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Johanna I Lutter,1 Rudolf A Jörres,2 Tobias Welte,3 Henrik Watz,4 Benjamin Waschki,5 Peter Alter,6 Franziska C Trudzinski,7 Johan Ohlander,1,8 Jürgen Behr,9 Robert Bals,10 Michael Studnicka,11 Rolf Holle,12 Claus F Vogelmeier,6 Kathrin Kahnert9 1Institute of Health Economics and Health Care Management, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Comprehensive Pneumology Center Munich (CPC-M), Ludwig-Maximilians-Universität München, Munich 80336, Germany; 3Department of Pneumology, Hannover Medical School, Hannover 30625, Germany; 4Pulmonary Research Institute at Lungen Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf 22927, Germany; 5Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; 6Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg (UMR), Germany, Member of the German Center for Lung Research (DZL), Marburg 35043, Germany; 7Department of Diagnostic & Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany; 8Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3584 CM, Netherlands; 9Department of Internal Medicine V, University of Munich (LMU), Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Munich, 80336, Germany; 10Department of Internal Medicine V – Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg 66424, Germany; 11Department of Pneumology, Paracelsus Medical University Salzburg, Universitätsklinikum Salzburg, Salzburg 5020, Austria; 12Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Ludwig-Maximilians-University Munich (LMU), Munich 81377, GermanyCorrespondence: Kathrin KahnertDepartment of Internal Medicine V, University of Munich (LMU), Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Ziemssenstr. 1, Munich 80336, GermanyEmail Kathrin.Kahnert@med.uni-muenchen.deBackground: Beyond smoking, several risk factors for the development of chronic obstructive pulmonary disease (COPD) have been described, among which socioeconomic status including education is of particular interest. We studied the contribution of education to lung function and symptoms relative to smoking in a group of never-smokers with COPD compared to a group of long-time ex-smokers with COPD.Methods: We used baseline data of the COSYCONET cohort, including patients of GOLD grades 1– 4 who were either never-smokers (n=150, age 68.5y, 53.3% female) or ex-smokers (≥ 10 packyears) for at least 10 years (n=616, 68.3y, 29.9% female). Socioeconomic status was analyzed using education level and mortality was assessed over a follow-up period of 4.5 years. Analyses were performed using ANOVA and regression models.Results: Spirometric lung function did not differ between groups, whereas CO diffusing capacity and indicators of lung hyperinflation/air-trapping showed better values in the never-smoker group. In both groups, spirometric lung function depended on the education level, with better values for higher education. Quality of life and 6-MWD were significantly different in never-smokers as well as patients with higher education. Asthma, alpha-1-antitrypsin deficiency, and bronchiectasis were more often reported in never-smokers, and asthma was more often reported in patients with higher education. Higher education was also associated with reduced mortality (hazard ratio 0.46; 95% CI 0.22– 0.98).Conclusion: Overall, in the COSYCONET COPD cohort, differences in functional status between never-smokers and long-time ex-smokers were not large. Compared to that, the dependence on education level was more prominent, with higher education associated with better outcomes, including mortality. These data indicate that non-smoking COPD patients’ socioeconomic factors are relevant and should be taken into account by clinicians.Keywords: COPD, never-smoker, education, socioeconomic status

Alterations of cognitive functions have been described in COPD. Our study aimed to disentangle the relationship between the degree of cognitive function and COPD characteristics including quality of life (QoL).Data from 1969 COPD patients of the COSYCONET cohort (GOLD grades 1–4; 1216 male/ 753 female; mean (SD) age 64.9 ± 8.4 years) were analysed using regression and path analysis. The DemTect screening tool was used to measure cognitive function, and the St. George‘s respiratory questionnaire (SGRQ) to assess disease-specific QoL.DemTect scores were =60 years of age. For statistical reasons, we used the average of both algorithms independent of age in all subsequent analyses. The DemTect scores were associated with oxygen content, 6-min-walking distance (6-MWD), C-reactive protein (CRP), modified Medical Research Council dyspnoea scale (mMRC) and the SGRQ impact score. Conversely, the SGRQ impact score was independently associated with 6-MWD, FVC, mMRC and DemTect. These results were combined into a path analysis model to account for direct and indirect effects. The DemTect score had a small, but independent impact on QoL, irrespective of the inclusion of COPD-specific influencing factors or a diagnosis of cognitive impairment.We conclude that in patients with stable COPD lower oxygen content of blood as a measure of peripheral oxygen supply, lower exercise capacity in terms of 6-MWD, and higher CRP levels were associated with reduced cognitive capacity. Furthermore, a reduction in cognitive capacity was associated with reduced disease-specific quality of life. As a potential clinical implication of this work, we suggest to screen especially patients with low oxygen content and low 6-MWD for cognitive impairment.

