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.

Keywords: E-cigarettes; EVALI; lipoid pneumonia; tetrahydrocannabinol (THC); vaping.

Figure 1

Interaction of ENDS use or vaping generated aerosols/lipids with the airway innate immune cells. The inhaled vapors/aerosols from ENDS use that consists of the hydrocarbons like oil and lipids, vitamin E acetate (VEA) and heavy metals end up in the alveolar regions where active efferocytosis of these aerosolized constituents leads to accumulation of lipid-laden AMs (Lipoid AMs or Foam cells) and the NET-release from the PMNs. The oxidative damage also the leads to the aggregation of oxidative derivatives of the cellular lipids and the surfactants. The AT-II cells secrete inflammatory factors and lung surfactants in the ELF, AMs, alveolar macrophages; AT-1, Alveolar type-1 cells; AT-2, Alveolar type-2 cells; PMNs, polymorphonuclear cells; NETs, neutrophil extracellular traps.