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Chronic obstructive pulmonary disease (COPD) is frequently associated with coronary artery disease (CAD). When considering computed tomography (CT) for COPD phenotyping, coronary vessel wall calcification would be a potential marker of cardiac disease. However, non-ECG gated scans as used in COPD monitoring do not comply with established quantitative approaches using ECG-triggered CT and the Agatston score. We studied the diagnostic potential of Agatston scores from non-triggered scans for cardiac disease. The study population was a sub-group of the COPD cohort COSYCONET that underwent CT scanning in addition to comprehensive clinical assessments, echocardiographic data and physician-based diagnoses of comorbidities. Agatston scores from non-contrast enhanced, non-triggered CT were used to identify a cut-off value for CAD via ROC analysis. 399 patients were included (152 female, mean age 66.0 ± 8.2 y). In terms of CAD, an Agatston score ≥1500 AU performed best (AUC 0.765; 95% CI: 0.700, 0.831) and was superior to the conventional cut-off value (400 AU). Using this value for defining groups, there were differences (p lt; 0.05) in lung function, left atrial diameter and left ventricular end-systolic diameter as well as CT-determined central airway wall thickness pointing towards a bronchitis phenotype. In multivariate analysis, BMI, hyperlipidemia, arterial hypertension, GOLD D (p lt; 0.05) but particularly Agatston score ≥1500 AU (Odds ratio 10.5; 95% CI: 4.8; 22.6)) were predictors of CAD. We conclude that in COPD patients, Agatston scores derived from non-ECG gated CT showed a much higher cut-off value (1500 AU) for actionable coronary artery disease than the score derived from ECG-triggered CT in cardiology patients.

High resting heart rate (RHR) is associated with higher mortality in the general population and in cardiovascular disease. Less is known about the association of RHR with outcome in chronic obstructive pulmonary disease (COPD). In particular, the time-updated RHR (most recent value before the event) appears informative. This is the first study to investigate the association of time-updated RHR with mortality in COPD. We compared the baseline and time-updated RHR related to survival in 2218 COPD patients of the German COSYCONET cohort (COPD and Systemic Consequences—Comorbidities Network). Patients with a baseline RHR > 72 beats per minute (bmp) had a significantly (p = 0.049) higher all-cause mortality risk (adjusted hazard ratio (HR) of 1.37 (1.00–1.87) compared to baseline RHR ≤ 72 bpm. The time-updated RHR > 72 bpm was markedly superior (HR 1.79, 1.30–2.46, p = 0.001). Both, increased baseline and time-updated RHR, were independently associated with low FEV1, low TLCO, a history of diabetes, and medication with short-acting beta agonists (SABAs). In conclusion, increased time-updated RHR is associated with higher mortality in COPD independent of other predictors and superior to baseline RHR. Increased RHR is linked to lung function, comorbidities and medication. Whether RHR is an effective treatment target in COPD, needs to be proven in controlled trials.

Background: Oxygenated hemoglobin(OxyHem) is a simple-to-measure marker of oxygen content capable of predicting all-cause mortality in stable chronic obstructive pulmonary disease (COPD). Objectives: We aimed to analyze its predictive value during acute exacerbations of COPD (AECOPD). Methods: In this retrospective study, data from 227 patients discharged after severe AECOPD at RoMed Clinical Center Rosenheim, Germany, between January 2012 and March 2018, was analyzed. OxyHem (hemoglobin concentration [Hb] × fractional SpO2, g/dL) was calculated from oxygen saturation measured by pulse oximetry and hemoglobin assessed within 24 h after admission. The follow-up (1.7 ± 1.5 years) covered all-cause mortality, including readmissions for severe AECOPD. Results: During the follow-up period, 127 patients died, 56 due to AECOPD and 71 due to other reasons. Survivors and non-survivors showed differences in age, FVC % predicted, C-reactive protein, hemoglobin, Cr, Charlson Comorbidity Index (CCI), and OxyHem (p < 0.05 each). Significant independent predictors of survival were BMI, Cr or CCI, FEV1 % predicted or FVC % predicted, Hb, or OxyHem. The predictive value of OxyHem (p = 0.006) was superior to that of Hb or SpO2 and independent of oxygen supply during blood gas analysis. OxyHem was also predictive when using a cutoff value of 12.1 g/dL identified via receiver operating characteristic curves in analyses including either the CCI (hazard ratio 1.85; 95% CI 1.20, 2.84; p = 0.005) or Cr (2.04; 95% CI 1.35, 3.10; p = 0.001) as covariates. Conclusion: The concentration of OxyHem provides independent, easy-to-assess information on long-term mortality risk in COPD, even if measured during acute exacerbations. It therefore seems worth to be considered for broader clinical use.

