Publications

Aerosolized nicotine from e-cigarettes alters gene expression, increases lung protein permeability, and impairs viral clearance in murine influenza infection

Maishan M, Sarma A, Chun LF, Caldera S, Fang X, Abbott J, Christenson SA, Langelier CR, Calfee CS, Gotts JE, Matthay MA

Frontiers in Immunology, 14:1076772

PMID: 36999019 · DOI: 10.3389/fimmu.2023.1076772

E-cigarette aerosol was generated by the tank-style Aspire Nautilus and drawn into a syringe by the Gram Universal Vaping Machine. Mice were exposed one hour per day over nine consecutive days to aerosol containing VG/PG with or without nicotine, then inoculated with influenza A virus. Exposure to aerosolized nicotine caused significantly lower MUC5AC in the distal airspaces, higher lung permeability to protein, and higher viral load at 7 days post inoculation. Nicotine caused relative downregulation of genes associated with ciliary function and fluid clearance and increased expression of pro-inflammatory pathways. These results show that acute exposure to aerosolized nicotine impairs clearance of viral infection and exacerbates lung injury.

Comparable Impairment of Vascular Endothelial Function by a Wide Range of Electronic Nicotine Delivery Devices

Rao P, Han DD, Tan K, Mohammadi L, Derakhshandeh R, Navabzadeh M, Goyal N, Springer ML

Nicotine & Tobacco Research, 24(7):1055–1062

PMID: 35100430 · DOI: 10.1093/ntr/ntac019

Using a Gram Universal Vaping Machine version 5.0, arterial flow-mediated dilation (FMD) was measured in rats exposed to aerosol from USONICIG ultrasonic vaping devices, previous generation e-cigarettes, JUUL pods (Virginia Tobacco, Mango, Menthol), IQOS heated tobacco product, and Marlboro Red cigarettes. Aerosol/smoke from all conditions except air significantly impaired FMD. A wide range of ENDS, including multiple types of e-cigarettes with and without nicotine, a heated tobacco product, and an ultrasonic vaping device devoid of heating coil, all impair FMD after a single vaping session comparably to combusted cigarettes.

Impairment of Endothelial Function by Cigarette Smoke Is Not Caused by a Specific Smoke Constituent, but by Vagal Input From the Airway

Nabavizadeh P, Liu J, Rao P, Ibrahim S, Han DD, Derakhshandeh R, Qiu H, Wang X, Glantz SA, Schick SF, Springer ML

Arteriosclerosis, Thrombosis, and Vascular Biology, 42:1324–1332

PMID: 36288292 · DOI: 10.1161/ATVBAHA.122.318051

Flow-mediated dilation (FMD) was measured in rats exposed to smoke from four types of research cigarettes, individual aldehyde gases, and inert carbon nanoparticles. All cigarette types impaired FMD by 20–46%. Individual aldehydes (acrolein, acetaldehyde) impaired FMD by approximately 50%, but inert carbon nanoparticles produced comparable impairment without any gas phase present. Bilateral cervical vagotomy blocked the impairment of FMD by tobacco smoke, demonstrating that acute endothelial dysfunction from inhaled products is caused by vagus nerve signaling initiated by airway irritation, not by a specific chemical constituent.

Assessing young adults' ENDS use via Ecological Momentary Assessment and a Smart Bluetooth enabled ENDS device

Li Z, Benowitz-Fredericks C, Ling PM, Cohen JE, Thrul J

Addictive Behaviors, 113:106659

PMID: 33031497 · DOI: 10.1016/j.addbeh.2020.106659

18 young adult ENDS users completed daily EMA diaries for 30 days while using a second-generation smart Bluetooth enabled ENDS device (Gram Smart Vaporizer) that collected puff data. The ENDS device collected approximately twice as many puffs per day as participants reported. Self-reported puff counts had the highest correlation with device-collected puff counts (r=0.49; p<.001). Self-reports potentially underestimate use of ENDS, and ENDS use behavior is likely higher than users estimate and report.

