Ventilatory "inefficiency" during exercise in obstructive lung disease-such as that resulting from increased dead space or ventilation-perfusion mismatch-is commonly interpreted as a perturbation that requires an additional increase in minute ventilation and thus in V̇E/V̇CO2 to preserve PaCO2 homeostasis. This observation raises a fundamental question: how could an increase in V̇E/V̇CO2 during exercise be actively directed toward defending PaCO2 stability if no known neural signal, governing respiration, directly encodes ventilatory "inefficiency"? We retrospectively analyzed the lung-function and anthropometric data, as well as ventilatory and gas-exchange responses obtained at rest, lactate threshold (LaT), and peak exercise, of 443 patients with obstructive lung disease who underwent cardiopulmonary exercise testing and spanning a wide range of V̇E/V̇CO2. Relationships between PETCO2 and V̇E/V̇CO2, estimated V̇A/V̇CO2, and V̇D/V̇CO2 were examined using power-law regression. Patients were then stratified by peak V̇E/V̇CO2, and group differences were assessed using Welch ANOVA, with effect sizes expressed as η² and Cohen's d. Across rest, LaT, and peak exercise, PETCO2 exhibited a continuous ≈1/x relationship with V̇E/V̇CO2 that closely paralleled PETCO2-V̇A/V̇CO2. Stratification by V̇E/V̇CO2 consistently identified very large effect sizes for PETCO2. This PETCO2-V̇E/V̇CO₂ "phenotype" was also present in the normocapnic range. Hypercapnia was observed only in patients with low V̇E/V̇CO2. Arterial PCO2 obtained just at the exercise cessation retained a similar pattern, remaining inversely related to peak V̇E/V̇CO₂. The present study supports the view that PaCO2 is emergent, and not defended, in this cohort of COPD patients. Implications for control of breathing during exercise are discussed.
Haouzi et al. (Thu,) studied this question.