C72-23 Elevated vE/vCo2 During Exercise in ILD Patients Is Not a Consequence of Impaired Pulmonary Gas Exchange

Introduction An elevated ventilatory equivalent for carbon dioxide (the ratio between minute ventilation (V̇E) and CO2 output (V̇CO2) during exercise has been associated with poor outcomes in interstitial lung disease (ILD). Such a high V̇E/V̇CO2 is traditionally attributed to excessive V̇E response compensating for increased dead space ventilation (V̇D). A high V̇E/V̇CO2 is therefore considered a marker of poor efficiency of the pulmonary gas exchange system during exercise. Since dead space (or V̇A/Q mismatch) cannot be directly sensed by the respiratory neurons, the fundamental question of the mechanisms of high V̇E/V̇CO2 in these patients remains unanswered. Methods We characterized the ventilatory response to exercise in 47 patients (64±14 years, 49% female) with ILD. Seventeen percent had IPF and 9% displayed a UIP pattern. Thirteen patients had resting pulmonary hypertension. Twenty underwent invasive CPET while 27 had non-invasive CPET. We determined the correlation between V̇E/V̇CO2 and PETCO2 and computed V̇A/V̇CO2 (863/ PETCO2) and V̇D/V̇CO2 (V̇E/V̇CO2− V̇A/V̇CO2) at the lactate threshold and peak exercise. We sought to determine whether a high V̇E/V̇CO2 ratio develops independently of V̇D. Patients were stratified by peak V̇E/V̇CO2 (<35, 35-45, >45). Finally, PaO2, PaCO2, pulmonary hemodynamics, arterial pH, and lung function were compared between groups using ANOVA. Results At the lactate threshold, when ventilation should not be hypocapnic, we observed an inverse relationship between V̇E/V̇CO2 and PETCO2 (figure, left panel). This pattern was independent of V̇D/V̇CO2. Patients with higher V̇E/V̇CO2 exhibited the highest V̇A/V̇CO2 ratio, leading to severe hypocapnia. At peak exercise (figure, right panel), the same pattern persisted with more profound hypocapnia. Patients with peak exercise V̇E/V̇CO2 >45 (n = 16, 34%) reached PETCO2 <25 mmHg. The only relevant difference was a lower DLCO in that group (55±17% vs 88±19% predicted, p < 0.004), with no differences in pulmonary hemodynamics, PaO2, lung volumes, lactate, or arterial pH. Of note, six patients failed to generate expected hypocapnia (low V̇E/V̇CO2) at peak exercise, an abnormal pattern of relative hypoventilation. Conclusions In ILD, elevated V̇E/V̇CO2 consistently indicates relative hyperventilation that surpasses the decline in pulmonary “efficiency,” irrespective of V̇D. This pattern is observed at both lactate threshold and peak exercise. These findings support the hypothesis of an excessive ventilatory drive in ILD, analogous to the disproportionate ventilatory response observed in other debilitating conditions such as heart failure. Thus, in ILD, the mechanisms of this hyperventilation remain hypothetical. This abstract is funded by: none