Firsthand and secondhand exposure levels of maltol-flavored electronic nicotine delivery system (ENDS) vapors disrupt amino acid metabolism

Electronic nicotine delivery system (ENDS) use has become a popular, generally regarded as safe, alternative to tobacco use. The e-liquids used for ENDS vapor generation commonly contain flavoring agents, such as maltol, which have been subjected to little investigation of their effects on lung health from ENDS usage. In the present study, we examined the impacts of firsthand (3.9 mM) and secondhand (3.9 µM) exposure levels to maltol-flavored ENDS vapors on lung metabolism. Bronchial airway epithelial BEAS-2B cells were exposed to ENDS vapors using a robotic system for controlled generation and delivery of exposures, and the effects on metabolism were evaluated using high-resolution metabolomics. The results show that maltol in e-liquids impacts lung airway epithelial cell metabolism at both firsthand and secondhand exposure levels. The effects of maltol were most notably seen in amino acid metabolism; oxidative stress was present with ENDS and not affected by maltol. Many effects of firsthand exposure were also observed with secondhand exposure, suggesting need for systematic investigation of both firsthand and secondhand effects of flavored ENDS vapors on lung metabolism and risk of lung disease.

Altered lung metabolism and mitochondrial DAMPs in lung injury due to acute kidney injury

Acute respiratory distress syndrome (ARDS) is a common cause of mortality in patients with acute kidney injury (AKI). Inflammatory crosstalk from the kidney to the lung has been shown to contribute to lung injury after AKI, but anti-inflammatory therapies have not been proven beneficial in human studies. Recently, AKI was shown to alter mitochondria and related metabolic pathways in the heart, but the impact of AKI on lung metabolism has not been investigated to our knowledge. In this study, we evaluated the metabolomic profile of the lung following renal ischemia and reperfusion to identify novel pathways that may be modifiable. We randomized C57BL/6 mice to 20 minutes of bilateral renal arterial clamping or sham operation under ketamine/xylazine anesthesia. At 4 hours after reperfusion, we found a significant increase in markers of lung injury, as well as significant metabolomic changes across lung, kidney, plasma and bronchoalveolar lavage fluid (BALF) compared to shams. Comparative analyses revealed that the fatty acid oxidation pathway was the most significantly altered metabolic pathway, a finding which is consistent with mitochondrial dysfunction systemically and in the lung. These metabolomic changes correlated with the extracellular accumulation of the mitochondrial damage associated molecular patterns (mtDAMPs), mitochondrial DNA (mtDNA) and transcription factor A, mitochondria (TFAM). Finally, we found that intraperitoneal injection of renal mtDAMPs caused metabolomic changes consistent with mitochondrial dysfunction in the lung in vivo. Mitochondrial function and mtDAMPs warrant further investigation as potential therapeutic targets in preventing lung injury due to AKI.