PG/VG in ecigs tied to lung damage in well-done experiment

As health officials struggle to understand the increasing number of serious lung disease, a new experimental study using mice may provide some clues about what is going on.

Matthew Madison and his colleagues published “Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine” in Journal of Clinical Investigation.  They exposed mice to e-cigarette aerosol without and with nicotine and found that the aerosol altered lipid (fat) balance in the lungs in ways that depressed the ability of the lung macrophages to fight infections and disrupted normal production of surfactants, chemicals in lungs that help keep the airsacs from collapsing.   This effect did not depend on the nicotine, but was related to the propylene glycol and vegetable glycerin that are the primary carriers in e-cigarettes.

The paper is technical, but worth reading because it points to the biological pathways that could be explaining these effects.  All the authorities investigating these cases as well as anyone who cares about e-cigs should read this paper.  It also add to the growing case that e-cigs are not just cigarettes without as much bad stuff, but also bring their own unique toxic effects.

The figure at the end of this blog post, taken from the paper, shows the many ways in which exposure to PG/VG from e-cigs (which the authors call ENDS, electronic nicotine delivery systems) disrupts normal lung function.

For people who don’t want to plow through the paper itself, Sara Harrison wrote an excellent story in Wired that explains the results in plan English.  So did NBC.  Both stories are worth reading.

While nicotine does not seem to be causing these effect, a recent paper by Robert Tarran from UNC showed e-cigs caused elevations in lung proteases in people who used e-cigs that were similar to smokers that seemed to depend on nicotine.  These changes are related to COPD.

All this information points to the idea that the spate of cases that are drawing attention are not just due to some contaminant in the e-cigs, but rather are fundamental to the product itself.  It may be that some other elements of specific products may be aggravating these conditions or it may depend on intensity of use.   My guess is that these cases have been around for a long time, but the prevalence of e-cig use had not yet become high enough to create enough cases for health authorities to see the problem.

Here is the abstract for the paper:

Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes.

The full citation is

Madison MC, Landers CT, Gu BH, Chang CY, Tung HY, You R, Hong MJ, Baghaei N, Song LZ, Porter P, Putluri N, Salas R, Gilbert BE, Levental I, Campen MJ, Corry DB, Kheradmand F.   Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine.  J Clin Invest. 2019 Sep 4. pii: 128531. doi: 10.1172/JCI128531. [Epub ahead of print].  It is available here.

The lung’s delicate surfactant layer is of critical importance to the organ’s overall physiology and innate immune function. Both alveolar type II cells and alveolar macrophages are the principal subsets that maintain and catabolize surfactant at the liquid-air interface. Our study reveals that ENDS exposure disrupts both the lipid and protein components of pulmonary surfactant, increasing phospholipid pools in the airway and decreasing the expression of the regulatory surfactant proteins SP-A and SP-D. Lipid deposition and impaired immune function are distinct features of alveolar macrophages upon chronic ENDS treatment. Upon viral infection, ENDS-exposed mice exhibit increased morbidity and mortality with excessive pulmonary damage and inflammation late in infection. Of chief importance, the ENDS-mediated effects observed in our model are independent of the presence of nicotine.