Introduction. Hallmarks of fibrotic interstitial lung disease (f-ILD) include severe hypoxemia, dyspnea and exercise limitation. Although ambulatory oxygen (O2) therapy is widely prescribed, standard low-flow O2 systems (nasal prongs) fail to meet patients' inspiratory demand on exertion resulting in incomplete correction of hypoxemia and limited symptomatic relief (1). Nasal high-flow O2 therapy (NHFO2) delivers heated, humidified, and O2-enriched air at high flow rates. It has recently emerged as a promising alternative to overcome the pre-specified limitations: NHFO2 is more effective in correcting hypoxemia and reducing dyspnea vs standard O2 therapy and consistently improved exercise capacity in f-ILD (2,3,4). In fact, NHF per se may exert independent physiological benefits such as washout of the anatomical dead space and reduced work of breathing (5). However, the respective effect of respiratory support and improved oxygenation on dyspnea and exercise tolerance remain unexplored in f-ILD.

Methods. Sixteen patients (9 men, 69±14y, 6 with idiopathic pulmonary fibrosis, total lung capacity= 71±24% predicted) randomly performed constant work-rate (WR) exercise tests (70% WRpeak) under 4 conditions: air, supplemental O2 (face mask; 9 L/min), NHF [50-70 L/min; inspired fraction of O2 (FiO2)=0.21] and NHFO2 (FiO2=0.5). We compared endurance time, isotime O2 saturation (SpO2), breathing pattern (respiratory inductive plethysmography), dyspnea (Borg CR10) and quadriceps muscle oxygenation (near-infrared spectroscopy) across conditions.

Results. Endurance time improved on O2 and NHFO2 vs air and NHF (683 [903], 690 [1338], 346 [247] and 319 [415] s, respectively; p<0.001). Of note, SpO2 was similar on O2 (98 [2]%) and NHFO2 (99 [3]%; p>0.05), improving from air (87 [17]%; p<0.001). Ventilation was lower on O2 and NHFO2 vs air (41±18, 40±20, 55±30 L/min p<0.001), driven by lower respiratory rates (33±8, 35±6, 39±7 br/min; p<0.05). Dyspnea improved on O2 and NHFO2 vs air (4 [3.5], 3.5 [2.5], 7 [3], respectively; p<0.001) and on NHFO2 vs NHF (6 [1.5]; p<0.05). NHF offered no independent benefits but numerically reduced ventilation vs air (~8 L·min-1,p=0.103). Supplemental O2 and NHFO2 similarly enhanced peak-exercise quadriceps muscle oxy-deoxyhemoglobin difference vs air and NHF (0.2±7.4, 1.9±9.6, -7.0±7.6, -6.2±6.3 μmol·s-1 from rest; p<0.001).

Discussion. This study is the first to disentangle the individual contribution of NHF and supplemental O2 on dyspnea and exercise performance in f-ILD. Our findings show that supplemental O2 (delivered via a non-rebreather face mask) and NHFO2 provide similar improvements in these outcomes at "iso-O2 saturation”, but no independent effect of NHF. This indicates that the key driver of dyspnea relief and improved exercise tolerance in f-ILD is enhanced oxygenation leading to reduced ventilatory demand and enhanced O2 delivery to skeletal muscles. While NHF may modestly reduce ventilation, it did not translate into symptomatic or functional improvement unless combined with adequate oxygenation.

Conclusion/perspectives. NHFO2 significantly alleviated dyspnea and enhanced exercise tolerance in f-ILD showing comparable efficacy to O2 supplementation when matched for O2 saturation. Our results underscore the importance of appropriately correcting hypoxemia, lowering ventilatory demand and improving skeletal muscle functioning to optimize functional and perceptual responses to exercise in this patient population. NHFO2 may thus potentiate the effect of rehabilitative exercise training as compared to standard care (typically O2 therapy through nasal prongs), an endeavor currently addressed in our research group.

References

• Jacobs, SS. (2020). Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med, 202(10), 121-141.
• Al Chikhanie ,Y. (2021). The effect of heated humidified nasal high flow oxygen supply on exercise tolerance in patients with interstitial lung disease : A pilot study. Respir Med, 86:106523.
• Harada, J. (2022). Effect of high-flow nasal cannula oxygen therapy on exercise tolerance in patients with idiopathic pulmonary fibrosis : A randomized crossover trial. Respirology, 27(2), 144-151.
• Badenes-Bonet, D. (2021). Impact of high-flow oxygen therapy during exercise in idiopathic pulmonary fibrosis: a pilot crossover clinical trial. BMC Pulm Med, 21(1), 355.
• Girault, C. (2022). Principes de fonctionnement, effets physiologiques et aspects pratiques de l'oxygénothérapie à haut debit [Operating principles, physiological effects and practical issues of high-flow nasal oxygen therapy]. Rev Mal Respir, 39(5), 455-468.