Validation of a nicotine vapor self-administration model in rats with relevance to electronic cigarette use

Smith LC, Kallupi M, Tieu L, Shankar K, Jaquish A, Barr J, Su Y, Velarde N, Sedighim S, Carrette LLG, Klodnicki M, Sun X, de Guglielmo G, George O

Neuropsychopharmacology (Nature), 45(11):1909–1919

PMID: 32544927 · DOI: 10.1038/s41386-020-0734-8

A novel model of voluntary electronic cigarette use in rats was developed using operant behavior and the Gram Universal Vaping Machine. Rats voluntarily exposed themselves to nicotine vapor, reaching blood nicotine levels similar to humans. Three weeks of daily nicotine vapor self-administration produced addiction-like behaviors including somatic signs of withdrawal, allodynia, anxiety-like behavior, and relapse-like behavior after 3 weeks of abstinence. The exposure also produced cardiopulmonary abnormalities and changes in nicotinic acetylcholine receptor subunit mRNA levels. These findings validate a novel animal model of nicotine vapor self-administration with relevance to electronic cigarette use in humans.

Dose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate

Matsumoto S, Fang X, Traber MG, Jones KD, Langelier C, Hayakawa Serpa P, Calfee CS, Matthay MA, Gotts JE

American Journal of Respiratory Cell and Molecular Biology, 63(6):748–757

PMID: 32822237 · DOI: 10.1165/rcmb.2020-0209OC

Adult mice and primary human alveolar epithelial type II cells were exposed to an aerosol of vitamin E acetate (VEA) generated by a Gram Universal Vaping Machine. VEA caused dose-dependent increases in lung water and BAL protein compared with control and JUUL-exposed mice, in association with increased BAL neutrophils, oil-laden macrophages, multinucleated giant cells, and inflammatory cytokines. VEA was directly absorbed by AT II cells, resulting in differential gene expression of several inflammatory pathways. Given the epidemiological and clinical characteristics of the EVALI outbreak, these results suggest that VEA plays an important causal role.

Reducing toxic reactive carbonyl species in e-cigarette emissions: testing a harm-reduction strategy based on dicarbonyl trapping

de Falco B, Petridis A, Paramasivan P, Troise AD, Scaloni A, Deeni Y, Stephens WE, Fiore A

RSC Advances, 10:21535–21544

DOI: 10.1039/D0RA02138E

Polyphenols including gallic acid, hydroxytyrosol, and epigallocatechin gallate were added to e-liquids and aerosolized using a Gram Universal Vaping Machine to test whether they could reduce harmful reactive carbonyl species. Analysis showed these compounds reduced formaldehyde, methylglyoxal, and glyoxal levels. Testing on lung cells revealed the resulting dicarbonyl-polyphenol adducts were not toxic. The findings suggest polyphenols may have potential value in commercial e-liquid formulations as a harm-reduction strategy.

JUUL and Combusted Cigarettes Comparably Impair Endothelial Function

Rao P, Liu J, Springer ML

Tobacco Regulatory Science, 6(1):30–37

PMID: 31930162 · DOI: 10.18001/TRS.6.1.4

Rats were exposed to aerosol from Virginia Tobacco flavor JUUL, an e-cig tank system using unflavored freebase nicotine e-liquid, Marlboro Red combustible tobacco cigarettes, or clean air using the Gram Vaping Machine. Aerosol/smoke from JUUL, previous generation e-cigs, and cigarettes all impaired flow-mediated dilation (FMD), with impairment ranging from 34%–58%. Nicotine was highest in serum from the JUUL group. Aerosol from JUUL and previous generation e-cigs impairs endothelial function in rats, comparable to impairment by cigarette smoke.

