Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury?

To the Editor:

Recent case series and related commentary published in the Journal highlight the recent epidemic of acute lung injury associated with e-cigarette use and its remaining obscure nature (1, 2). Although this cluster is novel, pulmonary illness associated with e-cigarette use is not new: there are at least seven published case reports from 2012 to 2018 describing similar conditions in e-cigarette users, with no identifiable infectious etiology (i.e., acute lung injury, atypical pneumonitis, eosinophilic pneumonia, hypersensitivity pneumonia, or lipoid pneumonia). Interestingly, of these seven reported cases, lung cell samples obtained via lavage or biopsy were available for five (3–7), and all five exhibited abnormally lipid-laden macrophages. Lipid-laden macrophages were also a prominent feature (>50%) in BAL of more recent case series from Utah (8). Such macrophages can trigger an inflammatory immune response (9) leading to lipoid pneumonia and other pneumonitis-like reactions. One report suggested that residual lipids in vegetable glycerin derived from incompletely processed vegetable oil might be the exogenous source of lipid in an e-cigarette user diagnosed with lipoid pneumonia (5). However, most of the publications related to this new entity focused on tetrahydrocannabinol, and a recent case series from the Mayo Clinic suggests chemical pneumonitis as a more probable etiopathology (10). The fact that not all e-cigarette–related lung injury cases were associated with tetrahydrocannabinol use, and that tetrahydrocannabinol vaping usually involves an oil vehicle (e.g., butane hash oils), does not rule out an important role for lipid-mediated lung injury in this clinical entity. This is particularly important to keep in mind given that most e-cigarette liquids contain vegetable glycerin as an essential component (helps make the e-cigarette aerosol visible). The implication is that many e-cigarette users who are currently asymptomatic (or experiencing milder symptoms for which they do not seek medical attention) may be undergoing lipid deposition in their airway, with concomitant inflammatory changes induced by lipid-laden macrophages and other immune cells. Therefore, we urge clinicians treating patients with acute and unexplained pulmonary complaints to identify whether the patient is an e-cigarette user and, if so, to obtain detailed history about their use and, when possible, to collect cell samples to determine whether evidence of lipid exposure is present. Similarly, we urge researchers to investigate lipid exposure and inhaled toxic substances in e-cigarette users systematically. Most important, we call for regulators to implement immediately strict regulation that prevents lipid and inhaled toxicants emissions from all e-cigarettes sold in the United States.