Efficacy of L-menthol on Breathlessness in Asthma

Dyspnea is a cardinal symptom in patients with lung disease, often triggered by daily-life physical activities. To date, an effective pharmacologic treatment to relieve chronic dyspnea is lacking. Recent pilot data support that inhaled L-menthol can markedly decrease laboratory-induced dyspnea in COPD and ILD patients, likely through increased afferent feedback of airflow in the airways by inducing a cooling sensation through olfactory stimulation. The aim of this study is therefore to assess the effectiveness and mechanisms of inhaled menthol for relief of patients with Asthma.

• L-menthol (Drug): (Sigma-Aldrich, St. Louis, US)
• Placebo (Other): Strawberry scent (Sigma-Aldrich, St. Louis, US)

Primary outcomes

• Breathlessness intensity [During submaximal test, at isotime during day 2 and day 3.]: The difference between treatment conditions in dyspnea intensity at iso-time. The Borg's modified 0-10 category ratio scale (Borg CR10) will be used, where 0 represents no perceived breathlessness at all, and 10 represents maximum breathlessness intensity ever experienced.

Secondary outcomes

• Dyspnea unpleasantness [During submaximal test, at iso-time during day 2 and day 3]: The difference between treatment conditions in dyspnea unpleasantness at iso-time. The Borg's modified 0-10 category ratio scale (Borg CR10) will be used, where 0 represents no perceived unpleasantness at all, and 10 represents maximum breathlessness unpleasantness experienced.
• Total time [At the end of submaximal test during day 2 and day 3.]: Time to the limit of tolerance (s) (tLIM)
• Exercise capacity [Submaximal test during day 2 and day 3.]: V'O2 (aerobic exercise capacity, absolute and in %pred)
• Peak dyspnea intensity [During submaximal test, at peak during day 2 and day 3.]: Dyspnea intensity at peak exercise. The Borg's modified 0-10 category ratio scale (Borg CR10) will be used, where 0 represents no perceived breathlessness at all, and 10 represents maximum breathlessness intensity ever experienced.
• Leg fatigue [During submaximal test, at day 2 and day 3.]: The Borg's modified 0-10 category ratio scale (Borg CR10) will be used, where 0 represents no perceived leg fatigue at all, and 10 represents maximum leg fatigue ever experienced.
• Ventilatory efficacy [During submaximal test, at day 2 and day 3.]: Efficacy of ventilation (VE/V'CO2-slope)
• Saturation [During submaximal test, at day 2 and day 3.]: O2-Saturation
• Stop reason [During submaximal test, at day 2 and day 3.]: Causes of stopping the test
• Adverse events [Through study completion, an average of 1 week.]: Any adverse events during the test
• Respiratory exchange ratio [During the submaximal test at day 2 and day 3.]: Respiratory exchange ratio (RER), defined as V'CO2/V'O2
• Heart rate [During the submaximal test at day 2 and day 3.]: Heart rate in beats/min
• Breathing frequency [During the submaximal test at day 2 and day 3.]: Breathing frequency in breaths/min
• Minute ventilation [During the submaximal test at day 2 and day 3.]: Ventilation per minute
• Tidal volume [During the submaximal test at day 2 and day 3.]: Tidal volume in liters
• Ventilatory reserve [During the submaximal test at day 2 and day 3.]: Defined as maximal voluntary ventilation (MVV) - VE

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* the subject has given written consent to participate in the study
* physician diagnosis of Asthma according to international guidelines
* mMRC (modified Medical Research Council) score of 1 or above
* age 18 years or older
* able to cycle
* able to understand and talk Swedish to participate in the study procedures, as judged by the Investigators.

Exclusion Criteria:

* resting peripheral oxygen saturation (SpO2) < 92%
* hospitalization or clinical instability during the last four weeks
* treatment with supplementary oxygen at rest or during exercise
* contraindication to exercise testing in accordance with clinical practice guidelines
* expected survival shorter than six months as judged by the Investigator
* medical conditions including congestive heart failure, acute coronary artery disease, neuromuscular diseases, severe psychiatric illness, and olfaction disorder.