Dataset Information

Multi-omics systems toxicology study of mouse lung assessing the effects of aerosols from two heat-not-burn tobacco products and cigarette smoke.

ABSTRACT: Cigarette smoke (CS) causes adverse health effects and, for smoker who do not quit, modified risk tobacco products (MRTPs) can be an alternative to reduce the risk of developing smoking-related diseases. Standard toxicological endpoints can lack sensitivity, with systems toxicology approaches yielding broader insights into toxicological mechanisms. In a 6-month systems toxicology study on ApoE-/- mice, we conducted an integrative multi-omics analysis to assess the effects of aerosols from the Carbon Heated Tobacco Product (CHTP) 1.2 and Tobacco Heating System (THS) 2.2-a potential and a candidate MRTP based on the heat-not-burn (HnB) principle-compared with CS at matched nicotine concentrations. Molecular exposure effects in the lungs were measured by mRNA/microRNA transcriptomics, proteomics, metabolomics, and lipidomics. Integrative data analysis included Multi-Omics Factor Analysis and multi-modality functional network interpretation. Across all five data modalities, CS exposure was associated with an increased inflammatory and oxidative stress response, and lipid/surfactant alterations. Upon HnB aerosol exposure these effects were much more limited or absent, with reversal of CS-induced effects upon cessation and switching to CHTP 1.2. Functional network analysis revealed CS-induced complex immunoregulatory interactions across the investigated molecular layers (e.g., itaconate, quinolinate, and miR-146) and highlighted the engagement of the heme-Hmox-bilirubin oxidative stress axis by CS. This work exemplifies how multi-omics approaches can be leveraged within systems toxicology studies and the generated multi-omics data set can facilitate the development of analysis methods and can yield further insights into the effects of toxicological exposures on the lung of mice.

SUBMITTER: Titz B

PROVIDER: S-EPMC7218232 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Multi-omics systems toxicology study of mouse lung assessing the effects of aerosols from two heat-not-burn tobacco products and cigarette smoke.

Titz Bjoern B Szostak Justyna J Sewer Alain A Phillips Blaine B Nury Catherine C Schneider Thomas T Dijon Sophie S Lavrynenko Oksana O Elamin Ashraf A Guedj Emmanuel E Tsin Wong Ee E Lebrun Stefan S Vuillaume Grégory G Kondylis Athanasios A Gubian Sylvain S Cano Stephane S Leroy Patrice P Keppler Brian B Ivanov Nikolai V NV Vanscheeuwijck Patrick P Martin Florian F Peitsch Manuel C MC Hoeng Julia J

Computational and structural biotechnology journal 20200425

Cigarette smoke (CS) causes adverse health effects and, for smoker who do not quit, modified risk tobacco products (MRTPs) can be an alternative to reduce the risk of developing smoking-related diseases. Standard toxicological endpoints can lack sensitivity, with systems toxicology approaches yielding broader insights into toxicological mechanisms. In a 6-month systems toxicology study on ApoE<sup>-/-</sup> mice, we conducted an integrative multi-omics analysis to assess the effects of aerosols ...[more]

PMID: 32419906

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Project description:Background: As e-cigarette popularity has increased, there is growing evidence to suggest that while they are highly likely to be considerably less harmful than cigarettes, their use is not free of risk to the user. There is therefore an ongoing need to characterise the chemical composition of e-cigarette aerosols, as a starting point in characterising risks associated with their use. This study examined the chemical complexity of aerosols generated by an e-cigarette containing one unflavored and three flavored e-liquids. A combination of targeted and untargeted chemical analysis approaches was used to examine the number of compounds comprising the aerosol. Contributions of e-liquid flavors to aerosol complexity were investigated, and the sources of other aerosol constituents sought. Emissions of 98 aerosol toxicants were quantified and compared to those in smoke from a reference tobacco cigarette generated under two different smoking regimes. Results: Combined untargeted and targeted aerosol analyses identified between 94 and 139 compounds in the flavored aerosols, compared with an estimated 72-79 in the unflavored aerosol. This is significantly less complex (by 1-2 orders of magnitude) than the reported composition of cigarette smoke. Combining both types of analysis identified 5-12 compounds over and above those found by untargeted analysis alone. Gravimetrically, 89-99% of the e-cigarette aerosol composition was composed of glycerol, propylene glycol, water and nicotine, and around 3% comprised other, more minor, constituents. Comparable data for the Ky3R4F reference tobacco cigarette pointed to 58-76% of cigarette smoke "tar" being composed of minor constituents. Levels of the targeted toxicants in the e-cigarette aerosols were significantly lower than those in cigarette smoke, with 68.5->99% reductions under ISO 3308 puffing conditions and 88.4->99% reductions under ISO 20778 (intense) conditions; reductions against the WHO TobReg 9 priority list were around 99%. Conclusion: These analyses showed that the e-cigarette aerosols contain fewer compounds and at significantly lower concentrations than cigarette smoke. The chemical diversity of an e-cigarette aerosol is strongly impacted by the choice of e-liquid ingredients.

Project description:ObjectivesIn addition to electronic cigarettes (e-cigarettes), tobacco companies have recently begun to sell heat-not-burn tobacco products, Ploom and iQOS in Japan. Previous research has reported an inverse association between combustible cigarette smoking and educational attainment, but little is known about the association for e-cigarettes, especially heat-not-burn tobacco products. Our objective was to analyze the relationship between educational attainment and e-cigarette and heat-not-burn tobacco use.SettingAn internet survey (randomly sampled research agency panelists) in Japan.ParticipantsA total of 7338 respondents aged 18-69 years in 2015 (3632 men and 3706women).Primary measuresAdjusted odds ratios (ORs) of educational attainment for current smoking (combustible cigarettes), e-cigarette ever-use, and heat-not-burn ever-use were calculated by multivariable logistic regression models using covariates including socio-demographic factors. Stratified analyses according to smoking status (combustible cigarettes) were additionally performed for e-cigarette ever-use and heat-not-burn tobacco product ever-use.ResultsAssociations between educational attainment and e-cigarette ever-use or heat-not-burn tobacco ever-use are not straightforward, although these associations are not statistically significant except for one cell. For example, using "graduate school" education as a reference category, adjusted ORs for "high school" were 1.44 (95% confidence interval [CI]: 0.85-2.44) for e-cigarettes ever-use and 0.75 (95% CI:0.19-2.97) for heat-not-burn tobacco product ever-use. Among current smokers, compared with "graduate school" (reference), those with lower educational attainment showed 0.6 to 0.7 ORs for e-cigarette ever-use: e.g.,"4-year university"(OR = 0.54, 95% CI:0.24-1.24) and "high school" (OR = 0.69, 95% CI: 0.30-1.60). Among former smokers, lower education indicated higher ORs for both e-cigarettes and heat-not-burn tobacco ever-use.ConclusionsThis study provides baseline information on educational gradients of e-cigarette and heat-not-burn tobacco products, ever-use. As heat-not-burn tobacco products are increasing their market share in Japan, continuous monitoring of these products will be necessary.

Dataset Information

Multi-omics systems toxicology study of mouse lung assessing the effects of aerosols from two heat-not-burn tobacco products and cigarette smoke.

Publications

Multi-omics systems toxicology study of mouse lung assessing the effects of aerosols from two heat-not-burn tobacco products and cigarette smoke.

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