Although the idea of reducing tobacco toxin exposure among continuing smokers is not a new concept, recent efforts by the tobacco industry to develop and market potential reduced-exposure products have resulted in an increased interest in examining this approach. The escalating introduction of potential reduced-exposure products has prompted the US Food and Drug Administration to sponsor a report from the Institute of Medicine and for the National Cancer Institute to convene an expert panel to consider the feasibility of this approach, the necessary science and systems that need to be in place in order to ensure public health, and the specific research areas that will need to be pursued. The identification of reliable and valid biomarkers for tobacco toxin exposure was determined to be a particularly important area of research.
Biomarkers can be considered as measures of the following: (1) toxins specifically related to exposure of tobacco constituents, such as nicotine or tobacco-specific nitrosamines; (2) risk contributors to disease, such as lipoproteins, C-reactive protein, WBC count; (3) disease markers such as pulmonary function; or (4) clinical outcome measures, such as hospitalizations, occurrence of disease, or death. Smokers compared to nonsmokers have significantly elevated risk factors for cardiovascular disease (CVD), and these risk factors improve among smokers after cessation of cigarettes. To date, few studies have examined the effects of changes in cigarette dose on cardiovascular risk factors. Of the studies that currently exist, the results show significant improvement on these measures; however, the sample sizes have tended to be small, and no control groups have been used.
In this study, the reliability and validity of measures of risk contributors to CVD were examined. The reliability of these measures was determined by examining the consistency of these measures over time during ad libitum tobacco use. The potential validity and sensitivity of these measures were determined by examining the dose-response relationship of these measures as the number of cigarettes smoked is reduced. We hypothesized that smoking reduction leads to a dose-related improvement on cardiovascular risk factors.
As a secondary aim, this study examined the feasibility of reducing the number of cigarettes smoked among smokers unwilling or unable to quit smoking. Prior studies have shown that smokers are able to reduce the number of cigarettes smoked with or without the use of pharmacologic agents; however, whether a significant proportion of the population is able to sustain this reduction or whether this reduction leads to significant reduction in biomarkers for disease has been called to question. Data were analyzed to determine the extent to which subjects were able to reduce smoking and the proportion of subjects able to sustain this reduction. We hypothesized that the majority of subjects can reduce smoking; however, sustaining significant reductions in smoking that leads to beneficial effects from smoking may be difficult to achieve.