Metabolic and cardiorespiratory effects of decreasing lung hyperinflation with budesonide/formoterol in COPD: a randomized, double-crossover, placebo-controlled, multicenter trial

Abstract

Background: Studies suggest that acute decreases in lung hyperinflation at rest improves cardiac function and increases lung vascular perfusion from decompression of a compromised heart. In those studies, changes in resting oxygen uptake induced by medications, an alternative explanation for compensatory increased cardiac function, were not explored.Methods: This double-blind, multicenter, double-crossover study enrolled adults with chronic obstructive pulmonary disease, resting hyperinflation, and > 10% improvement in inspiratory capacity after 2 inhalations of budesonide/formoterol 160/4.5 μg. Metabolic, cardiac, and ventilatory function were measured 60 min pre−/postdose at each visit. Primary endpoint was change in resting oxygen uptake for budesonide/formoterol versus placebo.Results: Fifty-one patients (median age: 63 years) received treatment. Compared with placebo, budesonide/ formoterol significantly increased resting oxygen uptake (mean change from baseline: 1.25 vs 11.37 mL/min; P = 0.007) as well as tidal volume and minute ventilation. This occurred despite improvements in the inspiratory capacity, forced vital capacity, and expiratory volume in 1 s. No significant treatment differences were seen for oxygen saturation, respiratory rate, and resting dyspnea. There was a numerical increase in oxygen pulse (oxygen uptake/heart rate). Correlations between inspiratory capacity and oxygen pulse were weak. Conclusions: Budesonide/formoterol treatment in resting hyperinflated patients with COPD results in significant deflation. The increase in oxygen uptake and minute ventilation at lower lung volumes, without changes in heart rate and with minimal improvement in oxygen pulse, suggests increased oxygen demand as a contributor to increased cardiac function.Trial registration: ClinicalTrials.gov identifier: NCT02533505.

Implications of Managing Chronic Obstructive Pulmonary Disease in Cardiovascular Diseases

“…(3) ICS-LABA: LABA-ICS combinations, though not advocated by guidelines as the primary treatment, are often widely prescribed in COPD, especially in primary care practice. Recently, it has been shown that administration of Budesonide/Formoterol results in significant reduction of hyperinflation, an increase in oxygen uptake, and minute ventilation at lower lung volumes, thereby potentially improving cardiac function as well [ 78 ]. A new LABA-ICS combination, fluticasone furoate/vilanterol, has been shown to reduce lung hyperinflation and improve right ventricular end-diastolic volume index, Left ventricular end-diastolic volume, and left atrial end-systolic volume, right ventricular stroke volume, and left atrial ejection fraction versus placebo [ 79 ].…”