Dataset Information

Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study.

ABSTRACT:

Background

Chronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular disease. The utility of beta-blockers for treating patients with COPD may be beneficial, but their safety remains uncertain, including worsening of dynamic hyperinflation (DH) during exercise. We hypothesised that among cardioselective beta-blockers celiprolol, due to its partial beta-2 agonist activity, may be safer than bisoprolol on exercise DH.

Methods

We measured isotime inspiratory capacity (IC) during cycle endurance testing in eleven moderate-severe COPD subjects, alongside other non-invasive cardiopulmonary exercise, bioreactance cardiac output, pulmonary function, biomarkers and daily domiciliary measures. Participants received titrated doses of either bisoprolol (maximim 5 mg) or celiprolol (maximum 400 mg) in randomised crossover fashion, each over 4 weeks.

Results

Clinically relevant DH occurred between resting and exercise isotime IC but showed no significant difference with either beta-blocker compared with post-run-in pooled baseline or between treatments. There were no other significant differences observed for remaining exercise ventilatory; non-invasive cardiac output; resting pulmonary function; beta-2 receptor and cardiac biomarkers; domiciliary pulmonary function, oxygen saturation and symptom outcomes, either between treatments or compared with baseline. No significant adverse effects occurred.

Conclusions

Significant DH in moderate-severe COPD subjects was no different between bisoprolol or celiprolol or versus baseline. A broad spectrum of other non-invasive cardiopulmonary and domiciliary safety outcomes was equally reassuring. Bronchoprotection with a concomitant long-acting muscarinic antagonist might be an important safety measure in this context.

Trial registration number

NCT02380053.

SUBMITTER: Anderson W

PROVIDER: S-EPMC10351271 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study.

Anderson William W Short Philip P Ross Rose R Lipworth Brian J BJ

BMJ open respiratory research 20230701 1

<h4>Background</h4>Chronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular disease. The utility of beta-blockers for treating patients with COPD may be beneficial, but their safety remains uncertain, including worsening of dynamic hyperinflation (DH) during exercise. We hypothesised that among cardioselective beta-blockers celiprolol, due to its partial beta-2 agonist activity, may be safer than bisoprolol on exercise DH.<h4>Methods</h4>We measured isotime inspi ...[more]

PMID: 37451701

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Project description:We investigated whether dual bronchodilator therapy (glycopyrrolate/formoterol fumarate; GFF; Bevespi Aerosphere) would increase exercise tolerance during a high-intensity constant work rate exercise test (CWRET) and the relative contributions of dead space ventilation (VD/VT) and dynamic hyperinflation (change in inspiratory capacity) to exercise limitation in chronic obstructive pulmonary disease (COPD). In all, 48 patients with COPD (62.9 ± 7.6 yrs; 33 male; GOLD spirometry stage 1/2/3/4, n = 2/35/11/0) performed a randomized, double blind, placebo (PL) controlled, two-period crossover, single-center trial. Gas exchange and inspiratory capacity (IC) were assessed during cycle ergometry at 80% incremental exercise peak work rate. Transcutaneous [Formula: see text] (Tc[Formula: see text]) measurement was used for VD/VT estimation. Baseline postalbuterol forced expiratory volume in 1 s (FEV1) was 1.86 ± 0.58 L (63.6% ± 13.9 predicted). GFF increased FEV1 by 0.18 ± 0.21 L relative to placebo (PL; P < 0.001). CWRET endurance time was greater after GFF vs. PL (383 ± 184 s vs. 328 ± 115 s; difference 55 ± 125 s; P = 0.013; confidence interval: 20-90 s), a 17% increase. IC on GFF was above placebo IC at all time points and fell less with GFF vs. PL (P ≤ 0.0001). Isotime tidal volume (1.54 ± 0.50 vs. 1.47 ± 0.45 L; P = 0.022) and ventilation (52.9 ± 19.9 vs. 51.0 ± 18.9 L/min; P = 0.011) were greater, and respiratory rate was unchanged (34.9 ± 9.2 vs. 35.1 ± 8.0 br/min, P = 0.865). Isotime VD/VT did not differ between groups (GFF 0.28 ± 0.08 vs. PL 0.27 ± 0.09; P = 0.926). GFF increased exercise tolerance in patients with COPD, and the increase was accompanied by attenuated dynamic hyperinflation without altering VD/VT.NEW & NOTEWORTHY This study was a randomized clinical trial (NCT03081156) that collected detailed physiology data to investigate the effect of dual bronchodilator therapy on exercise tolerance in COPD, and additionally to determine the relative contributions of changes in dead space ventilation (VD/VT) and dynamic hyperinflation to alterations in exercise limitation. We utilized a unique noninvasive method to assess VD/VT (transcutaneous carbon dioxide, Tc[Formula: see text]) and found that dual bronchodilators yielded a moderate improvement in exercise tolerance. Importantly, attenuation of dynamic hyperinflation rather than change in dead space ventilation was the most important contributor to exercise tolerance improvement.

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Project description:BackgroundPhysical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is associated with worse health status, and increased hospitalisation and mortality. Long-acting bronchodilators, either alone or in combination, have been shown to improve exercise intolerance. However, none of these studies were designed with physical activity as primary outcome. This study assessed the effect of indacaterol/glycopyrronium fixed dose combination (IND/GLY) 110/50 μg once daily (OD) versus placebo on lung hyperinflation (inspiratory capacity [IC]) and physical activity in patients with moderate-to-severe COPD.MethodsIn this multicentre, randomised, double-blind, placebo-controlled crossover study, patients received IND/GLY or placebo OD in two 21-day treatment periods (14-day washout between periods). Eligible patients were ≥40 years of age, current or ex-smokers (smoking history ≥10 pack-years), with post-salbutamol forced expiratory volume in 1 s (FEV1) 40-80 % predicted, and FEV1:forced vital capacity <0.70. The co-primary endpoints were peak IC after 21 days and average daily activity-related energy expenditure. Key secondary endpoints were average number of steps per day and the duration of at least moderate activity per day. Peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days were other secondary endpoints.ResultsA total of 194 patients were randomised (65.5 % male, mean age 62.8 years, mean FEV1 61.6 % predicted), with 183 (94.3 %) completing the study. Compared with placebo, IND/GLY significantly increased peak IC after 21 days (difference 202 mL, p < 0.0001), activity-related energy expenditure (difference 36.7 kcal/day, p = 0.040), and the average number of steps per day (difference 358, p = 0.029), with a trend towards an improvement in the duration of at least moderate activity (difference 4.4 min, p = 0.264). IND/GLY was associated with statistically significant improvements versus placebo in peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days. The incidence of treatment-emergent adverse events was 22.8 % with IND/GLY and 22.9 % with placebo.ConclusionsIn this study, compared with placebo, IND/GLY reduced hyperinflation, and, despite no patient education or lifestyle advice, improved daily physical activity levels. This suggests that IND/GLY has the potential to impact two of the main clinical concerns in the care of patients with COPD.Trial registrationClinicalTrials.gov number: NCT01996319 .

Dataset Information

Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study.

Background

Methods

Results

Conclusions

Trial registration number

Publications

Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study.

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