***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: Purpose Triple therapy using salmeterol/fluticasone propionate ( FP ) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease ( COPD ) , but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients . The effects of of salmeterol/fluticasone propionate 50/250 μg ( SFC250 ) twice daily plus tiotropium 18 μg ( TIO ) once daily and individual treatments on lung function were compared . Patients and methods Fifty three Japanese COPD patients participated in this r and omized , double-blind , double-dummy , Williams square design crossover study . Lung function was assessed by plethysmography and spirometry . Results The primary endpoint of postdose specific airway conductance area under the curve ( AUC0–4h ) on day 28 was significantly higher following SFC250 + TIO ( 0.854 ) compared with TIO ( 0.737 , 15.8 % ) and SFC250 ( 0.663 , 28.8 % ) alone . SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO ( 0.161 L , P<0.001 ) and SFC250 ( 0.103 L , P=0.008 ) . SFC250 + TIO significantly improved residual volume compared with TIO ( P<0.001 ) and SFC250 ( P=0.003 ) on day 28 . Nonsignificant improvements were seen in trough inspiratory capacity , total lung capacity , and thoracic gas volume . There was no mean change seen in rescue medication . Conclusion Triple therapy using SFC250 + TIO was well tolerated and gave a greater improvement in bronchodilation compared with TIO and SFC250 alone in Japanese patients with COPD . There was improvement in few symptoms , but no mean change was seen in patient-reported outcomes measured by rescue medication use Purpose : To provide information on the efficacy and safety of Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a Metered-Dose-Inhaler 230/42mcg ( FSC MDI ) and its comparable dose of Fluticasone Propionate/Salmeterol DISKUS 250/50mcg ( FSC DISKUS ) in patients with COPD . Methods : This multicenter , r and omized , double-blind , 12 week study was design ed to evaluate FSC MDI treatment responses as compared with FSC DISKUS . The primary comparison of interest was non-inferiority between the FSC MDI treatment group and the FSC DISKUS treatment group assessed in terms of 2-hour post-dose FEV1 change from baseline at endpoint . The non-inferiority criterion bound was 75mL ( lower confidence limit of -75mL ) . Inclusion criteria : Male or female aged ≥ 40 , post-bronchodilator FEV1 ≤ 70 % predicted normal , FEV1/FVC ≤ 70 % and ≥ 10 pack years smoking history . Adverse events were recorded by patients throughout the study on daily diary cards . Adverse events were collected in eCRFs at all clinic visits and during a final follow-up phone call . Results : Patients ( N=247 ) were r and omized to FSC MDI ( FEV1 % 49.3 ± 12.3 , FEV1/FVC 50.5 ± 10.0 ) and FSC DISKUS ( FEV1 % 48.4 ± 11.0 , FEV1/FVC 50.3 ± 10.3 ) . From an ANCOVA model the least squares ( LS ) mean difference ( FSC MDI– FSC DISKUS ) for the 2-hour post dose FEV1 at endpoint was -2.0mL ( 95 % CI -64mL , 59mL ) . Pre-dose FEV1 , FVC , PEF , and albuterol use were also similar between the two formulations . The most common adverse events ( AE ) during treatment were headache ( 8 % and 6 % of patients ) , nasopharyngitis ( 4 % and 6 % ) , cough ( 3 % and 4 % ) , and sinusitis ( 2 % and 5 % ) for FSC MDI and FSC DISKUS , respectively . Pneumonia was recorded as an AE for 2 ( 2 % ) patients in the FSC DISKUS arm . Conclusion : This is the first study to demonstrate that FSC MDI has a similar efficacy and safety profile to FSC DISKUS in COPD patients Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Long-acting muscarinic antagonist ( LAMA ) or long-acting β2-agonist ( LABA ) bronchodilators and their combination are recommended for the maintenance treatment of chronic obstructive pulmonary disease ( COPD ) . Although the efficacy of LAMAs and LABAs has been well established through r and omized controlled trials ( RCTs ) , questions remain regarding their cardiovascular ( CV ) safety . Furthermore , while the safety of LAMA and LABA monotherapy has been extensively studied , data are lacking for LAMA/LABA combination therapy , and the majority of the studies that have reported on the CV safety of LAMA/LABA combination therapy were not specifically design ed to assess this . Evaluation of CV safety for COPD treatments is important because many patients with COPD have underlying CV comorbidities . However , severe CV and other comorbidities are often exclusion criteria for RCTs , contributing to a lack in external validity and generalizability . Real-world observational studies are another important tool to evaluate the effectiveness and safety of COPD therapies in a broader population of patients and can improve upon the external validity limitations of RCTs . We examine what is already known regarding the CV and cerebrovascular safety of LAMA/LABA combination therapy from RCTs and real-world observational studies , and explore the advantages and limitations of data derived from each study type . We also describe an ongoing prospect