Aims: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases are thought to be linked through various factors. We aimed to assess the relationship between airway obstruction, lung hyperinflation and diastolic filling in COPD. Methods: The study population was a subset of the COPD cohort COSYCONET. Echocardiographic parameters included the left atrial diameter (LA), early (E) and late (A) transmitral flow, mitral annulus velocity (e'), E wave deceleration time (E[dt]), and isovolumic relaxation time (IVRT). We quantified the effect of various predictors including forced expiratory volume in 1 s (FEV1) and intrathoracic gas volume (ITGV) on the echocardiographic parameters by multiple linear regression and integrated the relationships into a path analysis model. Results: A total of 615 COPD patients were included (mean FEV1 52.6% predicted). In addition to influences of age, BMI and blood pressure, ITGV was positively related to e'-septal and negatively to LA, FEV1 positively to E(dt) (p < 0.05 each). The effect of predictors was most pronounced for LA, e'-septal and E(dt), and less for E/A, IVRT and E/e'. Path analysis was used to take into account the additional relationships between the echocardiographic parameters themselves, demonstrating that their associations with the predictors were maintained and robust. Conclusions: Airway obstruction and lung hyperinflation were significantly associated with cardiac diastolic filling in patients with COPD, suggesting a decreased preload rather than an inherently impaired myocardial relaxation itself. This suggests that a reduction in obstruction and hyperinflation could help to improve cardiac filling.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death with a considerable part of the population dying from cardiovascular diseases. High-sensitivity troponin I (hs-TnI) might help to better identify COPD patients at high risk of mortality. We aimed to study the predictive value of hs-TnI for all-cause mortality beyond established COPD assessments, and after consideration of relevant cardiovascular risk factors and prevalent cardiovascular diseases, in a broad population with stable COPD.Circulating hs-TnI concentrations together with a wide range of respiratory and cardiovascular markers were evaluated in 2085 patients with stable COPD across all severity stages enrolled in the multicentre COSYCONET cohort study. The primary outcome was all-cause mortality over 3 years of follow-up.Hs-TnI was detectable in 2020 (96.9%) patients. The median hs-TnI concentration was 3.8 ng·L−1 (interquartile range 2.5–6.6 ng·L−1), with levels above the 99th percentile reference limit of 27 ng·L−1 observed in 1.8% of patients. In Cox regression analyses including adjustments for airflow limitation, dyspnoea grade, exercise capacity and history of severe exacerbations, as well as traditional cardiovascular risk factors, estimated glomerular filtration rate, ankle–brachial index, N-terminal pro-brain natriuretic peptides and prevalent cardiovascular diseases, hs-TnI was a significant predictor for all-cause mortality, both as a continuous variable (hazard ratio (HR) for log hs-TnI 1.28, 95% CI 1.01–1.62) and categorised according to the cut-off of 6 ng·L−1 (HR 1.63, 95% CI 1.10–2.42).In patients with stable COPD, hs-TnI is a strong predictor of all-cause mortality beyond established COPD mortality predictors, and independent of a broad range of cardiovascular risk factors and prevalent cardiovascular diseases. Hs-TnI concentrations well below the upper reference limit provide further prognostic value for all patients with COPD when added to established risk assessments.

Introduction The COPD classification proposed by the Global Initiative for Obstructive Lung Disease was recently revised, and the A to D grouping is now based on symptoms and exacerbations only. Potential associations with comorbidities have not been assessed so far. Thus the aim of the present study was to determine the relationship between the revised (2017) GOLD groups A-D and major comorbidities. Methods We used baseline data from the COPD cohort COSYCONET. Comorbidities were identified from patient self-reports and disease-specific medication: gastrointestinal disorders, asthma, sleep apnea, hyperuricemia, hyperlipidemia, diabetes, osteoporosis, mental disorders, heart failure, hypertension, coronary artery disease. The A-D groups were based on either the COPD Assessment Test or the modified Medical Research Council scale. Exacerbations were also categorized as per GOLD recommendations. Results Data from 2228 patients were analyzed. Using GOLD group A as a reference, group D was associated with nearly all comorbidities, followed by group B and C. When groups A-D were dichotomized as AC vs. BD (symptoms) and AB vs. CD (exacerbations), all comorbidities correlated with symptoms and/or exacerbations. This was true for both mMRC- and CAT-based categorizations. Conclusions These findings suggest that the recently modified GOLD categorization is clinically relevant beyond being purely an assessment of symptoms and exacerbations. As the A-D groups correlated with the risk of important comorbidities, with some differences in terms of the correlation with symptoms and exacerbations, the findings underline the importance of identifying comorbidities in COPD, particularly in non-responders to therapy who have high symptoms and/or exacerbation rates.

Background There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T1 (T1 (TE)) depends on the echo-time (TE) and reflects regional pulmonary function. Purpose To investigate the potential diagnostic value of T1 (TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT. Study type Prospective non-randomized diagnostic study. Population Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference. Field strength/sequence Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for T1 (TE) mapping at TE1-5 = 70 μsec, 500 μsec, 1200 μsec, 1650 μsec, and 2300 μsec. Assessment Perfusion images were scored by three radiologists. T1 (TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired. Statistical tests Spearman rank correlation coefficients (ρ) were calculated between T1 (TE) and perfusion scores, clinical parameters and qCT. A P-value Results Median values were T1 (TE1-5 ) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T1 was observed from TE1 to TE2 , with no changes from TE2 to TE3 (P = 0.48), TE3 to TE4 (P = 0.94) or TE4 to TE5 (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman's correlations between T1 and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ -0.69) were found. Overall, correlations were strongest at TE2 , weaker at TE1 and rarely significant at TE4 -TE5 . Data conclusion In COPD patients, the increase of T1 (TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T1 and clinical parameters of disease at longer TEs, this suggests that T1 (TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T1 (TE) mapping might be developed further to provide diagnostic information beyond T1 at a single TE. Level of evidence 2 TECHNICAL EFFICACY: Stage 1.

