BACKGROUND AND OBJECTIVE: The available evidence on the effects of ambulatory oxygen on exercise impairment in patients with fibrotic interstitial lung diseases (F-ILD) is of limited quality. METHODS: We conducted a randomised, double-blind, placebo-controlled crossover trial with 32 normoxaemic F-ILD patients, desaturating to ≤ 88% during a baseline 6-minute walk test (6MWT) on ambient air. After determining the oxygen flow needed to prevent desaturation, patients completed two double-blind 6MWTs with either oxygen or placebo (compressed medical air) at the same personalised flow. Objective measures included oxygen saturation, pulse rate, and distance walked. Patient-reported outcomes, assessed via visual analogue scales, included end-of-test dyspnoea, fatigue, and preferences for walking with oxygen or placebo versus each other and ambient air. RESULTS: Ambulatory oxygen, compared to placebo, prevented desaturation, reduced tachycardia, increased walking distance by 37 m (95% CI: 10-74, p = 0.008), and lessened dyspnoea and fatigue. The mean preference score for oxygen over placebo was 2.6 (95% CI: 1.9-3.2, p <
0.0005), significantly greater than equivalence. The preference score for placebo over ambient air was -1.5 (-2.4 to 0.64, p = 0.005), significantly lower than equivalence, while the score for oxygen over ambient air was 0.4 (-0.7 to 1.5), not significantly different from equivalence. CONCLUSIONS: Our data confirm that ambulatory oxygen provides significant benefits beyond a placebo effect
although in some patients it is associated with a negative perception that may hinder treatment acceptance. This strengthens the evidence supporting current recommendations and suggests that incorporating patient preferences recorded at the time of the 6MWT into clinical discussions can aid shared decision making regarding ambulatory oxygen. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02668029.