title: A 7-month cigarette smoke inhalation study in C57BL/6 mice demonstrates reduced lung inflammation and emphysema following smoking cessation or aerosol exposure from a prototypic modified risk tobacco product.
abstract: Modified risk tobacco products (MRTP) are designed to reduce smoking-related health risks. A murine model of chronic obstructive pulmonary disease (COPD) was applied to investigate classical toxicology end points plus systems toxicology (transcriptomics and proteomics). C57BL/6 mice were exposed to conventional cigarette smoke (3R4F), fresh air (sham), or a prototypic MRTP (pMRTP) aerosol for up to 7 months, including a cessation group and a switching-to-pMRTP group (2 months of 3R4F exposure followed by fresh air or pMRTP for up to 5 months respectively). 3R4F smoke induced the typical adaptive changes in the airways, as well as inflammation in the lung, associated with emphysematous changes (impaired pulmonary function and alveolar damage). At nicotine-matched exposure concentrations of pMRTP aerosol, no signs of lung inflammation and emphysema were observed. Both the cessation and switching groups showed a similar reversal of inflammatory responses and no progression of initial emphysematous changes. A significant impact on biological processes, including COPD-related inflammation, apoptosis, and proliferation, was identified in 3R4F-exposed, but not in pMRTP-exposed lungs. Smoking cessation or switching reduced these perturbations to near sham-exposed levels. In conclusion, the mouse model indicated retarded disease progression upon cessation or switching to pMRTP which alone had no adverse effects.
authors.affiliation: Philip Morris International Singapore, Singapore.
authors.forename: Blaine
authors.initials: B
authors.lastname: Phillips
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Emilija
authors.initials: E
authors.lastname: Veljkovic
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Peck
authors.affiliation: Histovia GmbH, Schöne Aussicht 5, 51491 Overath, Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Buettner
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Elamin
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Guedj
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Gregory
authors.initials: G
authors.lastname: Vuillaume
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Ivanov
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Martin
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boué
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Walter K
authors.initials: WK
authors.lastname: Schlage
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Titz
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Marja
authors.initials: M
authors.lastname: Talikka
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vanscheeuwijck
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: julia.hoeng@pmi.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Peitsch
mesh_terms: D000336:Aerosols; D000818:Animals; D004334:Drug Administration Schedule; D004646:Emphysema / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D015208:Smoke Inhalation Injury / Q000473:pathology*; D016540:Smoking Cessation; D062789:Tobacco Products / Q000633:toxicity*
chemical_list: D000336:Aerosols
keywords: COPD; Computational network model; Histopathology; Mechanistic investigations; Systems toxicology; Tobacco-heating