Smoking Topography Study 2016

In 2005, the World Health Organization Framework Convention on Tobacco Control
(WHO FCTC) was established with the aim for a regulatory strategy as a response
to the globalization of the tobacco epidemic. One of their non-price measures
to reduce the demand for tobacco includes article 9: Regulation of the contents
of tobacco products. Cigarette product regulation is currently based on tar,
nicotine and carbon monoxide (TNCO) levels in cigarette smoke, which are
indicated on the package. This is not sufficient, since cigarette smoke
includes more than 7000 chemicals. There are aldehydes, VOCs, PAHs,
nitrosamines, metals and so much more measured in cigarette, causing
tobacco-related diseases.
In the future, regulation of these harmful cigarette constituents should be
based on more chemical classes, as the WHO suggested. However, in order to
introduce such class-based regulation, a scientific base is needed to define
upper limits of allowed amounts of chemicals (groups) in cigarette smoke
emissions and to ensure decreased harmful effects due to cigarette smoking. To
date, the causality between human exposure to specific cigarette smoke
compounds and the harmful effects is unknown. The first step in closing the gap
in knowledge between cigarette smoke exposure and developing tobacco-related
diseases includes a proper determination of human exposure to cigarette smoke
chemicals. Unfortunately, there is a lack of methodology to determine cigarette
smoke exposure in humans. The goal of this pilot study is to characterize
natural human smoking behavior. The smokers* exposure to cigarette smoke
emissions is determined by the smoking behaviour, which includes 1) the way a
cigarette is smoked, called smoking topography, and 2) holding cigarette
whereby ventilation holes may be blocked by rolling the cigarette between the
smokers* fingers.
In a laboratory setting, this is combined in a smoking regime used in smoking
machine experiments. For example, TNCO indicated on packages, is measured with
machine smoking following a standard International Organization for
Standardization (ISO) method, and differs per brand. However, smoking
topography data in human studies show a more intense human smoking behavior.
Therefore, a more intense regime with longer and more often puffs, such as the
Health Canada Intense (HCI), was also introduced. Although such changes in the
setup of the machine smoking experiments make it a useful tool for product
comparison, this approach remains a poor predictor for a smokers' exposure.
Hence, we do know that smokers have their own smoking topography, and that this
process differs per cigarette and situation. In other words, the smoker doses
himself and this cannot be mimicked on a smoking machine. The question arises
which factors lead to a certain manner of smoking. Smokers smoke to gain
nicotine, with additional production of carbon monoxide (CO). Inhalation of too
much CO gives the smoker an unpleasant negative sensation, which leads to an
adaptive way of puffing in order to prevent this. Of course, smoking is also
accompanied by the inhalation of harmful chemicals, but the smoker is not aware
of this during smoking and therefore does not adapt his smoking topography with
respect to that exposure. We hypothesize that a personal smoking profile is
based on withdrawing as much nicotine as possible while maintaining the
additionally produced CO at levels that do not induce adverse effects.
The current study aims at measuring smoking in a habitual rhythm without
imposing it as has been done thus far. With this, the smoking topography per
cigarette can be measured. Because the smoker can smoke when he wants, the
craving, or maybe just the habit to smoke at a certain point at the day, can be
recorded. During the day, blood, exhaled air, urine and saliva will be sampled
to measure nicotine, carbon monoxide, but also other cigarette smoke compounds
and their metabolites.
In the future, the personal smoking regimes of the participants will be
mimicked with machine smoking experiments, which results in the exact exposure
for that person based on when he smoked that cigarette. To link the observed
smoking behavior to the underlying biological mechanisms, this study is also
designed to measure exposure biomarkers in body fluids of smokers, such as
nicotine, the most abundant cigarette smoke chemicals and both their
metabolites.

How is a smokers* smoking behavior and topography influencing exposure to
cigarette smoke constituents?

Primary Objectives:
- What is the individual smoking topography of a smoker smoking his usual
brand, and does this change between cigarettes over the day?
- Can we connect the nicotine and carbon monoxide levels in blood and/or urine
with the smoking behavior over the day?
Secondary Objectives:
- Which (metabolites of) toxicants present in cigarette smoke can also be found
in exhaled air, saliva, urine and blood of smokers?

