Author(s): GASPARINI, A., BOCHICCHIO, G., TAM, E., ZAMBONI, F., TESO, M., BALDASSARRE, G., ZUCCARELLI, L., PATRUNO, V., BROCCA, L., BOTTINELLI, R., PELLEGRINO, M., CRISAFULLI, E., GRASSI, B., CAPELLI, C., Institution: UNIVERSITY OF VERONA, Country: ITALY, Abstract-ID: 1473

INTRODUCTION:
Chronic obstructive pulmonary disease (COPD) is characterized by impaired gas exchange resulting from ventilation to perfusion (VA/Q) heterogeneity. Increased physiological dead space (VD/VT) is responsible for wasted ventilation, reduced ventilatory efficiency, and VA/Q heterogeneity, which may amplify the alveolar–arterial PO2 gradient (A–a O₂ diff), potentially leading to frank hypoxemia. These indices describe distinct components of gas-exchange dysfunction that may differentially contribute to ventilatory inefficiency, hypercapnia, and impaired exercise performance. This study aimed to investigate the relationship between ventilatory efficiency, VD/VT, and A–a O₂ diff at rest and during incremental cardiopulmonary exercise testing (CPET) in patients with COPD.
METHODS:
14 patients (7 women, 7 men; 66±8 yy; 70±17 kg) with moderate-to-severe COPD (GOLD II–III, FEV₁ ≤50% predicted) and thirty-one age-matched healthy controls performed an incremental cycle-ergometer CPET. Ventilatory efficiency was assessed using VE/VCO₂ slope, intercept and nadir. In a subgroup of seven COPD patients and fourteen controls, physiological dead space (VD/VT) was estimated non-invasively using transcutaneous PCO₂ (1) and a mass-balance approach (2). The alveolar–arterial oxygen gradient was calculated from arterialized capillary blood gas analysis obtained at rest and peak exercise (3). Group differences were analysed using unpaired t-tests with Welch’s correction.
RESULTS:
The VE/VCO₂ slope did not differ between COPD and controls, whereas the VE/VCO₂ intercept was significantly higher in COPD (6.5 ± 1.9 vs 4.0 ± 2.4 L·min⁻¹, p = 0.001). The VE/VCO₂ nadir was also significantly higher in COPD compared with controls (36.0 ± 7.9 vs 28.4 ± 3.3, p = 0.003). Arterial O₂ saturation was lower in COPD than in controls at rest and peak exercise (both p<0.001) but remained above 90%. VD/VT was consistently elevated in COPD from rest to peak exercise (≈ +32% vs controls, p < 0.05), indicating increased wasted ventilation. A–a O₂ diff was significantly higher in COPD at rest and peak exercise (≈ +60% vs controls, p < 0.01) but did not parallel changes in ventilatory efficiency indices.
CONCLUSION:
During incremental exercise in COPD, ventilatory inefficiency is primarily associated with increased VD rather than impaired oxygenation. The dissociation between ventilatory efficiency indices and A–a O₂ diff suggests that wasted ventilation is a dominant contributor to ventilatory inefficiency during exercise. These findings support the use of non-invasive physiological markers to characterize exercise gas-exchange abnormalities in COPD.
Funding: MUR PRIN Project 2022, P2022XX7YL.

REFERENCES:
1. Cao M, et al. COPD. 2021 Feb; 18(1):16 - 25.
2. Whipp BJ, Ward SA. Br J Sports Med. 1998 Sep;32(3):199 – 211
3. Rahn, H., & Fenn, W. O. (1955). A graphical analysis of the respiratory gas exchange: The O2-CO2 diagram. American Physiological Society.