Effects of switching or cessation in ApoE−/− mice. Following 2 (study #1) or 3 (study #2) months of exposure to 3R4F cigarette smoke, mice were switched to fresh air (sham) or aerosol from THS 2.2 (study #1) or CHTP 1.2 (study #2). A 3R4F reference group was continued on cigarette smoke exposure. Selected groups and endpoints are shown; for the full data, see the original publications [61,64]. A. Adaptive change in response to irritation: squamous metaplasia of respiratory epithelium, nose level 1. B. Adaptive change in response to irritation: hyperplasia of respiratory epithelium, nose level 1. C. Lung inflammation: number of free lung cells in bronchoalveolar lavage fluid. D. Lung inflammation: yellow pigmented macrophages, left lung. E. Biological impact on the lungs: causal network models interpreting transcriptomics data. F. Lung disease: emphysematous changes (histopathology scores). G. Atherosclerosis: relative plaque size (morphometry) in the aortic arch. H. Heart response profiles: number of DEGs. I. Atherosclerosis: plaque volume (micro-CT data) in the aorta. DEG, differentially expressed gene; RBIF, relative biological impact factor; micro-CT, micro-computed tomography.