Effects of indacaterol versus tiotropium on exercise tolerance in patients with moderate COPD: a pilot randomized crossover study

Abstract

Objective:To compare a once-daily long-acting β2 agonist (indacaterol 150 µg) with a once-daily long-acting anticholinergic (tiotropium 5 µg) in terms of their effects on exercise endurance (limit of tolerance, Tlim) in patients with moderate COPD. Secondary endpoints were their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Methods:This was a randomized, single-blind, crossover pilot study involving 20 patients (mean age, 60.9 ± 10.0 years; mean FEV1, 69 ± 7% of predicted). Spirometric parameters, Transition Dyspnea Index scores, Tlim, and exertional dyspnea were compared after three weeks of each treatment (with a one-week washout period between treatments). Results:Nineteen patients completed the study (one having been excluded because of COPD exacerbation). Improvement in Tlim from baseline tended to be greater after treatment with tiotropium than after treatment with indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0.06). Tlim significantly improved from baseline after treatment with tiotropium (having increased from 396 ± 319 s to 493 ± 347 s; p = 0.010) but not after treatment with indacaterol (having increased from 393 ± 246 to 401 ± 254 s; p = 0.678). There were no differences between the two treatments regarding improvements in Borg dyspnea scores and lung hyperinflation at "isotime" and peak exercise. There were also no significant differences between treatments regarding Transition Dyspnea Index scores (1.5 ± 2.1 vs. 0.9 ± 2.3; p = 0.39). Conclusions:In patients with moderate COPD, tiotropium tends to improve Tlim in comparison with indacaterol. No significant differences were observed between the two treatments regarding their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Future studies, including a larger number of patients, are required in order to confirm our findings and explore mechanistic explanations. (ClinicalTrials.gov identifier: NCT01693003 [http://www.clinicaltrials.gov/])

Treatment with long acting muscarinic antagonists stimulates serum levels of irisin in patients with COPD

“…The inhalation of LAMA increased serum irisin between one and four hours after inhalation. This effect was significant only in patients that did not inhale LAMA for 48 h prior the experimental administration of LAMA, indicating that the effect of LAMA on irisin secretion remains for longer than h. These findings fit very well with the recent documentation that treatment with tiotropium, at a daily dose of 5 µg, resulted in a significant improvement in exercise tolerance in patients with moderate COPD, while treatment with indacaterol, at a daily dose of 150 µg, did not, although no significant differences were observed between the two treatments regarding their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea [13]. This clearly indicates that other mechanisms than sustained reductions of lung hyperinflation should be considered to explain improved exercise tolerance after treatment with LAMA.…”

“…However, the beneficial effects of LAMA for COPD patients cannot be based solely on their bronchodilatory and their anti-inflammatory actions [10][11][12]. LAMA have been shown to increase exercise endurance in patients with COPD, with an as yet unknown mechanism, other than reduction of lung hyperinflation [13].…”