Smoking - what all healthcare professionals need to know

Anwen.

1. The facts about smoking

Introduction

The detrimental effects of cigarette smoking on human health are wide ranging and affect every organ system in the body. Tobacco smoke is made up of numerous chemicals, many of which are toxic (including a large number of carcinogens).

Nicotine is the addictive compound in tobacco and it affects many parts of the nervous system and other cell types through interaction with specific nicotinic receptors. The effect of nicotine on individual smokers varies according to the efficiency and frequency of smoking, and the individual’s genetic characteristics, which will affect the way they metabolise the toxin (Benowitz & Hukkanen 2009).

Tobacco products pervade the whole body so several methods are required to measure the level of smoking and nicotine addiction. These may include questionnaires and the measurement of tobacco products in expired-air or biological fluids, either using sophisticated laboratory techniques or simpler point of care (poc) tests.

Smoking statistics

Smoking is still common, with about 10 million British adults smoking on a daily basis. This accounts for about 22% of the adult male population and 19% of women (OLS 2012). The number of smokers has fallen dramatically since its peak in the 1940s, when approximately 80% of men and 40% of women were smokers, although then nearly half the male smokers used a pipe or cigars. The percentage of tobacco users worldwide who now use manufactured cigarettes continues to increase, accounting for 96% of world tobacco sales (Wald & Nicolaides-Bouman 1991).

Although there has been a significant fall in tobacco consumption in the UK during the last fifty years, the rate of reduction has slowed since the 1970s. The greatest reduction in smokers has been in the professional and managerial classes. Only 16% of these sectors of the population are now male smokers, compared to 33% of those in routine and manual occupations. The figures for women are similar, with 12% of women in managerial positions smoking and 32% of those with manual jobs (OLS 2012).

The first large-scale trial evidence that smoking was harmful and caused lung cancer came from independent work in 1950 by Doll and Hill in the UK (Doll & Hill 1950) and Wynder and colleagues in the US (Wynder & Graham 1950). Many clinical studies have since established a strong link with heart disease, lung disease and various forms of cancer, with recent research showing increased susceptibility to infectious diseases, and changes to the immune system, affecting the skin, the eyes, ears and bones. Essentially, smoking harms every organ of the body (Benowitz & Hukkanen 2009) and the evidence linking cigarette smoking and ill health is now compelling.

The cost of smoking-related healthcare

In the UK, the cost to the NHS for treatment of smoking-related illnesses was estimated at £2.7 billion in 2006/07 (Callum et al. 2011) and £5.2 billion annually in 2009 (Allender 2009) (see Table 1.1). This includes expenditure on hospital admissions, GP consultations and prescriptions. However, the cost to society as a whole is much higher. This has been estimated at over £13 billion and includes the cost of loss in productivity and increased absenteeism (Nash & Featherstone 2010).

Table 1.1 Financial implications of smoking-related diseases in the UK

These costs are offset by government revenue from taxes on cigarettes, with the Treasury earning £9.7 billion in revenue from tobacco excise duties in the financial year 2011–2012. This amounts to approximately 2% of total government revenue, including VAT at an estimated £2.6 billion (TMA 2012). The annual value of tobacco sales in the UK was £13 billion over the same period (Walker 2013), but the overall sales of manufactured cigarettes fell by 6.4%. This equates to an estimated 2.5 billion fewer cigarettes per year (Hegarty 2013).

In recent years, the greater prevalence of smoking in lower socio-economic classes has led to a decline in the sale of premium brands and a corresponding growth in economy-priced cigarettes and roll-your-own (RYO) cigarettes. Lower-priced brands account for one in three cigarettes sold in the UK (Hegarty 2013), and sales of loose tobacco for hand assembly are worth £1.9 billion annually.

The relative risks of roll-your-own cigarettes

RYO cigarettes have significant additional health consequences because they have higher tar yields, compared with manufactured brands. RYO produce more tar than the current maximum level of 15mg allowed for manufactured cigarettes. Filters are frequently not included in RYO, and this has been shown to increase the amount of tar inhaled by 50%. Consequently, the nicotine yield is also higher, with 70% of RYO cigarettes producing a nicotine yield above the permitted level of 0.7mg per cigarette (Darrall & Figgins 1998).

Studies have shown that people who use RYO are generally more addicted to nicotine and are less likely to wish to stop smoking. Some highly addicted smokers use RYO because it gives them more control over the nicotine ‘dose’ (Young et al. 2006). In the past, RYO smokers were generally older working-class men, but recent figures show that 55% of users are now women (Gallus et al. 2014). One-third of poorer smokers use RYO because they are cheaper, with one study reporting that about 38% of all RYO tobacco smoked in the UK is smuggled in (HMRC 2012).

The components of tobacco smoke

Cigarettes are manufactured using leaves from the tobacco plant (Nicotiana tabacum), blending from two main leaf varieties: yellowish ‘bright’ Virginia tobacco, which contains approximately 3% nicotine; and ‘burley’ tobacco which has a higher nicotine content at about 4%. This is dried, fragmented and mixed with additives to make the tobacco products more palatable. The additives include humectants to prolong the product’s shelf life, sugars to make the smoke seem milder and easier to inhale and flavourings such as chocolate and vanilla.

When the cigarette is lit, the process of burning produces temperatures ranging from 400 to 580°C at the smouldering tip, which increase to 700°C when the cigarette is drawn. This produces a wide range of chemicals derived from the organic leaves, the additives and the paper.

The smoke produced is a complex mixture of chemical compounds, which is either sidestream smoke from the burning tip, or mainstream smoke that is drawn into the mouth and exhaled (see Table 1.2). These chemicals include volatile organic chemicals, gases and particulates, which form an aerosol consisting of carbon-containing polymers with adsorbed heavy metals. Analysis has identified 2,256 different smoke components, with 98 found to be dangerous to human health (Talhout et al. 2011).

