What are the mechanisms underlying vaping-induced lung injury?

Alexander, Laura E. Crotty; Bellinghausen, Amy L.; Eakin, Michelle N.

doi:10.1172/jci138644

Cited by 32 publications

(39 citation statements)

References 20 publications

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“…Whether EVALI results from processes similar to or different from those discussed here, such as oxidative stress [126,127] or from alternative mechanisms such as lipid deposition [128,129]…”

Section: Dose-response Gradientmentioning

confidence: 83%

“…Thus, VEA is strongly suspected of being a causal factor for EVALI, although a small minority of affected patients deny having vaped THC [ 125 ], and other constituents have been suggested for consideration [ 126 ]. Whether EVALI results from processes similar to or different from those discussed here, such as oxidative stress [ 126 , 127 ], or from alternative mechanisms such as lipid deposition [ 128 , 129 ], is unknown at present. The most recent brands of e-cigarettes have cytotoxic effects and disrupt lung functioning [ 71 , 130 , 131 ], suggesting that the issues we have noted may be contributory for EVALI.…”

Section: Discussionmentioning

confidence: 99%

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E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies

et al. 2020

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BackgroundUse of electronic cigarettes (e-cigarettes) is prevalent among adolescents and young adults but there has been limited knowledge about health consequences in human populations. We conduct a systematic review and meta-analysis of results on respiratory disorder from studies of general-population samples and consider the mapping of these results to findings about biological processes linked to e-cigarettes in controlled laboratory studies.MethodWe conduct a literature search and meta-analysis of epidemiological studies on the association of e-cigarette use with asthma and with chronic obstructive pulmonary disease (COPD). We then discuss findings from laboratory studies about effects of e-cigarettes on four biological processes: cytotoxicity, oxidative stress/inflammation, susceptibility to infection, and genetic expression.ResultsEpidemiological studies, both cross-sectional and longitudinal, show a significant association of e-cigarette use with asthma and COPD, controlling for cigarette smoking and other covariates. For asthma (n=15 studies), the pooled adjusted odds ratio (AOR) was 1.39 (CI 1.28–1.51); for COPD (n=9 studies) the AOR was 1.49 (CI 1.36–1.65). Laboratory studies consistently show an effect of e-cigarettes on biological processes related to respiratory harm and susceptibility to illness, with e-cigarette conditions differing significantly from clean-air controls though sometimes less than for cigarettes.ConclusionsThe evidence from epidemiological studies meets established criteria for consistency, strength of effect, temporality, and in some cases a dose-response gradient. Biological plausibility is indicated by evidence from multiple laboratory studies. We conclude that e-cigarette use has consequences for asthma and COPD, which is of significant concern for respirology and public health.

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Section: Dose-response Gradientmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies

et al. 2020

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“…Activation of neutrophils speeds their demise, by neutrophil extracellular trap formation (NETosis) and apoptosis, such that activation may not be paired with increased numbers of neutrophils if chemokines such as IL-8 are not released. In the particular case of increased activation of neutrophils, it has been shown that prolonged activation of these cells can lead to detrimental effects to the host and can even cause severe disease, including pneumonia and ARDS (Abraham, 2003;Galani and Andreakos, 2015), with ARDS being the main clinical feature of both EVALI (Alexander et al, 2020; and COVID-19 (Matthay et al, 2020;Xu et al, 2020). More recently, it has been shown that severity of COVID-19 is associated with increased activation of neutrophils (Leppkes et al, 2020;Radermecker et al, 2020;Zuo et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2

et al. 2021

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Conventional smoking is known to both increase susceptibility to infection and drive inflammation within the lungs. Recently, smokers have been found to be at higher risk of developing severe forms of coronavirus disease 2019 (COVID-19). E-cigarette aerosol inhalation (vaping) has been associated with several inflammatory lung disorders, including the recent e-cigarette or vaping product use-associated lung injury (EVALI) epidemic, and recent studies have suggested that vaping alters host susceptibility to pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the impact of vaping on lung inflammatory pathways, including the angiotensin-converting enzyme 2 (ACE2) receptor known to be involved in SARS-CoV-2 infection, mice were exposed to e-cigarette aerosols for 60 min daily for 1–6 months and underwent gene expression analysis. Hierarchical clustering revealed extensive gene expression changes occurred in the lungs of both inbred C57BL/6 mice and outbred CD1 mice, with 2,933 gene expression changes in C57BL/6 mice, and 2,818 gene expression changes in CD1 mice (>abs 1.25-fold change). Particularly, large reductions in IgA and CD4 were identified, indicating impairment of host responses to pathogens via reductions in immunoglobulins and CD4 T cells. CD177, facmr, tlr9, fcgr1, and ccr2 were also reduced, consistent with diminished host defenses via decreased neutrophils and/or monocytes in the lungs. Gene set enrichment (GSE) plots demonstrated upregulation of gene expression related to cell activation specifically in neutrophils. As neutrophils are a potential driver of acute lung injury in COVID-19, increased neutrophil activation in the lungs suggests that vapers are at higher risk of developing more severe forms of COVID-19. The receptor through which SARS-CoV-2 infects host cells, ACE2, was found to have moderate upregulation in mice exposed to unflavored vape pens, and further upregulation (six-fold) with JUUL mint aerosol exposure. No changes were found in mice exposed to unflavored Mod device-generated aerosols. These findings suggest that specific vaping devices and components of e-liquids have an effect on ACE2 expression, thus potentially increasing susceptibility to SARS-CoV-2. In addition, exposure to e-cigarette aerosols both with and without nicotine led to alterations in eicosanoid lipid profiles within the BAL. These data demonstrate that chronic, daily inhalation of e-cigarette aerosols fundamentally alters the inflammatory and immune state of the lungs. Thus, e-cigarette vapers may be at higher risk of developing infections and inflammatory disorders of the lungs.

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“…When VEA is heated to the typical temperatures of an ENDS, it decomposes into the highly toxic ketene gas [ 10 ]. When tested in animals, VEA caused acute lung injury when inhaled through E-cigarette aerosols, confirming it as the probable chemical responsible for EVALI [ 11 , 12 ]. While there is substantial evidence associating VEA with many cases of EVALI, there are other adulterants that likely are responsible in a subset of cases.…”

Section: E-cigarette or Vaping Product Use-associated Lung Injurymentioning

confidence: 99%

Vaping-related lung injury

et al. 2020

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The use of electronic nicotine delivery systems has increased in popularity dramatically over the past decade. Although lung diseases caused by vaping have been reported since the modern invention of the electronic cigarette, in the summer of 2019, patients began to present to health care centers at epidemic levels with an acute respiratory illness relating to vaping, which the Center for Disease Control termed E-cigarette or vaping product use-associated lung injury (EVALI). This review discusses electronic nicotine delivery systems as well as the etiology, clinical presentation, imaging findings, pathologic features, treatment, and long-term consequences of EVALI. We conclude with the practical impact EVALI has had on the practice of pathology.

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What are the mechanisms underlying vaping-induced lung injury?

Cited by 32 publications

References 20 publications

E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies

E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies

Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2

Vaping-related lung injury

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