Clinical laboratory evaluation of potential reduced exposure products for smokers

Abstract

Smoking-related cancer and other disease account for more than 400,000 U.S. deaths annually. Smoking cessation reduces smoking-related disease rates, but relapse rates are high. Thus, interest in reducing the harm of continued smoking is growing. Potential reduced exposure products (PREPs) are marketed to reduce smokers' exposure to smoke toxicants such as carbon monoxide (CO) and carcinogens and may be harm reduction tools. New PREPs are proliferating, but past experience with "low-yield" cigarettes that failed to reduce smokers' toxicant exposure suggests that comprehensive evaluation is necessary to predict if these new products are likely to alter the harm caused by smoking. The purpose of the study was to develop clinical laboratory methods for PREP evaluation. Smokers (N = 35) completed four, 5-day conditions that differed by product used: Advance, Eclipse, own brand cigarettes, or no cigarettes. Carcinogen (as assessed by one nitrosamine and one polycyclic aromatic hydrocarbon biomarker) and nicotine exposure were assessed via thrice-weekly urine sampling. Withdrawal symptoms were measured daily, and smoking behavior was assessed on the first and last day of each condition. Relative to own brand, Advance reduced exposure to the nitrosamine NNK and CO, and Eclipse reduced exposure to nicotine and the nitrosamine NNK, increased exposure to CO, and resulted in larger, longer, and more frequent puffs. No smoking reduced exposure to the nitrosamine NNK, CO, and nicotine, whereas withdrawal was elevated (all p values <.05). Clinical laboratory evaluation of PREPs for smokers is valuable for measuring users' smoke toxicant exposure, withdrawal, and smoking behavior and should be incorporated into a comprehensive PREP evaluation strategy.

Waterpipe tobacco smoking: Knowledge, attitudes, beliefs, and behavior in two U.S. samples

“…Extant research suggests that a single waterpipe use episode can increase blood nicotine levels well beyond those observed after a single cigarette (e.g., over 50 ng/ml for waterpipe, Shafagoj et al, 2002; as compared with approximately 6 ng/ml for a cigarette, Breland et al, 2006). However, 79% of U.S. respondents considered waterpipe less addictive than cigarettes, and most respondents reported not being hooked and having no intention to quit.…”

Evaluating oral noncombustible potential-reduced exposure products for smokers

“…While some PREPs for smokers involve tobacco combustion (e.g., Breland, Kleykamp, & Eissenberg, 2006), others involve orally administered noncombustible tobacco products. For example, Star Scientific markets Ariva, a compressed tobacco tablet intended for "adult smokers in situations where they cannot or choose not to smoke."…”

Developing the science base for reducing tobacco harm

“…In one study, when use of Advance over 5 days was compared with usual-brand cigarettes (N=12), a significant reduction was observed for urinary total NNAL (51%) with no significant reductions in cotinine and a slight but significant reduction in CO levels (Breland, Acosta, & Eissenberg, 2003). In a more recent within-subject, 5-day study with Advance (N=35), a significant reduction was observed in the Advance condition for urinary total NNAL (37%) compared with own-brand cigarettes, but no differences were observed in 1-HOP, cotinine, or alveolar CO levels at day five (Breland, Kleykamp, & Eissenberg, 2006). In summary, the results from these studies show modest reductions in exposure to one of the tobacco-specific nitrosamines.…”

“…Studies also have shown no changes in other biomarkers such as peripheral blood measures (e.g., fibrinogen, hemoglobin, platelets), lung function, pulmonary epithelial permeability (unlike the Stewart et al [2006] findings), vital signs (Frampton et al, 2000;Rennard et al, 2002) or total NNAL and 1-HOP concentrations (Breland et al, 2006). Increases have been observed for CO exposure when using Eclipse (Breland et al, 2006;Frampton et al, 2000;Rennard et al, 2002;Stewart et al, 2006) and for some of the biomarkers for inflammation and oxidative stress (Stewart et al, 2006). Eclipse also has been examined when used in conjunction with cigarettes (Fagerström, Hughes, & Callas, 2002;Fagerström, Hughes, Rasmussen, & Callas, 2000), which may be more reflective of the naturalistic use of this product.…”

“…For example, compared with usual brands of cigarettes, Eclipse has shown a significant reduction in respiratory tract inflammation over 2 months of use in heavy smokers (35% improvement in alveolar inflammatory cells and 46% improvement in bronchitis index; Rennard et al, 2002), a significant reduction (70%-79%) in urine mutagenicity after 1 week of use (Bowman et al, 2002;Smith et al, 1996), improvement in high-density lipoprotein cholesterol and reduction in circulating lymphocyte activation after 2 or 4 weeks of use (Frampton et al, 2000); and modest increase in lung permeability halflife (indicative of improvement in pulmonary epithelial injury) after 2 and 4 weeks of use in some smokers (Stewart et al, 2006). Studies also have shown no changes in other biomarkers such as peripheral blood measures (e.g., fibrinogen, hemoglobin, platelets), lung function, pulmonary epithelial permeability (unlike the Stewart et al [2006] findings), vital signs (Frampton et al, 2000;Rennard et al, 2002) or total NNAL and 1-HOP concentrations (Breland et al, 2006). Increases have been observed for CO exposure when using Eclipse (Breland et al, 2006;Frampton et al, 2000;Rennard et al, 2002;Stewart et al, 2006) and for some of the biomarkers for inflammation and oxidative stress (Stewart et al, 2006).…”