Acute electronic vapour product whole aerosol exposure of 3D human bronchial tissue results in minimal cellular and transcriptomic responses when compared to cigarette smoke

Abstract

The use of electronic vapour products (EVPs) continues to increase worldwide and with advances in cell culture systems, molecular biology and the computational sciences there is also accumulating evidence of their potential reduced toxicity and reduced potential harm when compared to cigarette smoke. To further understand the potential risks and health effects associated with exposure to EVP aerosols we have assessed the cellular and transcriptomic response from a commercially available lung tissue culture system (MucilAirTM) following a single sub-cytotoxic exposure to cigarette smoke and the equivalent nicotine delivered dose of EVP aerosol. The transcriptomic, cellular (cilia beat frequency (CBF) and percent active area (%AA), trans epithelial electrical resistance (TEER), histology) and cytokine release were assessed at 4- and 48- hours following recovery from air, EVP aerosol (8.4% V/V: mybluTM blueberry flavour, 2.4% nicotine) and 3R4F smoke (3.5% V/V: exposure). No pathological changes were observed at either recovery time point from any exposure. Air and EVP aerosol exposure had no effect on CBF, %AA nor TEER at 48 hours. Exposure to cigarette smoke resulted in a decrease in TEER, an increase in CBF and the release of proinflammatory cytokines at both recovery time points. Although the number of significantly expressed genes was minimal following exposure to EVP aerosol, exposure to 3R4F smoke resulted in a significant upregulation of several disease relevant pathways. These data provide evidence that following an acute exposure to EVP aerosol there is significantly less damage to lung cells in culture than the equivalent, nicotine based, dose of cigarette smoke.

Multi-endpoint analysis of human 3D airway epithelium following repeated exposure to whole electronic vapor product aerosol or cigarette smoke

“…Although we have not looked at transcriptomics in this study, in a related study by Phillips et al (2021) assessed the acute response to non-cytotoxic doses of my blu and 3R4F. No pathological changes were observed at either recovery time point from any exposure (48 h).…”

“…Air and EVP aerosol exposure had no effect on CBF, CAA nor TEER at 48 h. Exposure to cigarette smoke resulted in a decrease in TEER and an increase in CBF and the release of proinflammatory cytokines at both recovery time points. Although the number of significantly expressed genes was minimal following exposure to EVP aerosol, exposure to 3R4F smoke resulted in a significant upregulation of several disease relevant pathways (oxidative stress and inflammation) ( Phillips et al, 2021 ). These functional findings as expected are mirrored in the current longer-term study we report here (28 days) with EVP and 3R4F.…”

Assessment of Carbon Nanotubes on Barrier Function, Ciliary Beating Frequency and Cytokine Release in In Vitro Models of the Respiratory Tract

“…The different ratio of cilia-bearing to mucus-producing cells between the tissues may be the reason for this difference. The average CBF of MucilAir™ tissues in the literature are indicated as 15.8 ± 0.3 Hz and 11.7 ± 1.2 Hz [ 43 , 45 ], and Beyeler et al observed higher CBF in the peripheral than in the central region [ 18 ]. This trend was also to some extent seen in the EpiAirway™ tissues but not in the MucilAir™ tissues of this study.…”

Fundamentals of vaping-associated pulmonary injury leading to severe respiratory distress

“…Transcriptomic profiling is a powerful tool for identifying cellular reprogramming consequential to environmental stress. Transcriptional profiling of vape fluid exposure has primarily involved cell culture models examining acute changes after short-term exposure protocols ( 80 , 81 , 82 , 83 , 84 ). Such studies have implicated vape juice for induction of genes associated with inflammation, metabolic/biosynthetic processes, extracellular membrane, apoptosis, lipid metabolism, and hypoxia.…”