Article

Biomarkers to assess the utility of potential reduced exposure tobacco products.

University of Minnesota Cancer Center, Minneapolis, MN, USA.
Nicotine & Tobacco Research (Impact Factor: 2.81). 09/2006; 8(4):600-22. DOI: 10.1080/14622200600858166
Source: PubMed

ABSTRACT To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test potential reduced exposure products. This paper represents the deliberations of four workgroups that focused on four tobacco-related heath outcomes: Cancer, nonmalignant pulmonary disease, cardiovascular disease, and fetal toxicity. The goal of these workgroups was to identify biomarkers that offer some promise as measures of exposure or toxicity and ultimately may serve as indicators for future disease risk. Recommendations were based on the relationship of the biomarker to what is known about mechanisms of tobacco-related pathogenesis, the extent to which the biomarker differs among smokers and nonsmokers, and the sensitivity of the biomarker to changes in smoking status. Other promising biomarkers were discussed. No existing biomarkers have been demonstrated to be predictive of tobacco-related disease, which highlights the importance and urgency of conducting research in this area.

0 Bookmarks
 · 
84 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tobacco consumption is high amongst the people of Xxx. This study was carried out in 2011 in a rural community of Xxx, to compare pathological parameters associated with tobacco use in relation to nicotine metabolism between smokers, chewers, and a control group. A total of 216 volunteers provided blood and urine samples for testing nicotine metabolites, C-reactive protein, and cell counts. Data were analyzed using ANOVA, correlation, and t-tests using STATA. Differences in blood pressure amongst the groups indicate a role of smoking in preventing a rise in BP with age, likely attributable to a different mechanism of metabolism of tobacco constituents.
    Substance Use &amp Misuse 02/2014; · 1.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract There are established guidelines for bioanalytical assay validation and qualification of biomarkers. In this review, they were applied to a panel of urinary biomarkers of tobacco smoke exposure as part of a "fit for purpose" approach to the assessment of smoke constituents exposure in groups of tobacco product smokers. Clinical studies have allowed the identification of a group of tobacco exposure biomarkers demonstrating a good doseresponse relationship whilst others such as dihydroxybutyl mercapturic acid and 2-carboxy-1-methylethylmercapturic acid - did not reproducibly discriminate smokers and non-smokers. Furthermore, there are currently no agreed common reference standards to measure absolute concentrations and few inter-laboratory trials have been performed to establish consensus values for interim standards. Thus, we also discuss in this review additional requirements for the generation of robust data on urinary biomarkers, including toxicant metabolism and disposition, method validation and qualification for use in tobacco products comparison studies.
    Biomarkers 07/2013; 18(6). · 2.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: In a previous clinical study, levels of biomarkers of exposure (BoEs) for specific toxicants were significantly reduced in smokers who switched from conventional cigarettes to reduced toxicant prototype (RTP) cigarettes. Very little is known about the biological variability of tobacco smoke BoEs within individuals and sub-groups, and the descriptive group-comparison statistics might not be sufficient to understand such changes. Therefore, we assessed how different statistical methods could be used to interpret changes in urine BoE levels at the individual level. Methods: We used non-parametric statistical reference limits, the empirical rule and reference change values (RCVs) to assess changes in levels of BoEs related to four toxicants in cigarettes smoke. Current smokers [of 6 mg and 1 mg International Organization for Standardization (ISO) tar yields] were allocated to switching to RTP groups or non-switching control groups within their respective tar bands. There were two 6 mg tar study groups, with a non-switching group (CC6, n=46) and a group switching to an RTP containing tobacco-substitute sheet and modified filter (TSS6, n=49); and three 1 mg tar smoker groups, with one non-switching (CC1, n=42), a group switching to an RTP containing tobacco-substitute sheet and modified filter (TSS1, n=44) and one switching to an RTP containing an enzyme-treated tobacco and modified filter (BT1, n=47). Results: Assessment of the direction of change showed that up to the 100% of subjects experienced a decrease in levels of some BoEs. Between 49% and 64% of subjects in the switching groups were classified as having decreased levels of 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) by the non-parametric criterion, whereas only 2%-6% had reduced levels of N-nitrosoanatabine (NAT). Of non-switchers, in 7%-14% of those smoking 1 mg ISO tar yield cigarettes increases were classified across all BoEs. RCVs highlighted patterns with more detail, showing that most changes occurred within 14 days of switching. Among smokers who switched to 6 mg RTPs, 40%, 44%, 6% and 15%, respectively, were classified as experiencing significant decreasing levels of HPMA, 3-hydroxypropylmercapturic acid, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and NAT, whereas in the two 1 mg switching groups 46%, 22%, 11% and 52% and 43%, 27%, 2% and 16% had decreased levels of the same biomarkers. Up to five subjects in the 6 mg non-switching group were classified as having increased levels of all BoEs. Conclusions: Although we believe that is not possible to determine whether the observed changes in BoEs reflect biological relevance, the use of reference values enables assessment of changes in BoEs at the individual level. Estimates of the BoE variability between subjects might aid study design and setting minimum targets for smoke toxicant yields for future development of RTPs.
    Clinical Chemistry and Laboratory Medicine 10/2013; · 2.96 Impact Factor

Preview

Download
4 Downloads
Available from