The long-term risks associated with cigarette smoking, particularly cancer [
1,
2], cardiovascular disease [
3] and chronic obstructive pulmonary disease [
4], are well established. Few longitudinal studies, however, have assessed spontaneous changes in smoking behaviour, and especially whether a smoker’s nicotine uptake remains constant or changes over time. Studies in adult smokers have shown stable values for cigarette consumption and concentrations of carboxyhaemoglobin (a biomarker for exposure to carbon monoxide) over periods of several months when smoking the same product [
5‐
7].
Previous longitudinal studies of spontaneous product switching
A small number of longitudinal studies have investigated the effects of spontaneous product switching on smoking behaviour [
8‐
12] and the extent of compensatory smoking behaviour. Compensation occurs when a smoker changes their smoking behaviour in some way, for example, puff volume, frequency or the number of cigarettes smoked, in response to smoking a cigarette of higher or lower smoke yield. Complete compensation occurs when a smoker maintains their intake following a change, no compensation results in a change that is proportional to the change in product yield, and incomplete compensation describes changes between these two extremes [
13]. In a study in the USA, conducted by the American Cancer Society between 1959 and 1972 on changes in cigarette consumption in relation to changes in tar and nicotine yield, data from 28,561 male smokers were reported [
8]. By the end of the study, 16,991 (59%) smokers had changed to cigarettes with lower tar and nicotine yields than at the start of the study, 8,190 (29%) had not changed, and 3,380 (12%) had changed to cigarettes with higher yields. Among smokers who had switched to cigarettes with increased tar and nicotine yields, 29% had also increased the number of cigarettes they smoked per day, while 39% had decreased the number smoked. Likewise, although 32% of smokers who had switched to lower tar and nicotine products smoked more cigarettes per day, 34% smoked fewer. The data suggest that changes in cigarette consumption were not related to smokers changing to cigarettes of higher or lower tar and nicotine yields, though the yields of tar and nicotine in the cigarettes smoked during this period would have been significantly higher than those typically seen today in most countries.
The effects of changing to lower tar yield cigarettes was investigated over a period of 13 years (1971–1984) in nearly 600 male smokers [
9]. Average cigarette consumption reduced over the study period, but to a lesser extent in smokers who had changed to lower tar cigarettes than in those who had not. At the 1984 follow-up, similar amounts of urinary nicotine metabolites were excreted by smokers who had and had not changed to lower tar cigarettes at data collection, which suggests compensatory smoking behaviour following switching. In a study of the effects of spontaneous switching on nicotine and carbon monoxide exposure in 203 smokers, a reduction in cigarette consumption of 6.6 cigarettes per day was observed in smokers who changed spontaneously to lower nicotine yield cigarettes, with smaller reductions in consumption for smokers who had not changed product or who had changed to higher nicotine yield cigarettes (1.9 and 1.8 fewer cigarettes, respectively) [
10]. For the smokers who changed to lower nicotine yield cigarettes, absolute plasma cotinine levels were reduced, however, plasma cotinine levels per cigarette were little altered, which suggests an increase in smoking intensity. In a longitudinal study in South Germany, 41 smokers changed their cigarette during the study, 13 of whom changed to a lower tar product [
11]. The extent of the reductions in cotinine concentrations suggested 55% compensation.
In 2002–2005, Muhammad-Kah and colleagues assessed spontaneous product switching in 2,542 smokers in the USA, of whom 68 switched to higher tar products and 23 switched to lower tar products, with subsequent decreases of two cigarettes and increases of two cigarettes per day, respectively [
12]. Substantial variability and insufficient power to detect significant differences in biomarkers of exposure, however, led to no definitive conclusions being reported.
Since 2004, in the European Union the maximum permitted tar and nicotine yields have been 10 mg and 1 mg per cigarette, respectively, measured using International Organization for Standardization (ISO) methods [
14]. Following the introduction of these regulations, long-term changes in consumption [
15], nicotine uptake, exposure to smoke toxicants and the effects of switching to cigarettes of lower yields are unclear. The World Health Organization (WHO) Study Group on Tobacco Product Regulation (TobReg) identified a number of research areas as being key to enhancing this knowledge [
16], which include assessment of whether an increase or decrease in nicotine content per unit (e.g. per cigarette) would be beneficial to a population’s health and investigation of contents and design features that might reduce toxicity, consumer appeal and/or the potential for dependency. In 2009, the US Food and Drug Administration was given jurisdiction over tobacco products via the US Family Smoking Prevention and Tobacco Control Act, and in 2012 issued draft guidance on the key areas to be investigated in making marketing applications for modified-risk tobacco products, which includes the requirement for post-market surveillance studies [
17]. The FDA is also considering product standards, which could involve the limiting of harmful and potentially harmful constituents and nicotine.
Study objectives
We plan to undertake a longitudinal study to address some of the TobReg research aims [
16], to provide insights into appropriate study designs for undertaking post marketing surveillance programmes. We will study the effects of spontaneous product switching over a 5 year period on the following features of smoking behaviour: average daily cigarette consumption, mouth-level exposure (MLE) to nicotine and tar [
18]; uptake of nicotine, assessed by measurement of urinary and salivary biomarkers of exposure; and exposure to the smoke toxicant 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ([NNK] a tobacco-specific nitrosamine) through the measurement of metabolites in urine. Secondary objectives are to assess any compensatory smoking behaviour and changes in quality of life and sensory perception following spontaneous product switching.