Hospital staff and their children were recruited for the study. Data obtained from prematurely born children who were participating in a long-term follow-up study and from children who had undergone exercise testing for growth hormone secretion were also employed. Subjects were excluded if they had an FEVX of <80% of their predicted value based on age, race, sex, and height. The study had the approval of the Institutional Review Board of the Montreal Children’s Hospital/McGill Research Institute. For children, an informed consent was obtained from one of the parents as well as from the child.
For each subject, height was measured in stocking feet on a stadiometer and weight was measured using an electronic balance. Expiratory spirometry was performed according to American Thoracic Society criteria.
To determine maximal work capacity, all subjects, except the two being evaluated for growth hormone secretion, performed a maximal progressive test using an electronically braked cycle ergometer. The workload was increased in 1-min increments, which were chosen according to the sex and height of the subject so that exhaustion would occur within 5 to 10 min. The maximum workload was the highest workload at which a subject was able to maintain a pedaling speed of 60 rpm. Heart rate was monitored continually and recorded via ECG. Inspired ventilation was measured by a dry gas meter (Parkinson Cowan; Manchester, UK). Exhalation was via a unidirectional valve to a variable-volume mixing chamber adjusted to the subject’s vital capacity. Mixed expired gas was analyzed and recorded continuously for fractional concentrations of oxygen and carbon dioxide using a mass spectrometer (Marquette Electronics; Milwaukee). Vo2 and carbon dioxide production (Vco2) were calculated using the nitrogen balance technique, based on values for ventilation and mixed expired concentrations of oxygen and carbon dioxide obtained during the last 10 s of each workload. Details of the method have been described previously.
After a rest period of at least 30 min, a steady-state exercise test was performed at approximately half maximal work capacity in adults and children with the exception of two adult men who were evaluated at two-thirds maximal work capacity in order to increase the range of Vo2 measured. For the two children being tested for growth hormone levels, the steady-state test was performed at half the predicted maximal work capacity based on sex and height. Exercise at a constant workload was performed until steady-state conditions were reached for Vo2, Vco2, and heart rate. This usually occurred within 4 to 5 min.
At steady state, a rebreathing procedure was performed using the equilibrium method in which each subject rebreathed from a bag containing a mixture of a high concentration of C02 (11 to 13.5%) and oxygen (76.5 to 79%) at a volume of two-thirds the vital capacity.
In children, after steady state had been reestablished (a minimum of 60 s), a second rebreathing procedure was performed using the exponential method. For this, the subject rebreathed a mixture of 4% C02 and 96% oxygen at a volume of 1.5 to 2 times the tidal volume.
PvC02 was calculated for the equilibrium method using the method of Collier in which the plateau value of PetC02 between 6 and 10 s (PeqC02) was determined; the extrapolation procedure described by Denison et al was used when an absolute plateau was not obtained. The downstream correction was applied to this value to correct for alveolar-to-blood Pco2 differences. For the exponential method, PvC02 was calculated using the method of Defares.2 PetC02 values between 1.5 and 13 s were used for Vo2 < % max and those between 1.5 and 11s for higher values of Vo2, to avoid the effects of recirculation. PetC02 was linearized to time by log transformation and successive iterations of the asymptote were performed to derive a best fit line using least squares linear regression analysis. Using the fitted line, the projected PetC02 value at 20 s of rebreathing was used as the estimate of PvC02.
Q was determined by dividing the Vco2 by the venous-arterial C02 content difference, which was derived from the C02 tensions, assuming a hemoglobin of 150 g/L, a pH of 7.40, and an oxygen saturation of 97% for arterial blood. It was assumed that the oxygen saturation of the mixed venous blood was 100% during the rebreathing procedure, because of the high concentration of oxygen in the rebreathing gas mixture. Vo2 and Vco2 were calculated for the 15 s prior to each rebreathe. PaC02 was estimated from PetC02 using a correction factor as described by Jones:
PaC02=5.5 + 0.9 • PetC02 — 0.0021 • tidal volume. PvC02 was estimated by the equilibrium method.
Analysis of Data
PvC02 as obtained by the equilibrium method, with and without downstream correction, was compared to that obtained by the exponential method using analysis of variance. The relationships between the corrected and uncorrected PvC02 values obtained by the equilibrium method and the values obtained by the exponential method were assessed by linear regression analysis.
Q obtained by the equilibrium method with and without downstream correction was plotted against Vo2 and assessed by linear regression analysis. Stepwise linear regression analyses were also performed to look at the effects of weight, sex, and subject category (adults, normal children, prematurely born children, children being evaluated for growth hormone levels).
For regression equations, slopes and intercepts were compared with those in the literature using the unpaired t test: because the standard errors (SEs) were not available for the values from the literature, the differences between the values obtained in this study and those in the literature were divided by the standard errors of the values obtained in this study.