A randomised crossover trial to investigate the clinical utility of orally delivered oxygen nanobubbles in Pulmonary Fibrosis

<bold>Background:</bold> For Pulmonary Fibrosis (PF) patients, hypoxia may contribute to decreased exercise performance and increased breathlessness. Orally delivered oxygen nanobubbles (ONB) increases tissue oxygenation in hypoxic tumours in mice and increases mean power output in athletes. <bold>Aim:</bold> The purpose of this study was to investigate whether drinking ONB would increase the exercise capacity of PF patients during a 6 Minute Walk Test (6MWT). <bold>Methods:</bold> We conducted an <italic>in vivo</italic>, randomised, cross-over, double-blind, placebo-controlled trial over 1 day in PF patients. Each participant performed two 6MWTs, 10 minutes after consumption of ONB or placebo (PLA). A washout period of 2 hours separated the two 6MWTs. The primary outcome measure was Minute Walk Distance (6MWD). Secondary outcome measures were changes in Heart rate (HR), Oxygen saturation (SpO2), and breathlessness. <bold>Results:</bold> Twenty-seven patients with Pulmonary Fibrosis completed the study. Drinking ONB resulted in participants walking 9.3m (0.8-17.8m; p<0.05) less compared to PLA. Secondary outcomes showed that drinking ONB did not lead to significant improvements in SpO2 (1.3%, p=0.39), HR (−4.2 bpm, p=0.26) or breathlessness (0.1, p=0.63) post the 6MWT compared to drinking PLA. An exploratory analysis showed that drinking ONB first resulted in an increase in the 6MWD after 2 hours, which was not seen with participants that drank PLA first. <bold>Conclusions:</bold> Orally administered ONB did not improve a PF patients’ exercise performance within 10 minutes of administration of the drink. There may be a delayed effect on exercise ability and future work is planned to explore this.