Pulmonary function tests: Standard pulmonary function tests including spirometry, lung volumes and carbon monoxide diffusing capacity of the lungs (DLCO) were obtained at baseline according to previously described guidelines , and related to normal values of Knudson , Goldman and Becklake , and Cotes , respectively.
Exercise test: After the insertion of an arterial cannula in a radial artery, subjects were seated on an electrically braked cycle ergometer (Quinton Corival 400, A-H Robins, Washington) and connected to the exercise circuit through a mouthpiece. Five-breath averages of oxygen uptake (VO2) and carbon dioxide output were measured by an automated system equipped with a pneumotachograph, oxygen and carbon dioxide analyzers and a mixing chamber (Quinton Qplex, A-H Robins). After 5 mins of rest, a progressive stepwise exercise test was performed up to the individual’s maximum capacity. Each exercise step lasted 1 min, and increments of 10 and 20 watts were used in COPD and normal subjects, respectively. At 1 min intervals during exercise, dyspnea and leg fatigue perception were rated on a modified Borg scale , and arterial blood was sampled for plasma lactate (La) concentration determination. Blood gases were also analyzed at rest and maximal exercise. During the exercise, blood samples were placed on ice and centrifuged at room temperature immediately after termination of the exercise test. Lactate concentrations were measured on plasma with an enzymatic technique (Kit Lactate, Boehringer Mannheim, Mannheim, Germany).