Chronic Obstructive Pulmonary Disease, Dyspnea
Conditions
Keywords
Menthol
Brief summary
Menthol inhalation (MI) is a novel and promising treatment option for acute relief of dyspnea, however, the underlying ventilatory and/or neural related mechanisms for this relief in symptoms remain unknown. The overall aim of this research project is to systematically examine the mechanisms of dyspnea relief from MI in healthy individuals and those with COPD.
Detailed description
The project is structured in 5 work packages (WP), each including a different sample of healthy volunteers (WP1, 2) or patients with COPD (WP3, 4, 5), respectively with a 1:1 female/male ratio in each WP. Each WP will be single-blind, placebo-controlled cross-over trial to investigate the effects of MI compared to placebo in healthy volunteers during resistive loaded breathing (WP1), in healthy volunteers during cycling exercise (WP2), in people with COPD who have dyspnea at rest (WP3), and in people with COPD during cycling exercise (WP4, 5).
Interventions
OTHERMenthol inhalation
300 milligrams of L-menthol will be deposited on to a cellulose swab and secured inside the lower portion of a sealed facemask.
OTHERStrawberry scent
600 microliters of 100% natural strawberry flavoring will be deposited onto on to a cellulose swab and secured inside the lower portion of a sealed facemask.
OTHERMenthol inhalation and facial airflow
Menthol will be administered using a noseplug and facial airflow will be applied with a tabletop fan.
OTHERStrawberry scent and airflow to leg
Strawberry will be administered using a noseplug and airflow to the leg will be applied with a tabletop fan.
OTHERMenthol inhalation and airflow to leg
Menthol will be administered using a noseplug and airflow to the leg will be applied with a tabletop fan.
OTHERStrawberry inhalation and facial airflow
Strawberry will be administered using a noseplug and facial airflow will be applied with a tabletop fan.
Sponsors
KU Leuven
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age: 18 years of age or older * Able to speak, read, and write Dutch or English * Normal pulmonary function: forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio\>0.70; FEV1≥80%predicted (WP1 and 2 only) * Non-smoker or former smokers (smoke-free ≥12 months prior to enrolment) (WP1 and 2 only) * Clinically stable COPD (based on clinical judgment of the study physician that have not had exacerbations requiring escalation of medical therapy (i.e., short course of oral corticosteroids or antibiotics) within the preceding 14 days (WP3 and 4 only)
Exclusion criteria
* Contraindication to exercise testing (e.g., significant cardiovascular, musculoskeletal, neurological disease; see Table 4 from ERS/ATS consensus statement) * Significant pulmonary or extra-pulmonary disease that, based on clinical assessment, could influence dyspnea and/or impair exercise capacity (with the exception of COPD in WP3 and 4) * Body mass index \<18.5 or \>35 kg/m2 * An ulcer or tumor in the esophagus, a nasal septum deviation, or recent nasopharyngeal surgery * Severe facial trauma including cribriform plate disruption (bone separating brain from nasal cavity) * Allergies to latex and sensitivities to local anesthetics * Inability to give informed consent, including those with significant cognitive impairment * Alcohol consumption within 12 hours of study visit * Current smoker\* * History of early menopause (age \<45 years) * Pregnancy or desire to become pregnant while in trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in respiratory-related evoked potentials (RREP) with menthol vs. strawberry. | 1 week | RREPs will be measured using an electroencephalogram (EEG) sensor cap connected to a high-density 129 channel EEG system during breathing trials and exercise tests. Inspiration will briefly be interrupted for 150 milliseconds every two to six breaths by activation of the occluder, which induces the RREP in the EEG signal. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Difference in diaphragmatic electromyography with menthol vs. strawberry. | 1 week | Diaphragmatic electromyography will be measured using a multi-pair electrode catheter during breathing trials and exercise tests. and used as an index of neural respiratory drive. |
| Difference in dyspnea with menthol vs. strawberry (+ facial airflow or airflow to leg in WP5). | 1 week | Dyspnea ratings will be measured using the Borg 0-10 category ratio scale and will be assessed at the end of each 5-minute breathing trial (WP1 and 3), and at baseline, every minute during (WP4,5) or halfway through the test (WP2), and at peak of each cycle exercise test. 0 represents no dyspnea at all and then 10 the most maximal dyspnea ever experienced or could be imagined experiencing. |
| Difference in the rate of perceived inspiratory airflow. | 1 week | Participants will be asked: In which of the four conditions did your airflow feel easier when breathing in? at the end of each study visit. |
| Perception of a cooling sensation. | 1 week | Participants will be asked: In which of the four conditions did you feel a fresh or cooling sensation when breathing in? at the end of each study visit. |
| Difference in activation of extra-diaphragmatic inspiratory muscles with menthol vs. strawberry. | 1 week | Activation of extra-diaphragmatic inspiratory muscles will be measured using bipolar surface electrodes during breathing trials (WP3) and exercise testing (WP4). |
| Difference in the cardiorespiratory responses to exercise with menthol vs. strawberry. | 1 week | Cardiorespiratory responses to exercise will be measured on a breath-by-breath basis using a commercially available cardiopulmonary testing system during exercise testing. |
| Difference in leg discomfort ratings with menthol vs. strawberry (+facial airflow or airflow to leg in WP5). | 1 week | Leg discomfort will be measured using the Borg 0-10 category ratio scale at baseline, every minute during (WP4, 5) or halfway through the test (WP2), and at peak of each cycle exercise test. 0 represents no leg discomfort at all and then 10 the most maximal leg discomfort ever experienced or could be imagined experiencing. |
| Difference in exercise endurance time with menthol vs. strawberry (+ facial airflow or airflow to leg in WP5). | 1 week | Exercise endurance time will be measured during submaximal constant load cycle exercise testing (WP4, 5). |
| Difference in the reasons for stopping exercise with menthol vs. strawberry (+facial airflow or airflow to leg in WP5). | 1 week | Participants will be asked to give their reasons for stopping (e.g., breathing discomfort, leg discomfort, a combination of breathing and leg discomfort, or other) and attributing a percentage to each of breathing discomfort and leg discomfort to total 100 (WP 2, 4 and 5). |
| Difference in ratings of affective state on the dimensions of valence and arousal with menthol vs. strawberry (+ facial airflow or airflow to leg in WP5). | 1 week | Dimensions of valence and arousal will be measured using the 9-point Self-Assessment Manikin scale for valence (1 -unpleasant to 9 -pleasant) and arousal (1-calm to 9-aroused) at the end of each breathing trial (WP 1 and 3) and at peak exercise (WP 2, 4 and 5). |
| Difference in the Neural Drive to Breathe (P0.1) | 1 week | The neural drive to breathe will be measured using airway occlusion pressure (P0.1), evoked by inspiratory occlusions delivered during the test (WP1 and 2). |
| Difference in respiratory pressures with menthol vs. strawberry. | 1 week | Respiratory pressures will be measured using esophageal and gastric balloons during breathing trials and exercise testing. |
Countries
Belgium
Contacts
Primary ContactDaniel Langer
Outcome results
None listed