title: Evaluation of the tobacco heating system 2.2. Part 9: Application of systems pharmacology to identify exposure response markers in peripheral blood of smokers switching to THS2.2.
abstract: As part of current harm reduction strategies, candidate modified risk tobacco products (MRTP) are developed to offer adult smokers who want to continue using tobacco product an alternative to cigarettes while potentially reducing individual risk and population harm compared to smoking cigarettes. One of these candidate MRTPs is the Tobacco Heating System (THS) 2.2 which does not burn tobacco, but instead heats it, thus producing significantly reduced levels of harmful and potentially harmful constituents (HPHC) compared with combustible cigarettes (CC). A controlled, parallel group, open-label clinical study was conducted with subjects randomized to three monitored groups: (1) switching from CCs to THS2.2; (2) continuous use of non-menthol CC brand (CC arm); or (3) smoking abstinence (SA arm) for five days. Exposure response was assessed by measuring biomarkers of exposure to selected HPHCs. To complement the classical exposure response measurements, we have used the previously reported whole blood derived gene signature that can distinguish current smokers from either non-smokers or former smokers with high specificity and sensitivity. We tested the small signature consisting of only 11 genes on the blood transcriptome of subjects enrolled in the clinical study and showed a reduced exposure response in subjects that either stopped smoking or switched to a candidate MRTP, the THS2.2, compared with subjects who continued smoking their regular tobacco product.
authors.affiliation: PMI R&D, Philip Morris Products S.A., Neuchatel, Switzerland(1).
authors.forename: Florian
authors.initials: F
authors.lastname: Martin
authors.affiliation: PMI R&D, Philip Morris Products S.A., Neuchatel, Switzerland(1).
authors.forename: Marja
authors.initials: M
authors.lastname: Talikka
authors.affiliation: PMI R&D, Philip Morris Products S.A., Neuchatel, Switzerland(1).
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Ivanov
authors.affiliation: PMI R&D, Philip Morris Products S.A., Neuchatel, Switzerland(1).
authors.forename: Christelle
authors.initials: C
authors.lastname: Haziza
authors.affiliation: PMI R&D, Philip Morris Products S.A., Neuchatel, Switzerland(1). Electronic address: Hoeng@pmi.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.affiliation: PMI R&D, Philip Morris Products S.A., Neuchatel, Switzerland(1).
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Peitsch
mesh_terms: D000336:Aerosols; D015415:Biomarkers / Q000097:blood; D003257:Consumer Product Safety; D066300:Electronic Nicotine Delivery Systems / Q000009:adverse effects*; D004867:Equipment Design; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers; D023281:Genomics; D040261:Harm Reduction; D006358:Hot Temperature; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D011044:Poland; D018570:Risk Assessment; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects* / Q000097:blood / Q000235:genetics; D016540:Smoking Cessation / Q000379:methods; D000074606:Smoking Prevention; D049490:Systems Biology; D019460:Tobacco Industry; D062789:Tobacco Products / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000336:Aerosols; D015415:Biomarkers; D005819:Genetic Markers; D012906:Smoke
keywords: Blood; Exposure response; Gene expression signature; MRTP; Novel tobacco heating system; Smoking