***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 It is unclear whether elevated plasma C reactive protein ( CRP ) is causally related to chronic obstructive pulmonary disease ( COPD ) . The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian r and omisation design . Methods The authors measured high-sensitivity CRP in plasma , genotyped for four single nucleotide polymorphisms in the CRP gene , and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32 652 individuals from the Copenhagen General Population Study . Results Elevated plasma CRP  > 3 mg/l compared with < 1 mg/l was associated with risk estimates of 1.8 and 2.8 for spirometry-based COPD and of 1.6 and 1.8 for hospitalisation due to COPD in the Copenhagen City Heart Study and the Copenhagen General Population Study , respectively . Genotype combinations of the four CRP polymorphisms were associated with up to a 62 % increase in plasma CRP . However , these genotype combinations did not associate with increased risk of COPD or hospitalisation due to COPD in either cohort or in the two cohorts combined . On instrumental variable analysis , a doubling of plasma CRP versus a doubling of genetically elevated CRP result ed in ORs for COPD of 1.27 ( 95 % CI 1.25 to 1.30 ) versus 1.01 ( 0.81 to 1.26 ) and for COPD hospitalisation of 1.47 ( 1.43 to 1.51 ) versus 0.82(0.59 to 1.13 ) . Conclusion Although elevated CRP is related to both a diagnosis of COPD and subsequent hospital admission , genetically elevated plasma CRP is not associated with an increased risk of clinical COPD . This suggests that the association between CRP levels and COPD is not causal Rationale : Chronic obstructive pulmonary disease ( COPD ) is associated with a 2–3-fold increase in the risk of ischaemic heart disease , stroke and sudden death . The mechanisms responsible for this association are not clear and appear to be independent of smoking history . Objective : We test the hypothesis that patients with COPD have increased arterial stiffness and blood pressure in comparison with age and smoking matched controls . Methods : In a prospect i ve case control study , we recruited 102 patients with COPD and 103 healthy controls matched for age and smoking status . Patients were assessed by clinical history and spirometry , with  arterial stiffness and blood pressure  determined using radial artery applanation tonometry and sphygmomanometry . Results : Patients with COPD had increased arterial stiffness compared with matched controls , with elevated augmentation pressure ( 17 ( 1 ) vs 14 ( 1 ) mm Hg ; p = 0.005 ) and a reduced time to wave reflection ( 131 ( 1 ) vs 137 ( 2 ) ms ; p = 0.004 ) . These differences were associated with increases in both diastolic ( 82 ( 1 ) vs 78 ( 1 ) mm Hg ; p = 0.005 ) and systolic blood pressure ( 147 ( 2 ) vs 132 ( 2 ) mm Hg ; p<0.001 ) . Serum C reactive protein concentrations were threefold higher in patients ( 6.1 ( 0.9 ) vs 2.3 ( 0.4 ) mg/l ; p = 0.001 ) . Data are presented as mean ( SEM ) . Conclusions : Patients with COPD have increased arterial stiffness and blood pressure in comparison with controls matched for age and smoking status . We speculate that increased systemic inflammation and vascular dysfunction could potentially explain the excess cardiovascular morbidity and mortality associated with COPD Background Health-related quality of life ( HRQL ) is considered as an important outcome parameter in patients with chronic diseases . This study aim ed to assess the role of disease-specific HRQL for long-term survival in patients of different diagnoses with chronic hypercapnic respiratory failure ( CHRF ) . Methods In a cohort of 231 stable patients ( chronic obstructive pulmonary disease ( COPD ) , n = 98 ; non- COPD ( obesity-hypoventilation syndrome , restrictive disorders , neuromuscular disorders ) , n = 133 ) with CHRF and current home mechanical ventilation ( HMV )  , HRQL was assessed by the disease-specific Severe Respiratory Insufficiency ( SRI ) question naire and its prognostic value was prospect ively evaluated during a follow-up of 2–4 years , using univariate and multivariate regression analysis . Results HRQL was more impaired in COPD ( mean ± SD SRI- summary score ( SRI-SS ) 52.5 ± 15.6 ) than non- COPD patients ( 67.6 ± 16.4 ; p < 0.001 ) . Overall mortality during 28.9 ± 8.8 months of follow-up was 19.1 % ( 31.6 % in COPD , 9.8 % in non- COPD ) . To identify the overall role of SRI , we first evaluated the total study population . SRI-SS and its subdomains ( except attendance symptoms and sleep ) , as well as body mass index ( BMI ) , leukocyte number and spirometric indices were associated with long-term survival ( p < 0.01 each ) . Of these , SRI-SS , leukocytes and forced expiratory volume in 1 s ( FEV1 ) turned out to be independent predictors ( p < 0.05 each ) . More specifically , in non- COPD patients SRI-SS and most of its subdomains , as well as leukocyte number , were related to survival ( p < 0.05 ) , whereas in patients with COPD only BMI and lung function but not SRI were predictive . Conclusion In patients with CHRF and HMV , the disease-specific SRI was an overall predictor of long-term survival in addition to established risk factors . However , the SRI predominantly beared information regarding long-term survival in non- COPD patients , while in COPD patients objective measures of the disease state were superior . This on one h and highlights the significance of HRQL in the long-term course of patients with CHRF , on the other h and it suggests that the predictive value of HRQL depends on the underlying disease Background In addition