Six-month systems toxicology inhalation/cessation study in ApoE-/- mice to investigate cardiovascular and respiratory exposure effects of two reduced risk tobacco products compared with conventional cigarettes
Cigarette smoking causes adverse health effects that may occur shortly after smoking initiation and lead to the development of cardiovascular disease, respiratory disease (chronic obstructive pulmonary disease), and various cancers. To reduce the risk of smoking-related diseases, Philip Morris International is developing reduced risk products (RRP) to which adult smokers can switch instead of continuing to smoke cigarettes.
Engaging a systems toxicology approach combining physiological, histological, and -omics endpoints, the effects of a six-month exposure to cigarette smoke (CS) or to aerosols from two RRPs, the carbon heated tobacco product (CHTP) and the tobacco heating system (THS), were investigated in ApoE-/- mice. In addition, the impact of cessation or switching to CHTP aerosol exposure after three months of CS exposure was evaluated.
Our results demonstrated that exposure to CS at a concentration of 28.0 µg nicotine/L causes adverse effects on the lungs, including increased lung volume, lung inflammation, aortic plaque formation, and a dysregulation of the heart transcriptome. In contrast, exposure to either THS or CHTP aerosol at matched nicotine concentrations did not induce lung inflammation or enhance plaque development. Cessation or switching to CHTP aerosol exposure reversed lung inflammatory responses and halted progression of aortic plaques. Transcriptomics analysis revealed that multiple biological pathways were impacted significantly in heart tissue by CS exposure but not by exposure to CHTP or THS aerosols. Both cessation and switching to CHTP aerosol reduced these perturbations to levels similar to those in sham-exposed animals.
In conclusion, in this study, exposure to aerosol from either THS or CHTP had minimal adverse respiratory and cardiovascular effects. In addition, cessation or switching to CHTP aerosol exposure delayed the progression of CS-induced atherosclerotic and lung emphysematous changes.