A lower impact of an acute exposure to electronic cigarette aerosols than to cigarette smoke in human organotypic buccal and small airway cultures was demonstrated using systems toxicology assessment

Anita R Iskandar,Laura Ortega Torres,Celine Merg,Manuel C Peitsch,Emmanuel Guedj,Athanasios Kondylis,Yang Xiang,Sandro Steiner,Patrice Leroy,Willie J Mckinney,Florian Martin,Keyur Trivedi,Nikolai V Ivanov,Filippo Zanetti,Julia Hoeng,Kyeonghee Monica Lee,Utkarsh Doshi,Shoaib Majeed,Stefan Frentzel

doi:10.1007/s11739-019-02055-x

Abstract

In the context of tobacco harm-reduction strategy, the potential reduced impact of electronic cigarette (EC) exposure should be evaluated relative to the impact of cigarette smoke exposure. We conducted a series of in vitro studies to compare the biological impact of an acute exposure to aerosols of “test mix” (flavors, nicotine, and humectants), “base” (nicotine and humectants), and “carrier” (humectants) formulations using MarkTen® EC devices with the impact of exposure to smoke of 3R4F reference cigarettes, at a matching puff number, using human organotypic air–liquid interface buccal and small airway cultures. We measured the concentrations of nicotine and carbonyls deposited in the exposure chamber after each exposure experiment. The deposited carbonyl concentrations were used as representative measures to assess the reduced exposure to potentially toxic volatile substances. We followed a systems toxicology approach whereby functional biological endpoints, such as histopathology and ciliary beating frequency, were complemented by multiplex and omics assays to measure secreted inflammatory proteins and whole-genome transcriptomes, respectively. Among the endpoints analyzed, the only parameters that showed a significant response to EC exposure were secretion of proteins and whole-genome transcriptomes. Based on the multiplex and omics analyzes, the cellular responses to EC aerosol exposure were tissue type-specific; however, those alterations were much smaller than those following cigarette smoke exposure, even when the EC aerosol exposure under the testing conditions resulted in a deposited nicotine concentration approximately 200 times that in saliva of EC users.

Highlights

Cigarette craving hinders success in smoking cessation, but studies have shown that substituting cigarettes with other sources of nicotine can facilitate accomplishing smoking abstinence [1]
To compare the in vitro biological effects of the mixtures fairly, basic physical characteristics of aerosols will demonstrate that the observed effects were not influenced significantly by the particle size
We determined the effects of exposure on the morphology of buccal and small airway cultures 48 h after exposure

Summary

Introduction

Cigarette craving hinders success in smoking cessation, but studies have shown that substituting cigarettes with other sources of nicotine can facilitate accomplishing smoking abstinence [1]. Song et al reported that EC use did not lead to significant alterations in the inflammatory cell counts, and mRNA and microRNA gene expression despite increased cytokines in the urine [6]. Another clinical study reported that switching to EC significantly reduced diastolic blood pressure short-term this effect was not significant after adjusting for other factors [7]. The committee stated that “in vitro toxicological tests, and short-term human studies suggest that e-cigarettes are likely to be far less harmful than combustible cigarettes,” the absolute risks of the product cannot be determined at present [3]. Understanding the health effects of EC, requires the determination of the risk of using them and the biological effects relative to those of combustible tobacco cigarette use [3]

Methods

Results

Discussion

Conclusion