Oxidized phospholipid and transcriptomic signatures of THC-related vaping associated lung injury
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.
Authors
- Hernán F. Peñaloza (ORCID: https://orcid.org/0000-0002-1593-678X)
- Naina Kohli
- Svetlana N. Samovich (ORCID: https://orcid.org/0000-0001-5731-122X)
- Faraaz Shah (ORCID: https://orcid.org/0000-0002-2847-7738)
- Karina C. Lockwood
- Tomeka Suber (ORCID: https://orcid.org/0000-0002-7062-0278)
- Vladimir A. Tyurin (ORCID: https://orcid.org/0000-0002-3474-1697)
- Rama K. Mallampalli (ORCID: https://orcid.org/0000-0002-5782-4495)
- William Bain (ORCID: https://orcid.org/0000-0001-8506-0552)
- Jason J. Rose (ORCID: https://orcid.org/0000-0003-1347-9148)
- Valerian E. Kagan (ORCID: https://orcid.org/0000-0002-7245-1885)
- Yulia Y. Tyurina (ORCID: https://orcid.org/0000-0003-0287-2091)
- Zeyu Xiong (ORCID: https://orcid.org/0000-0002-3652-1890)
- Hülya Bayır (ORCID: https://orcid.org/0000-0003-2361-4120)
- Tolani F. Olonisakin (ORCID: https://orcid.org/0000-0002-8342-3409)
- Bryan J. McVerry (ORCID: https://orcid.org/0000-0002-1175-4874)
- Barbara A. Methé (ORCID: https://orcid.org/0000-0001-8711-1448)
- Mohammadreza Tabary (ORCID: https://orcid.org/0000-0002-3746-7371)
- Fan Li (ORCID: https://orcid.org/0000-0002-0868-1694)
- Kong Chen (ORCID: https://orcid.org/0000-0001-6980-5454)
- Yingze Zhang
- Janet Lee (ORCID: https://orcid.org/0000-0002-6812-6043)
- Kelvin Li (ORCID: https://orcid.org/0000-0003-3922-5664)
- Alison Morris
- Lauren Furguiele
Institutions
- University of Maryland, Baltimore (US)
- Pontificia Universidad Católica de Chile (CL)
- University of Pittsburgh (US)
- Washington University in St. Louis (US)
- The Ohio State University Wexner Medical Center (US)
- VA Pittsburgh Healthcare System (US)
- University of Pittsburgh Medical Center (US)
- Johns Hopkins Hospital (US)
- Millennium Institute on Immunology and Immunotherapy (CL)
- Columbia University (US)
- Edward Via College of Osteopathic Medicine (US)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41598-024-79585-8
- Citations
- 5
- Primary Topic
- Alcohol Consumption and Health Effects
- Type
- article
- Field-Weighted Citation Impact
- 2.12
Funders
- University of Pittsburgh
- National Institutes of Health
- Center for Research Computing, University of Pittsburgh