***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: Chronic Obstructive Pulmonary Disease ( COPD ) is the fourth-leading cause of chronic morbidity and mortality in North America and its burden continues to increase . Tiotropium has been shown to reduce exacerbations , hospitalizations , symptoms , and improve health-related quality of life in patients with COPD . Its effect on mortality and its effects relative to long-acting beta-agonists ( LABAs ) , however , remain unknown . To examine the association between tiotropium use compared to LABA use on all-cause mortality in older patients with COPD , a longitudinal , population -based cohort study was conducted in Ontario , Canada . Subjects were individuals 65 years and older discharged from hospital with a diagnosis of COPD between January 1 , 2003 and March 31 , 2006 . The hazard of receiving a prescription for tiotropium compared to a long-acting beta-agonist on all-cause mortality at 180 days post-hospital discharge , controlling for a number of potential confounders , was eliminated . Data from 7218 eligible patients were analyzed . Of these , 1046 ( 14.5 % ) died in the follow-up period . Patients who received tiotropium were 20 % less likely to die than those receiving a long-acting beta-agonist ( hazard ratio 0.80 , 95 % confidence interval 0.70 to 0.93 ) . In conclusion , in older patients recently discharged from hospital for COPD , receiving tiotropium was found to be associated with reduced mortality at 6 months compared to receiving a long-acting beta-agonist . This result suggests that tiotropium might also be associated with decreased mortality compared to no treatment at all . R and omized placebo-control trials are needed to confirm these findings Background Exercise training improves exercise tolerance in chronic obstructive pulmonary disease ( COPD ) . Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation , one of the pathophysiological factors contributing to exertional dyspnea in COPD patients . Aim To determine whether tiotropium enhances the effects of exercise training in patients with COPD . Design Multicenter , 25 week r and omized , double-blind , placebo-controlled , parallel-group study . Setting Twelve Italian Pulmonary Units practicing pulmonary rehabilitation . Patients and intervention Two hundred thirty four COPD patients ( 196 males ; mean age : 67.4 ± 7.6 ; forced expiratory volume at 1 second ( FEV1 ) : 41.4 ± 13.0 % predicted ) were r and omised to tiotropium 18 μg or placebo inhalation capsules  taken once daily . Both groups underwent a 8 week pulmonary rehabilitation program ( PR ) consisting of 3 exercise training session per week . Measurements Baseline , at the end of PR and after 12 weeks , patients completed pulmonary function testing , six minute walking test ( 6MWT ) , the Baseline and Transition Dyspnea Index ( BDI and TDI ) , and the St. George ’s Respiratory Question naire ( SGRQ ) . Results Relative to placebo , tiotropium had larger trough and post- study drug FEV1 responses on all test days . At the end of and 12 weeks following PR , patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo . Compared to the period immediately prior to PR , the mean improvement in 6MWT was only 29.7 meters ( 7.1 % ) for the combined cohort . Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo ( p < 0.01 ) . At 12 weeks after PR , TDI focal scores were 2.71 for tiotropium and 2.11 for placebo ( p = 0.16 ) . Reduction in all four SGRQ component scores , indicating an improvement in health-related quality of life , was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically significant . During the study period , there were fewer exacerbations and exacerbation days in the tiotropium group . Conclusion Although significant improvements were observed with perceived dyspnea , compared to placebo , the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT BACKGROUND : A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis , each given by metered dose inhaler to asthmatic patients . METHODS : Twelve asthmatic patients of mean age 29.9 years , with a forced expiratory volume in one second ( FEV1 ) 92.9 % predicted and forced expiratory flow 25 - 75 % ( FEF25 - 75 ) 69.5 % predicted , on less than or equal to 400 micrograms/day inhaled corticosteroid , were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400 , 1000 , 1600 , 2000 micrograms and fluticasone propionate 500 , 1000 , 1500 , 2000 micrograms . Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later . RESULTS : Serum cortisol levels compared with placebo ( mean 325.2 nmol/l ) were suppressed by fluticasone at doses of 1500 micrograms ( 211.6 nmol/l ) and 2000 micrograms ( 112.3 nmol/l ) and by budesonide at 2000 micrograms ( 243.4 nmol/l ) . Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms ( 95 % CI for difference 42.9 to 219.2 ) . The dose ratio ( geometric mean ) for the relative potency was 2.89 fold ( 95 % CI 1.19 to 7.07 ) . In terms of percentage suppression versus placebo , fluticasone propionate also produced greater effects ( means and 95 % CI for difference ) : budesonide 1600 micrograms ( 16.0 ) versus fluticasone propionate 1500 micrograms ( 40.9 ) ( 95 % CI -0.6 to 50.6 ) , budesonide 2000 micrograms ( 26.0 ) versus fluticasone 2000 micrograms ( 65.2 ) ( 95 % CI 10.5 to 67.8 ) . Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range ( 150 nmol/l ) for fluticasone and five of 24 for budesonide . Fluticasone propionate also caused greater ACTH suppression than budesonide ( as % versus placebo ) : budesonide 1600 micrograms ( 12.0 ) versus fluticasone propionate 1500 micrograms ( 31.9 ) ( 95 % CI 7.6 to 32.1 ) , budesonide 2000 micrograms ( 13.5 ) versus fluticasone propionate 2000 micrograms ( 44.4 ) ( 95 % CI 13.2 to 48.7 ) . For overnight 10 hour urinary cortisol ( nmol/10 hours ) there was a difference between the lowest doses of the two drugs : budesonide 400 micrograms ( 37.2 ) versus fluticasone propionate 500 micrograms ( 19.9 ) ( 95 % CI 6.9 to 27.8 ) . CONCLUSIONS : Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption . Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients Introduction : Concerns have been raised regarding the safety of extended use of long-acting β2-agonists ( LABAs ) . The safety of arformoterol ( 50 µg QD ) , and salmeterol ( 42 µg BID ) , was assessed over 12 months in subjects with COPD . The study also examined the occurrence of tolerance with these agents , i.e. whether improvement in airway function diminished or frequency of exacerbations increased with 12-months of use . Methods : Subjects with COPD ( mean FEV1 1.2 L , ~41 % predicted ) were enrolled in the study and r and omized to receive nebulized arformoterol 50 µg QD ( n = 528 ) or salmeterol 42 µg BID ( MDI ; n = 265 ) in a prospect i ve , multicenter , open-label , 12-month trial . The frequency of adverse events , COPD exacerbations , and use of short-acting bronchodilator agents were assessed throughout the study period . Pulmonary function was also examined . Results : Among treated subjects , the frequency of adverse events was similar for those taking arformoterol ( 90.5 % ) and salmeterol ( 88.3 % ) . Tremor was more frequent among subjects treated with arformoterol ( 13.4 % ) than those treated with salmeterol ( 1.1 % ) . The frequency of COPD exacerbations did not increase over 12 months for arformoterol and salmeterol ( weeks 0—13 : 15.7 % and 11.7 % , respectively ; weeks 39—52 : 10.0 % and 9.4 % , respectively ) . Supplemental ipratropium bromide and rescue racemic albuterol use decreased for both groups by 0.8 to 1.5 actuations/day , decreases that remained stable throughout the 52-week study . Mean predose ( trough ) FEV1 improved for arformoterol and salmeterol at week 13 ( 7.1 % ± 17.0 and 7.6 % ± 17.8 , respectively ) and the improvement continued at week 52 ( 5.9 % and 6.2 % , respectively ) . Mean peak percent predicted postdose FEV1 over the course of the 52-week study declined by about 2 % for both treatments , but throughout was higher for arformoterol than for salmeterol . Conclusion : In this trial , both arformoterol 50 µg QD and salmeterol 42 µg BID were well tolerated in patients with COPD . Both LABAs produced effective bronchodilation and their use was not associated with the development of clinical ly meaningful tolerance over a 1-year treatment period Abstract Background : Current guidelines for the treatment of chronic obstructive pulmonary disease ( COPD ) recommend the use of long-acting bronchodilators in the maintenance management of COPD . Combining bronchodilators that work through different mechanisms is recommended in patients with continuous symptoms . Objective : We conducted this study to confirm and further investigate the efficacy and safety of nebulized formoterol as an add-on therapy to maintenance tiotropium in patients with COPD . Methods : This r and omized , double-blind , placebo-controlled , parallel-group study ( NCT00507234 ) was conducted at 24 US sites from March to October 2007 in 155 patients aged ≥40 years with post-bronchodilator forced expiratory volume in 1 second ( FEV1 ) ≥25 % to < 65 % predicted normal . COPD patients receiving open-label tiotropium bromide 18 μg once daily during a 1- to 2-week run-in period were r and omized to receive either formoterol fumarate inhalation solution 20 μg or placebo by nebulization twice daily for 6 weeks while continuing treatment with tiotropium . Outcomes included serial spirometry , inspiratory capacity ( IC ) , baseline dyspnoea index/transition dyspnoea index ( BDI/TDI ) , daily symptom scores , salbutamol ( albuterol ) use and health status measured by the St George ’s Respiratory Question naire ( SGRQ ) . Main outcome measures : The primary efficacy endpoint was st and ardized absolute FEV1 area under the curve over 3 hours ( AUC0–3 ) at week 6 . Results : Treatment groups ( formoterol plus tiotropium , n = 78 ; placebo plus tiotropium , n=77 ) were comparable at baseline . At 6 weeks , FEV1 AUC0–3was significantly greater in the formoterol group compared with the placebo group ( 1.57 vs 1.38 L [ p<0.0001 ] ) . Similarly , formoterol plus tiotropium  improved other lung function measures , including FEV1 , forced vital capacity and post-dose IC at day 1 , and maintained efficacy through week 6 . Formoterol plus tiotropium decreased rescue albuterol use throughout the study ( p<0.05 ) . Mean TDI , SGRQ and most symptom scores did not differ between the two treatment groups . Overall , 37 % of formoterol plus tiotropium recipients experienced adverse events versus 51 % of those receiving placebo plus tiotropium . Conclusions : The addition of nebulized formoterol to tiotropium in maintenance treatment of COPD provided clinical ly meaningful , statistically significant and sustained improvements in pulmonary function without additional adverse effects BACKGROUND Ipratropium and albuterol , combined in a single formulation , is widely used as 
    Output:
    
The majority of the studies showed that the medications evaluated provided symptom relief ; improved the quality of life and pulmonary function of patients ; and prevented exacerbations .
The medications studied are safe to use in the management of COPD and have few adverse effects