The Smoking Topography Study 2016 is an observational study, with the duration
of 2,5 weeks in total. Participants will stay for 36 hours, including two
nights, with a temporary residency at the Apart Hotel Randwyck.
In this study it is important that the participants are able to smoke
cigarettes *ad libitum*. Because it is impossible to monitor this smoking
topography at all times at home, we have to measure the smoking at a research
location. Therefore, this study includes two times overnight staying at the
Apart Hotel Randwyck in a homelike atmosphere where standardized meals are
served and cigarettes can be smoked when and how the participant desires. The
smoking topography of every smoked cigarette will be monitored through the
CRESSmicro device, which records the puff length, the puff interval, the puff
flow and the puff volume. Furthermore, the exact time point of smoking (i.e.
the moment the cigarette is lit) is noted in the experiment time table.
Due to this setup, the smoking topography measurements do not take place at
scheduled time points and therefore only one participant at the time will be
measured. Total duration of the study will be 2,5 weeks, including 5 smoking
individuals.
Participants are their own control by measuring baseline samples (t=baseline).
This sampling takes place immediately after waking up and thus before the first
cigarette is smoked. These baseline measurements include urine, exhaled air,
blood and saliva.
Goal of the study is to follow the smoker in his personal daily life smoking
schedule. They can smoke when they want or feel the urge to smoke. Therefore,
the sampling time points and the amount of cigarettes smoked are unknown per
participant. Despite the unknown time points on forehand, smoking topography of
every single cigarette in the next 24 hours is measured. During the whole
experiment, we make use of experimental time. Lighting the first cigarette of
the day is the start of the experiment and noted as time point 0 (t=0). This is
probably shortly after the baseline measurements.
All spent cigarette butts are collected in separate plastic bags per
participant with the experimental smoking time noted. Because it is very
important not to interfere with the daily life smoking schedule, the experiment
day is divided into timeslots for urine and a fixed time point for saliva
sampling.
Urine will be collected during four time periods. The first time point includes
the baseline measurement before the first cigarette is smoked. Next, all urine
between t=0 and t=6 hours is collected in one beaker, urine between t=6 and
t=12 is collected in a beaker and finally the same for all urine between t=12
and t=24 hours in another beaker. The participant is asked to empty his bladder
just before the timeslots end. This results in 4 urine samples per participant.
Saliva is withdrawn at t=baseline, and at t=0 (immediately after the first
cigarette), t=6, t=12 and t=24. This results in five saliva samples per
participant.
The exhaled air and blood samples are collected immediately after smoking a
cigarette to have the most accurate measure associated with the cigarette
smoking. However, the smoking time points are uncertain due to the chosen setup
of this study. However, since all smokers included smoke around 20 cigarettes a
day, they will at least smoke every 2 hours. Therefore, we have made time
periods of 2 hours in which the first cigarette smoked is used for sampling
blood and exhaled air, immediately after finishing smoking. The time periods
are within one urine collection period, to avoid different samplings within a
short time that can interfere with the habitual smoking of the participant.
At baseline, the participant is asked to exhale via a mouthpiece whereby the
exhaled air is collected in a Tedlar bag. The exhaled air just before and after
finishing smoking the first cigarette is collected (t=0). The same is done
immediately after the first cigarette between t=1 and t=3, between t=3 and t=5,
between t=7 and t=9 and between t=9 and t=11. This results in 13 exhaled air
samples per participant.
To avoid multiple punctures, the participants get a peripheral venous catheter
at baseline, after which the baseline blood sample is withdrawn. The next blood
sample is withdrawn just before and after finishing smoking the first cigarette
(t=0). Then, the same sampling points are used as for exhaled breath sampling,
i.e. just before and immediately after the first cigarette between t=1 and t=3,
between t=3 and t=5, between t=7 and t=9 and between t=9 and t=11. This results
in 13 blood samples per participant.

The participating smokers smoke according to their habitudinal smoking pattern,
and are therefore not increasingly exposed to the harmful health effects of
cigarette smoking. The invasive part of the study is their stay for two nights
and a day in a hotel, and the sampling of blood, saliva, urine and exhaled air.