***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 / Aims Patients with chronic obstructive pulmonary disease ( COPD ) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning . The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation . Methods Data of 133 patients with severe airflow limitation were analyzed in a prospect i ve , non-interventional study . A clinical symptom question naire was completed by patients at baseline . In patients having morning symptoms , defined by at least one or more prominent or aggravating symptom during morning activities , a morning activity question naire was also completed at baseline and following 2 months of COPD treatment . Results The most frequently reported COPD symptom was breathlessness ( 90.8 % ) . Morning symptoms were reported in 76 ( 57 % ) patients ; these had more frequent and severe clinical COPD symptoms . The most frequently reported morning activity was getting out of bed ( 82.9 % ) . The long acting muscarinic antagonist  ( odds ratio [ OR ] , 6.971 ; 95 % confidence interval [ CI ] , 1.317 to 11.905 ) and chest tightness ( OR , 0.075 ; 95 % CI , 0.011 to 0.518 ) were identified as significantly related to absence of morning symptoms . There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment . Conclusions Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities . These patients also have more prevalent and severe COPD symptoms . The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD Background The combination of aclidinium bromide , a long-acting anticholinergic , and formoterol fumarate , a long-acting beta2-agonist ( 400/12 μg twice daily ) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease ( COPD ) , and is approved in the European Union as a maintenance treatment . The effect of this combination on symptoms of COPD and exacerbations is less well established . We examined these outcomes in a pre-specified analysis of pooled data from two 24-week , double-blind , parallel-group , active- and placebo-controlled , multicentre , r and omised Phase III studies ( ACLIFORM and AUGMENT ) . Methods Patients ≥40 years with moderate to severe COPD ( post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity < 70 % and FEV1 ≥30 % but < 80 % predicted normal ) were r and omised ( ACLIFORM : 2:2:2:2:1 ; AUGMENT : 1:1:1:1:1 ) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg , aclidinium 400 μg , formoterol 12 μg or placebo via Genuair ™ /Pressair ® . Dyspnoea ( Transition Dyspnoea Index ; TDI ) , daily symptoms ( EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [ E-RS ] question naire ) , night-time and early-morning symptoms , exacerbations ( Healthcare Re source Utilisation [ HCRU ] and EXACT definitions ) and relief-medication use were assessed . Results The pooled intent-to-treat population included 3394 patients . Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 ( all p < 0.05 ) . Over 24 weeks , significant improvements in E-RS total score , overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies ( all p < 0.05 ) . The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo ( p < 0.05 ) but not monotherapies ; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo ( p < 0.01 ) and aclidinium ( p < 0.05 ) . Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo ( all p < 0.05 ) but not the monotherapies . Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium ( p < 0.01 ) . Conclusions Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo , aclidinium and formoterol in patients with moderate to severe COPD . Furthermore , aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo . Trial registration NCT01462942 and NCT01437397 ( Clinical Trials.gov UNLABELLED Indacaterol is a novel , inhaled , long-acting β(2)-agonist providing 24-h bronchodilation with once-daily ( o.d . ) dosing in patients with COPD . In this double-blind , incomplete block crossover study , patients with moderate-to-severe COPD were r and omised to receive three treatment cycles from : indacaterol 300 μg o.d . dosed PM or AM , salmeterol 50 μg twice daily or placebo , each for 14 days . Trough FEV(1 ) was measured 24 h after indacaterol , and 12 h after salmeterol . Ninety-six patients ( mean age : 64 years ; post-bronchodilator FEV(1 ) 57 % predicted , FEV(1)/FVC 55 % ) were r and omised ; 83 completed . After 14 days , the difference vs. placebo  in trough FEV(1 ) for PM indacaterol was 200 mL ( p < 0.001 [ primary analysis ] ) and for AM indacaterol was 200 mL ( p < 0.001 ) . Compared with salmeterol , trough FEV(1 ) for PM indacaterol was 110 mL higher ( p < 0.001 ) , and for AM indacaterol was 50 mL higher ( p = NS ) . Over 14 days , vs. placebo , both PM and AM indacaterol improved the % of nights with no awakenings ( by 11.9 and 8.1 points ; p < 0.01 ) ; the % of days with no daytime symptoms ( by 6.7 and 5.5 points ; p < 0.05 ) ; and the % of days able to perform usual activities ( by 6.7 and 7.8 points ; p < 0.05 ) . Indacaterol provided 24-h bronchodilation and improvement in symptoms regardless of whether taken regularly in the morning or evening . CLINICAL TRIAL REGISTRATION Clinical Trials.gov NCT00615030 Abstract Background : This Phase III study evaluated the efficacy and safety of twice-daily aclidinium 200 μg and 400 μg versus placebo in the treatment of moderate-to-severe COPD . Methods : In this 12-week , double-blind , multicenter trial , patients were r and omized ( 1:1:1 ) to inhaled twice-daily aclidinium 200 μg , aclidinium 400 μg , or placebo . Primary and secondary endpoints were changes from baseline in trough FEV1 and peak FEV1 at Week 12 , respectively . Health status ( St. George 's Respiratory Question naire [ SGRQ ] ) , COPD symptoms ( Transitional Dyspnea Index [ TDI ] , night and early morning symptoms ) , and safety were also assessed . Results : A total of 561 patients ( mean age , 64 ± 9 years ) with a mean baseline FEV1 of 1.36 ± 0.54 L ( 47.2 % of predicted value ) were r and omized . At Week 12 , aclidinium 200 μg and 400 μg showed significant improvements from baseline in mean ( 95 % CI ) trough FEV1 compared with placebo by 86 ( 45 , 127 ) mL and 124 ( 83,164 ) mL , respectively , and in peak FEV1 by 146 ( 101 , 190 ) mL and 192 ( 148 , 236 ) mL , respectively ( p ≤ 0.0001 for all ) . Both aclidinium doses also provided significant improvements in SGRQ , TDI and almost all COPD symptom scores compared with placebo ( p < 0.05 for all ) . Incidences of adverse events ( AEs ) were similar across treatment groups . The incidence of anticholinergic AEs was low and similar across groups ( dry mouth : 0.5%–1.6 % ; constipation : 0%-1.1 % ) . Conclusions : Treatment of moderate-to-severe COPD patients with twice-daily aclidinium 200 μg and 400 μg was associated with significant improvements in bronchodilation , health status , and COPD symptoms . Both doses were well tolerated and had safety profiles similar to placebo . Trial Registration : This ACCORD I study ( AClidinium in Chronic Obstructive Respiratory Disease I ) was registered on clinical trials.gov ( NCT00891462 ) as “ Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease ( COPD ) ” Background Symptoms , particularly dyspnea , and activity limitation , have an impact on the health status and the ability to function normally in patients with chronic obstructive pulmonary disease ( COPD ) . Methods To develop an electronic patient diary ( eDiary ) , qualitative patient interviews were conducted from 2009 to 2010 to identify relevant symptoms and degree of bother due to symptoms . The eDiary was completed by a subset of 209 patients with moderate-to-severe COPD in the 26-week QVA149 SHINE study . Two morning assessment s ( since awakening and since the last assessment ) and one evening assessment were made each day . Assessment s covered five symptoms ( “ shortness of breath , ” “ phlegm/mucus , ” “ chest tightness , ” “ wheezing , ” and “ coughing ” ) and two impact items ( “ bothered by COPD ” and “ difficulty with activities ” ) and were scored on a 10-point numeric scale . Results Patient compliance with the eDiary was 90.4 % at baseline and 81.3 % at week 26 . Correlations between shortness of breath and impact items were > 0.95 . Regression analysis showed that shortness of breath was a highly significant ( P<0.0001 ) predictor of impact items . Exploratory factor analysis gave a single factor comprising all eDiary items , including both symptoms and impact items . Shortness of breath , the total score ( including five symptoms and two impact items ) , and the five-item symptom score from the eDiary performed well , with good consistency and reliability . The eDiary showed good sensitivity to change , with a 0.6 points reduction in the symptoms scores ( on a 0–10 point scale ) representing a meaningful change . Conclusion The eDiary was found to be valid , reliable , and responsive . The high correlations obtained between “ shortness of breath ” and the ratings of “ bother ” and “ difficulty with activities ” confirmed the relevance of this symptom in patients with COPD . Future studies will be required to explore further psychometric properties and their ability to differentiate between COPD treatments Background A previous Phase IIIb study ( NCT01462929 ) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium , and improvement of symptoms versus placebo . This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study . Methods Symptomatic patients ( defined as those with Evaluating Respiratory Symptoms [ E-RS ™ ] in COPD baseline score ≥10 units ) received aclidinium bromide 400 μg twice daily ( BID ) , tiotropium 18 μg once daily ( QD ) , or placebo , for 6 weeks . Lung function , COPD respiratory symptoms , and incidence of adverse events ( AEs ) were assessed . Results In all , 277 symptomatic patients were included in this post hoc analysis . Aclidinium and tiotropium treatment improved forced expiratory volume in 1 second ( FEV1 ) from baseline to week 6 at all time points over 24 hours versus placebo . In addition , improvements in FEV1 from baseline during the nighttime period were observed for aclidinium versus tiotropium on day 1 ( aclidinium 157 mL , tiotropium 67 mL ; P<0.001 ) and week  
    Output:
    
The accumulated evidence indicated that the symptomatic burden of COPD appears greatest in the morning , particularly upon waking , and that these morning symptoms have a substantial impact on patients ’ ability to function normally through the day ; they also worsen quality of life .
The literature also confirmed the importance of pharmacotherapy in the management of daytime COPD symptoms , and in helping normalize daily functioning .