; however , antibiotics were needed significantly more often for only the short-term period ( P = 0.011 ) . In addition , there was a significantly higher symptom score with albuterol vs. salmeterol treatment during the second half of the long-term period ( 1.24 vs. 0.89 , P = 0.001).In conclusion , long-term high-dose salmeterol was equally safe and was associated with better pulmonary function , fewer interventions , and fewer respiratory symptoms compared to st and ard therapy with albuterol in a population of out patients with mild to moderate CF We evaluated patients with cystic fibrosis ( CF ) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement . For the first 4 days of study , all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics . During this time , the patients showed significant improvement in mean FVC , FEV1 , and maximal midexpiratory flow rate ( FEF25 - 75 ) . In 12 of 13 trials , the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days . In these 12 trials , the patients were stratified by their initial FVC and r and omized to receive either parenteral tobramycin and ticarcillin ( n = 7 ) or placebo ( n = 5 ) , in addition to continued aerosol and chest physiotherapy . In the remaining trial , the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group . During the next 14 days of therapy , the antibiotic group showed significantly ( p less than 0.01 ) greater reductions in log10 colony-forming units ( cfu ) of P. aeruginosa per gram of sputum and greater increases in FVC , FEV1 , and FEF25 - 75 than did the placebo group . The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly ( p less than 0.001 ) with the degree of improvement in FVC , FEV1 , and FEF25 - 75 . ( ABSTRACT TRUNCATED AT 250 WORDS In a recent investigation we found that hospitalized patients with cystic fibrosis who received 0.5 cc of  0.5 % albuterol nebulizer solution TID significantly increased their pulmonary function across the day , but fell back to baseline overnight . To determine whether this fall could be prevented by the long-acting beta-2 agonist salmeterol at both st and ard ( 2 puffs : 42 mcg BID ) and high ( 4 puffs , 84 mcg BID ) doses , we evaluated the effects of salmeterol vs. albuterol ( 2 puffs , 180 mcg QID , and 4 puffs , 360 mcg BID ) in a placebo-controlled three-way r and om crossover , double-blind trial . Eighteen patients in the low-dose group and 10 of the same 18 patients in the high-dose group completed the 3 consecutive days of testing and received either salmeterol , albuterol , or placebo with each of four chest physiotherapy sessions given at 7 AM , 11 AM , 3 PM 
    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 To investigate the effects of inhaled beta-agonists on sub-maximal and maximal exercise capacity , breathing pattern , dyspnoea , leg-discomfort and spirometry in patients with cystic fibrosis ( CF ) . OBJECTIVES Eight patients performed two maximal incremental cycle-ergometry tests on separate days with inhaled placebo or salbutamol ( 600 microg ) administered before each test in a r and omized , double-blind , placebo-controlled crossover trial . Primary outcomes were exercise duration ( Exdur ) in seconds ( s ) and maximal oxygen uptake ( VO2max ) in litres/minute ( L/min ) . Forced expiratory volume in 1 s ( FEV1 ) was measured immediately pre-inhaler , post-inhaler and post-exercise . Dyspnoea and leg-discomfort were assessed post-exercise . RESULTS Within-day FEV1 comparisons demonstrated that the placebo test day FEV1 improved significantly post-exercise ( 0.11 L , p<0.05 ) and the salbutamol test day FEV1 improved significantly post-inhaler ( 0.22 L , p<0.001 ) and post-exercise ( 0.07 L , p<0.01 ) . Between-day FEV1 comparisons demonstrated significant improvements in post-inhaler ( 0.17 L , p<0.05 ) and post-exercise ( 0.13 L , p<0.05 ) FEV1 following salbutamol . Sub-maximal and maximal exercise showed no significant difference as shown by Exdur ( 547+/-154 s vs. 529+/-127 s ) and VO2max ( 1.9+/-0.5 L/min vs. 1.9+/-0.6 L/min ) . No significant change in breathing pattern , dyspnoea or leg-discomfort was detected . The study had a power of 92 % to detect a 10 % improvement in Exdur . CONCLUSIONS In adults with CF , salbutamol improves post-exercise FEV1 and is safe when administered immediately before exercise but does not improve exercise capacity , exercise-induced dyspnoea or leg-discomfort BACKGROUND Inhaled , short-acting beta-adrenergic agonists ( SAbetaAs ) are widely prescribed in cystic fibrosis ( CF ) subjects , despite a lack of convincing data for efficacy and the potential for these agents to result in airway instability . We tested the hypothesis