Review of biomarkers to assess the effects of switching from cigarettes to modified risk tobacco products.

Context: One approach to reducing the harm caused by cigarette smoking, at both individual and population level, is to develop, assess and commercialize modified risk alternatives that adult smokers can switch to. Studies to demonstrate the exposure and risk reduction potential of such products generally involve the measuring of biomarkers, of both exposure and effect, sampled in various biological matrices.Objective: In this review, we detail the pros and cons for using several biomarkers as indicators of effects of changing from conventional cigarettes to modified risk products.Materials and methods: English language publications between 2008 and 2017 were retrieved from PubMed using the same search criteria for each of the 25 assessed biomarkers. Nine exclusion criteria were applied to exclude non-relevant publications.Results: A total of 8876 articles were retrieved (of which 7476 were excluded according to the exclusion criteria). The literature indicates that not all assessed biomarkers return to baseline levels following smoking cessation during the study periods but that nine had potential for use in medium to long-term studies.Discussion and conclusion: In clinical studies, it is important to choose biomarkers that show the biological effect of cessation within the duration of the study.

Does use of flue-cured rather than blended cigarettes affect international variation in mortality from lung cancer and COPD?

We compared risk of lung cancer and chronic obstructive pulmonary disease (COPD) associated with flue-cured and blended cigarettes. Mortality and smoking data were collected for 1971-2000 by sex, age, and period for three countries with a mainly flue-cured market and four with a blended market. Epidemiological relative risk estimates for current and ex smoking were summarized. Smoking statistics and mortality were compared between flue-cured cigarette and blended cigarette countries. Unadjusted mortality rates were generally lower in blended cigarette countries early on, with the difference diminishing or reversing by the 1990s. Differences by cigarette type were rarely significant, due to variations, particularly for COPD, between countries within cigarette type. Current smoking prevalence was generally lower in blended cigarette countries in 1971-1975, with the difference reducing over time. Differences by type were never significant, with blended cigarette countries varying markedly. Ex-smoking increased over time and was lower for blended cigarette countries, generally not significantly. Consumption per smoker was somewhat lower for blended cigarette countries. Relative risk estimates for smoking, derived mainly from U.S. and UK studies, varied little by cigarette type. Conclusions based on estimated smoking-related excess mortality were similar to those based on unadjusted mortality rates. There was little indication of any difference between flue-cured and blended cigarettes on risk of lung cancer or COPD. Our approach could have detected differences of about 40% for male lung cancer, or twofold differences for females or for COPD, had they existed. Between-country differences in rates of two major diseases predominantly caused by smoking cannot materially be explained by whether the countries use flue-cured or blended cigarettes.

The role of ammonia in the transfer of nicotine from tobacco to mainstream smoke.

This study has examined the possible effects of ammonia-forming ingredients added to tobacco and of ammonia in mainstream (MS) smoke on the nicotine transfer from tobacco to smoke. The U.S. 1998 Marlboro Lights King Size cigarette was used as a control for four test variants that differed from the control as follows: first, a reduction in ammonia-forming ingredients added to the reconstituted tobaccos; second, no ammonia-forming ingredients added to the reconstituted tobaccos; third, no ingredients at all added to the reconstituted tobaccos; and fourth, no ingredients at all added to the entire tobacco blend. Data were obtained on nicotine in tobacco, tar and nicotine and ammonia in MS smoke, soluble ammonia in the cigarette tobacco, "tobacco pH," and "smoke pH" using the FTC machine-smoking paradigm. Previous research on these cigarettes demonstrated that >99% of the MS smoke nicotine was captured and quantified by the FTC method. Statistically significant increases in soluble ammonia and MS smoke ammonia were observed for those cigarettes with ammonia-forming ingredients added to the reconstituted tobacco. However, ingredients, including ammonia and ammonia-forming compounds added to the tobacco or ammonia in the mainstream smoke in the Marlboro Lights King Size cigarette, did not increase the relative nicotine transfer or the "pH of aqueous extracts of MS smoke." "Tobacco pH" and "smoke pH" had no scientific or practical value for the cigarettes in this study.

On the deposition of volatiles and semivolatiles from cigarette smoke aerosols: relative rates of transfer of nicotine and ammonia from particles to the gas phase.

The hypothesis that elevated levels of ammonia-releasing compounds in tobacco and ammonia in mainstream (MS) smoke increase the rate and amount of nicotine evaporation from the particles of MS smoke aerosol was examined by kinetic modeling and experiments with MS cigarette smoke. Computational simulation of a kinetic mechanism describing volatile loss of nicotine, ammonia, and acetic acid from an aqueous solution was used to compute the time-dependent concentration of all species in the model. Because of the high volatility of ammonia relative to that of nicotine, variation over a wide range of initial ammonia concentration had no significant effect upon the rate of loss of nicotine from the model system. The effects of a variation in the volatile loss rate constant for ammonia and for the acid were examined. The simulations show that ammonia is lost from the model solution at a greater rate than nicotine and acid, and the loss of volatile acid has a significant role in the rate and amount of nicotine loss. Simulations with a model system undergoing a continuous steady addition of ammonia showed that high rates of ammonia addition could significantly increase the rate of nicotine volatile loss from the model solution. A series of smoking experiments was performed using blended cigarettes connected to a denuder tube. Deposition of smoke constituents can occur directly from the gas phase and by the deposition of smoke aerosol particles themselves. As nicotine exists >99% in the particle phase of MS smoke, in the absence of particle deposition, denuder tube deposition of nicotine occurs via the evaporation-deposition pathway. Solanesol, a nonvolatile tobacco and smoke terpene, was used to quantify the amount of particle deposition onto the denuder tube. The amount of ammonia deposited on the denuder tube was an order of magnitude greater than that of nicotine, showing that ammonia evaporates from the MS smoke particles much faster than does nicotine. The experimental results were supported and explained by the aqueous model simulations. Included in these experiments are cigarettes that differ in their MS smoke ammonia content by a factor of ca. five. However, an increased amount of MS smoke ammonia does not increase the rate of nicotine loss from the particles. The combined results support the conclusion that ammonia in mainstream smoke has little effect, if any, upon the rate and amount of nicotine evaporation from MS smoke particles.