Cardiopulmonary Exercise Testing in Combined Pulmonary Fibrosis and Emphysema

Abstract

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a distinct entity among fibrosing lung diseases with a high risk for lung cancer and pulmonary hypertension (PH). Notably, concomitant PH was identified as a negative prognostic indicator that could help with early diagnosis to provide important information regarding prognosis. Objectives: The current study aimed to determine whether cardiopulmonary exercise testing (CPET) can be helpful in differentiating patients having CPFE with and without PH. Methods: Patients diagnosed with CPFE in 2 German cities (Hemer and Greifswald) over a period of 10 years were included herein. CPET parameters, such as peak oxygen uptake (peak VO₂), functional dead space ventilation (V_Df/V_T), alveolar-arterial oxygen difference (AaDO₂), arterial-end-tidal CO₂ difference [P(a-ET)CO₂] at peak exercise, and the minute ventilation-carbon dioxide production relationship (VE/VCO₂ slope), were compared between patients with and without PH. Results: A total of 41 patients with CPET (22 with PH, 19 without PH) were analyzed. Right heart catheterization was performed in 15 of 41 patients without clinically relevant complications. Significant differences in peak VO₂ (861 ± 190 vs. 1,397 ± 439 mL), VO₂/kg body weight/min (10.8 ± 2.6 vs. 17.4 ± 5.2 mL), peak AaDO₂ (72.3 ± 7.3 vs. 46.3 ± 14.2 mm Hg), VE/VCO₂ slope (70.1 ± 31.5 vs. 39.6 ± 9.6), and peak P(a-ET)tCO₂ (13.9 ± 3.5 vs. 8.1 ± 3.6 mm Hg) were observed between patients with and without PH (p < 0.001). Patients with PH had significantly higher V_Df/V_T at rest, V_T1, and at peak exercise (65.6 ± 16.8% vs. 47.2 ± 11.6%; p < 0.001) than those without PH. A cutoff value of 44 for VE/VCO₂ slope had a sensitivity and specificity of 94.7 and 72.7%, while a cutoff value of 11 mm Hg for P(a-ET)CO₂ in combination with peak AaDO₂ >60 mm Hg had a specificity and sensitivity of 95.5 and 84.2%, respectively. Combining peak AaDO₂ >60 mm Hg with peak VO₂/body weight/min <16.5 mL/kg/min provided a sensitivity and specificity of 100 and 95.5%, respectively. Conclusion: This study provided initial data on CPET among patients having CPFE with and without PH. CPET can help noninvasively detect PH and identify patients at risk. AaDO₂ at peak exercise, VE/VCO₂ slope, peak P(a-ET)CO₂, and peak VO₂ were parameters that had high sensitivity and, when combined, high specificity.