Differentiating the Effects of Substance P and Beta-endorphin

This study is a randomized, controlled clinical trial comparing the acute effects of oral aprepitant (selective antagonist of substance P receptor) vs. placebo on ratings of breathlessness during resistive load breathing in patients with COPD. Four hours after randomization, all patients will receive intravenous naloxone (antagonist of opioid receptors) to block the effects of endogenous opioids on perception of breathlessness. The two competing hypothesis of the study are: Breathing difficulty will be induced by the patient breathing thru a tube with fine wire mesh for approximately 10 - 20 minutes in the laboratory. Approximately 20 patients with COPD will be recruited from the out-patient clinic at the Dartmouth-Hitchcock Medical Center. The population will consist of female or male adults at least 50 years of age, at least 10 pack-year history of smoking, and a diagnosis of COPD associated with chronic bronchitis based on standard criteria.