Gas exchange efficiency slopes to assess exercise tolerance in chronic obstructive pulmonary disease

Abstract

Background: In patients with chronic obstructive pulmonary disease (COPD), the clinical use of the minute ventilation-carbon dioxide production ([Formula: see text]_E-[Formula: see text]_CO2) slope has been reported as a measure of exercise efficiency, but the oxygen uptake efficiency slope (OUES), i.e., the slope of oxygen uptake ([Formula: see text]_O2) versus the logarithmically transformed [Formula: see text]_E, has rarely been reported.

Methods: We hypothesized that the [Formula: see text]_E-[Formula: see text]_CO2 slope is more useful than OUES in clinical use for the pathophysiological evaluation of COPD. Then, we investigated the cardiopulmonary exercise testing parameters affecting each of these slopes in 122 patients with all Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD grades selected from our database.

Results: Compared with the GOLD I-II group (n = 51), peak [Formula: see text]_O2 (p < 0.0001), OUES (p = 0.0161), [Formula: see text]_E at peak exercise (p < 0.0001), and percutaneous oxygen saturation (SpO₂) at peak exercise (p = 0.0004) were significantly lower in the GOLD III-IV group (n = 71). The GOLD III-IV group was divided into two groups by the exertional decrease in SpO₂ from rest to peak exercise: 3% or less (the non-desaturation group: n = 23), or greater than 3% (the desaturation group: n = 48). OUES correlated only weakly with peak [Formula: see text]_O2, [Formula: see text]_E at peak exercise, and the difference between inspired and expired mean O₂ concentrations (ΔF_O2) at peak exercise, i.e., an indicator of oxygen consumption ability throughout the body, in the GOLD III-IV group with exertional hypoxemia. In contrast, the [Formula: see text]_E-[Formula: see text]_CO2 slope was significantly correlated with ΔF_O2 at peak exercise, regardless of the COPD grade and exertional desaturation. Across all COPD stages, there was no correlation between the [Formula: see text]_E-[Formula: see text]_CO2 slope and [Formula: see text]_E at peak exercise, and stepwise analysis identified peak [Formula: see text]_O2 (p = 0.0345) and ΔF_O2 (p < 0.0001) as variables with a greater effect on the [Formula: see text]_E-[Formula: see text]_CO2 slope.

Conclusions: The OUES may be less useful in advanced COPD with exertional hypoxemia. The [Formula: see text]_E-[Formula: see text]_CO2 slope, which is independent of [Formula: see text]_E, focuses on oxygen consumption ability and exercise tolerance in COPD, regardless of the exertional hypoxemia level and COPD grade. Therefore, the [Formula: see text]_E-[Formula: see text]_CO2 slope might be useful in establishing or evaluating tailor-made therapies for individual patient's pathologies in COPD as an indicator focusing on oxygen consumption ability.

Keywords: Carbon dioxide; Exercise tolerance; Gas exchange; Oxygen; Pulmonary rehabilitation; Ventilatory efficiency.

Fig. 1

Calculation of OUES. a) The relationship between oxygen uptake (_O2: mL ⋅ min⁻¹) and the common logarithm of minute ventilation (_E: L ⋅ min⁻¹) (b) the relationship between _O2 (mL ⋅ min⁻¹) and _E (L ⋅ min⁻¹). _O2 and _E obtained from breath-by-breath gas-exchange measurements in one COPD patient with GOLD I (75 years old, 64.2 kg) were used. OUES was calculated as the slope of the regression line relating _O2 (mL ⋅ min^− 1) to the common logarithm of _E (L ⋅ min^− 1) by the equation: _O2 = slope × log _10E + intercept. where the constant ‘slope’ is the OUES. Basically, to avoid possible irregular breathing patterns, data from the 3-min resting period, from the first minute of exercise, and from a plateau in _O2 were excluded from the calculation of the OUES. Green cross: exercise starting point; blue crosses: period during which OUES was calculated

Fig. 2

In all COPD stages, correlations of the oxygen uptake efficiency slope (OUES) (upper panel) and the _E/_CO2 slope (bottom panel) with exertional variables during cardiopulmonary exercise testing. Correlations of OUES with peak _O2 (a), _E at peak exercise (b), O₂ pulse at peak exercise (c), and ΔF_O2 at peak exercise (d) are shown. Correlations of the _E/_CO2 slope with peak _O2 (e), ΔF_O2 at peak exercise (f), and ΔF_O2 max. during exercise (g) are shown. ΔF_O2: difference between inspired and expired mean oxygen concentrations; ΔF_O2 max.: highest ΔF_O2 value during exercise; O₂ pulse: _O2/heart rate; _E: minute ventilation; _O2: oxygen uptake. Closed circle: Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II group (n = 51). Open circle: GOLD III-IV group (n = 71). The shaded area indicates the CI. The correlation coefficient (r) was obtained in the analysis of all COPD stages

Fig. 3

In COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) III and IV stages, the correlations of oxygen uptake efficiency slope (OUES) (upper panel) and the _E/_CO2 slope (bottom panel) with exertional variables during cardiopulmonary exercise testing classified by oxygen (O₂) desaturation level. Correlations of OUES with peak _O2 (a), _E at peak exercise (b), O₂ pulse at peak exercise (c), and ΔF_O2 at peak exercise (d) are shown. Correlations of the _E/_CO2 slope with peak _O2 (e), ΔF_O2 at peak exercise (f), and ΔF_O2 max. during exercise (g) are shown. ΔF_O2: difference between inspired and expired mean oxygen concentrations; ΔF_O2 max.: highest ΔF_O2 value during exercise; O₂ pulse: _O2/heart rate; _E: minute ventilation; _O2: oxygen uptake. Closed triangle and solid line: group with O₂ desaturation of 3% or less during exercise (n = 23). Open triangle and dotted line: group with O₂ desaturation greater than 3% during exercise (n = 48). The shaded area indicates the CI. The correlation coefficient (r) was obtained in the analysis for each group

Fig. 4

Relationship between oxygen uptake (_O2: mL ⋅ min⁻¹) and minute ventilation (_E: L ⋅ min⁻¹) in (a) GOLD III-IV without exertional desaturation, 3% or less decrease (n = 23) and (b) GOLD III-IV with exertional desaturation, greater than 3% decrease (n = 48). Plots from left to right at rest, at 2 min, and at peak exercise. To see whether it is inappropriate to represent the relationship of _O2 to _E as a line, the dotted line is a straight line connecting the resting and 2-minute plots. GOLD: Global Initiative for Chronic Obstructive Lung Disease. Mean ± standard error. *: p < 0.05 between the non-desaturation and desaturation groups in _E (x-component)