Peer-Reviewed Publications

    Biological and functional changes in healthy adult smokers who are continuously abstinent from smoking for one year: Protocol for a prospective, observational, multicenter cohort study

    Tran, C. T.; Felber Medlin, L.; Lama, N.; Taranu, B.; Ng, W.; Haziza, C.; Picavet, P.; Baker, G.; Lüdicke, F.
    Published
    Jun 7, 2019
    DOI
    10.2196/12138
    PMID
    31199335
    Link to publication
    Topic
    Summary

    Background: The harm of smoking results mainly from long-term exposure to harmful and potentially harmful constituents (HPHCs) generated by tobacco combustion. Smoking cessation (SC) engenders favorable changes of clinical signs, pathomechanisms, and metabolic processes that together could reduce the harm of smoking-related diseases to a relative risk level approximating that of never-smokers over time. In most SC studies, the main focus is on the quitting rate of the SC program being tested. As there is limited information in the literature on short to multiple long-term functional or biological changes following SC, more data on short to mid-term favorable impacts of SC are needed. Objective: The overall aim of the study was to assess the reversibility of the harm related to smoking over 1 year of continuous smoking abstinence (SA). This has been verified by assessing a set of biomarkers of exposure to HPHCs and a set of biomarkers of effect indicative of multiple pathophysiological pathways underlying the development of smoking-related diseases. Methods: This multiregional (United States, Japan, and Europe), multicenter (42 sites) cohort study consisting of a 1-year SA period in an ambulatory setting was conducted from May 2015 to May 2017. A total of 1184 male and female adult healthy smokers, willing to quit smoking, were enrolled in the study. Nicotine replacement therapy (NRT) was provided for up to 3 months upon the subject’s request. SC counseling and behavioral support were continuously provided. Biomarkers of exposure to HPHCs and biomarkers of effect were assessed in urine and blood at baseline, Month 3, Month 6, and Month 12. Cardiovascular biomarkers of effect included parameters reflecting inflammation (white blood cell), lipid metabolism (high-density lipoprotein cholesterol), endothelial function (soluble intercellular adhesion molecule-1), platelet function (11-dehydrothromboxane B2), oxidative stress (8-epi-prostaglandin F2 alpha), and carbon monoxide exposure (carboxyhemoglobin). Respiratory biomarkers of effect included lung function parameters and cough symptoms. The biomarkers of effect to evaluate genotoxicity (total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) and xenobiotic metabolism (cytochrome P450 2A6 activity) were also assessed. Continuous SA was verified at each visit following the actual quit date using self-reporting and chemical verification. Safety assessments included adverse events and serious adverse events, body weight, vital signs, spirometry, electrocardiogram, clinical chemistry, hematology and urine analysis safety panel, physical examination, and concomitant medications. Results: In total, 1184 subjects (50.1% male) were enrolled; 30% of them quit smoking successfully for 1 year. Data analyses of the study results are ongoing and will be published after study completion. Conclusions: This study provides insights into biological and functional changes and health effects, after continuous SA over 1 year. Study results will be instrumental in assessing novel alternative products to cigarettes considered for tobacco harm reduction strategies. Trial Registration: ClinicalTrials.gov NCT02432729; http://clinicaltrials.gov/ct2/show/NCT02432729 (Archived by WebCite at http://www.webcitation.org/78QxovZrr) International Registered Report Identifier (IRRID): DERR1-10.2196/12138

    Related Publications

    Reduced Exposure To Harmful And Potentially Harmful Constituents after 90 Days Of Use Of Tobacco Heating System 2.2 Menthol In Japan: A Comparison With Continued Cigarette Use Or Smoking Abstinence

    Clinical

    Psychometric Evaluation of the mCEQ applied to Cigarettes and Heat-Not-Burn Products in the US and Japan

    Clinical

    Pharmacokinetics Of Nicotine And Subjective Effects Following The Single Use Of A Non-Menthol And Menthol Version Of Tobacco Heating System 2.2 In Two Studies In Japan: A Comparison With Single Use Of A Combustible Cigarette And Nicotine Gum

    Clinical

    Comparison of Abdominal Aortic Aneurysm Growth in Adult Smoking Patients Who Either Switch to IQOS, Continue Smoking, or Quit Smoking

    Clinical

    Systematic review of the relation between smokeless tobacco and cancer of the pancreas in Europe and North America

    Clinical

    Reduced exposure to Harmful and Potentially Harmful Constituents after 90 days of use of Tobacco Heating System 2.2 Menthol in Japan: A comparison with continued cigarette use or smoking abstinence

    Clinical

    Reduced Exposure To Harmful And Potentially Harmful Constituents after 90 Days Of Use Of Tobacco Heating System 2.2 Menthol In Japan: A Comparison With Continued Cigarette Use Or Smoking Abstinence

    Clinical

    Psychometric Evaluation of the mCEQ applied to Cigarettes and Heat-Not-Burn Products in the US and Japan

    Clinical

    Pharmacokinetics Of Nicotine And Subjective Effects Following The Single Use Of A Non-Menthol And Menthol Version Of Tobacco Heating System 2.2 In Two Studies In Japan: A Comparison With Single Use Of A Combustible Cigarette And Nicotine Gum

    Clinical

    Comparison of Abdominal Aortic Aneurysm Growth in Adult Smoking Patients Who Either Switch to IQOS, Continue Smoking, or Quit Smoking

    Clinical

    Systematic review of the relation between smokeless tobacco and cancer of the pancreas in Europe and North America

    Clinical

    Reduced exposure to Harmful and Potentially Harmful Constituents after 90 days of use of Tobacco Heating System 2.2 Menthol in Japan: A comparison with continued cigarette use or smoking abstinence

    Clinical

    PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
    ​
    Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.