Figure 1. Trial recruitment flowchart and experimental protocol.

Flowchart showing recruitment, randomization, and data collection from subjects in blocks 1 and 2. In block 1, subjects received a breathing intervention consisting of 15 episodes of breathing mild hypoxia (fraction of inspired oxygen [Fio₂] = 0.09) for 90 seconds alternating with 60-second normoxia (Fio₂ = 0.21). This intervention was repeated once daily for 5 days. Alternatively, subjects received 5 days of continuous normoxia. Overground walking speed and endurance were quantified by the 10-Meter Walk Test and 6-Minute Walk Test, respectively, at baseline (BL), within 60 minutes after acute intermittent hypoxia (AIH) on the first (D1) and fifth (D5) exposure days, and in follow-ups (F/U) at 1 week (F1, i.e., D8) and 2 weeks (F2, i.e., D15). In block 2, subjects received a combinatorial intervention of daily AIH and overground walking (dAIH + walking). After the breathing intervention and a 35- to 45-minute rest period, subjects walked overground at maximal exertion for 30 minutes each day. Overground walking speed and endurance were quantified at BL, D1, D5, F1, and F2. dSHAM = daily normoxia.