Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine

Madison, Matthew C.; Landers, Cameron T.; Gu, Bon Hee; Chang, Cheng Yen; Tung, H.Y. Lim; You, Ran; Hong, Monica Jeongsoo; Baghaei, Nima; Li, Song; Porter, Paul B.; Putluri, Nagireddy; Salas, Ramiro; Gilbert, Brian E.; Levental, Ilya; Campen, Matthew J.; Corry, David B.; Kheradmand, Farrah

doi:10.1172/jci128531

Cited by 303 publications

(306 citation statements)

References 61 publications

Supporting

Mentioning

272

Contrasting

Unclassified

Order By: Relevance

“…Surfactant proteins are important to prevent lung atelectasis and the reduction of SP-A may suggest excess accumulation of lipids in the alveolar space as we demonstrated with this acute exposure. Consistent with our observations, reduced surfactant proteins in BALF and lung homogenates have been seen in mice exposed to ENDS independent of nicotine [14].…”

Section: Resultssupporting

confidence: 91%

“…The increase in eotaxin (Figure 6B) suggests eosinophilic chemotaxis in the lung tissue and lavage as eotaxin plays a major role in recruiting eosinophils to the sites of inflammation [35]. Corroborating our data, exposure to ENDS has been shown to augment the levels of IL-6 in BALF along with increased neutrophils and CD4+ cells [14].…”

Section: Resultssupporting

confidence: 61%

“…Exposure to certain electronic nicotine delivery systems (ENDS) cartridges has recently increased hospitalizations due to respiratory failure [6–8,13,14]. According to case reports since 2012, e-cig users with symptoms without direct etiology have undergone various diagnoses, including acute lung injury, atypical pneumonitis, and eosinophilic or lipoid pneumonia [6,13].…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

Muthumalage

Lucas

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Recently, there has been an outbreak associated with the use of e-cigarette or vaping products, associated lung injury (EVALI). The primary components of vaping products, vitamin E acetate (VEA) and medium-chain triglycerides (MCT) may be responsible for acute lung toxicity. Currently, little information is available on the physiological and biological effects of exposure to these products. We hypothesized that these e-cig cartridges and their constituents (VEA and MCT) induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury. We studied the potential mechanisms of cartridge aerosol induced inflammatory response by evaluating the generation of reactive oxygen species by MCT, VEA, and cartridges, and their effects on the inflammatory state of pulmonary epithelium and immune cells both in vitro and in vivo. Cells exposed to these aerosols generated reactive oxygen species, caused cytotoxicity, induced epithelial barrier dysfunction, and elicited an inflammatory response. Using a murine model, the parameters of acute toxicity to aerosol inhalation were assessed. Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF). In mouse plasma, eicosanoid inflammatory mediators, leukotrienes, were significantly increased. Plasma from e-cig users also showed increased levels of hydroxyeicosatetraenoic acid (HETEs) and various eicosanoids. Exposure to e-cig cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. In addition, we determined at SARS-COV-2 related proteins and found no impact associated with aerosol exposures from these tested cartridges. Overall, this study demonstrates acute exposure to specific e-cig cartridges induces in vitro cytotoxicity, barrier dysfunction, and inflammation and in vivo mouse exposure induces acute inflammation with elevated pro-inflammatory markers in the pathogenesis of EVALI.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

Muthumalage

Lucas

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The highly publicized lung illnesses from vaping, including "popcorn lung" and e-cigarette or vaping product use-associated lung injury, alert us to the potential for lung injury from vaping, which is on the rise especially in young persons. Preclinical studies show that e-cigarette aerosols can damage lung tissue, cause inflammation, and diminish the lungs' ability to respond to infection (3).…”

mentioning

confidence: 99%

Collision of the COVID-19 and Addiction Epidemics

Volkow

2020

Annals of Internal Medicine

661

689

View full text Add to dashboard Cite

“…A possible mechanism for the presence of lipid-laden macrophages in the bronchoalveolar lavage fluid is suggested by a mouse study showing that exposure to e-cigarette vapour (60% propylene glycol and 40% vegetable glycerine) for 4 months, independent of nicotine, led to altered alveolar macrophage and epithelial cell lipid homeostasis with aberrant phospholipids and increased surfactant-associated phospholipids in the airway (Madison et al, 2019). Additionally, they reported evidence of downregulated innate immunity against viral pathogens in resident macrophages and poor response to viral challenge.…”

mentioning

confidence: 99%

E-cigarette or vaping product use-associated lung injury

Ind

2020

Br J Hosp Med

View full text Add to dashboard Cite

E-cigarette or vaping product use-associated lung injury is a recently recognised, acute pulmonary syndrome which has been reported (particularly from June to October 2019) throughout the USA, but not in Europe (although one probable case, in the UK, has been reported; Medicines and Healthcare products Regulatory Agency, 2020 ). It presents acutely, most often in young men, as severe pulmonary consolidation, usually with respiratory failure. The mortality is around 2%. The cause(s) are unknown, but it is associated with vaping, particularly using unlicensed cannabis-containing products with tetrahydrocannabinol. Vitamin E acetate, often present in tetrahydrocannabinol-containing vape products as a solvent, has been implicated, as it has been identified in the bronchoalveolar lavage fluid of patients with e-cigarette or vaping product use-associated lung injury. This article reviews the recent literature, including clinical features, presentation and investigations, and possible mechanisms, in the context of vaping practices in the USA and the UK.

show abstract

Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine

Cited by 303 publications

References 61 publications

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

Collision of the COVID-19 and Addiction Epidemics

E-cigarette or vaping product use-associated lung injury

Contact Info

Product

Resources

About