to smoking , acute exacerbations are considered to be a contributing factor to progression of chronic obstructive pulmonary disease ( COPD ) . However , these findings come from studies including active smokers , while results in ex-smokers are scarce and contradictory . The purpose of this study was to evaluate if frequent acute moderate exacerbations are associated with an accelerated decline in forced expiratory volume in one second ( FEV1 ) and impairment of functional and clinical outcomes in ex-smoking COPD patients . Methods A cohort of 100 ex-smoking patients recruited for a 2-year follow-up study was evaluated at inclusion and at 6-monthly scheduled visits while in a stable condition . Evaluation included anthropometry , spirometry , inspiratory capacity , peripheral capillary oxygen saturation , severity of dyspnea , a 6-minute walking test , BODE ( Body mass index , airflow Obstruction , Dyspnea , Exercise performance ) index , and quality of life ( St George ’s Respiratory Question naire and Chronic Respiratory Disease Question naire ) . Severity of exacerbation was grade d as moderate or severe according to health care utilization . Patients were classified as infrequent exacerbators if they had no or one acute exacerbation/year and frequent exacerbators if they had two or more acute exacerbations/year . R and om effects modeling , within hierarchical linear modeling , was used for analysis . Results During follow-up , 419 ( 96 % moderate ) acute exacerbations were registered . At baseline , frequent exacerbators had more severe disease than infrequent exacerbators according to their FEV1 and BODE index , and also showed greater impairment in inspiratory capacity , forced vital capacity , peripheral capillary oxygen saturation , 6-minute walking test , and quality of life . However , no significant difference in FEV1 decline over time was found between the two groups ( 54.7±13 mL/year versus 85.4±15.9 mL/year in frequent exacerbators and infrequent exacerbators , respectively ) . This was also the case for all other measurements . Conclusion Our results suggest that frequent moderate exacerbations do not contribute to accelerated clinical and functional decline in COPD patients who are ex-smokers Background Although it is known that patients with chronic obstructive pulmonary disease ( COPD ) generally do have an increased heart rate , the effects on both mortality and non-fatal pulmonary complications are unclear . We assessed whether heart rate is associated with all-cause mortality , and non-fatal pulmonary endpoints . Methods A prospect i ve cohort study of 405 elderly patients with COPD was performed . All patients underwent extensive investigations , including electrocardiography . Follow-up data on mortality were obtained by linking the cohort to the Dutch National Cause of Death Register and information on complications ( exacerbation of COPD or pneumonia ) by scrutinizing patient files of general practitioners . Multivariable cox regression analysis was performed . Results During the follow-up 132 ( 33 % ) patients died . The overall mortality rate was 50/1000 py ( 42–59 ) . The major causes of death were cardiovascular and respiratory . The relative risk of all-cause mortality increased with 21 % for every 10 beats/minute increase in heart rate ( adjusted HR : 1.21 [ 1.07–1.36 ] , p = 0.002 ) . The incidence of major non-fatal pulmonary events was 145/1000 py ( 120–168 ) . The risk of a non-fatal pulmonary complication increased non-significantly with 7 % for every 10 beats/minute increase in resting heart rate ( adjusted HR : 1.07 [ 0.96–1.18 ] , p = 0.208 ) . Conclusions Increased resting heart rate is a strong and independent risk factor for all-cause mortality in elderly patients with COPD . An increased resting heart rate did not result in an increased risk of exacerbations or pneumonia . This may indicate that the increased mortality risk of COPD is related to non-pulmonary causes . Future r and omized controlled trials are needed to investigate whether heart-rate lowering agents are worthwhile for COPD patients RATIONALE Accurate prediction of mortality helps select patients for interventions aim ed at improving outcome . OBJECTIVES Because chronic obstructive pulmonary disease is characterized by low- grade systemic inflammation , we hypothesized that addition of inflammatory biomarkers to established predictive factors will improve accuracy . METHODS A total of 1,843 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study were followed for 3 years . Kaplan-Meier curves , log-rank analysis , and Cox proportional hazards analyses determined the predictive value for mortality of clinical variables , while C statistics assessed the added discriminative power offered by addition of biomarkers . MEASUREMENTS AND MAIN RESULTS At recruitment we measured  anthropometrics , spirometry , 6-minute walk distance , dyspnea , BODE index , history of hospitalization , comorbidities , and computed tomography scan emphysema . White blood cell and neutrophil counts , serum or plasma levels of fibrinogen , chemokine lig and 18 , surfactant protein D , C-reactive protein , Clara cell secretory protein-16 , IL-6 and -8 , and tumor necrosis factor 
    Output:
    
Shorter 6MWD and elevated fibrinogen and CRP were associated with exacerbation , and shorter 6MWD , higher heart rate , CRP and IL-6 were associated with hospitalisation .
Few studies examined associations with musculoskeletal measures .
Conclusion Findings suggest 6MWD , heart rate , CRP , fibrinogen and WCC are associated with clinical outcomes in patients with stable COPD .