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BACKGROUND: Arterial oxygen desaturation frequently occurs in patients with COPD during daily activities at home. Oxygen flow is usually set at fixed and low rates for ambulatory patients. We evaluated an innovative closed-loop system (FreeO2) that automatically adjusts the oxygen flow to the patient's needs in subjects with COPD during walking followed by recovery time, such as during ambulatory conditions. METHODS: Patients with COPD who exhibited oxygen desaturation on exertion were included in the study. Subjects performed endurance shuttle walk tests followed by 10 min of recovery. The tests were conducted in a random order and in crossover with the 3 following conditions: subjects breathing (1) air at 2 L/min, (2) oxygen at 2 L/min, or (3) FreeO2 (variable oxygen flow). ..., pulse rate, ... breathing frequency, and oxygen flow were continuously recorded during the 3 conditions. The primary outcome was the percentage of time within the ... target of 92-96%. Secondary outcomes included the endurance shuttle walk test time and distance. RESULTS: Sixteen subjects with COPD were recruited. The percentage of time with ... in the target range (92-96%) was higher while using the FreeO2. and time with severe oxygen desaturation ... <88%) was lower with Free02 in comparison with constant-flow oxygen and air testing conditions (0.6% vs 23.9% vs 52.2%, P < .001). In comparison with air, walking distance was increased by 35% with oxygen (P - .045) and by 63% with FreeO2 (P < .001). The walking distance was increased by 17% with FreeO2 in comparison with constant oxygen, but the difference was not statistically significant (P = .22). CONCLUSIONS: Automatic titration of oxygen flow during walking to maintain oxygen saturation in a specified range improves oxygenation and may improve exercise tolerance during daily activity, such as walking, in patients with COPD in comparison with room air and fixed oxygen administration. (ClinicalTrials.gov registration: NCT02150434.) [ABSTRACT FROM AUTHOR]