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

MARILLIER, M., M. GRUET, A.-C. BERNARD, B. CHAMPIGNEULLE, S. VERGES, O. MORAN-MENDOZA, and J. A. NEDER. Beyond the Lungs: O-2 Supplementation Improves Cerebral Oxygenation and Fatigue during Exercise in Interstitial Lung Disease. Med. Sci. Sports Exerc., Vol. 55, No. 10, pp. 1735-1744, 2023. 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 O-2 supplementation would be associatedwith 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 O-2 (fraction of inspired O-2 = 0.41 +/- 0.08) for the same duration. Near-infrared spectroscopy and the ratingof-fatigue (ROF) scale assessed prefrontal cortex oxygenation and perceived fatigue, respectively. Results: Patients showed severe exertional hypoxemia (Tlim O-2 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 mu mol 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 O-2 led to improved HbDiff (+1.7 +/- 2.4 mu mol from rest; no longer differing fromcontrols) and lower ROF scores (3.7 +/- 1.2, P < 0.001 vs air) in patients. There was a significant correlation between O-2-induced changes inHbDiff and ROF scores throughout exercise in f-ILD (rrepeated- measures correlation = -0.51, P < 0.001). Conclusions: Supplemental O-2 improved cerebral oxygenation during exercise in f-ILD, which was moderately associated with lower ratings of perceived fatigue. Reversing cerebral hypoxia with O-2 supplementation may thus have positive effects on patients' disablement beyond those expected from lower ventilation and dyspnea in this patient population.