Carolina Fischer,1 Rudolf A Jörres,1 Peter Alter,2 Franziska C Trudzinski,3 Önder Yildirim,4 Robert Bals,5 Claus F Vogelmeier,2 Diego Kauffmann-Guerrero,6 Jürgen Behr,6 Henrik Watz,7 Rolf Holle,8 Kathrin Kahnert6 And members of the COSYCONET study group1Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany; 2Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg (UMR), Germany, Marburg, Germany; 3Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany; 4Institute of Lung Biology and Disease (ILBD), Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany; 5Department of Internal Medicine V - Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany; 6Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany; 7Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Grosshansdorf, Germany; 8Institute for Medical Informatics, Biometry and Epidemiology, University Hospital, LMU Munich, Munich, GermanyCorrespondence: Kathrin Kahnert, Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Ziemssenstraße 1, Munich, 80336, Germany, Email Kathrin.Kahnert@med.uni-muenchen.deIntroduction: In many chronic diseases, including COPD, the patients’ basic knowledge of the disorder has been shown to be relevant for the course of the disease. We studied which clinical and functional characteristics were related to this knowledge as well as the patients’ satisfaction with their knowledge about COPD.Methods: The study population comprised 645 patients of GOLD grades 1– 4 who participated in Visit 6 of the COSYCONET cohort (COPD and Systemic Consequences - Comorbidities Network). The assessments covered a broad panel of clinical and functional characteristics, including generic and disease-specific quality of life and the COPD Assessment Test (CAT). The study aim was addressed by two questions, referring to patients’ knowledge of the meaning of FEV1 and the overall satisfaction with their knowledge of COPD.Results: Knowledge of FEV1 was higher in patients of higher spirometric GOLD grades or exacerbation risk, in males, with higher educational level, and after participation in a prior educational training on COPD. Patients with more detailed knowledge showed a higher satisfaction with their knowledge. Satisfaction was associated with higher generic quality of life and a lower CAT score. Furthermore, satisfaction was higher in patients with a treatment plan but lower in patients with cardiac comorbidities. It appeared that females with basic education, high burden from COPD and low quality of life had the greatest knowledge deficits.Discussion: The results suggest room for education programs adapted to the educational level of the participants. They also emphasize the major role of a disease management plan for the patients.Keywords: chronic obstructive pulmonary disease, knowledge, education, satisfaction

Background 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.

Background: Capnovolumetry is of interest as a method for the diagnosis of obstructive airway diseases, requiring little cooperation from the patient. Objective: To help in the interpretation of capnovolumetric parameters, we aimed to identify their correspondence to conventional lung function indices. Methods: We studied 978 patients from a diagnostic study with complete functional data and the clinical diagnosis of asthma, chronic obstructive pulmonary disease (COPD), or no respiratory disease. Using path analysis, four capnovolumetric parameters (slope of expiratory phase 3, ratio of slopes of phases 3 and 2, volume of phase 2, and the ratio area/volume of phase 3) previously identified as predictors of airway obstruction in terms of spirometry and body ple­thysmography, were analyzed regarding their relationship to each other and the diagnostic categories of asthma or COPD versus control, or obstruction versus no obstruction. We then identified four lung function parameters showing relationships as much as possible isomorphic to those between capnovolumetric parameters. Results: The four capnovolumetric parameters were related to COPD and obstruction via both direct and indirect influences, but only two of them to asthma. Regarding the correspondence to lung function parameters, the slope of expiratory phase 3 corresponded best to the ratio of residual volume to total lung capacity, the ratio of slopes of phases 3 and 2 to forced expiratory volume in 1 s, the volume of phase 2 to forced expired flow at 50% of vital capacity, and the ratio area/volume of phase 3 to forced vital capacity. Conclusions: Our results indicated an intricate relationship of capnovolumetric parameters to each other and to airway obstruction, asthma, or COPD. The correspondence to conventional lung function measures seemed to reflect the entities lung hyperinflation, overall ventilatory impairment, bronchoconstriction, and ventilated lung volume, in that order. These findings might be helpful for clinicians in the interpretation of capnovolumetry.

Subjects with obesity show an increased prevalence of airway obstruction but it is not clear in each case whether this reflects genuine lung disease. Via intentional increase in end-expiratory lung volume we studied the detection of obesity-induced airway obstruction in lung-healthy obese subjects.The primary study population comprised 66 lung-healthy obese subjects and 23 normal weight subjects. Measurements were performed in a body plethysmograph allowing for recording and quantification of breathing loops in terms of specific airway resistance at both normal and intentionally elevated end-expiratory lung volume. The change in volume was documented by a shutter maneuver.The voluntary increase of lung volume led to a significant reduction of expiratory airway resistance in 11 of the 66 obese subjects. This reduction could be quantified by a change of total expiratory resistance (sRtEX) of1 kPa*s but was also clearly visible in the breathing loops. sRtEX showed the largest change among all resistance parameters. The loops of normal weight subjects remained virtually unaffected by the change in lung volume. Moreover, those of 5 obese patients with COPD who were measured for comparison partially showed a reduction of resistance but airway obstruction remained.The proposed breathing maneuver was simple to perform and allowed for a quantitative and qualitative detection of obesity-induced airway obstruction. This might help in reducing the likelihood of misdiagnosis and overtreatment of obese patients.

Background In hospitalized patients with SARS-CoV-2 infection, outcomes markedly differ between locations, regions and countries. One possible cause for these variations in outcomes could be differences in patient treatment limitations (PTL) in different locations. We thus studied their role as predictor for mortality in a population of hospitalized patients with COVID-19. Methods In a region with high incidence of SARS-CoV-2 infection, adult hospitalized patients with PCR-confirmed SARS-CoV-2 infection were prospectively registered and characterized regarding sex, age, vital signs, symptoms, comorbidities (including Charlson comorbidity index (CCI)), transcutaneous pulse oximetry (SpO2) and laboratory values upon admission, as well as ICU-stay including respiratory support, discharge, transfer to another hospital and death. PTL assessed by routine clinical procedures comprised the acceptance of ICU-therapy, orotracheal intubation and/or cardiopulmonary resuscitation. Results Among 526 patients included (median [quartiles] age 73 [57; 82] years, 47% female), 226 (43%) had at least one treatment limitation. Each limitation was associated with age, dementia and eGFR (p 2, hemoglobin, leucocyte numbers, estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), Interleukin-6 and LDH were predictive for death (p 5 G/l, CRP > 7 mg/l and SpO2 Conclusion In hospitalized patients with SARS-CoV-2, the percentage of patients with treatment limitations was high. PTL were linked to age, comorbidities and eGFR assessed upon admission and strong, independent risk factors for mortality. These findings might be useful for further understanding of COVID-19 mortality and its regional variations. Clinical trial registration ClinicalTrials.gov Identifier: NCT04344171

Komorbiditaten haben einen masgeblichen Einfluss auf die Prognose von Patienten mit COPD. Deutschlands groste COPD-Kohorte COSYCONET liefert Erkenntnisse zu aktuellen Entwicklungen, insbesondere der Rolle von Symptomen und Exazerbationen, der Diagnostik wichtiger Stoffwechselerkrankungen sowie der Blutgasanalyse bei stabilen COPD-Patienten.

