Addressing the challenges of E-cigarette safety profiling by assessment of pulmonary toxicological response in bronchial and alveolar mucosa models

Abstract

Limited toxicity data on electronic cigarette (ECIG) impede evidence-based policy recommendations. We compared two popular mixed fruit flavored ECIG-liquids with and without nicotine aerosolized at 40 W (E-smoke) with respect to particle number concentrations, chemical composition, and response on physiologically relevant human bronchial and alveolar lung mucosa models cultured at air–liquid interface. E-smoke was characterized by significantly increased particle number concentrations with increased wattage (25, 40, and 55 W) and nicotine presence. The chemical composition of E-smoke differed across the two tested flavors in terms of cytotoxic compounds including p-benzoquinone, nicotyrine, and flavoring agents (for example vanillin, ethyl vanillin). Significant differences in the expression of markers for pro-inflammation, oxidative stress, tissue injury/repair, alarm anti-protease, anti-microbial defense, epithelial barrier function, and epigenetic modification were observed between the flavors, nicotine content, and/ or lung models (bronchial or alveolar). Our findings indicate that ECIG toxicity is influenced by combination of multiple factors including flavor, nicotine content, vaping regime, and the region of respiratory tree (bronchial or alveolar). Toxic chemicals and flavoring agents detected in high concentrations in the E-smoke of each flavor warrant independent evaluation for their specific role in imparting toxicity. Therefore, multi-disciplinary approaches are warranted for comprehensive safety profiling of ECIG.

Differential Effect of SARS-CoV-2 Spike Glycoprotein 1 on Human Bronchial and Alveolar Lung Mucosa Models: Implications for Pathogenicity

“…NCI-H441 cells were co-cultured with HULEC-5a (ATCC CRL-3244), representative of human lung microvascular endothelial cells for this purpose. Details of the development of alv-ALI model and its characteristics have been described recently [24]. The characterization included light-, confocal-, transmission electron microscopy, and transepithelial electrical resistance measurement of the differentiated H441 at the ALI condition.…”

“…The characterization included light-, confocal-, transmission electron microscopy, and transepithelial electrical resistance measurement of the differentiated H441 at the ALI condition. Morphological characterization of the alveolar mucosa model demonstrated the presence of tight junction protein 1, lamellar bodies, surfactant protein C, microvilli, lipid bodies, desmosome, and tight junctions [24].…”

In vitro determinants of e-cig aerosol condensate bioavailability and toxicity: Influence of cell culture parameters and utility of a normalized dose metric in e-cigarette studies

“…Serum proteins could compete with cellular targets for binding to the test compounds or could facilitate the cellular uptake of the compounds resulting respectively, in the inhibition or enhancement of cytotoxicity [53]. E-cig aerosols are multi-constituent [3, 5] and their composition depends not only on the initial e-liquid formulation, but also on vaping parameters [58, 59]. Therefore, the nature (or lack thereof) of interactions between e-cig aerosol components and serum proteins will determine how serum influences the cytotoxic potency of individual e-cig aerosol preparations.…”

Circulating Secretoglobin Family 1A Member 1 (SCGB1A1) Levels as a Marker of Biomass Smoke Induced Chronic Obstructive Pulmonary Disease

“…of the PBEC-ALI and PBEC-ALI/CB model have been described previously [ 16 ]. The cells used in this study are well characterized and have been used in connection with several other projects [ 16 , 17 , 18 ]. The PBEC were harvested from healthy bronchial tissues obtained from donors in connection with lobectomy following their written and informed consent.…”

“…We exposed each insert to 0.25%, 0.5%, and 1% CSC by adding CSC solution (dissolved in a small volume cell culture media; total volume: 80 µL) on the apical surface of PBEC-ALI and PBEC-ALI/CB models. Following 24 h of incubation, the transcript expression of SCGB1A1 was assessed using quantitative real time polymerase chain reaction (qRT-PCR) as explained previously [ 18 ]. Sham exposed samples (80 µL cell culture media) served as control and actin beta ( ACTB ) was used as the reference gene.…”