Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System.

Introduction: This study examined changes in biomarkers of exposure (BoE) after 5 days of nicotine-salt pod system (NSPS) use, compared with continuation of usual-cigarette smoking and cigarette abstinence, among adult combustible cigarette smokers.

Aims And Methods: A randomized, open-label, parallel-cohort, confinement study of healthy adult smokers, naive to NSPS use, was conducted. Participants (N = 90) were randomized to six cohorts (n = 15 each): exclusive ad libitum use of NSPS (four flavors: Virginia Tobacco, Mint, Mango, Creme), continuation of usual-brand cigarette smoking, or cigarette abstinence.

Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum.

Rationale: We previously reported that following a short-term product use period, use of non-menthol Vuse Solo electronic cigarettes (ECs) resulted in product effect-related subjective responses and nicotine uptake between those of combustible cigarettes (high-abuse liability comparator) and nicotine gum (low-abuse liability comparator); the results were generally closer to those of nicotine gum.

Objective: Using a similar design to the previous study, we evaluated the abuse liability of three menthol-flavored Vuse Solo ECs with the same nicotine contents (14, 29, and 36 mg) in a group of EC-naïve, menthol cigarette smokers, relative to comparator products.

Methods: Six-hour nicotine uptake and ratings of subjective effects were used to determine abuse liability and pharmacokinetics.

Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability.

Rationale: Electronic cigarettes (ECs) are becoming popular alternatives for smokers, but there has been limited study of their abuse liability.

Objectives: The objective of this study was to evaluate the abuse liability of three Vuse Solo ECs, ranging from 14 to 36 mg in nicotine content, relative to high- and low-abuse liability comparator products (usual brand combustible cigarettes and nicotine gum, respectively) in a group of 45 EC-naïve smokers.

Methods: Enrolled subjects' ratings of subjective effects and nicotine uptake over 6 h were used to measure abuse liability and pharmacokinetics following in-clinic use of each EC.

Measurement of cardiovascular and pulmonary function endpoints and other physiological effects following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers.

Acute changes in select physiological parameters associated with cardiovascular physiology (systolic and diastolic blood pressure (BP) and heart rate (HR)), pulmonary function (FVC, FEV1, and exhaled CO and NO) and adverse events were measured in 105 clinically confined subjects who were randomized into groups that either completely or partially switched from conventional cigarettes to e-cigarettes or completely discontinued using tobacco and nicotine products altogether. Use of the e-cigarettes for five days under the various study conditions did not lead to higher BP or HR values, negative respiratory health outcomes or serious adverse health events. Reductions in BP and HR vital signs were observed in most of the participants that either ceased tobacco and nicotine products use altogether or switched completely to using e-cigarettes.

Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes.

Background: Electronic cigarettes (e-cigarettes) are popular alternatives to conventional cigarettes among adult smokers wishing to reduce their exposure to harmful smoke constituents. However, little information exists on the relative internal exposures resulting from the exclusive or dual use of e-cigarettes.

Methods: Measurements of product use; adverse events; changes in smoking urge; and blood, urine and exhaled breath biomarkers of exposure (BoE) representing toxicants believed to contribute to smoking related diseases were made at baseline and after five days of product use in 105 clinically-confined smokers randomized into groups that partially or completely substituted their usual brand combustible cigarette with commercial e-cigarettes, or discontinued all nicotine and tobacco products.

Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers.

Changes in fifteen urine, blood and exhaled breath BoEs of HPHCs representing classes of compounds reported by FDA to be significant contributors to smoking-associated disease risks were measured in 105 clinical-confined subjects following randomization and a five-day forced-switch from usual brand conventional combustible cigarettes to: (i) exclusive commercial e-cigarette use; (ii) dual-use of commercial e-cigarettes and the subject's usual cigarette brand; or (iii) discontinued use of all tobacco or nicotine products. Levels of urinary biomarkers in subjects that completely substituted their usual cigarette with e-cigarettes were significantly lower (29-95%) after 5 days. Percent reductions in eight of nine urinary BoEs were indistinguishable to smokers who had quit smoking, except for nicotine equivalents, which declined by 25-40%.

Nicotine delivery, tolerability and reduction of smoking urge in smokers following short-term use of one brand of electronic cigarettes.

Background: This randomized, partially single-blinded, 6-period crossover clinical study of adult smokers compared the nicotine pharmacokinetics, impacts on smoking urge and tolerability of various formulations of one brand of e-cigarettes with that of a tobacco cigarette.

Methods: Five e-cigarettes with different e-liquid formulations containing 1.6 % and 2.

Cardiovascular effects caused by increasing concentrations of diesel exhaust in middle-aged healthy GSTM1 null human volunteers.

Context: Epidemiological studies have shown an association between the incidence of adverse cardiovascular effects and exposure to ambient particulate matter (PM). Diesel exhaust (DE) is a major contributor to ambient PM and gaseous emissions in urban areas.

Objective: This was a pilot study designed to evaluate concentration-dependent effects of short-term exposure to whole DE on the cardiovascular system in order to identify a threshold concentration that can elicit biological responses in healthy human volunteers.

Synergistic effects of exposure to concentrated ambient fine pollution particles and nitrogen dioxide in humans.

Context: Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants.

Comparison of gene expression profiles induced by coarse, fine, and ultrafine particulate matter.

Coarse, fine, and ultrafine particulate matter (PM) fractions possess different physical properties and chemical compositions and may produce different adverse health effects. Studies were undertaken to determine whether or not gene expression patterns may be used to discriminate among the three size fractions. Airway epithelial cells obtained from 6 normal individuals were exposed to Chapel Hill coarse, fine or ultrafine PM (250 μg/ml) for 6 and 24 h (n=3 different individuals each).

Exposure to concentrated coarse air pollution particles causes mild cardiopulmonary effects in healthy young adults.

Background: There is ample epidemiologic and toxicologic evidence that exposure to fine particulate matter (PM) air pollution [aerodynamic diameter < or = 2.5 microm (PM(2.5))], which derives primarily from combustion processes, can result in increased mortality and morbidity.

Assessing the role of particulate matter size and composition on gene expression in pulmonary cells.

Identifying the mechanisms by which air pollution causes human health effects is a daunting task. Airsheds around the world are composed of pollution mixtures made up of hundreds of chemical and biological components with an extensive array of physicochemical properties. Current in vivo approaches are limited to the identification of associations between pollutants and health but do not allow for the identification of precise biological mechanisms of effect or the component(s) responsible for the effect.

Metal particulate matter components affect gene expression and beat frequency of neonatal rat ventricular myocytes.

Soluble particulate matter (PM) components (e.g., metals) have the potential to be absorbed into the bloodstream and transported to the heart where they might induce the expression of inflammatory cytokines and remodel electrical properties.

Evaluation of potential losartan-phenytoin drug interactions in healthy volunteers.

Background: Phenytoin, a cytochrome P450 (CYP) 2C9 substrate, has a narrow therapeutic index and nonlinear pharmacokinetics. Therefore there is the potential for significant concentration-related adverse effects when phenytoin is coadministered with other CYP2C9 substrates. Losartan, an antihypertensive agent, is also a substrate for CYP2C9.