Effects of lung deflation induced by tiotropium/olodaterol on the cardiocirculatory responses to exertion in COPD

Background: Hyperinflation has been associated with negative cardiocirculatory consequences in patients with chronic obstructive pulmonary disease (COPD). These abnormalities are likely to worsen when the demands for O-2 increase, e.g., under the stress of exercise. Thus, pharmacologically-induced lung deflation may improve cardiopulmonary interactions and exertional cardiac output leading to higher limb muscle blood flow and oxygenation in hyperinflated patients with COPD. Methods: 20 patients (residual volume = 201.6 +/- 63.6% predicted) performed endurance cardiopulmonary exercise tests (75% peak) 1 h after placebo or tiotropium/olodaterol 5/5 mu g via the Respimat (R) inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Cardiac output was assessed by signal-morphology impedance cardiography. Near-infrared spectroscopy determined quadriceps blood flow (indocyanine green dye) and intra-muscular oxygenation. Results: Tiotropium/olodaterol was associated with marked lung deflation (p < 0.01): residual volume decreased by at least 0.4 L in 14/20 patients (70%). The downward shift in the resting static lung volumes was associated with less exertional inspiratory constraints and dyspnoea thereby increasing exercise endurance by similar to 50%. Contrary to our premises, however, neither central and peripheral hemodynamics nor muscle oxygenation improved after active intervention compared to placebo. These results were consistent with those found in a subgroup of patients showing the largest decrements in residual volume (p < 0.05). Conclusions: The beneficial effects of tiotropium/olodaterol on resting and operating lung volumes are not translated into enhanced cardiocirculatory responses to exertion in hyperinflated patients with COPD. Improvement in exercise tolerance after dual bronchodilation is unlikely to be mechanistically linked to higher muscle blood flow and/or O-2 delivery.