Statistical analysis plan for "A randomised, controlled study to evaluate the effects of switching from cigarette smoking to using a tobacco heating product on health effect indicators in healthy subjects".

Tobacco harm reduction strategies aim to substitute smoking with potentially reduced risk products (PRRPs) such as e-cigarettes and tobacco-heating products (THPs). The health benefits of switching from smoking to PRRPs is unknown. A randomised controlled trial is being conducted to increase understanding of the health effects of switching from smoking to a THP in a 12-month long ambulatory study (ISRCTN81075760).

Evaluating the effects of switching from cigarette smoking to using a heated tobacco product on health effect indicators in healthy subjects: study protocol for a randomized controlled trial.

Tobacco heating products (THPs) are a potentially safer alternative to combustible cigarette smoking. Through continued use, THPs may reduce smoking-related disease risk, whilst maintaining the sensorial experience and nicotine delivery sought by smokers. While literature evidence of the biological effects of THP aerosol exposure is increasing, there remains a knowledge gap with respect to substantiation of THP reduced risk potential in longer term real-life use.

Nicotine pharmacokinetics of electronic cigarettes: A review of the literature.

E-cigarettes are battery-powered electronic devices from which users can inhale nicotine following its aerosolisation from a liquid solution. Some regulators and public health bodies consider e-cigarettes as potentially playing a major role in tobacco harm reduction. Their ability to provide nicotine to smokers in both amount and in a manner and form generally similar to cigarette smoking have been proposed as key components to help smokers reduce or cease the use of combustible cigarettes.

Changes in Biomarkers of Exposure on Switching From a Conventional Cigarette to Tobacco Heating Products: A Randomized, Controlled Study in Healthy Japanese Subjects.

Background: Smoking is a leading cause of numerous human disorders including pulmonary disease, cardiovascular disease, and cancer. Disease development is primarily caused by exposure to cigarette smoke constituents, many of which are known toxicants. Switching smokers to modified risk tobacco products (MRTPs) has been suggested as a potential means to reduce the risks of tobacco use, by reducing such exposure.

A randomised, controlled, two-Centre open-label study in healthy Japanese subjects to evaluate the effect on biomarkers of exposure of switching from a conventional cigarette to a tobacco heating product.

Background: Smoking is a leading cause of numerous human disorders including lung cancer, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease. The development of modified risk tobacco products (MRTPs) has been suggested as a possible way to reduce the risks of tobacco smoking by reducing exposure to cigarette smoke toxicants. This study is designed to investigate whether biomarkers of such exposure are reduced when smokers switch from smoking commercial cigarettes to using either a novel or a commercially-available tobacco heating product (THP).

E-cigarette Nicotine Delivery: Data and Learnings from Pharmacokinetic Studies.

Objectives: E-cigarettes could potentially play a major role in tobacco harm reduction by delivering nicotine in a vapor containing significantly fewer toxicants than cigarette smoke and may aid smoking behavior changes such as reduction or cessation.

Methods: We examined blood nicotine levels in smokers who were non-accustomed to e-cigarette use (Study 1) and accustomed e-cigarette users (Study 2). We compared nicotine levels when participants used a closed modular system e-cigarette to those when participants smoked a cigarette.

An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories.

Background: Biomarkers have been used extensively in clinical studies to assess toxicant exposure in smokers and non-smokers and have recently been used in the evaluation of novel tobacco products. The urinary metabolite 3-HPMA, a metabolite of the major tobacco smoke toxicity contributor acrolein, is one example of a biomarker used to measure exposure to tobacco smoke. A number of laboratories have developed liquid chromatography with tandem mass spectrometry (LC-MS/MS) based methods to measure urinary 3-HPMA; however, it is unclear to what extent the data obtained by these different laboratories are comparable.

A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of phenolic polycyclic aromatic hydrocarbons (OH-PAH) in urine of non-smokers and smokers.

