VE-VCO2 Slope During Cardiopulmonary Exercise Test Predicts Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study

Background: Cardiopulmonary Exercise Test (CPET) serves as an integrative assessment tool to evaluate cardiac function, respiratory responses, and neuromuscular capacity in patients with chronic obstructive pulmonary disease (COPD) during incremental cycling exercise. VE-VCO2 slope during CPET was not fully understood in predicting acute exacerbations of COPD (AECOPD). This study aims to establish a predictive model for AECOPD based on the VE-VCO2 slope. Methods: In total, 79 patients with COPD were recruited between 2013 and 2019. All participants underwent baseline pulmonary function tests and CPET and were followed up for 5 years thereafter. Independent two-sample t -tests and Chi-square tests were used to compare AECOPD and Non-AECOPD groups. Univariate and multivariate Cox regression analyses were utilized to identify predictive factors for AECOPD. The diagnostic performance of these variables was evaluated by receiver operating characteristic (ROC) curve analysis. The optimal cutoff values calculated by Youden’s index. Kaplan-Meier survival analysis between subgroups was based on the optimal cutoff values. Generating Forest plots to visualize Cox regression analysis results. Results: The AECOPD group contains 62 participants and the Non-AECOPD group contains 17 participants. Groups comparisons revealed significant differences in VE-VCO2 slope, age, BMI, FEV1%predicted, FEV1/FVC ratio, and EqCO2. Multivariate Cox regression analysis identified VE-VCO2 slope (OR = 1.19, 95% CI: 1.09– 1.29, p < 0.001), age (OR = 1.05, 95% CI: 1.02– 1.09, p = 0.005), and FEV1%predicted (OR = 0.96, 95% CI : 0.94– 0.99, p = 0.015) as significant predictors of AECOPD. The ROC curve analysis results about the above predictors found that the AUC of VE-VCO2 slope is highest independently in 1 year, 3 years and 5 years, with the optimal cutoff values = 28.42 in 5 years (hazard ratio = 3.18, 95% CI: 1.639– 6.2, p < 0.001). Conclusion: The stratification of VE-VCO2 slope ≥ 28.42 was an independent predictor of AECOPD. Our study established VE-VCO2 slope as a novel stratified clinical biomarker for predicting AECOPD. Keywords: COPD, exacerbation, CPET, VE-VCO2 slope, ventilation-perfusion mismatch