Forster, Roughton and their colleagues (1, 2) have reported a method of subdividing the components of the pulmonary diffusing capacity by measurement of the apparent diffusing capacity at different alveolar oxygen tensions. This development followed preparatory work by the same authors (3,4) in which the kinetic factors involved in CO and hemoglobin combination were reported. The principles underlying the measurements have been fully discussed by Forster in a recent review (5).Lewis, Lin, Noe and Komisaruk (6) reported on the measurement of pulmonary capillary blood volume in normal subjects, using the single breath method of determining the pulmonary diffusing capacity. They found average values of 65 ml for the pulmonary capillary blood volume at rest and 98 ml CO per minute per mm Hg for the membrane diffusion component. In four subjects both of these quantities increased somewhat during exercise. They did not report any results on patients. McNeill, Rankin and Forster (7), using a similar technique of measuring the pulmonary diffusing capacity by a single breath method, found similar values at rest for the pulmonary capillary blood volume, but a lower value for the membrane component, which was about 63.5 ml CO per minute per mm Hg in normal subjects at rest. These authors reported the results of this measurement in five patients with various types of pulmonary fibrosis, two with pulmonary hypertension, two with pulmonary congestion, and three with chronic obstructive emphysema. The most significant findings were the decrease in membrane diffusion component ib patients with pulmonary fibrosis, and the increase generally found in pulmonary capillary blood volume in patients with increased pressure in the lesser circulation.The present study reports the measurement of * Supported by a grant from the National Research Council of Canada.these two components of the pulmonary diffusing capacity by a steady state method during exercise in 14 normal subjects and in a group of 22 patients. This work was undertaken to study the reliability of the results obtainable with this technique, and to explore its usefulness in investigative work. METHODSThe apparatus used in this work has recently been described in full (8). A steady state measurement of diffusing capacity (DL) is made, the mean alveolar CO tension being calculated from an assumed value of respiratory dead space. Technical details and a study of the errors of this method have been presented previously (8). The determination of pulmonary capillary blood volume (Va) and membrane diffusion component (DM) involves the measurement of the pulmonary diffusing capacity at two different oxygen tensions. Each experiment whether on a normal subject or a patient consisted in the measurement of the diffusing capacity on either 60 or 100 per cent oxygen, followed by its determination on air. All estimates were made during moderate or light exercise.In a typical determination, the subject attained a steady state on the exercise treadmill for 5 minutes, and was then switch...

The pulmonary function of 24 normal subjects ranging in age from 20 to 50 years has been studied at rest and during exercise. At rest there is a significant decrease with age in the pulmonary diffusing capacity and the level of diffusing capacity attained on exercise at any particular oxygen uptake decreases with increasing age. Simultaneous measurements of O2 uptake, ventilation, end tidal O2 and CO2 concentration and calculated alveolar CO2 concentration, using the Bohr equation, show no evidence that any of these measurements are significantly influenced by age. The predicted maximal O2 diffusing capacity ( J. Appl. Physiol. 6: 588, 1954) predicts with fair accuracy the diffusing capacity for carbon monoxide that will be found in any given individual at an O2 uptake of about 2.8 l/min. It correctly predicts the change in CO diffusing capacity with increasing age. Reasons are given for suggesting that the decrease in pulmonary diffusing capacity observed may be explained by a diminution in cardiac output with increasing age. Submitted on November 21, 1958

Pulmonary capillary blood flow (Qc) in the exercising subject was calculated from the rate of disappearance of N2O during steady state breathing of an N2O-He-O2 mixture. Measurements were made after alveolar rinsing (reciprocal of N2 washout) had occurred, and up to 30 sec, a time period accompanied by minimal recirculation, since FaNN2O during this period did not rise significantly. Repeatability of the method, judged as the difference of a second estimate from a first on the same subject, was comparable to that reported for the direct Fick technique in resting subjects (31 of 33 paired observations agreed within 20%). Results over a wide range agreed with almost simultaneous measurements by a dye dilution technique (24 of 26 paired observations agreed within 20%), and when related to pulse rate and to Vo2, were comparable to those of the other workers whose subjects were studied in a similar posture. Indeed, this technique (using the indirect Fick principle under “steady state” conditions) probably attains its greatest accuracy during exercise when other methods become less easily applicable. Submitted on December 18, 1961