Abstract
INTRODUCTION: Liberal administration of supplemental oxygen (O(2)) is ubiquitous across numerous healthcare settings. However, appropriate O(2) titration targets remain controversial and despite numerous large-scale randomised trials, there is an ongoing lack of consensus regarding optimal oxygenation strategies and the absence of high-quality mechanistic data pertaining to the potential proinflammatory effects of hyperoxia. METHODS AND ANALYSIS: We hypothesise that (1) short-term exposure to hyperoxia will induce mild pulmonary inflammation and cellular injury and that (2) hyperoxia will accentuate pulmonary inflammation and cellular injury in the setting of inhaled lipopolysaccharide challenge. To test our hypotheses, we will conduct a randomised, double-blind, placebo-controlled study of hyperoxia administered via a high-flow nasal O(2) delivery system (fractional inspired oxygen 1.0, 60 L/min flow rate) compared with synthetic medical air. Blocked randomisation will be undertaken by an independent clinical trials statistician. Healthy non-smoking adult volunteers (<45 years of age), taking no regular medications will be recruited. Bronchoalveolar lavage (BAL) will be performed at 6 hours. The study outcome measures will include BAL markers of inflammation and injury (including but not limited to interleukin (IL)-8, IL-6, tumour necrosis factor alpha), BAL differential cell counts, BAL markers of oxidative stress (superoxide dismutase and glutathione), alveolar epithelial cell injury (SP-D, vWF, RAGE) and markers of systemic inflammation (neutrophils and plasma C-reactive protein). ETHICS AND DISSEMINATION: Dissemination of the research findings will be achieved in the following ways: (1) Our findings will be presented at national and international meetings with open-access abstracts online and (2) in accordance with the open-access policies proposed by the leading research funding bodies we aim to publish the findings in high quality peer-reviewed open-access journals. TRIAL REGISTRATION NUMBER: NCT05414370.