Background Adherence to COPD medication is often considered to be lower than in other chronic diseases. In view of the frequent comorbidities of COPD, the economic impact of nonadherence and the potential for adverse effects, a direct comparison between the adherence to respiratory and nonrespiratory medication in the same patients seems of particular interest. Objectives We aimed to investigate the intake of respiratory and nonrespiratory medication in the same patients with COPD and frequent comorbidities. Method Within the COPD cohort COSYCONET, we contacted 1042 patients, mailing them a list with all medication regarding all their diseases, asking for regular, irregular and non-intake. Results Valid responses were obtained in 707 patients covering a wide spectrum of drugs. Intake of LABA, LAMA or ICS was regular in 91.9% of patients, even higher for cardiovascular and antidiabetes medication but lower for hyperlipidemia and depression/anxiety medication. Regular intake of respiratory medication did not depend on GOLD groups A-D or grades 1-4, was highest in patients with concomitant cardiovascular disorders and was lowest for concomitant asthma. It was slightly larger for LAMA and LABA administered via combined compared to single inhalers, and lower when similar compounds were prescribed twice. Most differences did not reach statistical significance owing to the overall high adherence. Conclusion Our results indicate a high adherence to respiratory medication in participants of a COPD cohort, especially in those with cardiovascular comorbidities. Compared to the lower adherence reported in the literature for COPD patients, our observations still suggest some room for improvement, possibly through disease management programs.

Background In light of overall increasing healthcare expenditures, it is mandatory to study determinants of future costs in chronic diseases. This study reports the first longitudinal results on healthcare utilization and associated costs from the German chronic obstructive pulmonary disease (COPD) cohort COSYCONET. Material and methods Based on self-reported data of 1904 patients with COPD who attended the baseline and 18-month follow-up visits, direct costs were calculated for the 12 months preceding both examinations. Direct costs at follow-up were regressed on baseline disease severity and other co-variables to identify determinants of future costs. Change score models were developed to identify predictors of cost increases over 18 months. As possible predictors, models included GOLD grade, age, sex, education, smoking status, body mass index, comorbidity, years since COPD diagnosis, presence of symptoms, and exacerbation history. Results Inflation-adjusted mean annual direct costs increased by 5% (n.s., €6,739 to €7,091) between the two visits. Annual future costs were significantly higher in baseline GOLD grades 2, 3, and 4 (factors 1.24, 95%-confidence interval [1.07-1.43], 1.27 [1.09-1.48], 1.57 [1.27-1.93]). A history of moderate or severe exacerbations within 12 months, a comorbidity count >3, and the presence of dyspnea and underweight were significant predictors of cost increase (estimates ranging between + €887 and + €3,679, all p Conclusions Higher GOLD grade, comorbidity burden, dyspnea and moderate or severe exacerbations were determinants of elevated future costs and cost increases in COPD. In addition we identified underweight as independent risk factor for an increase in direct healthcare costs over time.

There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary TTo investigate the potential diagnostic value of TProspective non-randomized diagnostic study.Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference.Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for TPerfusion images were scored by three radiologists. TSpearman rank correlation coefficients (ρ) were calculated between TMedian values were TIn COPD patients, the increase of T2 TECHNICAL EFFICACY: Stage 1.

Background and Aims Chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD) represent global public health problems with high disease-related morbidity and mortality. However, the interaction between both diseases remains unclear. Method In a novel murine model, cigarette smoke (CS)-induced lung injury was combined with a CKD model (CS-CKD model). In 2,314 patients of the prospective multi-center COSYCONET study, urinary Dickkopf-3 (DKK3), a renal tubular stress marker, was quantified. The association between urinary DKK3 and trajectories of FEV1 and estimated glomerular filtration rate (eGFR), exercise capacity, risk of exacerbation, and mortality was determined (follow-up 37.1 months). Results In the CS-CKD model, CKD was associated with higher systemic and pulmonary inflammation, and the combination of CKD and CS significantly aggravated kidney inflammation as well as fibrosis and increased renal expression of DKK3. Abrogation of Dkk3 attenuated kidney injury and pulmonary inflammation alike. In COPD patients, higher urinary DKK3 was associated with rapidly declining FEV1 (OR 3.36, P Conclusion In summary, the present study identified a strong pathophysiological link between lung and kidney dysfunction, which is at least partially mediated by DKK3. Urinary DKK3 allows identification of COPD patients at increased risk for deteriorating pulmonary and kidney function as well as adverse outcomes. These patients might particularly benefit from preventive therapeutic strategies as a personalized-medicine approach.

Background Both allergen-specific IgE and total IgE in serum play a major role in asthma. However, the role of IgE in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts. Methods COSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specific to common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients. WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE in serum was elevated (≥ 100 IU/l) or normal in patients with COPD. Results Both in COSYCONET and WISDOM, total IgE was elevated (≥ 100 IU/l) in > 30% of the patients, higher in men than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6% of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this difference was also observed in the subgroups of not currently smoking men and of men without a history of asthma. Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest tertiles of total IgE (> 91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12–2.34) or allergen-specific IgE (> 0.19 IU/ml, adjusted OR: 2.15, 95% CI 1.32–3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung function, smoking status, history of asthma, history of allergy). Conclusion These data suggest that IgE may play a role in specific COPD subgroups. Clinical trials using antibodies targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum IgE, could elucidate potential therapeutic implications of our observations.

