Cigarette smoke retention and bronchodilation in patients with COPD. A controlled randomized trial.

INTRODUCTION: Bronchodilators are the cornerstone for symptomatic treatment of chronic obstructive pulmonary disease (COPD). Many patients use these agents while persisting in their habit of cigarette smoking. We hypothesized that bronchodilators increase pulmonary retention of cigarette smoke and hence the risk of smoking-related (cardiovascular) disease. Our aim was to investigate if bronchodilation causes increased pulmonary retention of cigarette smoke in patients with COPD. METHODS: A double-blinded, placebo-controlled, randomized crossover trial, in which COPD patients smoked cigarettes during undilated conditions at one session and maximal bronchodilated conditions at the other session. Co-primary outcomes were pulmonary tar and nicotine retention. We performed a secondary analysis that excludes errors due to possible contamination. Secondary outcomes included the biomarkers C-reactive protein and fibrinogen, and smoke inhalation patterns. RESULTS: Of 39 randomized patients, 35 patients completed the experiment and were included in the final analysis. Bronchodilation did not significantly increase tar retention (-4.5%, p = 0.20) or nicotine retention (-2.6%, p = 0.11). Secondary analysis revealed a potential reduction of retention due to bronchodilation: tar retention (-3.8%, p = 0.13), and nicotine retention (-3.4%, p = 0.01). Bronchodilation did not modify our secondary outcomes. CONCLUSIONS: Our results do not support the hypothesis that cigarette tar and nicotine retention in COPD patients is increased by bronchodilation, whereas we observed a possibility towards less retention. TRIAL REGISTRATION: www.clinicaltrials.gov: NCT00981851.

The linear relationship between cigarette tar and nicotine yields: regulatory implications for smoke constituent ratios.

Cigarette smoke analyte yields are often expressed as ratios relative to tar or nicotine yields, usually to compare different products or to estimate human uptake of smoke in relation to nicotine uptake measurements. The method, however, can lead to distorted interpretations, especially in the case of ratios from ultra-low tar yield cigarettes. In brief, as tar yields decrease below the 5­6 mg per cigarette range, the tar-to-nicotine ratio (TNR) decreases rapidly in a non-linear fashion. If, however, the nicotine yield, rather than the ratio, is plotted versus the tar yield, the non-linearity disappears and a straight line is obtained, with a slight positive intercept for nicotine on the ordinate. Unlike the ratio, the slope appears to depend only on the concentration of the nicotine in the blend and does not appear to vary with smoking parameters such as puff volume, puff interval or length smoked or with cigarette design parameters such as length, circumference or the amount of filtration or filter ventilation. Therefore, such a slope is analogous to the TNR although, unlike that ratio, it is invariant. Even more simply, the concentration of the nicotine in the blend, at least for American blend-style cigarettes, provides a similar index.

Population pharmacokinetic analysis of carboxyhaemoglobin concentrations in adult cigarette smokers.

AIMS: To develop a population-based model to describe and predict the pharmacokinetics of carboxyhaemoglobin (COHb) in adult smokers. METHODS: Data from smokers of different conventional cigarettes (CC) in three open-label, randomized studies were analysed using NONMEM (version V, Level 1.1). COHb concentrations were determined at baseline for two cigarettes [Federal Trade Commission (FTC) tar 11 mg; CC1, or FTC tar 6 mg; CC2]. On day 1, subjects were randomized to continue smoking their original cigarettes, switch to a different cigarette (FTC tar 1 mg; CC3), or stop smoking. COHb concentrations were measured at baseline and on days 3 and 8 after randomization. Each cigarette was treated as a unit dose assuming a linear relationship between the number of cigarettes smoked and measured COHb percent saturation. Model building used standard methods. Model performance was evaluated using nonparametric bootstrapping and predictive checks. RESULTS: The data were described by a two-compartment model with zero-order input and first-order elimination with endogenous COHb. Model parameters included elimination rate constant (k(10)), central volume of distribution (Vc/F), rate constants between central and peripheral compartments (k(12) and k(21)), baseline COHb concentrations (c0), and relative fraction of carbon monoxide absorbed (F1). The median (range) COHb half-lives were 1.6 h (0.680-2.76) and 30.9 h (7.13-367) (alpha and beta phases, respectively). F1 increased with increasing cigarette tar content and age, whereas k(12) increased with ideal body weight. CONCLUSION: A robust model was developed to predict COHb concentrations in adult smokers and to determine optimum COHb sampling times in future studies.

