Background. Cerebral hypoxia may exacerbate perceived fatigue. Exertional hypoxaemia dose-dependently impairs cerebral oxygenation in fibrotic interstitial lung disease (f-ILD). It is unknown whether normalizing cerebral oxygenation with O₂ supplementation would translate into improved perceived fatigue during exercise in f-ILD.

Methods. Fourteen patients (12 men, 72±8 years, 8 with idiopathic pulmonary fibrosis) performed a constant-load (60% peak) cycle test to symptom limitation on medical air (Tlim_air). Fourteen controls cycled up to Tlim_air of an age- and sex-matched patient. Patients repeated the test on supplemental O₂ (41±8%) up to Tlim_air. Prefrontal cortex oxy-deoxyhemoglobin difference (Hb_Diff) and perceived fatigue were respectively assessed by near-infrared spectroscopy and the rating-of-fatigue (ROF) scale.

Results. Patients showed severe exertional hypoxaemia (O₂ saturation= 80±8% after 17±4 min); they had poorer Hb_Diff [-3.5±4.7 (range: -17.6 to +1.9) vs +1.9±1.7 µmol from rest] and greater fatigue (ROF= 6.2±2.0 vs 2.6±2.3) vs controls on air (p<0.001). Supplemental O₂ improved Hb_Diff (+1.7±2.4 µmol from rest; not differing from controls) and lowered ROF scores (3.7±1.2; p<0.001 vs air) in patients. Supplemental O₂-induced changes in Hb_Diff correlated with those in ROF throughout exercise in f-ILD (r_{repeated-measures correlation}= -0.51; p<0.001).

Conclusion. Supplemental O₂ normalized cerebral oxygenation and improved perceived fatigue during exercise in f-ILD. This is the first study to suggest that reversing cerebral hypoxia with supplemental O₂ may have positive effects on patients? disablement beyond those expected from lower ventilation and dyspnoea.