Polycyclic aromatic hydrocarbons (PAH) are products of the incomplete combustion of organic materials and, therefore, occur ubiquitously in the environment and also in tobacco smoke. Since some PAH have been classified as carcinogens, it is important to have access to suitable analytical methods for biomarkers of exposure to this class of compounds. Past experience has shown that measuring a profile of PAH metabolites is more informative than metabolites of a single PAH.

A cross-sectional investigation of biomarkers of risk after a decade of smoking.

Two groups of 20 healthy volunteers with cigarettes of different tar yield were compared with a group of 20 never smokers over 24 h for several biomarkers. All groups were of similar mean ages and the smokers had smoked for a homogeneous period of approximately 10 yr. The groups were assessed using routine medical parameters as well as biomarkers of recent smoke exposure and other biomarkers that were under evaluation as possible markers of risk for smoking-associated diseases.

Determination of tobacco-specific N-nitrosamines in urine of smokers and non-smokers.

Tobacco-specific N-nitrosamines (TSNA) include 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N'-nitrosonornicotine (NNN), N'-nitrosoanabasine (NAB) and N'-nitrosoanatabine (NAT) and are found in tobacco and tobacco smoke. TSNA are of interest for biomonitoring of tobacco-smoke exposure as they are associated with carcinogenesis. Both NNK and NNN are classified by IARC as Group 1 carcinogens.

Urinary excretion of phenolic polycyclic aromatic hydrocarbons (OH-PAH) in nonsmokers and in smokers of cigarettes with different ISO tar yields.

Polycyclic aromatic hydrocarbons (PAH) are products of the incomplete combustion of organic materials, and they occur ubiquitously in the environment. They are also present in tobacco smoke. Some PAH have been classified as carcinogens; therefore, it is important to develop and assess suitable biomarkers for PAH exposure.

Simultaneous determination of four tobacco-specific N-nitrosamines (TSNA) in human urine.

Tobacco-specific N-nitrosamines (TSNA) include 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonornicotine (NNN), N-nitrosoanabasine (NAB) and N-nitrosoanatabine (NAT). TSNA are suggested to play an important role in tobacco smoke carcinogenesis. We have developed and validated an LC-MS/MS method for the determination of total (free and conjugated) TSNA in human urine.

Cardiovascular biomarkers in groups of established smokers after a decade of smoking.

To investigate tools for evaluation of smoking-associated disease initiation and progression, we examined basic clinical parameters and biomarkers of cardiovascular disease risk, in a group of healthy volunteers with an average 10-year smoking history. A small cross-sectional study of never-smokers, moderate smokers and smokers was performed. Caucasians were recruited to match pre-defined cigarette tar yields and cigarettes smoked per day.

Measurement of oxidative DNA damage induced by mainstream cigarette smoke in cultured NCI-H292 human pulmonary carcinoma cells.

Cigarette smoke is a complex dynamic mixture of more than 4800 chemicals distributed between the particulate and vapour phases. It is widely acknowledged that cigarette smoke is capable of causing oxidative damage in DNA, either directly or through generation of reactive oxygen species. In this study, we have used a novel system for exposing cultured NCI-H292 human pulmonary carcinoma cells at the air-liquid interface, to investigate the potential effects of cigarette smoke on oxidative DNA damage by use of the modified comet assay with formamidopyrimidine N-glycosylase (FPG) and endonuclease III (Endo III) to reveal purine and pyrimidine lesions, respectively.

Smoking selectively accelerates carotid atherosclerosis in hypertensive patients.

Background And Objectives: Left ventricular hypertrophy, carotid atherosclerosis and renal dysfunction are indicators of target organ damage in hypertension, and independent risk factors for both fatal and non-fatal cardio- and cerebrovascular events. In the general population, smoking is associated with increases in left ventricular mass and carotid intima-media thickness (IMT), and impaired renal function. The aim of the present study was to evaluate whether smoking affects the development of target organ damage in patients with arterial hypertension.