Pulmonary Toxicity and the Pathophysiology of Electronic Cigarette, or Vaping Product, Use Associated Lung Injury

Abstract

New emerging tobacco products, especially electronic cigarettes (E-Cig) or electronic nicotine delivery systems (ENDS), have gained a huge popularity, particularly in younger populations. The lack of sufficient evidence-based health effect studies has promoted widespread use/abuse with the assumption that E-Cig or ENDS and/or vaping products are safer and less toxic than conventional tobacco smoking. However, the recent escalation in acute lung injuries and their associated fatalities among ENDS or vaping product users has now brought attention to this silent epidemic via investigation into the constituents of ENDS/vaping products and their toxic effects on pulmonary health. Accordingly, CDC has declared an "outbreak" of the e-cigarette or vaping product use associated lung injury (EVALI). EVALI is characterized by sterile exogenous pneumonitis like reaction with substantial involvement of innate immune mechanisms. Vitamin-E acetate (VEA) is found in counterfeit cartridges and bronchoalveolar lavage fluid of EVALI patients. Other reports implicated the presence of aromatic/volatile hydrocarbons and oils consisting of medium-chain triglycerides (MCT oil), including terpenes and mineral oil in tetrahydrocannabinol (THC) containing counterfeit vaping products. These compounds are involved in oxidative stress and inflammatory responses in the lung. Here, we provide the perspectives on the recent case reports on EVALI, etiology, and discuss pulmonary toxicity as well as the mechanisms underlying EVALI susceptibility and lung pathophysiology.

Chemical Constituents Involved in E-Cigarette, or Vaping Product Use-Associated Lung Injury (EVALI)

“…It is believed that various hydrocarbons and reactive aldehydes are formed when e-liquids are heated to high temperatures around 500 • F/260 • C. All these cartridges, including CBD containing cartridges, are used at the common voltages (e.g. 3.5V to 5.5 V) using a specific device [20]. These conditions were used to generate aerosols for the detection of chemical constituents.…”

Molecular mechanism of SARS-CoV-2 components caused ARDS in murine model

“…In our study, inhibitors targeting neutrophils include P38 inhibitor, ERK inhibitor, MPO inhibitor and elastase inhibitor can reduce the neutrophil infiltration into lung, but not elastase, but single inhibitor may offer no protection from SARS-Cov-2 viral mimic induced pathogenesis of ARDS, and as such multiple inhibitors may need to be simultaneously utilized. During the process of neutrophil activation, neutrophil extracellular traps (NETs) are released which consists of DNA/Histone 1 backbones and various pro-inflammatory proteins against virus infection, but dysregulation of NETs produces substantial lung injury 40,41 .…”

Chemical constituents involved in e-cigarette, or vaping product use-associated lung injury (EVALI)

“…All these cartridges, including CBD containing cartridges, are used at the common voltages (e.g. 3.5V to 5.5 V) using a specific device (Chand et al 2019). These conditions were used to generate aerosols for the detection of chemical constituents.…”

“…Aside from the detected e-liquid chemical constituents, the lipid derivatives from the ‘endogenous’ source, such as the epithelial lining fluid (ELF) and/or lung surfactants by interacting with exogenous hydrocarbons with phospholipids and surfactants of the ELF, may also occur. This may be associated with the inflammatory responses using these counterfeit cartridges seen in the lungs of patients with EVALI (Chand et al 2019). It remains to be seen whether the identified chemicals have any role for pathological changes in the lung, such as centrilobular ground-glass nodules and ground-glass opacities with subpleural sparing, as seen in patients with EVALI.…”