that inhaled albuterol would improve maximal exercise performance in CF subjects with airflow obstruction , as a result of acute bronchodilation . METHODS R and omized , double-blind , placebo-controlled crossover study of the effect of inhaled albuterol on maximal exercise performance in 20 stable adult CF patients ( mean + /- SD age , 23.3 + /- 6.1 years ; FEV(1 ) , 57.65 + /- 17.13 % of predicted ) . RESULTS Ventilatory limitation to exercise was demonstrated in 16 subjects ( 80 % ) . Significant bronchodilation occurred with exercise alone ( end-exercise FEV(1 ) , 2.24 + /- 0.8 L ; vs preexercise FEV(1 ) , 2.09 + /- 0.77 L ; p < 0.0001 ) , but albuterol result ed in significantly greater exercise-induced bronchodilation than placebo ( change in FEV(1 ) , 0.3 + /- 0.15 L vs 0.15 + /- 0.11 L ; 95 % confidence interval [ CI ] , + 0.07 to + 0.23 ; p < 0.001 ) . However , there was no difference in maximal workload achieved  ( albuterol , 158 + /- 46 W ; vs placebo , 158 + /- 45 W ; 95 % CI , - 4.41 to + 4.71 ; p = 0.95 ) , nor any other measure of exercise performance including maximal oxygen uptake . CONCLUSIONS Despite causing significant acute bronchodilation , inhaled albuterol did not improve maximal exercise performance in ventilatory-limited CF adults , adding to the body of literature that fails to show any clinical benefit of SAbetaAs in CF subjects . The current results provide further evidence to question the widespread use of these agents , although the potential for adrenergic beta-agonists to instead improve submaximal exercise performance merits further investigation The efficacy of inhaled sympathomimetic and anticholinergic agents on airway obstruction in cystic fibrosis ( CF ) has been proven in several studies . However , studies comparing combined therapy with monotherapy led to divergent results , probably due to different study design s , different dosages , and the small numbers of patients investigated . Therefore , we wanted to answer the question which inhalation has the best short term effect : a sympathomimetic or an anticholinergic agent , or the combination of both . We investigated 17 patients with CF on 4 successive days in the morning , using pulmonary function testing before and 30 min after inhalation . Each patient received aerosolized salbutamol ( SB , maximum dose ( max . ) 2.5 mg ) , ipratropium bromide ( IB , max . 0.5 mg ) , the combination of both , or placebo ( normal saline ) in a r and omized , double-blind crossover design . The mean forced expiratory volume in the first second improved significantly ( adjusted P-value < 0.017 ) after each treatment compared to placebo . Analysis of variance showed that SB and combination therapy with SB and IB were superior to IB alone , without significant difference between SB and combination therapy . Response of a patient to combined therapy was usually associated with response to SB . Long-term efficacy and side effects of treatment with bronchodilators still remain to be investigated after this short term study . We conclude that in CF patients bronchodilator therapy with sympathomimetic agents is usually sufficient . Only in cases with proven additional benefit from inhalation by anticholinergics should combination therapy be recommended BACKGROUND Tiotropium Respimat improved lung function in a phase 2 trial in patients with cystic fibrosis ( CF ) . We investigated its efficacy and safety in a phase 3 trial , including a pre-specified pooled analysis of the phase 2 and 3 trials . METHODS 12-week , r and omized , double-blind , placebo-controlled trial of tiotropium Respimat 5 μg once daily in patients with CF ( N=463 ) . RESULTS Co- primary efficacy endpoints showed no statistical difference between tiotropium and placebo : percent-predicted forced expiratory volume in 1s ( FEV1 ) area under the curve from 0 - 4h ( AUC0 - 4h ) ( 95 % CI ) : 1.64 % ( 0.27,3.55 ; p=0.092 ) ; percent-predicted trough FEV1 ( 95 % CI ) 1.40 % ( 0.50,3.30 ; p=0.15 ) . Adverse events were similar between groups . Pooled phase 2/3 trial results showed a treatment difference in favor of tiotropium : percent-predicted FEV1 AUC0 - 4h ( 95 % CI ) : 2.62 % ( 1.34,3.90 ) . CONCLUSION Tiotropium was well tolerated in patients with CF ; lung function improvements compared with placebo were not statistically significant in the phase 3 trial . CLINICAL TRIALS These studies are registered with clinical trial identifier numbers NCT00737100 and NCT01179347 NCT00737100 NCT01179347 . These studies are also registered with the EudraCT number : 2008 - 001156 - 43 and 2010 - 019802 - 17 The efficacy and tolerability of high-dose salmeterol ( 100 mcg , BID ) and albuterol ( 2.5 