Hypercapnic ventilatory response (HCVR) techniques have not previously been adequately validated in patients with chronic obstructive pulmonary disease (COPD). We have tested the hypothesis that end-tidal PCO₂ may be used to test the HCVR in COPD during non-steady-state rebreathing, despite the fact that large (arterial–end-tidal) PCO₂ differences (P(a–et)CO₂) exist during air breathing.

Eight patients and 11 healthy volunteers underwent steady-state HCVR testing and non-steady-state rebreathing HCVR testing, using Pa and PetCO₂.

In COPD patients, PetCO₂ was lower than PaCO₂ by a constant amount throughout steady-state HCVR, but equalised with PaCO₂ during non-steady-state HCVR. Consequently there were no differences in HCVR slope using either method (steady-state p=0.91; rebreathing p=0.73), or HCVR intercept in rebreathing (p=0.68) whether PaCO₂ or PetCO₂ was used. The steady-state HCVR intercept using PetCO₂ was greater than that using PaCO₂ (p=0.02). In healthy volunteers PetCO₂ equalised with PaCO₂ during steady-state HCVR, but was progressively greater than PaCO₂ during non-steady-state. Consequently, there was no difference in HCVR slope (p=0.21) or intercept (p=0.46) whether PaCO₂ or PetCO₂ was used. During non-steady-state there was a P(a–et)CO₂ difference in slope (p=0.03) and intercept (p=0.04).

In COPD patients non-steady-state HCVR using PetCO₂ is well tolerated, which is as accurate as PaCO₂. HCVR slope may be derived using PetCO₂ during steady-state testing, though there may be errors in intercept compared to use of PaCO₂. In healthy volunteers PetCO₂ may be used to estimate PaCO₂ during steady-state but not rebreathing HCVR.