The beneficial effects of tiotropium/olodaterol on resting and operating lung volumes do not translate into enhanced cardiocirculatory responses to exertion in hyperinflated patients with chronic obstructive pulmonary disease (COPD), according study results published in Respiratory Medicine.
Investigators conducted a single-center, randomized double-blind placebo-controlled crossover trial (ClinicalTrials.gov Identifier: NCT03425617) at Queen’s University & Kingston General Hospital in Ontario, Canada. They sought to noninvasively determine exertional stroke volume and cardiac output, quadriceps (leg) blood flow, and oxygenation in response to placebo and a potent long-acting muscarinic antagonist/long-acting beta agonist combination (tiotropium/olodaterol) in a group of hyperinflated patients with COPD. In addition, the researchers aimed to explore whether pharmacologically induced lung deflation may improve cardiopulmonary interactions and exertional cardiac output, thus leading to higher limb muscle blood flow and oxygenation in these individuals.
A total of 20 stable patients who were followed in an institutional COPD outpatient clinic and presented with Global Initiative for Chronic Obstructive Lung Disease spirometric stages II or III (ie, postbronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity < lower limit of normal with postbronchodilator FEV1 30% ≤ FEV1 <80% predicted). The participants, who had a residual volume of 201.6%±63.6% predicted, performed endurance cardiopulmonary exercise tests (75% peak) 1 hour after receiving placebo or tiotropium/olodaterol 5/5 µg via inhaler. Patients’ cardiac output was evaluated with the use of signal-morphology impedance cardiography. Near-infrared spectroscopy was used to establish quadriceps blood flow and intramuscular oxygenation.
Treatment with tiotropium/olodaterol was associated with significantly marked lung deflation (P <.01), with residual volume decreasing by ≥0.4 L in 70% (14 of 20) of participants. The downward shift in resting static lung volumes was linked to less exertional inspiratory constraints and dyspnea, thereby increasing exercise endurance by ~50%. Neither central and peripheral hemodynamics nor muscle oxygenation, however, improved after treatment with tiotropium/olodaterol vs placebo. The results were consistent with those reported in a subgroup of patients who demonstrated the largest decrements in residual volume (P <.05).
The investigators concluded that based on the results of this study, improvement in exercise tolerance after dual bronchodilation therapy in patients with COPD is not likely to be mechanistically associated with higher muscle blood flow and/or oxygen delivery. Despite marked lung deflation at rest with positive effects on dynamic lung mechanics, dyspnea, and exercise tolerance, the researchers were not able to detect a signal that linked the lower lung volumes to enhanced central hemodynamics and their salutary consequences to muscle perfusion and oxygenation.
Berton DC, Marques RD, Palmer B, O’Donnell DE, Neder JA. Effects of lung deflation induced by tiotropium/olodaterol on the cardiocirculatory responses to exertion in COPD. Respir Med. 2019;157:59-68.