Oxidized phospholipid and transcriptomic signatures of THC-related vaping associated lung injury

Abstract E-cigarette/vaping-associated lung injury (EVALI) is strongly associated with vitamin E acetate and often occurs with concomitant tetrahydrocannabinol (THC) use. To uncover pathways associated with EVALI, we examined cytokines, transcriptomic signatures, and lipidomic profiles in bronchoalv...

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Main Authors: Tomeka L. Suber, Mohammadreza Tabary, William Bain, Tolani Olonisakin, Karina Lockwood, Zeyu Xiong, Yingze Zhang, Naina Kohli, Lauren Furguiele, Hernán Peñaloza, Bryan J. McVerry, Jason J. Rose, Faraaz Shah, Barbara Methé, Kelvin Li, Rama K. Mallampalli, Kong Chen, Li Fan, Alison Morris, Vladimir A. Tyurin, Svetlana N. Samovich, Hülya Bayir, Yulia Y. Tyurina, Valerian Kagan, Janet S. Lee
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-79585-8
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Summary:Abstract E-cigarette/vaping-associated lung injury (EVALI) is strongly associated with vitamin E acetate and often occurs with concomitant tetrahydrocannabinol (THC) use. To uncover pathways associated with EVALI, we examined cytokines, transcriptomic signatures, and lipidomic profiles in bronchoalveolar lavage fluid (BALF) from THC-EVALI patients. At a single center, we prospectively enrolled mechanically ventilated patients with EVALI from THC-containing products (N = 4) and patients with non-vaping acute lung injury and airway controls (N = 5). BALF samples were analyzed by Luminex multiplex assay, RNA sequencing, and mass spectrometry. After treating BEAS-2B lung epithelial cells with vaping and non-vaping BALF, LDH release was quantified. THC-EVALI BALF had significant increases in IFNγ, CCL2, CXCL5, and MMP2 relative to non-vaping patients. RNA sequencing showed enrichment for biological oxidation, glucuronidation, and fatty acid metabolism pathways. Oleic acid and arachidonic acid metabolites were increased in THC-EVALI, as were oxidized phosphatidylethanolamines (PE) such as PE(38:4). THC-EVALI BALF induced more LDH release compared to BALF from non-vaping patients. Thus, THC-EVALI is characterized by altered phospholipid composition, accumulation of lipid oxidation products, and increased pro-inflammatory mediators that may contribute to epithelial cell death. These findings serve as a framework to study novel oxidized phospholipids implicated in the pathogenesis of EVALI.
ISSN:2045-2322