Peter Alter,1 Barbara A Mayerhofer,2 Kathrin Kahnert,3 Henrik Watz,4 Benjamin Waschki,5,6 Stefan Andreas,7,8 Frank Biertz,9 Robert Bals,10 Claus F Vogelmeier,1 Rudolf A Jörres2 1Department of Medicine, Pulmonary and Critical Care Medicine, Philipps University of Marburg (UMR), Member of the German Center for Lung Research (DZL), Marburg, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the Center for Lung Research (DZL), Munich, Germany; 3Department of Internal Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 4Pulmonary Research Institute at Lungen Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 5Department of Pneumology, LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 6Department of General and Interventional Cardiology, University Heart Center, Hamburg, Germany; 7Department of Cardiology and Pneumology, University Medical Center, Goettingen, Germany; 8Lung Clinic, Immenhausen, Germany; 9Institute for Biostatistics, Center for Biometry, Medical Informatics and Medical Technology, Hannover Medical School, Hannover, Germany; 10Department of Internal Medicine V - Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, GermanyCorrespondence: Peter AlterDepartment of Medicine, Pulmonary and Critical Care Medicine, Philipps University of Marburg (UMR), Member of the German Center for Lung Research (DZL), Baldingerstrasse 1, Marburg 35033, GermanyTel +49 6 421 586 6140Email Alter@uni-marburg.de&#x00A0Rudolf A JörresInstitute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the Center for Lung Research (DZL), Ziemssenstrasse 1, Munich 80336, GermanyTel +49 8 944 005 2466Email Rudolf.Joerres@med.uni-muenchen.de &#x00A0Background: A substantial prevalence of cardiovascular disease is known for COPD, but detection of its presence, relationship to functional findings and contribution to symptoms remains challenging. The present analysis focusses on the cardiovascular contribution to COPD symptoms and their relationship to the patients’ diagnostic status, medication and echocardiographic findings.Methods: Patients from the COPD cohort COSYCONET with data on lung function, including FEV1, residual volume/total lung capacity (RV/TLC) ratio, diffusing capacity TLCO, and echocardiographic data on left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD), medical history, medication, modified British Medical Research Council dyspnea scale (mMRC) and Saint Georges Respiratory Questionnaire (SGRQ) were analyzed.Results: A total of 1591 patients (GOLD 0–4: n=230/126/614/498/123) fulfilled the inclusion criteria. Ischemic heart disease, myocardial infarction or heart failure were reported in 289 patients (18.2%); 860 patients (54%) received at least one cardiovascular medication, with more than one in many patients. LVEF56 mm was found in 204 patients (12.8%), of whom 74 (36.3%) had neither a cardiovascular history nor medication. Among 948 patients (59.6%) without isolated hypertension, there were 21/55 (38.2%) patients with LVEF56 mm, who lacked both a cardiac diagnosis and medication. LVEDD and LVEF were linked to medical history; LVEDD was dependent on RV/TLC and LVEF on FEV1. Exertional COPD symptoms were best described by mMRC and the SGRQ activity score. Beyond lung function, an independent link from LVEDD on symptoms was revealed.Conclusion: A remarkable proportion of patients with suspicious echocardiographic findings were undiagnosed and untreated, implying an increased risk for an unfavorable prognosis. Cardiac size and function were dependent on lung function and only partially linked to cardiovascular history. Although the contribution of LV size to COPD symptoms was small compared to lung function, it was detectable irrespective of all other influencing factors. However, only the mMRC and SGRQ activity component were found to be suitable for this purpose.Keywords: COPD, heart failure, echocardiography, medication, dyspnea, symptoms

BackgroundConventional measures to evaluate COPD may fail to capture systemic problems, particularly musculoskeletal weakness and cardiovascular disease. Identifying these manifestations and assessing their association with clinical outcomes (ie, mortality, exacerbation and COPD hospital admission) is of increasing clinical importance.ObjectiveTo assess associations between 6 min walk distance (6MWD), heart rate, fibrinogen, C reactive protein (CRP), white cell count (WCC), interleukins 6 and 8 (IL-6 and IL-8), tumour necrosis factor-alpha, quadriceps maximum voluntary contraction, sniff nasal inspiratory pressure, short physical performance battery, pulse wave velocity, carotid intima-media thickness and augmentation index and clinical outcomes in patients with stable COPD.MethodsWe systematically searched electronic databases (August 2018) and identified 61 studies, which were synthesised, including meta-analyses to estimate pooled HRs, following Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.ResultsShorter 6MWD and elevated heart rate, fibrinogen, CRP and WCC were associated with higher risk of mortality. Pooled HRs were 0.80 (95% CI 0.73 to 0.89) per 50 m longer 6MWD, 1.10 (95% CI 1.02 to 1.18) per 10 bpm higher heart rate, 3.13 (95% CI 2.14 to 4.57) per twofold increase in fibrinogen, 1.17 (95% CI 1.06 to 1.28) per twofold increase in CRP and 2.07 (95% CI 1.29 to 3.31) per twofold increase in WCC. 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.ConclusionFindings suggest 6MWD, heart rate, CRP, fibrinogen and WCC are associated with clinical outcomes in patients with stable COPD. Use of musculoskeletal measures to assess outcomes in patients with COPD requires further investigation.Trial registration numberCRD42016052075.