[Behavioral control of breathing and the effect of endogenous opiates in chronic obstructive pulmonary disease]

Dyspnea is a common symptom in patients with chronic obstructive pulmonary disease (COPD) but its mechanism is unclear. It is known that the opiate antagonist, naloxone, restores in some patients with COPD the ability to compensate for a flow-resistive load (N Engl J Med 1981; 304; 1190-5). We studied the effect of naloxone on the threshold of resistive load detection (RLD) and on sensation of breathlessness in patient with COPD. Naloxone (NLX, 2mg, IV) and placebo (P, Physiologic saline, 10ml) were administered in a randomized double-blind fashion, on separate days, to sixteen patients. The threshold for RLD was assessed by added resistance (delta R; 0.3-6.9cmH2O/L/sec) where the subject detected the load 50% of the time. This was analyzed in two ways; one by the ratio of added resistance divided by background resistance (Ro) and the other, by the mouth pressure (P) at the threshold. The patient squeezed a handgrip as ventilation increased and perception of breathlessness was assessed by a degree of squeezed handgrip (Gf; 0-100%). The threshold for breathlessness was estimated by Gf divided by ventilatory volume (Gf/VE) and P0.1 at the point of endtidal PCOz of 50mmHg (Gf/P0.1%/cmH2O), respectively. The threshold for RLD remained unchanged but Gf/VE increased significantly after NLX instillation (delta R/Ro: 0.55 +/- 0.28 during P vs 0.52 +/- 0.36 during NLX, NS. P: 0.89 +/- 0.44 during P vs 0.97 +/- 0.54 during NLX, NS. Gf/VE: 0.76 +/- 0.57 during P vs 1.38 +/- 0.62 during NLX, P < 0.01). FRC, VE, f, T1, TE and P0.1 did not significantly change after NLX.(ABSTRACT TRUNCATED AT 250 WORDS)