Portable low-flow nasal oxygen versus ambient air in patients with chronic lung disease and exercise-induced hypoxaemia: a randomised controlled crossover non-inferiority trial.

BACKGROUND: Exercise-induced desaturation is a common symptom in chronic lung disease (CLD) and is associated with functional limitation and increased mortality. Although portable low-flow supplemental oxygen therapy (SOT) is commonly prescribed for exercise-induced hypoxaemia, evidence for SOT to improve performance is inconsistent. METHOD: This pragmatic, randomised, controlled, non-inferiority crossover trial enrolled patients with chronic obstructive pulmonary and interstitial lung disease who exhibited exercise-induced oxygen desaturation of >3%. Each patient performed two 6-minute walk distance (6MWD) tests in randomised order: one breathing ambient air and one using low-flow SOT delivered by a portable backpack concentrator (1-2 L/min). The primary outcome was 6MWD, secondary outcomes included perceived exertion and preference of the interventions. A predefined non-inferiority margin of 35 m was used. RESULTS: Forty patients were enrolled (mean age 66±13 years; 14 women; 20 with chronic obstructive pulmonary disease (COPD), 20 with interstitial lung disease (ILD)). The mean difference in 6MWD between ambient air and SOT was 0 m (95% CI -14 to 13 m; p<0.001 for non-inferiority). Secondary outcomes demonstrated significantly lower dyspnoea scores with SOT both overall and within COPD/ILD subgroups. Patient preferences were split, with 49% favouring ambient air and 51% preferring SOT. A clinically meaningful improvement in 6MWD of >35 m was found in five patients. CONCLUSION: In patients with CLD and exercise-induced desaturation, ambient air was non-inferior to pulsed low-dose SOT by portable concentrator in 6MWD, but SOT improved dyspnoea. These findings highlight the need for more effective, patient-acceptable oxygen delivery systems and further research to identify responders to SOT. TRIAL REGISTRATION NUMBER: NCT06385301.