The impact of COPD on polyneuropathy : results from the German COPD cohort COSYCONET

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

Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD: Results from COSYCONET

We studied whether in patients with stable COPD blood gases (BG), especially oxygenated hemoglobin (OxyHem) as a novel biomarker confer information on disease burden and prognosis and how this adds to the information provided by the comorbidity pattern and systemic inflammation. Data from 2137 patients (GOLD grades 1-4) of the baseline dataset of the COSYCONET COPD cohort were used. The associations with dyspnea, exacerbation history, BODE-Index (cut-off 8000/mu L was 2.33 (95% CI: 1.60-3.39, p<0.0001). In stable COPD, the concentration of oxygenated hemoglobin provided additional information on disease state, especially mortality risk. OxyHem can be calculated from hemoglobin concentration and oxygen saturation without the need for the measurement of PaO2. It thus appears well suited for clinical use with minimal equipment, especially for GPs

Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD : Results from COSYCONET

We studied whether in patients with stable COPD blood gases (BG), especially oxygenated hemoglobin (OxyHem) as a novel biomarker confer information on disease burden and prognosis and how this adds to the information provided by the comorbidity pattern and systemic inflammation. Data from 2137 patients (GOLD grades 1–4) of the baseline dataset of the COSYCONET COPD cohort were used. The associations with dyspnea, exacerbation history, BODE-Index (cut-off ≤2) and all-cause mortality over 3 years of follow-up were determined by logistic and Cox regression analyses, with sex, age, BMI and pack years as covariates. Predictive values were evaluated by ROC curves. Capillary blood gases included SaO2, PaO2, PaCO2, pH, BE and the concentration of OxyHem [haemoglobin (Hb) x fractional SaO2, g/dL] as a simple-to-measure correlate of oxygen content. Inflammatory markers were WBC, CRP, IL-6 and -8, TNF-alpha and fibrinogen, and comorbidities comprised a broad panel including cardiac and metabolic disorders. Among BG, OxyHem was associated with dyspnoea, exacerbation history, BODE-Index and mortality. Among inflammatory markers and comorbidities, only WBC and heart failure were consistently related to all outcomes. ROC analyses indicated that OxyHem provided information of a magnitude comparable to that of WBC, with optimal cut-off values of 12.5 g/dL and 8000/µL, respectively. Regarding mortality, OxyHem also carried independent, additional information, showing a hazard ratio of 2.77 (95% CI: 1.85–4.15, p  8000/µL was 2.33 (95% CI: 1.60–3.39, p < 0.0001). In stable COPD, the concentration of oxygenated hemoglobin provided additional information on disease state, especially mortality risk. OxyHem can be calculated from hemoglobin concentration and oxygen saturation without the need for the measurement of PaO2. It thus appears well suited for clinical use with minimal equipment, especially for GPs

Pirfenidone vs. nintedanib in patients with idiopathic pulmonary fibrosis: A retrospective cohort study.

Background: Two antifibrotic drugs, pirfenidone and nintedanib, are licensed for the treatment of patients with idiopathic pulmonary fibrosis (IPF). However, there is neither evidence from prospective data nor a guideline recommendation, which drug should be preferred over the other. This study aimed to compare pirfenidone and nintedanib-treated patients regarding all-cause mortality, all-cause and respiratory-related hospitalizations, and overall as well as respiratory-related health care costs borne by the Statutory Health Insurance (SHI). Methods: A retrospective cohort study with SHI data was performed, including IPF patients treated either with pirfenidone or nintedanib. Stabilized inverse probability of treatment weighting (IPTW) based on propensity scores was applied to adjust for observed covariates. Weighted Cox models were estimated to analyze mortality and hospitalization. Weighted cost differences with bootstrapped 95% confidence intervals (CI) were applied for cost analysis. Results: We compared 840 patients treated with pirfenidone and 713 patients treated with nintedanib. Both groups were similar regarding two-year all-cause mortality (HR: 0.90 95% CI: 0.76; 1.07), one-year all cause (HR: 1.09, 95% CI: 0.95; 1.25) and respiratory-related hospitalization (HR: 0.89, 95% CI: 0.72; 1.08). No significant differences were observed regarding total (€−&nbsp;807, 95% CI: €−&nbsp;2977; €1220) and respiratory-related (€−&nbsp;1282, 95% CI: €−&nbsp;3423; €534) costs. Conclusion: Our analyses suggest that the patient-related outcomes mortality, hospitalization, and costs do not differ between the two currently available antifibrotic drugs pirfenidone and nintedanib. Hence, the decision on treatment with pirfenidone versus treatment with nintedanib ought to be made case-by-case taking clinical characteristics, comorbidities, comedications, individual risk of side effects, and patients’ preferences into account

Treatment of COPD Groups GOLD A and B with inhaled corticosteroids in the COSYCONET cohort - determinants and consequences.

