JMIR Publications

ABSTRACT

Background:

The harm of cigarette smoking results mainly from long-term exposure to harmful and potentially harmful constituents (HPHC) generated by the combustion of tobacco. Smoking cessation (SC) engenders favorable changes of clinical signs, pathomechanisms, and metabolic processes that together could reduce the harm and risk 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 successful quitting rate of the SC program being tested. As limited information on short- to multiple long-term functional/biological changes following SC is available in the literature, more data on short to mid-term favorable impacts of SC are needed.

Objective:

The overall study aim was to assess the reversibility of the harm related to smoking over one year of continuous smoking abstinence (SA). This has been verified by assessing a set of biomarkers of exposure (BoExp) to HPHCs and a set of clinical risk endpoints (CRE) indicative of multiple pathophysiological pathways underlying the development of smoking-related diseases.

Methods:

This multiregional (United States, Japan, Europe), multicenter (42 sites) cohort study consisting of a one-year SA period in an ambulatory setting and a 28-day safety follow-up period was conducted from May 2015 to May 2017. A total of 1,184 male and female adult healthy smokers, willing to quit smoking, were enrolled in the study. Nicotine replacement therapy (NRT) was provided for up to three months upon subject’s request, and SC counseling and behavioral support were continuously provided. BoExp to HPHCs and CREs were assessed in urine and blood at baseline, Month 3, Month 6, and Month 12. Cardiovascular CREs 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 CREs included lung function parameters and cough symptoms. The CREs 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 cigarette self-reporting and chemical verification. Safety assessments included adverse events/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, 1,184 subjects (50.1% male) were enrolled; 30% of them quit smoking successfully for one year. Data analyses of the study results (including safety data) are ongoing and will be published after study completion.

Conclusions:

The current study provides insights into biological and functional changes, and health effects, after continuous SA over one year. Study results will be instrumental in assessing novel alternative products to cigarettes considered for tobacco harm reduction strategies. Clinical Trial: ClinicalTrials.gov identifier: NCT02432729