Abstract
This study uses a highly fidelity computational simulator of pulmonary physiology to evaluate the impact of a soluble guanylate cyclase (sGC) modulator on gas exchange in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) as a complication. Three virtual patients with COPD were configured in the simulator based on clinical data. In agreement with previous clinical studies, modeling systemic application of an sGC modulator results in reduced partial pressure of oxygen (PaO2) and increased partial pressure of carbon dioxide (PaCO2) in arterial blood, if a drug‐induced reduction of pulmonary vascular resistance (PVR) equal to that observed experimentally is assumed. In contrast, for administration via dry powder inhalation (DPI), our simulations suggest that the treatment results in no deterioration in oxygenation. For patients under exercise, DPI administration lowers PH, whereas oxygenation is improved with respect to baseline values.
Highlights
WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? þ Using a high-fidelity pulmonary simulator, calibrated to data from three patients with Chronic obstructive pulmonary disease (COPD) involved in a previous clinical trial, we showed that administering an soluble guanylate cyclase (sGC) via dry powder inhalation (DPI) can reduce pulmonary hypertension (PH) without deteriorating oxygenation, when administration is combined with exercise
WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? þ A modulator of sGC has recently been shown in a clinical study to improve pulmonary hemodynamics in patients with COPD and PH as a complication
WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? þ Using a high-fidelity pulmonary simulator, calibrated to data from three patients with COPD involved in a previous clinical trial, we showed that administering an sGC via DPI can reduce PH without deteriorating oxygenation, when administration is combined with exercise
Summary
WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? þ Using a high-fidelity pulmonary simulator, calibrated to data from three patients with COPD involved in a previous clinical trial, we showed that administering an sGC via DPI can reduce PH without deteriorating oxygenation, when administration is combined with exercise. Various vasodilating drugs with different modes of action have been investigated in clinical studies.[9] Most of these studies considered systemic applications (oral administration), some considered administration via inhalation. These studies aimed for a dilation or relaxation of the pulmonary arterial vessels, lowering pulmonary vascular resistance.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
