Menthol for Dyspnea Relief in Health and COPD

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 forcedvital 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 2only)

• Clinically stable COPD (based on clinical judgment of the study physician that havenot had exacerbations requiring escalation of medical therapy (i.e., short course oforal 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 COPDin WP3 and 4)

• Body mass index <18.5 or >35 kg/m2

• An ulcer or tumor in the esophagus, a nasal septum deviation, or recentnasopharyngeal surgery

• Severe facial trauma including cribriform plate disruption (bone separating brainfrom nasal cavity)

• Allergies to latex and sensitivities to local anesthetics

• Inability to give informed consent, including those with significant cognitiveimpairment

• 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