Background: In COPD patients of GOLD groups A and B, a high degree of treatment with inhaled corticosteroids (ICS) has been reported, which is regarded as overtreatment according to GOLD recommendations. We investigated which factors predict ICS use and which relationship it has to clinical and functional outcomes, or healthcare costs. Methods: We used pooled data from visits 1 and 3 of the COSYCONET cohort (n=2741, n=2053, interval 1.5 years) including patients categorized as GOLD grades 1-4 and GOLD group A or B at both visits (n=1080). Comparisons were performed using ANOVA, and regression analyses using propensity matching and inverse probability weighting to adjust for differences between ICS groups. These were defined as having ICS at both visits (always) vs no ICS at both visits (never). Measures were divided into predictors of ICS treatment and outcomes. Results: Among 1080 patients, 608 patients were eligible for ICS groups (n=297 never, n=311 always). Prior to matching, patients with ICS showed significantly (p&lt;0.05 each) impaired lung function, symptoms and exacerbation history. After matching, the outcomes generic quality of life and CO diffusing capacity were increased in ICS patients (p&lt;0.05 each). Moreover, costs for respiratory medication, but not total health care costs, were significantly elevated in the ICS group by 780€ per year. Conclusion: ICS therapy in COPD GOLD A/B patients can have small positive and negative effects on clinical outcomes and health care costs, indicating that the clinical evaluation of ICS over-therapy in COPD requires a multi-dimensional approach

Gender-specific differences in COPD symptoms and their impact for the diagnosis of cardiac comorbidities.

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 &lt; 0.05) between men and women. Beyond this, the relationship between functional parameters and comorbidities versus symptoms showed gender-specific differences, especially for single CAT items. In men, item 8 (energy), mMRC, smoking status, BMI, age and spirometric lung function was related to cardiac disease, while in women primarily age was predictive. 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

Midregional proatrial naturetic peptide (MRproANP) and copeptin (COPAVP) as predictors of all-cause mortality in recently diagnosed mild to moderate COPD—results from COSYCONET

Abstract Background MRproANP and COPAVP are prognostic markers for mortality in chronic obstructive pulmonary disease (COPD). Furthermore, these biomarkers predict mortality due to cardiovascular diseases, which are important prognostically determining comorbidities in patients with COPD. However, less is known about these biomarkers in recently diagnosed mild to moderate COPD. Therefore, we analyzed these biomarkers as potential predictors of mortality in recently diagnosed mild to moderate COPD. Methods The blood biomarkers considered were copeptin (COPAVP), midregional adrenomedullin (MRproADM), midregional proatrial naturetic peptide (MRproANP), and fibrinogen. Analyses were performed in patients with stable “recently diagnosed mild to moderate COPD” defined by GOLD grades 0–2 and diagnosis of COPD ≤ 5 years prior to inclusion into the COSYCONET cohort (COPD and Systemic Consequences—Comorbidities Network), using Cox regression analysis with stepwise adjustment for multiple COPD characteristics, comorbidities, troponin and NT-proBNP. Results 655 patients with recently diagnosed mild to moderate COPD were included. In the initial regression model, 43 of 655 patients died during the 6-year follow-up, in the final model 27 of 487. Regression analyses with adjustment for confounders identified COPAVP and MRproANP as statistically robust biomarkers (p < 0.05 each) of all-cause mortality, while MRproADM and fibrinogen were not. The fourth quartile of MRproANP (97 pmol/L) was associated with a hazard ratio of 4.5 (95%CI: 1.6; 12.8), and the fourth quartile of COPAVP (9.2 pmol/L) with 3.0 (1.1; 8.0). The results for MRproANP were confirmed in the total cohort of grade 0–4 (n = 1470 finally). Conclusion In patients with recently diagnosed mild to moderate COPD, elevated values of COPVP and in particular MRproANP were robust, independent biomarkers for all-cause mortality risk after adjustment for multiple other factors. This suggests that these markers might be considered in the risk assessment of early COPD

Additional file 1 of Midregional proatrial naturetic peptide (MRproANP) and copeptin (COPAVP) as predictors of all-cause mortality in recently diagnosed mild to moderate COPD—results from COSYCONET

Additional file 1: Table S1. Results of consecutive Cox regression analyses in all patients of grades GOLD 0-4. Hazard ratios are given for the respective biomarkers in the upper quartile versus the three lower quartiles. * Age, BMI, FEV1% predicted, TLCO % predicted, SGRQ total score, 6-minute walking distance, ≥1 moderate/severe exacerbations in the previous year, smoking status, pack years, hypercapnia (PaCO2 >55 mmHg), hypoxemia (PaO2 <60 mmHg). ** All variables of model 2 plus sex, hypertension, diabetes, hyperlipidemia, log HbA1c, and log CRP. *** All variables of model 3 plus heart failure, coronary artery disease, history of myocardial infarction, history of stroke, ankle-brachial index ≤0.90, log NT-proBNP, left-ventricular ejection fraction from echocardiography