Electronic Cigarettes and Vaping-Associated Lung Injury (EVALI): A Rural Appalachian

Experience

E-cigarettes, also known as Electronic Nicotine Delivery Systems (ENDS), include a diverse group
of battery-powered devices that produce an aerosol by heating liquid which typically contains a
solvent (vegetable glycerin-VG, propylene glycol-PG, or a mixture), flavoring agents (e.g.
diacetyl and 2,3-pentanedione), and nicotine. The evaporation of the liquid on the heating
element is followed by rapid cooling to generate an aerosol that is directly inhaled or ‘vaped’ by
the user through a mouthpiece. Vaping of propylene glycol and glycerol aerosols at high
wattage and in large amounts was shown to induce a sustained gas-exchange disturbance and
lower respiratory tract epithelial injury in young healthy tobacco smokers. In addition to the
expected chemical components, identified contaminants include polycyclic aromatic
hydrocarbons, nitrosamines, volatile organic compounds (VOCs), toxic metals, and endotoxins.
Rahul Sangan, et al. report the first large case series of EVALI from an academic center in the
rural Appalachian region. The report includes BAL analysis via Oil-Red-O and quantitative
Prussian blue stains, chemical analysis of vaping liquid, and post-discharge interview.
Rahul Sangan, et al. series of consecutive patients hospitalized with a diagnosis of EVALI shows
a significantly higher proportion of critically ill patients compared to other series, with 10/17
(59%) requiring ICU care and 7/17 (41%) requiring invasive mechanical ventilation or ECMO. Of
the 17 patients, 9 had a history of using THC or were positive for THC on UDS. Additionally, nine
patients also had UDS positive for opiates (5), benzodiazepines (3), cocaine (1), and
amphetamines (1). The presence of drugs and additives in the vaping compounds may also have
played a role in the severity of EVALI.
Lipoid pneumonia has been reported as the predominant injury pattern with vaping-related
injuries. In Rahul Sangan, et al. series of 17 total patients, 9 (53%) were diagnosed with lipoid
pneumonia based on lipid-laden macrophages detected in BAL. Interestingly, only 4/9 patients
with lipoid pneumonia had a history of THC use or a positive UDS. This differs from recent
findings by Blount et al., who reported vitamin E associated lung injury, 94% of whom had
detectable THC in BAL samples. The addition of flavoring compounds or other additives in
vaping products may be responsible for the ‘chemical injury’ of the lung and disruption of
surfactants. Interestingly, this may redefine the injury pattern as ‘endogenous’ lipoid
pneumonia rather than previously reported exogenous lipoid pneumonia.
Numerous acute and chronic respiratory diseases are associated with disrupted iron
homeostasis in the lungs. Rahul Sangan, et al. identified four patients with lipoid pneumonia
clinical presentation with high BAL macrophage iron content. All these patients developed
leukocytosis and were hypoxic on presentation, requiring varying degrees of oxygen support,
ICU care, and mechanical ventilation. We hypothesize that high BAL macrophage iron load may
reflect the severity of underlying lung inflammation induced by e-cigarette use and believe that
this may be an important analysis in BAL for prognostication triaging of EVALI patients admitted
with respiratory distress.
Chemical evaluation, although limited to six patients, provided important insight. Propylene
glycol (a common base for liquid vaping solutions) and nicotine were detected in all samples, as
expected. Monoterpenes are related to plant products and essential oils and suggest the
presence of flavoring compounds of THC. Monoterpenes were present in aerosol samples for all
patients who tested positive for THC. One unique finding was the presence of linalool, an anti-
inflammatory substance with properties similar to vitamin E acetate. Although linalool has
shown some therapeutic potential, it can dysregulate normal inflammatory pathways, which
could potentially disrupt subsequent response to pathogens and insults. The similarity in
activity to vitamin E acetate may be coincidental, but it may also offer a glimpse into potential
mechanisms of toxicity associated with EVALI, and E-cigarette additives with anti-inflammatory
activity should be investigated further.