James MD; Respiratory Investigation Unit, Queen’s University, Kingston, Canada
McCleary J; Back GD; Alosta KA; et al

Copd: Journal of Chronic Obstructive Pulmonary Disease. 23(1):2650696,
2026 Mar 24.

A sizable fraction of dyspneic patients with only mild to moderate COPD
exhibit a heightened ventilatory response to exercise relative to
metabolic demands, i.e. a high ventilation (V.E)/CO2 output (V.CO2). The
lack of continuous assessment of gas exchange efficiency and estimates of
arterial CO2 partial pressure has hindered our understanding of the
physiological underpinnings of this dynamic phenomenon. We compared key
indices of gas exchange efficiency relative to the intra-breath CO2
profile as a function of expired volume using breath-by-breath volumetric
capnography in 30 patients (FEV1 = 76 +/- 17%) and 30 sex- and age-matched
controls during incremental cycle ergometry. Wasted ventilation in the
physiological dead space (VDphys) was calculated as the sum of airway and
alveolar (alv) dead space divided by tidal volume (VT). Transcutaneous
(tc) readings provided estimates of arterialised PCO2. Patients exhibited
lower exercise tolerance, reporting higher dyspnoea throughout exercise (p
< 0.05). Higher V.E/V.CO2 was associated with higher absolute (L) alveolar
dead space (VDalv), but similar VT; thus, both VDphys/VT and VDalv/VT were
consistently higher in patients (p < 0.05). V.E/V.CO2 was elevated (>=34)
in normocapnic patients (PtcCO2>=35 mmHg) who had a high VDphys/VT
(>=0.3); conversely, high V.E/V.CO2 coexisted with a lower VDphys/VT only
in hypocapnic subjects (p < 0.05). Higher VDalv and lower PtcCO2 were
independently associated with a high V.E/V.CO2 nadir and iso-work rate
dyspnoea (p < 0.001). Based on this innovative, high-density
data-acquisition approach, we conclude that both wasted ventilation and
alveolar hyperventilation, in a highly variable combination, contribute to
excessive ventilation in dyspneic patients with mild-to-moderate COPD