Improvements in Lung Diffusion Capacity following Pulmonary Rehabilitation in COPD with and without Ventilation Inhomogeneity

Background: Lung diffusing capacity (DLCO) and lung volume distribution predict exercise performance and are altered in COPD patients. If pulmonary rehabilitation (PR) can modify DLCO parameters is unknown. Objectives: To investigate changes in DLCO and ventilation inhomogeneity following a PR program and their relation with functional outcomes in patients with COPD. Methods: This was a prospective, observational, multicentric study. Patients were evaluated before and after a standardized 3-week PR program. Functional assessment included body plethysmography, DLCO, transfer factor (KCO) and alveolar volume (VA), gas exchange, the 6-min walking test (6MWT) and exercise-related dyspnea. Patients were categorized according to the severity of airflow limitation and presence of ventilation inhomogeneity, identified by a VA/TLC <0.8. Results: Two hundred and fifty patients completed the study. Baseline forced expiratory volume in 1 s (FEV₁) % predicted (mean ± SD) was 50.5 ± 20.1 (76% males); 137 patients had a severe disease. General study population showed improvements in 6MWT (38 ± 55 m; p < 0.01), DLCO (0.12 ± 0.63 mmol × min^-1 kPa^-1; p < 0.01), lung function and dyspnea. Comparable improvements in DLCO were observed regardless of the severity of disease and the presence of ventilation inhomogeneity. While patients with VA/TLC <0.8 improved the DLCO increasing their VA (177 ± 69 ml; p < 0.01), patients with VA/TLC >0.8 improved their KCO (8.1 ± 2.8%; p = 0.019). The latter had also better baseline lung function and higher improvements in 6MWT (14.6 ± 6.7 vs. 9.0 ± 1.8%; p = 0.015). Lower DLCO at baseline was associated with lower improvements in 6MWT, the greatest difference being between subjects with very severe and mild DLCO impairment (2.7 ± 7.4 vs. 14 ± 2%; p = 0.049). Conclusions: In COPD patients undergoing a PR program, different pathophysiological mechanisms may drive improvements in DLCO, while ventilation inhomogeneity may limit improvements in exercise tolerance.