Self-titration of nicotine: evidence from the Scottish Heart Health Study.

Data from 2754 cigarette smokers who smoke no other forms of tobacco are extracted from the baseline cross-sectional survey of the Scottish Heart Health Study. Carbon monoxide in expired-air (CO-E), serum thiocynate and serum cotinine measurements from these smokers are compared with the carbon monoxide (CO), nicotine and tar yields of the cigarettes which they smoke, controlling for daily cigarette consumption, the sex of the smoker and the other cigarette yields. CO-E is found to increase positively with CO and tar yield, but inversely with nicotine yield. Thiocyanate increases positively with CO, is not significantly affected by tar, but increases inversely with nicotine. Cotinine is affected only by tar, in a positive direction for women. We conclude that smokers appear to self-titrate their consumption of nicotine by more aggressive smoking of lower-strength cigarettes.

Effects of varying marijuana smoking profile on deposition of tar and absorption of CO and delta-9-THC.

We investigated the effects of previously observed differences in smoking technique for marijuana (M) versus tobacco (T) on the amount of inhaled tar, the percentage retention of inhaled tar in the lung, the pre- to postcigarette boost in blood carboxyhemoglobin (COHb) and in serum delta-9-tetrahydrocannabinol (THC concentrations), and psychophysiologic responses to THC (increased heart rate and subjective "high"). Ten healthy, habitual smokers of M were studied on 6 separate days. On each day, subjects smoked a single M cigarette (approximately 900 mg, 1.24% delta-9-THC) using one of 6 different smoking profiles typical for marijuana [puff volume (PV) approximately 70 ml; breathholding time, (BHT) 14-16 s] or tobacco (PV approximately 45 ml; BHT 4-5 s) or a combination of the two techniques (PV approximately 70 ml and BHT 4-5 s; or PV approximately 45 ml and BHT 14-16 s). Inhaled volume (1.5 liters), interpuff interval (30 s) and number of puffs (6) were all fixed, except that for the approximately 45-ml PV condition, the number of puffs was increased to 10 in 2 additional sessions to standardize the total amount of cigarette consumed to that of the approximately 70-ml PV condition. The longer BHT significantly increased both percent retention of tar in the lung and the pre- to postsmoking rise in blood COHb, serum THC and heart rate, independent of puff volume and number. In contrast, the larger PV had no significant influence on these variables for the same amount of cigarette consumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Tar, CO and delta 9THC delivery from the 1st and 2nd halves of a marijuana cigarette.

Previous in vitro studies suggest that, with successive puffs from a marijuana cigarette, delta-9-THC becomes concentrated in the remaining uncombusted portion of the cigarette. These observations are consistent with the common practice of smoking marijuana cigarettes to a smaller butt length than that to which tobacco cigarettes are smoked. The purpose of the present study was to compare the delivery of delta-9-THC, as well as total insoluble smoke particulates (tar) and carbon monoxide, from the distal ("first") versus the proximal ("second") halves of a standard marijuana cigarette during "natural" smoking of marijuana. On 4 separate days, ten habitual marijuana users smoked nearly all or approximately 1/2 of a standard marijuana cigarette (83 mm length; 800-900 mg; 1.24% THC), as follows: day 1, "whole" cigarette (60 mm smoked, leaving a 23-mm butt); day 2, "first" half (first 30 mm); day 3, "second" half (second 30 mm) after the "first" half was presmoked with a syringe; and day 4, "second" half after the "first" half was excised. A previously described smoking apparatus (20) was used for measurement of puff volume and inhaled tar. Puff volume and number were allowed to vary spontaneously (provided that the specified length of cigarette was consumed), while inhaled volume (1.5 liters), breathholding time (14 s) and interpuff interval (30 s) were held constant. Blood samples were withdrawn prior to smoking and serially after completion of smoking for analysis of blood carboxyhemoglobin (COHb) and serum delta-9-THC. Heart rate was measured before and 5 min after smoking. Subjects rated their level of "high" 20 min after completion of smoking.(ABSTRACT TRUNCATED AT 250 WORDS)