Analysis of V/Q-matching—a safety “biomarker” in pulmonary drug development?

Effect of indacaterol on arterial blood gases in patients suffering from acute exacerbation of COPD

“…The outcome of V A /Q mismatch is admixture of venous blood to oxygenated blood leading to a decrease in PaO 2 , the arterial saturation of haemoglobin with oxygen, and thereby the arterial oxygen content that reaches the left-sided circulation [24]. However, although LABAs have an acute vasodilator action in the airways, the modest contribution of bronchial circulation to the lung's blood flow indicates that it does not participate significantly in gas exchange and suggests that the impact of the vasodilating effect of b 2 -agonists on V/Q inequality is small and unimportant [25].…”

Effects of Different Pulmonary Vasodilators on Arterial Saturation in a Model of Pulmonary Hypertension

“…This pragmatic approach is also feasible for larger clinical trials since in essence the measurement of SaO 2 is used as a safety biomarker [11]. The caveat is that a drop in SaO 2 might be caused by different mechanisms unrelated to VQM (e.g., by a drop in central venous saturation [SvO 2 ], e.g., associated with increased oxygen extraction due to reduced CO and/or impaired organ perfusion, changes in hemoglobin content).…”

“…Therefore, oxygenation as a safety biomarker needs to be closely followed in all patients at risk [11]. Using a preclinical animal model mimicking the heterogeneous ventilation perfusion patterns in the lung of patients with secondary PH forms, we evaluated the “desaturation-potential” of bosentan, sildenafil, and the sGC stimulators BAY 41–8543 and riociguat (currently in clinical development for PAH and chronic thromboembolic pulmonary hypertension [CTEPH]).…”

Biomarkers for intensive care medicine patients: the (stony) path into a bright future?

“…Urbschat et al (2011) highlight established and novel urine and serum biomarkers of AKI, which have progressed to clinical phase with regard to their diagnostic and prognostic value. Amen et al (2011) demonstrate that V/Q matching is a powerful biomarker to assess therapy response and prognosis in pulmonary disease. And last but not least, Kramer et al (2011) summarize the current knowledge regarding remodeling biomarker in terminal HF and in patients pre-and postimplantation of left ventricular assist devices or total artificial hearts.…”

“…This will include endothelial dysfunction and coagulation disorders in systemic inflammatory syndroms and sepsis (Paulus et al, 2011), organ transplantation (Sawitzki et al, 2011), acute kidney injury (AKI) (Urbschat et al, 2011), respiratory disease (Amen et al, 2011) as well as HF and artificial heart transplantation (Kramer et al, 2011). The first review of the present special issue written by Paulus et al (2011) summarize the clinically used coagulation biomarkers with regard to their pathophysiological background.…”