BACKGROUND: Lung function impairment in COPD is known to be related to reductions of left heart size, while short-term interventional trials with bronchodilators showed positive effects on cardiac parameters. We investigated whether COPD maintenance therapy has analogous long-term effects. METHODS: Pooled data of GOLD grade 1-4 patients from visits 1 and 3 (1.5y apart) of the COSYCONET cohort were used. Medication was categorized as use of ICS, LABA+ICS, LABA+LAMA and triple therapy (LABA+LAMA+ICS), contrasting "always" versus "never". Echocardiographic parameters comprised left ventricular end-diastolic and -systolic diameter (LVEDD, LVESD), ejection fraction (LVEF) and left atrial diameter (LA). Associations were identified by multiple regression analysis, as well as propensity score analysis. RESULTS: Overall, 846 patients (mean age 64.5y; 41% female) were included, 53% using ICS at both visits, 51% LABA+ICS, 56% LABA+LAMA, 40% LABA+LAMA+ICS (triple) therapy. Conversely, 30%, 32%, 28% and 42% had no ICS, LABA+ICS, LABA+LAMA or triple therapy, respectively, at both visits. Among echocardiographic measures, only LA showed statistically significant associations (increases) with medication, whereby significant effects were linked to ICS, LABA+ICS and LABA+LAMA (p&nbsp

IntroductionThe measurement of fractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and might substitute for bronchial provocation (BP) tests. To evaluate the diagnostic accuracy of FeNO within a confirmatory study, the following hypotheses will be tested: (1) A FeNO cut-off >50 ppb (parts per billion) is suitable for diagnosing asthma (sensitivity 35%, specificity 95%); (2) If the clinical symptoms ‘allergic rhinitis’ and ‘wheezing’ are present, asthma can be diagnosed at FeNO >33 ppb with a positive predictive value (PPV) >70% and (3) A FeNO >33 ppb can predict responsiveness to inhaled corticosteroid (ICS) with a PPV >70%.Methods and analysisA prospective diagnostic study will be conducted in three practices of pneumologists in Germany. 300 patients suspected of suffering from asthma will be included. As an index test, patients perform FeNO measurement with the device NIOX VERO. As reference a test, patients are examined with whole bodyplethysmography and BP, if necessary. After 3 months, patients with an asthma diagnosis will be examined again to verify the diagnosis and evaluate ICS responsiveness. Patients who did not receive an asthma diagnosis at the initial examination will be phoned after 3 months and asked about persistent respiratory symptoms to exclude false negative findings. As a primary target, sensitivity and specificity of FeNO >50 ppb will be determined. As a secondary target the PPV for asthma at FeNO >33 ppb, when the symptoms ‘allergic rhinitis’ and ‘wheezing’ are present, will be calculated. Regarding ICS responsiveness, the PPV of FeNO >33 ppb will be determined.Ethics and disseminationThe study was approved by the Ethical Committee of the Technical University of Munich (Reference number 122/20 S). The major results will be published in peer-reviewed academic journals and disseminated through conferences.Trial registration numberDRKS00021125.

Background In chronic obstructive pulmonary disease (COPD), gender-specific differences in the prevalence of symptoms and comorbidity are known. Research question We studied whether the relationship between these characteristics depended on gender and carried diagnostic information regarding cardiac comorbidities. Study design and methods The analysis was based on 2046 patients (GOLD grades 1–4, 795 women; 38.8%) from the COSYCONET COPD cohort. Assessments comprised the determination of clinical history, comorbidities, lung function, COPD Assessment Test (CAT) and modified Medical Research Council dyspnea scale (mMRC). Using multivariate regression analyses, gender-specific differences in the relationship between symptoms, single CAT items, comorbidities and functional alterations were determined. To reveal the relationship to cardiac disease (myocardial infarction, or heart failure, or coronary artery disease) logistic regression analysis was performed separately in men and women. Results Most functional parameters and comorbidities, as well as CAT items 1 (cough), 2 (phlegm) and 5 (activities), differed significantly (p Interpretation Gender-specific differences in COPD not only comprised differences in symptoms, comorbidities and functional alterations, but also differences in their mutual relationships. This was reflected in different determinants linked to cardiac disease, thereby indicating that simple diagnostic information might be used differently in men and women. Clinical trial registration The cohort study is registered on ClinicalTrials.gov with identifier NCT01245933 and on GermanCTR.de with identifier DRKS00000284, date of registration November 23, 2010. Further information can be obtained on the website http://www.asconet.net.

Background In general practice (GP), the diagnosis of obstructive airway diseases much relies on diagnostic questions, in view of the limited availability of lung function. We systematically assessed the relative importance of such questions for diagnosing asthma and chronic obstructive pulmonary disease (COPD), either without or with information from spirometry. Methods We used data obtained in a pulmonary practice to ensure the validity of diagnoses and assessments. Subjects with a diagnosis of COPD (n=260), or asthma (n=433), or other respiratory diseases (n=230), and subjects without respiratory diseases (n=364, controls) were included. The diagnostic questions comprised eight items, covering smoking history, self-attributed allergic rhinitis, dyspnea, cough, phlegm and wheeze. Optionally standard parameters of the flow-volume-curve were included. Decision trees for the diagnosis of COPD and asthma were constructed, moreover a probabilistic diagnostic network based on the results of path analyses describing the relationship between variables. Results In the decision trees, age, sex, current smoking, wheezing, dyspnea upon mild exertion, self-attributed allergic rhinitis, phlegm, forced expiratory volume in one second (FEV1), and expiratory flow rates were relevant, depending on the diagnostic comparison, while cough, dyspnea upon strong exertion and ex-smoker status were not relevant. In contrast, the probabilistic network for the diagnosis of COPD and asthma versus controls incorporated all diagnostic questions, i.e., dyspnea upon mild or strong exertion, current smoking, ex-smoking, wheezing, cough and phlegm but from spirometry only FEV1. Depending on the individual pattern, the probability for COPD could raise from 25% to 81%, while the diagnostic gain for asthma was lower. Conclusions The study developed simple diagnostic algorithms for asthma and COPD that take into account the relative importance of clinical signs and history, as well as spirometric data if available. The diagnostic accuracy was especially high for COPD. These algorithms may be helpful as a starting point in the standardisation of diagnostic strategies in GP practices. Trial registration The study is registered under DRKS00013935 at German Clinical Trials Register (DRKS, Date of registration 01/03/2018).

