Matthias Urban

Soluble receptor of advanced glycation end-products and endothelial dysfunction in COPD

BACKGROUND Chronic obstructive pulmonary disease (COPD) is accompanied by an increased cardiovascular risk which is aggravated by the incidence of acute exacerbations (AE). Endothelial function, as well as the soluble receptor for advanced glycation end-products (sRAGE), both markers of cardiovascular risk, has been shown to be decreased in stable COPD. OBJECTIVES We aimed to investigate a possible link between sRAGE and endothelial function in AE of COPD. We hypothesize that circulating levels of sRAGE and endothelial function are impaired during AE and improve after clinical recovery, respectively. METHODS We enrolled patients admitted to hospital due to an AE of COPD without overt cardiovascular comorbidities. Study related procedures comprised spirometry, measurement of plasma sRAGE levels and the quantification of endothelial function by means of the flow-mediated dilation technique (FMD). All measurements were scheduled during hospitalization and after confirmed clinical stability. RESULTS We recruited 29 patients (27% female) with moderate to severe COPD. Median sRAGE concentration was 525 pg/mL (371-770, 1st-3rd quartile) and mean FMD 6.7 ± 3.6% at AE. There was a significant increase of sRAGE levels to 876 pg/mL (633-1371, 1st-3rd quartile, p < 0.001) and a simultaneous improvement in FMD (10.0 ± 3.4%, p < 0.001) after clinical recovery. There was a significant positive association between sRAGE and FMD (regression coefficient = 2.43; p = 0.01) in our study sample. CONCLUSION Our results indicate a substantial decrease in sRAGE levels and endothelial function during AE, with evidence of improvements after clinical recovery. sRAGE may contribute to cardiovascular risk in COPD.

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD

Background Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls. Methods The study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score. Results Patients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample. Conclusion B-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels.

Tobacco addiction and smoking cessation in Austrian migrants: a cross-sectional study

Objective Recent observations revealed substantial differences in smoking behaviour according to individuals’ migration background. However, smoking cessation strategies are rarely tailored on the basis of a migration background. We aimed to determine whether smoking behaviour and preferences for smoking cessation programmes differ between Austrian migrant smokers and Austrian smokers without a migration background. Study design Cross-sectional study. Setting Recruitment and interview were performed at public places in Vienna, Austria. Participants The 420 smokers included: 140 Bosnian, 140 Turkish migrant smokers of the first or second generation, as well as 140 Austrian smokers without a migration background. Methods We cross-sectionally assessed determinants of smoking behaviour and smoking cessation of every participant with a standardised questionnaire. Primary outcome measure The Fagerström Test for Nicotine Dependence. Secondary outcome measures Determinants of smoking behaviour, willingness to quit smoking and smoking cessation. Results Nicotine addiction expressed via the Fagerström score was significantly higher in smokers with a migration background versus those without (Bosnian migrant smokers 4.7±2.5, Turkish migrant smokers 4.0±2.0, Austrian smokers without a migration background 3.4±2.3, p<0.0001). Bosnian and Turkish migrant smokers described a greater willingness to quit, but have had more previous cessation trials than Austrian smokers without a migration background, indicating an increased demand for cessation strategies in these study groups. They also participated in counselling programmes less often than Austrian smokers without a migration background. Finally, we found significant differences in preferences regarding smoking cessation programmes (ie, preferred location, service offered in another language besides German, and group rather than single counselling). Conclusions We found significant differences in addictive behaviour and cessation patterns between smokers with and without a migration background. Our results indicate a strong demand for adjusting cessation programmes to the cultural background.

Effects of Roflumilast on subclinical atherosclerosis in COPD - a randomized controlled trial

Background: COPD is associated with an excess atherosclerotic risk. Both, COPD and atherosclerosis are mediated by systemic inflammation. Roflumilast, as an anti-inflammatory drug, revealed potential atheroprotective effects in patients with COPD. Aims: To investigate the effects of Roflumilast on subclinical atherosclerosis (i.e. arterial stiffness, endothelial dysfunction) and a potential association with systemic inflammation in COPD. Methods: 80 COPD patients were randomized to receive Roflumilast or placebo for 24 weeks. Arterial stiffness was measured by pulse wave velocity (PWV) and augmentation index (AIx). Endothelial dysfunction was assessed via reactive hyperemia index (RHI), circulating levels of asymmetric dimethylarginine (ADMA) and matrix metalloproteinase-9 (MMP-9). Systemic inflammation was quantified by C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Results: 67 patients completed the study, 33 of which received Roflumilast and 34 received placebo. The primary endpoint, change from baseline PWV, did not show a significant difference between Roflumilast and placebo (1.07 [95% CI 0.98 – 1.17] vs. 0.99 [95% CI 0.91 – 1.08], p = 0.214). Roflumilast did not improve AIx or markers of endothelial dysfunction (RHI, ADMA, MMP-9) and systemic inflammation (CRP, IL-6, TNF-alpha). We observed a significant improvement of 6-minute walking test with Roflumilast compared to placebo (59.2 [95% CI 18.3 – 100] vs. 0.69 [95% CI -39.7 – 42.1], p = 0.045). Conclusions: Our study does not support an atheroprotective effect of Roflumilast. However, there might be an improvement of exercise capacity with Roflumilast in patients with COPD.