i ve , observational , comparative post-authorization safety study of a LAMA/LABA combination therapy ( umeclidinium/vilanterol ) and LAMA monotherapy ( umeclidinium ) versus tiotropium , with a focus on the relative merits of the study design Background : Patients with chronic obstructive pulmonary disease ( COPD ) often experience symptoms and problems with activities early in the morning . This is the first study to compare the effect of budesonide/formoterol and salmeterol/fluticasone on lung function , symptoms and activities early in the morning . Methods : Lung function ( peak expiratory flow [ PEF ] and forced expiratory volume in 1 second [ FEV 1 ] ) and symptoms were measured at bedside and activities were measured during the morning using a six-item question naire concerning basic morning routines . In a r and omised , double-blind , multicentre , cross-over study , 442 patients with COPD aged ≥40 years ( pre-bronchodilator FEV1 ≤50 % ; FEV1/vital capacity < 70 % )  received budesonide/formoterol ( 320/9 µg , one inhalation twice daily ) dry powder inhaler ( DPI ) or salmeterol/fluticasone ( 50/500 µg , one inhalation twice daily ) DPI daily , for 1 week each , separated by a 1- to 2-week washout . Lung function ( PEF and FEV1 ) shortly after rising from bed in the morning , symptoms and basic morning activities were assessed by electronic diary ( e-Diary ) recordings . Results : Budesonide/formoterol and salmeterol/fluticasone treatment increased morning PEF 5 minutes post-dose , measured as a mean improvement from baseline over the full study period ( primary endpoint ; adjusted mean change : 15.1 l/min and 14.2 l/min , respectively [ difference 1.0 l/min ; p = 0.603 ] ) . Mean morning FEV1 improved more following budesonide/ formoterol treatment versus salmeterol/fluticasone at 5 minutes ( 0.12 l versus 0.09 l ; p = 0.090 ) and 15 minutes ( 0.14 l versus 0.10 l ; p < 0.05 ) post-dose . Budesonide/formoterol demonstrated a more rapid onset of effect as reflected by increases in e-Diary-recorded PEF and FEV 1 from pre-dose to 5 and 15 minutes post-dose ( all p < 0.001 ) and spirometry at the clinic measured after the first dose ( FEV1 p < 0.001 ; 5 minutes post-dose ) . Improvements in symptom scores within 15 minutes after drug administration were similar for both drugs , but budesonide/formoterol treatment result ed in significantly greater improvements in total morning activities score ( getting washed , dried , dressed , eating breakfast and walking around the home ; 0.22 versus 0.12 respectively , p < 0.05 ) . Both treatments were well tolerated . Conclusions : Short-term treatment with budesonide/formoterol DPI or salmeterol/fluticasone DPI was effective in patients with COPD .  Budesonide/formoterol had a more rapid onset of effect compared with salmeterol/fluticasone and result ed in greater improvements in ability to perform morning activities despite the lower inhaled corticosteroid dose The Indacaterol : Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol ( INSTEAD ) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease ( COPD ) exacerbations from salmeterol/fluticasone ( SFC ;  inhaled corticosteroid  ( ICS ) regimen ) to indacaterol monotherapy ( non-ICS regimen ) . This 26-week , double-blind , double-dummy , parallel-group , phase IV study , r and omised 581 patients with moderate COPD to indacaterol 150 μg once daily or SFC 50/500 μg twice daily . Patients had been receiving SFC 50/500 μg for ≥3 months , with no COPD exacerbations for more than a year before the study ( patients for whom ICS is not recommended ) . The primary objective was to demonstrate non-inferiority of indacaterol to SFC , measured by trough forced expiratory volume in 1 second ( FEV1 ) after 12 weeks ( non-inferiority margin of 0.06 L ) . The primary objective was met , with a mean treatment difference of 9 mL ( 95 % CI -45–26 mL ) . There were no significant differences between treatments in terms of breathlessness ( transition dyspnoea index ) or health status ( Saint George ’s Respiratory Question naire ) at weeks 12 or 26 , or rescue medication use or COPD exacerbation rates over 26 weeks . Safety profiles of both treatments were as expected . This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 μg with no efficacy loss . Moderate COPD patients can switch from salmeterol/fluticasone to indacaterol with no efficacy loss Objectives To test the reliability , validity and responsiveness of the 13-item Shortness of Breath with Daily Activities ( SOBDA ) question naire , and determine the threshold for response and minimal important difference ( MID ) . Design 6 week , r and omised , double-blind , placebo-controlled study . Setting 40 centres in the USA between 29 October 2009 and 1 July 2010 . Primary and secondary outcome measures 547 patients with chronic obstructive pulmonary 
    Output:
    
FP/SAL is recommended for the initiation therapy just in a small percentage of symptomatic patients that are at high risk of exacerbation with blood eosinophil counts ≥300 cells per μl .