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Eur Respir J. 2019 Apr 7. pii: 1802445. doi: 10.1183/13993003.02445-2018. [Epub ahead of print]

Riociguat for treatment of pulmonary hypertension in COPD - a translational study.

Author information

1
Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
2
Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
3
Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany norbert.weissmann@innere.med.uni-giessen.de.

Abstract

Chronic obstructive pulmonary disease (COPD) which comprises the phenotypes of chronic bronchitis and emphysema is often associated with pulmonary hypertension (PH). However, currently no approved therapy exists for PH-COPD. Signalling of the nitric oxide/cyclic guanoside monophosphate (NO-cGMP) axis plays an important role in PH and COPD.We investigated the treatment effect of riociguat, which promotes the NO-cGMP pathway, in the mouse model of smoke-induced PH and emphysema in a curative approach and retrospectively analysed the effect of riociguat treatment on PH in single patients with PH-COPD.In mice with established PH and emphysema (after 8 months of cigarette smoke exposure) riociguat treatment for another 3 months fully reversed PH. Moreover, histological hallmarks of emphysema were decreased. Microarray analysis revealed involvement of different signalling pathways, e.g. related to matrix metalloproteinases (MMPs). MMP activity was decreased in vivoby riociguat. In PH-COPD patients treated with riociguat (n=7) the pulmonary vascular resistance, airway resistance and circulating MMP levels decreased, while oxygenation at rest was not significantly changed.Conclusions: Riociguat may be beneficial for treatment of PH-COPD. Further long-term prospective studies are necessary to investigate the tolerability, efficacy on functional parameters and the effect specifically on pulmonary emphysema in COPD patients.

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