OBJECTIVES: The objective of the study is to determine the impact of changing reference standards (RS), namely spirometry vs. whole-body plethysmography (WBP), on estimation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and clinical signs and symptoms (CSS) as index tests regarding asthma diagnosis. STUDY DESIGN AND SETTING: This was a diagnostic study conducted in 393 patients attending a private practice of pneumologists with complaints suspicious of asthma. First, the index tests were compared with the diagnostic results of spirometry in terms of forced expiratory volume in the first second (FEV1) responsiveness. Second, the index tests were compared with the results of WBP in terms of specific airway resistance and FEV1 responsiveness. Areas under the curve (AUC) were compared with a generalized estimating equation approach based on binary logistic regression. RESULTS: FeNO values and CSS 'wheezing' and 'allergic rhinitis' showed higher specificities (P

Background It has been reported that canine scent tests offer the possibility to screen for cancer. Assuming that breath samples can be collected with carrier materials, we tested the practicability of different carrier materials to be presented to dogs, and validated and compared results with an eNose. Moreover, we hypothesised that cancer detection ability of dogs differs according to their working experience. Materials and Methods In a methodological approach two dog teams participated, one using experienced working dogs and the other ordinary household dogs to find discover which dogs were better qualified and the best training method. To find best carrier material for breath sampling we compared charcoal containing glass tubes with fleece masks. In a second validating part, experienced working dogs were trained with improved training strategies. For breath sampling two different, previously successfully tested fleece-based carrier materials were used: one was used with the dog team and both materials were compared with eNose. Results In the first part of the study it was shown overall that experienced working dogs performed better to family dogs and the dogs achieved a sensitivity of 45–59% and a specificity of 45–69%. Charcoal based breath sample carrier materials did not qualify for detection of VOC by dogs. In the second part of the study, the dogs achieved a specificity of 83% and a sensitivity of 56%, but with considerable differences between individual dogs. The eNose provided a specificity of 97% for both fleece based carrier materials and a sensitivity of 89% for fleece filled glass tubes and 100% for earloop masks. Measurements of breath samples collected directly in respiratory bags as reference measurements achieved a sensitivity and specificity of 100%. Conclusions Our data confirmed that diagnostic accuracy of dogs depended on the type of dog training and on the carrier materials. A comparison of breath samples analysis with an eNose achieved better results for both, sensitivity and specificity, than for dogs. The use of fleece masks or fleeces in glass tubes as a sampling material can be recommended as successful VOC carriers, encouraging their use for clinical screenings. Disclosure Information W. Biehl: None. H. Schmetzer: None. R. Koczulla: None. A. Hattesohl: None. R. Jorres: None. T. Duell: None. U. Althohn: None.

Background: Patients with COPD-specific symptoms and history but FEV1/FVC ratio ≥0.7 are a heterogeneous group (former GOLD grade 0) with uncertainties regarding natural history. Objective: We investigated which lung function measures and cutoff values are predictive for deterioration according to GOLD grades and all-cause mortality. Methods: We used visit 1–4 data of the COSYCONET cohort. Logistic and Cox regression analyses were used to identify relevant parameters. GOLD 0 patients were categorized according to whether they maintained grade 0 over the following 2 visits or deteriorated persistently into grades 1 or 2. Their clinical characteristics were compared with those of GOLD 1 and 2 patients. Results: Among 2,741 patients, 374 GOLD 0, 206 grade 1, and 962 grade 2 patients were identified. GOLD 0 patients were characterized by high symptom burden, comparable to grade 2, and a restrictive lung function pattern; those with FEV1/FVC above 0.75 were unlikely to deteriorate over time into grades 1 and 2, in contrast to those with values between 0.70 and 0.75. Regarding mortality risk in GOLD 0, FEV1%predicted and age were the relevant determinants, whereby a cutoff value of 65% was superior to that of 80% as proposed previously. Conclusions: Regarding patients of the former GOLD grade 0, we identified simple criteria for FEV1/FVC and FEV1% predicted that were relevant for the outcome in terms of deterioration over time and mortality. These criteria might help to identify patients with the typical risk profile of COPD among those not fulfilling spirometric COPD criteria.

