Twenty-eight day repeated exposure of human 3D bronchial epithelial model to heated tobacco aerosols indicates decreased toxicological responses compared to cigarette smoke.

Introduction:
This text provides an in-depth analysis of a study comparing the toxicological responses of human 3D bronchial epithelial models to heated tobacco aerosols and cigarette smoke. The study uses repeated exposures over a 28-day period to assess the effects of the two prototype heated tobacco products (p-hTPs) and the 1R6F reference cigarette. The key points of the study are summarized below.

Key Points:

* The study used fully differentiated 3D human bronchial epithelial models (Mucilair ™) purchased from Epithelix Sàrl.
* Whole aerosol/smoke aerosols were applied to the apical surfaces of the 3D models using the custom-built Smoke aerosol Exposure In Vitro System (SaEIVS).
* The p-hTPs consisted of a rechargeable device into which a consumable stick with a reconstituted tobacco portion was inserted.
* The p-hTPs were stored at room temperature, protected from light, in sealed portions per test within airtight containers, until use.
* The 1R6F reference cigarettes were stored frozen, sealed in the original packaging until conditioning according to International Organization for Standardization (ISO, 2018) Guideline 3402 (1999).
* Nicotine dosimetry of the cell culture medium was carried out at the timepoints detailed in Figure 1.
* LDh was used as a marker of cytotoxicity, histological evaluation of tissue architecture, goblet cell (Muc5aC) and ciliated cell (FoxJ1) markers, and cilia beat frequency and active area were assessed.
* Levels of six markers associated with combustible cigarette smoke exposure were additionally assessed, IL-6, IL-8, MMP-1, MMP-3, MMP-9 and TNF α.

Main Message:
The study found that the p-hTPs demonstrated substantially reduced toxicological outcomes compared to the 1R6F reference cigarette smoke. This was evident in the decreased cytotoxicity, histological changes, and in-flammatory responses observed in the 3D human bronchial epithelial models exposed to the p-hTPs. These findings suggest that p-hTPs have the potential for tobacco harm reduction by offering a potentially less harmful form of nicotine delivery to adult smokers. however, further studies are needed to determine the long-term health effects of p-hTPs and their potential role in smoking cessation.

Chapman F, Pour SJ, Wieczorek R, et al. Twenty-eight day repeated exposure of human 3D bronchial epithelial model to heated tobacco aerosols indicates decreased toxicological responses compared to cigarette smoke. Frontiers in toxicology. 2023;5:1076752. doi:10.3389/ftox.2023.1076752