Evaluation of biomarkers of exposure and potential harm in smokers, former smokers and never-smokers

Abstract

While BoE clearly differentiate between groups based on self-declared smoking status, most BoPH examined could not do so in a consistent manner. The dynamics of BoPH levels are not well understood. Future studies of BoPH should eliminate potential confounding factors and increase the number of subjects to allow the investigation of genetic polymorphism in metabolic pathways.

Changes in levels of biomarkers of exposure and biological effect in a controlled study of smokers switched from conventional cigarettes to reduced-toxicant-prototype cigarettes

“…11-dehydrothromboxane B2 is a urinary metabolite of the potent platelet agonist and vasoconstrictor, thromboxane A2. Raised concentrations of the urinary metabolite are associated with platelet activation and smoking status (Wennmalm et al, 1991;Lowe et al, 2009;Nowark et al, 1987;Frost-Pineda et al, 2011) and decrease significantly following smoking cessation (Rangemark et al, 1993;Saareks et al, 2001) or a switch to an electrically heated tobacco product . Throughout the study period, levels of 11-dehydrothromboxane B2 in the control group remained significantly higher than in the never-smoker group and became a significantly different from values in the ex-smoker group at the study midpoint and EOS time points (see Supplementary data: Appendix 2).…”

“…Some BoBE listed in the protocol (Shepperd et al, 2013) were not included for methodological reasons: all levels of interleukins 6 and 8 and tumour necrosis factor alpha were below the limit of quantification, and baseline levels of matrix metalloproteinases 1 and 9, tissue inhibitor of metalloproteinase 1 and vascular endothelial growth factor were not obtained due to delays in analysis that compromised the stability criteria. The most promising four BoBE (F2-isoprostanes [8-iso-PGF2 type lll and 8-iso-PGF2 Type Vl], white blood cells and s-ICAM-1) were assigned to the primary objective because of their reported association with smoking-related disease and abilities to differentiate between smoking status and demonstrate reversibility upon smoking cessation (Lowe et al, 2009;Lowe et al, 2013). All other BoBE were considered exploratory and were assigned to the secondary objectives.…”

The Relationship Between Cigarette Smoking and Biomarkers of Exposure Across Two Study Centers in Europe

“…The detailed description of the subject recruitment and study design at both centers has been described previously [9,10]. Briefly, never smokers, former smokers and regular smokers of cigarettes from two categories were recruited based on screening questionnaire responses and spot salivary or urinary cotinine measurements and exhaled breath carbon monoxide measurements, according to pre-defined inclusion and exclusion criteria.…”

“…We have previously described two separate studies conducted at geographically distinct sites across Europe: Leeds, UK [9] and Messina, Italy [10], in which the subjects were recruited according to similar criteria. Although there was a similarity between the recruitment criteria, there are distinct differences between the diets and lifestyles of these regions and the brands of cigarettes smoked were also different.…”

“…Although there was a similarity between the recruitment criteria, there are distinct differences between the diets and lifestyles of these regions and the brands of cigarettes smoked were also different. In the present study, these subjects were pooled and the original urinary biomarkers of exposure data from Leeds [9] and Messina [10] were re-examined with different statistical approaches. This larger subject pool allowed us to examine sub-groups in cigarettes per day (CPD) categories that are different from the original recruiting criteria and to establish whether data obtained from two separate European areas is suitable for combination, allowing for possible lifestyle and cigarette brand differences.…”