A six-month systems toxicology inhalation/cessation study in ApoE−/− mice to investigate cardiovascular and respiratory exposure effects of modified risk tobacco products, CHTP 1.2 and THS 2.2, compared with conventional cigarettes

• Published in: Food and chemical toxicology Vol. 126; pp. 113 - 141
• Main Authors: Phillips, Blaine, Szostak, Justyna, Titz, Bjoern, Schlage, Walter K., Guedj, Emmanuel, Leroy, Patrice, Vuillaume, Gregory, Martin, Florian, Buettner, Ansgar, Elamin, Ashraf, Sewer, Alain, Sierro, Nicolas, Choukrallah, Mohamed Amin, Schneider, Thomas, Ivanov, Nikolai V., Teng, Charles, Tung, Ching Keong, Lim, Wei Ting, Yeo, Ying Shan, Vanscheeuwijck, Patrick, Peitsch, Manuel C., Hoeng, Julia
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2019
• Subjects: Aerosols - adverse effects; Animals; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Cardiovascular System - drug effects; Cigarette smoking; Electronic Nicotine Delivery Systems; Emphysema; Female; Inflammation; Inhalation Exposure - adverse effects; Lung; Lung - drug effects; Mice; Mice, Knockout; Modified-risk tobacco products (MRTP); Nicotiana - adverse effects; Nicotiana - chemistry; Omics; Smoke - adverse effects; Tobacco Products - adverse effects; Tobacco Products - analysis; Inflammation; Cigarette smoking; Emphysema; Lung; Modified-risk tobacco products (MRTP); Omics
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2019.02.008

Smoking is one of the major modifiable risk factors in the development and progression of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Modified-risk tobacco products (MRTP) are being developed to provide substitute products for smokers who are unable or unwilling to quit, to lessen the smoking-related health risks. In this study, the ApoE-/- mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F, or aerosol from two potential MRTPs based on the heat-not-burn principle, carbon heated tobacco product 1.2 (CHTP1.2) and tobacco heating system 2.2 (THS 2.2), on the cardiorespiratory system over a 6-month period. In addition, cessation or switching to CHTP1.2 after 3 months of CS exposure was assessed. A systems toxicology approach combining physiology, histology and molecular measurements was used to evaluate the impact of MRTP aerosols in comparison to CS. CHTP1.2 and THS2.2 aerosols, compared with CS, demonstrated lower impact on the cardiorespiratory system, including low to absent lung inflammation and emphysematous changes, and reduced atherosclerotic plaque formation. Molecular analyses confirmed the lower engagement of pathological mechanisms by MRTP aerosols than CS. Both cessation and switching to CHTP1.2 reduced the observed CS effects to almost sham exposure levels.