Muscle Unloading During Exercise: Comparative Effects of Conventional Oxygen, NIV, and High-Flow Therapy on Neural Drive in Severe COPD

Objectives: This study aimed to evaluate how non-invasive ventilation (NIV) and high-flow nasal cannula therapy (HFT) versus conventional oxygen therapy (COT) affect neural ventilatory drive during exercise in patients with severe chronic obstructive pulmonary disease (COPD). Methods: We conducted an experimental, controlled study with one arm and three different conditions for the same cohort. After initial testing on conventional oxygen therapy (COT), patients exercised under NIV and HFT in sequential days and a random order. Participants: Twenty patients (mean age 60 years old (SD 3.9), 6 female) with severe COPD (30% women) on home NIV as a bridge to lung transplantation were enrolled in this study, with a mean FEV1 of 19.78% predicted and marked hyperinflation. Protocol: Participants performed constant-load cycling exercises at 75% maximum tolerated workload under three conditions: COT, NIV, and HFT. Neuro-respiratory drive (NRD) was measured using surface parasternal and sternocleidomastoid electromyography, and mixed ANOVA was performed to analyze repeated measures across conditions. Results: In total, 20 patients were included in this study. NIV demonstrated superior performance, with 60% lower NRD compared to COT (488.81 µV vs. 1180.63 µV, p < 0.05). HFT showed intermediate effects (807.8 µV). NIV also achieved greater reduction in respiratory rate (4.2 breaths/min), lower perceived exertion (Borg score decrease: 1.8 points), and more pronounced CO2 reduction (5.3 mmHg) compared to both COT and HFT. Conclusions: NIV significantly reduces NRD during exercise in severe COPD patients compared to HFT and COT. This supports its use as a valuable adjunct to pulmonary rehabilitation in severe COPD.