Background: Lung hyperinflation is major determinant of prognosis and response to therapy in COPD. It is linked to air trapping and usually determined by body plethysmography or gas dilution. As the availability of these methods is limited, the question arises to which extent hyperinflation can be estimated from spirometry. Methods: We used data from patients of GOLD grades 1–4 obtained in Visits 1–5 of the COPD cohort COSYCONET. Predictive parameters were derived from Visit 1 data, while Visit 2–5 data were used to assess reproducibility. Data from all visits were pooled to determine prediction models for males and females, including age, height and BMI as covariates. Hyperinflation was defined as residual volume to total lung capacity ratio (RV/TLC) above the ULN. Results: Visit 1 data from 1988 patients were available for analysis (FEV1 53.1±18.4 %pred; FVC 78.8±18.8 %pred; RV/TLC 0.547±0.107). In total, 7157 data sets were analyzed. Among measures of hyperinflation, RV/TLC turned out to be most reliable, with FEV1 %pred and FVC %pred being sufficient for prediction. Their relationship to RV/TLC could be depicted in nomograms. Even when neglecting the effects of covariates, RV/TLC above ULN could be predicted by FEV1 %pred, FVC %pred or their combination with an AUC of 0.882, 0.869 and 0.899. Other parameters, i.p. slow inspiratory vital capacity, did not play a role. Conclusions: The degree of hyperinflation in terms of RV/TLC can be estimated from forced spirometry, with an accuracy sufficient for inferring the presence of significant hyperinflation defined by RV/TLC above the upper limit of normal. This may be useful for clinical settings, where body plethysmography is not available.

Background: Progressive hypoxemia is a hallmark of fibrosing interstitial lung disease (fILD). OxyHem is a simple-to-measure correlate of oxygen content. We aimed to assess whether OxyHem correlates with outcomes in fILD. Methods: The database of our center was reviewed for fILDs. OxyHem (g/dL) was calculated as Hb x fractional SaO2. Clinical and functional data with absolute declines of FVC≥10% and/or DLCO≥15% were retrospectively analysed. Predictive values were evaluated by binary logistic and Cox regression analyses with age, gender, BMI, DLCO and FVC as covariates. Results:650 fILD patients (29% IPF, 28.6% cHP, 12.4% iNSIP, 16.3% uILD, 9.2% RA-ILD, 4.3% other ILD; 63.3% male, mean age 68.4 years) were analysed. The mean follow-up period was 16.8 months. Mean FVC was 74.4%pred., and 29.3% of patients showed a FVC decline ≥10%. OxyHem (mean13.4±1.4 g/dL) was strongly related to FVC decline ≥10% (odds ratio 1.33, p=0.0002) and also an independent predictor of the first occurrence of FVC decline ≥10% (hazards ratio [HR] 1.53, p=0.003). No similar relationships were observed for DLCO decline. Mortality was analysed in the IPF subgroup, in which 31/187 patients (16.4%) died. OxyHem Conclusion: OxyHem is an independent predictor of disease progression and outcomes in fILD. Future work has to validate these findings in larger cohorts.

Background: Bronchiectasis is known to be associated with COPD. We studied which degree of radiological alterations was associated with clinical signs of bronchiectasis in COPD. Methods: Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was analysed. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0-2), resulting in a total score of 0-12. We also included data from disease-specific questionnaires, medication, and lung function. Results: 1176 patients were included (mean age 67.3y, 61.1% males), among them 38 (3.2%) with patient-reported physicians’ diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). 429 patients had CT scans, with any signs of bronchiectasis in 46.6%, less than 50% bronchiectasis in ≤2 lobes in 18.6%, in 3-4 lobes in 10.0%, in 5-6 lobes in 15.9%, and more than 50% bronchiectasis in at least 1 lobe in 2.1%. Scores ≥4 were linked to elevated FRC/RV. Links to sputum production, composition (n=105) or inflammatory indices were borderline or absent. Triple therapy was associated with symptoms, but not radiological signs of bronchiectasis. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. AA1D was associated with radiological signs of bronchiectasis and only borderline with the clinical diagnosis. Conclusion: Clinical diagnosis and radiological signs of bronchiectasis showed only weak correlations in COPD patients. For a significant correspondence to symptoms and diagnosis, a threshold CT score implying radiological alterations in several lobes was needed, which was about one third of the maximum score.

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by multiple subtypes and variable disease progression. While FEV1 is an insufficient candidate for the prediction of disease progression, we investigated, whether copeptin correlates with clinical endpoints and mortality. Methods: We measured copeptin in plasma samples of 1 patients with stable COPD (GOLD 0-4, GOLD A-D) from the German COPD cohort study COSYCONET. Results: In the cross sectional analysis of a linear regression model that considers age, BMI, Gender, cardiovascular index, and packyears of smoking as confounders, copeptin correlated with the impairment of: airway obstruction (FEV1, sRawTot) (p Discussion/Conclusion: While previous groups studied copeptin in patients with COPD exacerbations, we provide evidence that copeptin is a suitable biomarker for all-cause mortality in stable COPD taking into account many covariates.

Background 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.

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of death, reducing life expectancy on average between 5 and 7 years. The survival time after diagnosis, however, varies considerably as a result of the heterogeneity of COPD. Therefore, markers that predict individual survival of COPD patients are of great value. We analyzed baseline molecular profiles and collected 54 months of follow-up data of the cohort study &ldquo, COPD and SYstemic consequences-COmorbidities NETwork&rdquo, (COSYCONET). Genome-wide microRNA signatures from whole blood collected at time of the inclusion in the study were generated for 533 COPD patients including patients that deceased during the 54-month follow-up period (n = 53) and patients that survived this period (n = 480). We identified two blood-born microRNAs (miR-150-5p and miR-320b) that were highly predictive for survival of COPD patients. The expression change was then confirmed by RT-qPCR in 245 individuals. Ninety percent of patients with highest expression of miR-150-5p survived the 54-month period in contrast to only 50% of patients with lowest expression intensity. Moreover, the abundance of the oncogenic miR-150-5p in blood of COPD patients was predictive for the development of cancer. Thus, molecular profiles measured at the time of a COPD diagnosis have a high predictive power for the survival of patients.

