Ventilatory inefficiency in obstructive lung disease reveals emergent [Formula: see text] equilibrium during exercise

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 [Formula: see text] homeostasis. This observation raises a fundamental question: how could an increase in V̇e/V̇co₂ during exercise be actively directed toward defending [Formula: see text] 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 [Formula: see text] 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, [Formula: see text] exhibited a continuous ≈1/x relationship with V̇e/V̇co₂ that closely paralleled [Formula: see text]-V̇a/V̇co₂. Stratification by V̇e/V̇co₂ consistently identified very large effect sizes for [Formula: see text]. This [Formula: see text]-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 [Formula: see text] is emergent, and not defended, in this cohort of patients with chronic obstructive pulmonary disease (COPD). Implications for control of breathing during exercise are discussed.NEW & NOTEWORTHY Despite very different levels of obstructive lung disease and ventilatory insufficiency, [Formula: see text] and [Formula: see text] display an inverse relationship with V̇e/V̇co₂ across exercise levels. Stratification by V̇e/V̇co₂ demonstrates that interindividual differences in V̇e/V̇co₂ were driven by changes in effective alveolar ventilation. These results support the view that [Formula: see text] stability is apparent during exercise. [Formula: see text] passively emerges from the interactions between a constrained respiratory plant at any ventilatory drive.