mg , BID ) were compared with those of albuterol ( 2.5 mg , BID ) in out patients with cystic fibrosis in a r and omized , double-blind , double-dummy , placebo-controlled , crossover study with both short- ( 4 weeks of each ) and long-term ( 24 weeks of each ) treatment periods . The primary outcome measure was the difference in mean change in forced expired volume in 1 sec ( FEV(1 ) ) from baseline to the end of each treatment , and secondary measures included changes in forced vital capacity ( FVC ) , forced expiratory flow between 25 - 75 % of FVC ( FEF(25 - 75 ) ) , patient-rated weekly symptom scores , number of extra ( rescue ) albuterol treatments , and number of antibiotic treatments . Tolerability was evaluated by changes in vital signs and adverse events .  Thirty-six out of 44 patients enrolled finished the short-term treatment period , and 19 out of 23 who continued the study also finished the long-term treatment period . There was no significant difference in the mean % change in FEV(1 ) from baseline to completion of 4 weeks with each drug in the short-term treatment period ( 0.1 % vs. 0.06 % , albuterol vs. salmeterol ; respectively ) . In the long-term treatment period , there was a significant decrease from baseline in FEV(1 ) with albuterol vs. salmeterol , as measured after both 12 and 24 weeks of each treatment ( -6.2 % vs. 1.8 % , P = 0.013 after 12 weeks , and -6.5 % vs. 1.7 % , P = 0.002 , after 24 weeks , respectively ) . In both treatment periods , salmeterol was well-tolerated . While there were more rescue treatments per patient per week with albuterol than with salmeterol treatment in both the short- and long-term periods ( 0.67 vs. 0.40 and 1.76 vs. 0.74 , respectively ) , rescue treatments were needed significantly more often for only the long-term period with albuterol compared to salmeterol ( P = 0.022 ) . Also , there were more antibiotic interventions with albuterol than with salmeterol treatment in both the short- and long-term periods ( 25 vs. 10 and 56 vs. 42 , respectively ) ; however , antibiotics were needed significantly more often for only the short-term period ( P = 0.011 ) . In addition , there was a significantly higher symptom score with albuterol vs. salmeterol treatment during the second half of the long-term period ( 1.24 vs. 0.89 , P = 0.001).In conclusion , long-term high-dose salmeterol was equally safe and was associated with better pulmonary function , fewer interventions , and fewer respiratory symptoms compared to st and ard therapy with albuterol in a population of out patients with mild to moderate CF We evaluated patients with cystic fibrosis ( CF ) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement . For the first 4 days of study , all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics . During this time , the patients showed significant improvement in mean FVC , FEV1 , and maximal midexpiratory flow rate ( FEF25 - 75 ) . In 12 of 13 trials , the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days . In these 12 trials , the patients were stratified by their initial FVC and r and omized to receive either parenteral tobramycin and ticarcillin ( n = 7 ) or placebo ( n = 5 ) , in addition to continued aerosol and chest physiotherapy . In the remaining trial , the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group . During the next 14 days of therapy , the antibiotic group showed significantly ( p less than 0.01 ) greater reductions in log10 colony-forming units ( cfu ) of P. aeruginosa per gram of sputum and greater increases in FVC , FEV1 , and FEF25 - 75 than did the placebo group . The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly ( p less than 0.001 ) with the degree of improvement in FVC , FEV1 , and FEF25 - 75 . ( ABSTRACT TRUNCATED AT 250 WORDS In a recent investigation we found that hospitalized patients with cystic fibrosis who received 0.5 cc of  0.5 % albuterol nebulizer solution TID significantly increased their pulmonary function across the day , but fell back to baseline overnight . To determine whether this fall could be prevented by the long-acting beta-2 agonist salmeterol at both st and ard ( 2 puffs : 42 mcg BID ) and high ( 4 puffs , 84 mcg BID ) doses , we evaluated the effects of salmeterol vs. albuterol ( 2 puffs , 180 mcg QID , and 4 puffs , 360 mcg BID ) in a placebo-controlled three-way r and om crossover , double-blind trial . Eighteen patients in the low-dose group and 10 of the same 18 patients in the high-dose group completed the 3 consecutive days of testing and received either salmeterol , albuterol , or placebo with each of four chest physiotherapy sessions given at 7 AM , 11 AM , 3 PM 
    Output:
    