Aldehydes in Cigarette Smoke Impair Vascular Endothelial Function

Rao P, Liu J, Springer ML

Circulation Research, 127(Suppl 1):A236

DOI: 10.1161/res.127.suppl_1.236

Conference abstract presented at the AHA Scientific Sessions 2020. Rats were exposed to individual aldehyde gases (acrolein and acetaldehyde) known to be present in cigarette smoke, and flow-mediated dilation (FMD) was measured. Both aldehydes significantly impaired vascular endothelial function, demonstrating that specific reactive carbonyl species in tobacco smoke contribute to the acute cardiovascular harm of smoking.

A Strategy for Efficiently Collecting Aerosol Condensate Using Silica Fibers: Application to Carbonyl Emissions from E-Cigarettes

Stephens WE, de Falco B, Fiore A

Chemical Research in Toxicology, 32(10):2053–2062

PMID: 31515993 · DOI: 10.1021/acs.chemrestox.9b00214

A simplified method for trapping low volatility components of e-cigarette aerosols using amorphous silica fibers (0.75 g of 4 μm diameter) within a 10 mL syringe, aerosolized using the Gram Universal Vaping Machine. On average, the silica wool traps about 94% of the vaporized liquid mass and retains higher levels of condensate before reaching saturation compared with Cambridge filter pads. Carbonyl concentrations were consistent with published experiments showing marked increases with variable power settings (10W to 50W). Compared with CFPs, this method requires only one vaping session for multiple analyte groups, traps more condensate per puff, and collects more condensate before saturation.

Vascular endothelial function is impaired by aerosol from a single IQOS HeatStick to the same extent as by cigarette smoke

Nabavizadeh P, Liu J, Havel CM, Ibrahim S, Derakhshandeh R, Jacob P III, Springer ML

Tobacco Control, 28(Suppl 1):s13–s19

PMID: 30206183 · DOI: 10.1136/tobaccocontrol-2018-054325

Anaesthetised rats were exposed via nose cone to IQOS aerosol from single HeatSticks, mainstream smoke from single Marlboro Red cigarettes, or clean air. FMD was impaired comparably by IQOS aerosol and cigarette smoke. When IQOS exposure was briefer, leading to comparable serum nicotine levels to the cigarette group, FMD was still comparably impaired. IQOS use does not necessarily avoid the adverse cardiovascular effects of smoking cigarettes.

An Exploration of Smoking-to-Vaping Transition Attempts Using a “Smart” Electronic Nicotine Delivery System

Blank ML, Hoek J, George M, Gendall P, Conner TS, Thrul J, Ling PM, Langlotz T

Nicotine & Tobacco Research, 21(10):1339–1346

PMID: 29878179 · DOI: 10.1093/ntr/nty093

11 daily smokers used Bluetooth-enabled Gram Smart Vaporizer devices that automatically recorded usage patterns for 8 weeks alongside self-reported cigarette consumption. Three distinct patterns emerged: immediate intensive adoption followed by rapid smoking reduction; gradual increase in device use with corresponding gradual smoking decrease but continuing dual use; and brief experimentation before returning to exclusive smoking. Real-time device monitoring technology enables detailed examination of smoking-to-vaping transitions.

An electronic cigarette vaping machine for the characterization of aerosol delivery and composition

Havel CM, Benowitz NL, Jacob P III, St Helen G

Nicotine & Tobacco Research, 19(10):1224–1231

PMID: 27281605 · DOI: 10.1093/ntr/ntw147

An electronic cigarette vaping machine assembled from commercially available parts — the Gram Universal Vaping Machine — was validated for reproducible aerosolization of e-liquids under controlled conditions. When using one ProTank 3 clearomizer, the coefficient of variation of aerosol generated ranged between 11.5% and 19.3%. Aerosol generation increased linearly at 3–6V across e-liquids. Acetaldehyde, acrolein, and formaldehyde generation increased markedly at voltages at or above 5V. The vaping machine reproducibly aerosolizes e-liquids and is useful for testing of nicotine and toxicant delivery.

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