Beyond the Lungs: O2 Supplementation Improves Cerebral Oxygenation and Fatigue during Exercise in Interstitial Lung Disease

Abstract

ABSTRACT Purpose Cerebral hypoxia may exacerbate the perception of fatigue. We previously demonstrated that exercise-related hypoxemia, a hallmark of fibrotic interstitial lung disease (f-ILD), dose dependently impairs cerebral oxygenation in these patients. It is unknown whether normalizing cerebral oxygenation with O2 supplementation would be associated with positive changes in a relevant patient-centered outcome during exercise in f-ILD, such as improved perceived fatigue. Methods Fourteen patients (12 males, 72 ± 8 yr, 8 with idiopathic pulmonary fibrosis, lung diffusing capacity for carbon monoxide = 44% ± 13% predicted) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) breathing medical air. Fourteen controls cycled up to Tlim of an age- and sex-matched patient. Patients repeated the test on supplemental O2 (fraction of inspired O2 = 0.41 ± 0.08) for the same duration. Near-infrared spectroscopy and the rating-of-fatigue (ROF) scale assessed prefrontal cortex oxygenation and perceived fatigue, respectively. Results Patients showed severe exertional hypoxemia (Tlim O2 saturation by pulse oximetry = 80% ± 8%); they had poorer cerebral oxygenation (e.g., oxy-deoxyhemoglobin difference [HbDiff] = −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) versus controls under air (P < 0.001). Reversal of exertional hypoxemia with supplemental O2 led to improved HbDiff (+1.7 ± 2.4 μmol from rest; no longer differing from controls) and lower ROF scores (3.7 ± 1.2, P < 0.001 vs air) in patients. There was a significant correlation between O2-induced changes in HbDiff and ROF scores throughout exercise in f-ILD (r repeated-measures correlation = −0.51, P < 0.001). Conclusions Supplemental O2 improved cerebral oxygenation during exercise in f-ILD, which was moderately associated with lower ratings of perceived fatigue. Reversing cerebral hypoxia with O2 supplementation may thus have positive effects on patients’ disablement beyond those expected from lower ventilation and dyspnea in this patient population.