Effect of l-menthol on breathlessness and exercise endurance in COPD: a randomised crossover trial.
5 affiliations
- 1Department of Health, Blekinge Institute of Technology, Karlskrona, Sweden.
- 2Department of Clinical Sciences in Lund, Division of Respiratory Medicine, Allergology and Palliative Medicine, Lund University, Lund, Sweden.
- 3Clinical Physiology, Department of Clinical Sciences, Lund University, Lund, Sweden.
- 4Department of Clinical Physiology, Skåne University Hospital, Lund, Sweden.
- 5Clinical Studies Sweden-Forum South, Skåne University Hospital, Lund, Sweden.
Abstract
Background and objective
Breathlessness is a leading cause of disability and reduced quality of life in COPD. Inhaled l-menthol may reduce breathlessness but data on its effect on exertional breathlessness is limited. We aimed to evaluate the effect of inhaled l-menthol on exertional breathlessness and exercise capacity in patients with COPD.Methods
This was a double-blinded, randomised (ratio 1:1), crossover trial (RCT) of l-menthol inhalation versus placebo. 20 participants with COPD performed two constant-load cycle cardiopulmonary exercise tests (CPET) to exhaustion, with either l-menthol or placebo (strawberry) scented patch in the mask in randomised order. The primary outcome was the difference in breathlessness intensity (Borg 0-10 scale) at isotime. Secondary outcomes were change in breathlessness unpleasantness and leg fatigue at isotime, exercise endurance time (EET), exertional physiological responses and multidimensional breathlessness (MDP).Results
Compared with placebo, inhaled l-menthol reduced breathlessness intensity at isotime (mean difference -0.8, 95% CI -1.6-0.0; p=0.042), corresponding to a moderate effect size (Cohen's d= -0.49). Isotime breathlessness unpleasantness (-0.7, -1.7-0.3) and emotional response score was lower with L-menthol (-2.2, -4.4-0.0). Leg discomfort (-0.5, -1.3-0.2) was numerically lower, EET was longer (0.9 min, -0.7-2.5) and physiological responses were unchanged.Conclusion
Inhalation of l-menthol reduced the intensity and emotional response of exertional breathlessness and increased the EET compared with placebo in patients with COPD. The unchanged physiological responses support a central brain effect and l-menthol might be a promising new treatment.
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BibTeX
@article{sandberg2026effect,
title = {{Effect of l-menthol on breathlessness and exercise endurance in COPD: a randomised crossover trial.}},
author = {Jacob Sandberg and Henrik Mosen and Magnus Ekström and Sara Jesperson and Zainab Ahmadi},
journal = {ERJ open research},
year = {2026},
month = sep,
doi = {10.1183/23120541.00495-2026},
url = {https://europepmc.org/article/MED/42899053},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Effect of l-menthol on breathlessness and exercise endurance in COPD: a randomised crossover trial.
AU - Jacob Sandberg
AU - Henrik Mosen
AU - Magnus Ekström
AU - Sara Jesperson
AU - Zainab Ahmadi
PY - 2026
DA - 2026/09/01
JO - ERJ open research
DO - 10.1183/23120541.00495-2026
UR - https://europepmc.org/article/MED/42899053
AB - Background and objective Breathlessness is a leading cause of disability and reduced quality of life in COPD. Inhaled l-menthol may reduce breathlessness but data on its effect on exertional breathlessness is limited. We aimed to evaluate the effect of inhaled l-menthol on exertional breathlessness and exercise capacity in patients with COPD.Methods This was a double-blinded, randomised (ratio 1:1), crossover trial (RCT) of l-menthol inhalation versus placebo. 20 participants with COPD performed two constant-load cycle cardiopulmonary exercise tests (CPET) to exhaustion, with either l-menthol or placebo (strawberry) scented patch in the mask in randomised order. The primary outcome was the difference in breathlessness intensity (Borg 0-10 scale) at isotime. Secondary outcomes were change in breathlessness unpleasantness and leg fatigue at isotime, exercise endurance time (EET), exertional physiological responses and multidimensional breathlessness (MDP).Results Compared with placebo, inhaled l-menthol reduced breathlessness intensity at isotime (mean difference -0.8, 95% CI -1.6-0.0; p=0.042), corresponding to a moderate effect size (Cohen's d= -0.49). Isotime breathlessness unpleasantness (-0.7, -1.7-0.3) and emotional response score was lower with L-menthol (-2.2, -4.4-0.0). Leg discomfort (-0.5, -1.3-0.2) was numerically lower, EET was longer (0.9 min, -0.7-2.5) and physiological responses were unchanged.Conclusion Inhalation of l-menthol reduced the intensity and emotional response of exertional breathlessness and increased the EET compared with placebo in patients with COPD. The unchanged physiological responses support a central brain effect and l-menthol might be a promising new treatment.
SN - 2312-0541
ER -