***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 Osteoporosis is one of the systemic features of COPD . A correlation between the emphysema phenotype of COPD and reduced bone mineral density ( BMD ) is suggested by some studies , however , the mechanisms underlying this relationship are unclear . Experimental studies indicate that IL-1β , IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema . The OPG/RANK/RANKL system is an important regulator of bone metabolism , and participates in the development of post-menopausal osteoporosis . Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied . Methods Eighty male patients ( current or former smokers ) completed a chest CT scan , pulmonary function test , dual x-ray absorptiometry measurements and question naires .  Among these subjects , thirty patients with normal BMD and thirty patients with low BMD were selected r and omly for measurement of IL-1β , IL-6 , TNF-α ( flow cytometry ) and OPG/RANK/RANKL ( ELISA ) . Twenty age-matched healthy volunteers were recruited as controls . Results Among these eighty patients , thirty-six had normal BMD and forty-four had low BMD . Age , BMI and CAT score showed significant differences between these two COPD groups ( p < 0.05 ) . The low-attenuation area ( LAA% ) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD ( r = 0.741 ; p < 0.0001 ) . Forward logistic regression analysis showed that only LAA% ( p = 0.005 ) and BMI ( p = 0.009 ) were selected as explanatory variables . The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls ( p < 0.05 ) , but the difference between the two COPD groups did not reach significance . The levels of IL-6 and TNF-α among the three groups were significantly different ( p < 0.05 ) . The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls ( p < 0.05 ) , and correlated negatively with lumbar vertebral BMD , but positively with LAA% . Conclusions Radiographic emphysema is correlated with low BMD in current and former smokers with COPD . IL-1β , IL-6 , TNF-α , and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD Background Because chronic obstructive pulmonary disease ( COPD ) is a heterogeneous condition , the identification of specific clinical phenotypes is key to developing more effective therapies . To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort ( NCT00292552 ) . Methods and Findings Six inflammatory biomarkers in peripheral blood ( white blood cells ( WBC ) count and CRP , IL-6 , IL-8 , fibrinogen and TNF-α levels ) were quantified in 1,755 COPD patients , 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years . We found that , at baseline , 30 % of COPD patients did not show evidence of systemic inflammation whereas 16 % had persistent systemic inflammation . Even though pulmonary abnormalities were similar in these two groups , persistently inflamed patients during follow-up had significantly increased all-cause mortality ( 13 % vs. 2 % , p<0.001 ) and exacerbation frequency ( 1.5 ( 1.5 ) vs. 0.9 ( 1.1 ) per year , p<0.001 ) compared to non-inflamed ones . As a descriptive study our results show associations but do not prove causality . Besides this , the inflammatory response is complex and we studied only a limited panel of biomarkers , albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice . Conclusions Overall , these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment 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-α were determined at recruitment and subsequent visits . A total of 168 of the 1,843 patients ( 9.1 % ) died . Nonsurvivors were older and had more severe airflow limitation , increased dyspnea , higher BODE score , more emphysema , and higher rates of comorbidities and history of hospitalizations . The best predictive model for mortality using clinical variables included age , BODE , and hospitalization history ( C statistic of 0.686 ; P < 0.001 ) . One single biomarker ( IL-6 ) significantly improved the C statistic to 0.708 , but this was further improved to 0.726 ( P = 0.003 ) by the addition of all biomarkers . CONCLUSIONS The addition of a panel of selected biomarkers improves the ability of established clinical variables to predict mortality in chronic obstructive pulmonary disease . Clinical trial registered with www . clinical trials.gov ( NCT00292552 ) Despite a number of studies on biomarkers in chronic obstructive pulmonary disease ( COPD ) , only a few disease-related markers have been identified , yet we still have no satisfactory markers specific to innate immune system and neutrophil activation , which is essential in airway inflammation in COPD . Recent biological studies indicated that lipocalins ( LCNs ) might be involved in airway inflammation and innate immunity ; however , results from available studies on the association of LCNs with COPD are not consistent . We carried out a multicenter prospect i ve observational cohort study to investigate the differences in serum levels  of LCN1 and LCN2 between subjects with COPD ( n=58 ) and healthy controls ( n=29 ) . Several vali date d inflammatory markers , including C-reactive protein , tumor necrosis factor-α , interleukin-6 , and interleukin-8 , were measured . The correlation of LCN1 and LCN2 with clinical features such as smoking habits , lung function , symptoms , and disease category was also analyzed . When comparing with healthy controls , serum levels of LCN1 ( 66.35±20.26 ng/mL versus 41.16±24.19 ng/mL , P<0.001 ) and LCN2 ( 11.29±3.92 ng/mL versus 6.09±5.13 ng/mL , P<0.001 ) were both elevated in subjects with COPD after adjusting for age , sex , smoking habits , and inflammatory biomarkers . Smoking history and tobacco exposure , as quantified by pack-year , had no impact on systemic expressions of LCN1 and LCN2 in our study . Blood levels of LCN1 and LCN2 , respectively , were negatively correlated to COPD Assessment Test and Modified Medical British Research Council score ( P<0.001 ) . Disease category by Global Initiative for Chronic Obstructive Lung Disease grade 1–4 or group A – D was not associated with levels of LCNs . Patient-reported exacerbations and body mass index were also tested , but no relationship with LCNs was found . In summary , serum concentrations of LCN1 and LCN2 were both elevated in patients with COPD , with their levels correlating to COPD Assessment Test and Modified Medical British Research Council score . These findings warrant large-scale and longitudinal studies to vali date LCNs as circulating biomarkers for COPD Background : Inflammatory markers are increased in chronic obstructive pulmonary disease ( COPD ) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance . Methods : The Health Aging and Body Composition ( Health ABC ) study is a prospect i ve observational cohort of well functioning individuals aged 70–79 years . A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation , muscle strength , and exercise capacity . These associations were compared in participants with and without obstructive lung disease ( OLD ) . Results : Of the 3075 participants enrolled in the Health ABC cohort , OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results . Of the participants with OLD , 35 % , 38 % , and 27 % participants had mild , moderate , and severe OLD , respectively . Participants with OLD had lower quadriceps strength ( 102.5 Nm v 108.9 Nm , p = 0.02 ) , lower maximum inspiratory pressure ( 64.7 cm H2O v 74.2 cm H2O , p<0.0001 ) , higher systemic interleukin (IL)-6 levels ( 2.6 pg/ml v 2.2 pg/ml , p<0.0001 ) , and higher C-reactive protein ( CRP ) levels ( 3.5 mg/l v 2.5 mg/l , p<0.0001 ) than those with normal spirometry . In participants with OLD and those with normal spirometry , forced expiratory volume in 1 second ( FEV1 ) was associated with IL-6 ( adjusted regression coefficients ( β ) = −5.3 ( 95 % CI −9.1 to−1.5 ) and −3.1 ( 95 % CI −4.3 to −1.9 ) , respectively ) . IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry ( β = −6.4 ( 95 % CI −12.8 to −0.03 ) and −3.4 ( 95 % CI −5.4 to −1.3 ) , respectively , for IL-6 and β = −10.1 ( 95 % CI −18.7 to −1.5 ) and −3.8 ( 95 % CI −7 to −0.6 ) , respectively , for TNF ) . IL-6 , quadriceps strength , and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups . Conclusions : In well functioning elderly subjects with or without OLD , IL-6 is associated with reduced FEV1 , quadriceps strength , and exercise capacity 
    Output:
    
This meta- analysis indicated that patients with stable COPD had higher serum IL-6 concentrations than healthy controls .
No evidence showing positive or negative association between IL-6 concentrations and the severity of pulmonary function impairment was found .
The correlation between IL-6 levels and pulmonary function was weak in different severities of stable COPD patients