Suber Tomeka L, Tabary Mohammadreza, Bain William, Olonisakin Tolani, Lockwood Karina, Xiong Zeyu, Zhang Yingze, Kohli Naina, Furguiele Lauren, Peñaloza Hernán, McVerry Bryan J, Rose Jason J, Shah Faraaz, Methé Barbara, Li Kelvin, Mallampalli Rama K, Chen Kong, Fan Li, Morris Alison, Tyurin Vladimir A, Samovich Svetlana N, Bayir Hülya, Tyurina Yulia Y, Kagan Valerian, Lee Janet S
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.
Sci Rep. 2024 Dec 30;14(1):31622. doi: 10.1038/s41598-024-79585-8.
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.
电子烟/雾化相关肺损伤（EVALI）与醋酸维生素E密切相关，且常与同时使用四氢大麻酚（THC）有关。为了揭示与EVALI相关的途径，我们检测了THC-EVALI患者支气管肺泡灌洗液（BALF）中的细胞因子、转录组特征和脂质组概况。在一个单一中心，我们前瞻性纳入了因含THC产品导致EVALI的机械通气患者（N = 4）以及非雾化急性肺损伤患者和气道对照患者（N = 5）。通过Luminex多重检测、RNA测序和质谱分析BALF样本。在用雾化和非雾化BALF处理BEAS-2B肺上皮细胞后，对乳酸脱氢酶（LDH）释放进行定量。与非雾化患者相比，THC-EVALI的BALF中IFNγ、CCL2、CXCL5和MMP2显著增加。RNA测序显示生物氧化、葡萄糖醛酸化和脂肪酸代谢途径富集。THC-EVALI中油酸和花生四烯酸代谢产物增加，氧化磷脂酰乙醇胺（PE）如PE(38:4)也增加。与非雾化患者的BALF相比，THC-EVALI的BALF诱导更多的LDH释放。因此，THC-EVALI的特征是磷脂组成改变、脂质氧化产物积累以及促炎介质增加，这些可能导致上皮细胞死亡。这些发现为研究与EVALI发病机制相关的新型氧化磷脂提供了一个框架。
