Effects of hyperoxia on pulmonary inflammation and organ injury in a human in vivo model (HIPI): a randomised controlled trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: INTRODUCTION: It is uncertain whether hyperoxia contributes to adverse intensive care unit outcomes. Potential harm is likely mediated by oxidative stress driving pulmonary and systemic inflammation. METHODS: 1.0, 60 L/min) or synthetic medical air for 6 hours. Bronchoalveolar lavage (BAL) was performed at 6 hours following inhalation of 50 µg of LPS. Blood was collected at baseline, 6 hours and 24 hours. The primary outcome was BAL interleukin-8 (IL-8). Secondary outcome measures included markers of pulmonary and systemic inflammation. Untargeted metabolomic and lipidomic profiling of BAL fluid and plasma was performed by liquid chromatography-mass spectrometry to investigate oxidative stress. Transcriptomic analysis was also performed on whole blood. RESULTS: Between January 2023 and March 2024, twenty-two participants were recruited and completed all study procedures. BAL IL-8 did not differ between groups at 6 hours (hyperoxia 375.7 pg/mL (IQR 351.1-467.7) vs placebo 331.9 pg/mL (IQR 251.6-459), p=0.33). No between-group differences were observed in BAL cytokines or markers of systemic inflammation. Hyperoxia was associated with an approximately fourfold increase in BAL reduced glutathione (unadjusted p=0.02). Hyperoxia was associated with distinct transcriptional responses at 24 hours with 175 differentially expressed genes (padj <0.05), including upregulation of genes related to extracellular matrix remodelling, platelet activation and endothelial repair. DISCUSSION: In a human inhaled LPS challenge model, 6 hours of hyperoxia did not increase markers of pulmonary or systemic inflammation. TRIAL REGISTRATION NUMBER: NCT05414370.
Source: Thorax
Authors: Dermot Linden, Delia Dorrian, Michael Glenn, Shikha Tandel, Thea Mawhinney, Karl Welzenbach, Matthew J Rowland, Ming Yang, Laurent Klein, Emanuele Randazzo, Miriam Sindelar, Joerg Schlotterbeck, Alexander Cattini, Ahilanandan Dushianthan, Emma Crossley, Michael McKelvey, Melanie Bailey, John Conlon, Sharon Carr, Judy Bradley, Clifford C Taggart, David A Simpson, Joseph Kidney, Cecilia M O’Kane, Daniel Francis McAuley
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Award: G3575936724
OpenAlex ID: W7212107916