Background and Aims Chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD) represent a global public health problem worldwide. As such, both conditions are associated with high disease-related morbidity and mortality. However, it is unclear whether the presence of CKD aggravates the clinical course of COPD and vice versa. Method In a novel murine model of cigarette smoke (CS)-induced lung injury combined with an adenine nephropathy model, kidney and lung inflammation, and fibrosis were studied. Moreover, in 2,314 patients with stable COPD enrolled in the prospective, multi-centre COSYCONET study, urinary Dickkopf-3 (DKK3), a biomarker of kidney injury and CKD progression was quantified. The association between urinary DKK3 and trajectories of forced expiratory pressure in 1 second (FEV1) and estimated glomerular filtration rate (eGFR) during a median follow-up of 37.1 months, exercise capacity, risk of exacerbation, and mortality was determined. Results In the CKD-COPD animal model, the presence of kidney injury was associated with increased systemic and pulmonary inflammation, impaired pulmonary function, as well as more severe damage of the lung architecture. Moreover, CS enhanced kidney fibrosis. Accordingly, in the COPD patients from the COSYCONET study, higher urinary DKK3 was associated with declining FEV1 during follow-up (OR 3.36, 95% CI 2.22-5.08). Moreover, high urinary DKK3 was associated with higher risk for exacerbation (OR 1.24, 95% CI 1.03-1.50), lower 6-minute walking distance, and higher all-cause mortality (HR 1.49, 95% CI 1.08-2.05). Importantly, high urinary DKK3 was associated with declining eGFR during follow-up (OR 2.23, 95% CI 1.22-4.07) independently from baseline kidney function and proteinuria, which was confirmed by a machine learning approach. Conclusion These data uncover a novel pathophysiological link between CKD and COPD. Patient with COPD and concomitant CKD are at high risk for worsening pulmonary function and adverse outcomes. Elevated urinary DKK3 allows identification of COPD patients with progressive CKD. Measurement of urinary DKK3 in patients with COPD may therefore represent a novel tool for risk stratification and the identification of patients, who might in particular benefit from preventive therapeutic strategies to prevent progression of COPD and CKD as well.

Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0: absence, 1: ≤50%, 2: >50% BE-involvement for each lobe). 1176 patients were included (61%male, age 67.3y), among them 38 (3.2%) with reported physicians' diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). CT scans were obtained in 429 patients. Within this group, any signs of bronchiectasis were found in 46.6% of patients, whereby ≤50% BE occurred in 18.6% in ≤2 lobes, in 10.0% in 3-4 lobes, in 15.9% in 5-6 lobes; >50% bronchiectasis in at least 1 lobe was observed in 2.1%. Scores ≥4 correlated with an elevated ratio FRC/RV. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. In COPD patients, clinical diagnosis and radiological signs of BE showed only weak correlations. Correlations became significant with increasing BE-severity implying radiological alterations in several lobes. This indicates the importance of reporting both presence and extent of bronchiectasis on CT. Further research is warranted to refine the criteria for CT scoring of bronchiectasis and to determine the relevance of radiologically but not clinically detectible bronchiectasis and their possible implications for therapy in COPD patients.

Background: Guidelines for chronic obstructive pulmonary disease (COPD) recommend supplementing pharmacotherapy with non-pharmacological interventions. Little is known about the use of such interventions by patients. We analyzed the utilization of a number of non-pharmacological interventions and identified potential determinants of use.Methods: Based on self-reports, use of interventions (smoking cessation, influenza vaccination, physiotherapy, sports program, patient education, pulmonary rehabilitation) and recommendation to use were assessed in 1410 patients with COPD. The utilization was analyzed according to sex and severity of disease. Potential determinants of utilization included demographic variables and disease characteristics and were analyzed using logistic regression models.Results: Influenza vaccination in the previous autumn/winter was reported by 73% of patients. About 19% were currently participating in a reimbursed sports program, 10% received physiotherapy, 38% were ever enrolled in an educational program, and 34% had ever participated in an outpatient or inpatient pulmonary rehabilitation program. Out of 553 current or former smokers, 24% had participated in a smoking cessation program. While reports of having received a recommendation to use mainly did not differ according to sex, women showed significantly (p < 0.05) higher utilization rates than men for all interventions except influenza vaccination. Smoking was a predictor for not having received a recommendation for utilization and also significantly associated with a reduced odds of utilization. We found a correlation between recommendation to use and utilization.Conclusions: Utilization of non-pharmacological interventions was lower in men and smokers. A recommendation or offer to use by the physician could help to increase uptake.

The COPD Assessment Test (CAT) is in widespread use for the evaluation of patients with chronic obstructive pulmonary disease (COPD). We assessed whether the CAT items carry additional information beyond the sum score regarding COPD characteristics including emphysema. Patients of GOLD grades 1 to 4 from the COPD cohort COSYCONET (German COPD and Systemic Consequences - Comorbidities Network) with complete CAT data were included (n = 2270), of whom 493 had chest CT evaluated for the presence of emphysema. Comorbidities and lung function were assessed following standardised procedures. Cross-sectional data analysis was based on multiple regression analysis of the single CAT items against a panel of comorbidities, lung function, or CT characteristics (qualitative score, 15th percentile of mean lung density), with age, BMI and gender as covariates. This was supported by exploratory factor analysis. Regarding the relationship to comorbidities and emphysema, there were marked differences between CAT items, especially items 1 and 2 versus 3 to 8. This grouping was basically confirmed by factor analysis. Items 4 and 5, and to a lower degree 1, 2 and 6, appeared to be informative regarding the presence of emphysema, whereas the total score was not or less informative. Regarding comorbidities, similar findings as for the total CAT score were obtained for the modified Medical Research Council scale (mMRC) which was also informative regarding emphysema. Our findings suggest that the usefulness of the CAT can be increased if evaluated on the basis of single items which may be indicating the presence of comorbidities and emphysema.

Background Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. Methods We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. Results 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. Conclusion We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.

Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls. Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers. We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type. From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history. Genome-wide miRNA profiles were generated and evaluated using machine learning techniques. For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P