Effect of Inhaled Fentanyl on Dyspnea and Exercise Tolerance in Chronic Obstructive Pulmonary Disease (COPD)

Inclusion Criteria: * Post-bronchodilator forced expiratory volume in 1 sec (FEV1) 30-79% predicted, FEV1/forced vital capacity (FVC) ratio \<70%; * Clinically stable as defined by no changes in medication dosage or frequency of administration with no exacerbations or hospital admissions in the preceding 6 weeks; * A cigarette smoking history ≥20 pack-years; * Significant chronic activity-related dyspnea as defined by a Baseline Dyspnea Index focal score ≤ 6; * Body mass index (BMI) between 18.5 and 30.0 kg/m2; * Able to perform all study procedures and provide/sign informed consent. Exclusion Criteria: * A diffusing capacity of the lung for carbon monoxide (DLCO) \<40 %predicted; * Presence of active cardiopulmonary disease other than COPD that could contribute to dyspnea and exercise limitation; * Clinical diagnosis of sleep disordered breathing; * A history/clinical evidence of asthma, atopy and/or nasal polyps; * History of allergy or adverse reaction to fentanyl; * Presence of important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s); * Use of daytime oxygen or exercise-induced arterial oxygen desaturation to \<80% on room air; * Use of antidepressant drugs (i.e., monoamine oxidase inhibitors, serotonin reuptake inhibitors) in previous 2 weeks; * Use of opioid or pain relieving drugs (e.g., morphine, fentanyl, oxycodone, hydromorphone, methadone, levorphanol, codeine, hydrocodone, meperidine) in previous 4 weeks.