The link between tobacco smoke and cancer (specifically lung cancer) has been known for over sixty years. Analysis has found 55 known carcinogens in tobacco smoke. Of these, polycyclic aromatic hydrocarbons (PAHs) are the most common, with 20 different types having been identified (Hecht 1999).

Table 1.2 Chemical constituents of cigarette smoke

(Based on Talhout et al. 2011.)

Free radicals

Tobacco smoke is a mixture of a particulate phase and a gaseous phase, with the former including nicotine and ‘tar’, which includes the carcinogens. But also present are other chemicals, which induce cancer. These are generally referred to as free radicals or reactive oxygen species (ROS). They are highly charged, highly reactive forms of oxygen that can damage large molecules (such as proteins, lipids and DNA) in the delicate mucosal tissue of the buccal cavity and lungs. They also circulate in the bloodstream, causing structural and mutagenic changes (Maskos et al. 2005).

The gaseous phase of tobacco smoke includes carbon monoxide (CO), ammonia, formaldehyde, hydrogen cyanide and small molecular weight free radicals. Some of these chemicals have marked irritant and inflammatory properties and many have been shown to cause cancer (IARC 2004). The gaseous phase contains about 500 volatile organic and inorganic compounds, while the particulate phase consists of fine particles that can penetrate deep into the small, terminal spaces of the lungs or alveoli (IARC 2004).

Differing levels of toxins

The tar component is regarded as the most harmful (carcinogenic) element in tobacco smoke. Since the 1950s, the tar content of cigarettes has fallen from an average of 30mg to 11mg per cigarette. Under current regulations, the tar and nicotine yields must be displayed on packets, along with upper limits of nicotine and CO (DH 2009).

To reduce the harmful effects of tar in cigarettes, tobacco manufacturers developed low-tar cigarettes or ‘lites’. However, the main difference with these is not the tobacco content but the filters. These ‘low-tar’ filters are manufactured with ventilation holes near the junction of the filter and tobacco. Under standard smoking machine conditions, these holes allow air to be drawn into the mouth along with the cigarette smoke, thus diluting the concentration of nicotine and toxins on the filter. When the filter is analysed for tar and nicotine, it shows a lower yield.

People frequently turn to low-tar cigarettes, regarding them as a ‘healthier’ alternative. However, smokers often find these cigarettes less satisfying and insufficient for their nicotine needs. They therefore subconsciously draw on the cigarette harder, to compensate for the lack of nicotine, and this actually increases their intake of CO. Many smokers soon realise that inserting the cigarette further into their mouth, or blocking the ventilation holes with their fingers, improves the taste and level of satisfaction. However, this neutralises the mechanisms used to lower the tar, and the ‘lite’ cigarette effectively reverts back to a ‘normal’ form (Hoffmann & Hoffmann 1997). Recent evidence has shown that low-tar cigarettes are not well tolerated by smokers and do not help them quit (Benowitz et al. 2015).

While the ‘tar’ content adds to the smoker’s sensation, along with the particulate matter and gases, by far the main concern of the smoker is the ingestion of nicotine.

Nicotine

Nicotine is an alkaloid thought to be present in the tobacco plant as a natural insecticide, but it has a direct effect on the nerves in the human brain and nervous system, inducing addiction, compulsion and reward.

A small amount of nicotine from cigarette smoke is absorbed through the mucosa of the mouth, but most of it is absorbed through the lung lining. Nicotine is water soluble and it readily dissolves into the fluid lining of the alveoli and bronchioles. Acidifying the tobacco with additives (thus lowering the pH) increases its solubility and therefore the rate at which it is absorbed through the lungs. Tobacco used in pipes, cigars and smokeless tobacco is more alkaline, which aids absorption through the mouth and buccal mucosa (Henningfield et al. 2004).

Once it has passed through the mucosal epithelium, nicotine is absorbed into the bloodstream and quickly enters the arterial circulation and diffuses readily throughout the body. It has been estimated that nicotine reaches the brain in about 10 seconds; there it binds to specific nicotinic receptors on the surface of the nerve cells or neurons (Benowitz 1999).

Nicotinic receptors

Nicotinic receptors form part of the parasympathetic nervous system, which is sometimes described as the ‘feed or breed’ or ‘rest and repose’ system, which controls physiological functions such as eating, salivation, lacrimation, urination, digestion and sexual arousal. (It is opposite to the ‘fight or flight’ activities of the sympathetic nervous system, which involve adrenalin.) This may help to explain why smokers often use cigarettes after a meal or sex.

The usual neurotransmitter for the parasympathetic system is acetylcholine (ACh) and the receptors are referred to as acetylcholine receptors (AChR) or cholinergic receptors. Those that are specifically sensitive to nicotine are called nicotinic cholinergic receptors (nAChR). Nicotine stimulation of receptors in the brain has been implicated in a variety of brain functions, including learning, memory formation and reward.

Nicotine metabolism

Nicotine is rapidly broken down in the body, with an elimination half-life (time taken to break down to 50% of the original amount) varying from 1 to 4 hours, and averaging about 3 hours. However, there are considerable individual differences in nicotine concentrations in the plasma. These differences may be, at least in part, due to genetic factors but may also be caused by variations in the method and efficiency of smoking, or ‘smoke topography’. It is also well known that smokers can manipulate their intake of nicotine to serve their varying needs.

Nicotine in the bloodstream is rapidly and extensively metabolised by its first pass through the liver, producing a range of 20 different metabolites or breakdown products, the most important of which is cotinine (Kyerematen & Vesell 1991). The elimination half-life of cotinine is much longer than that of nicotine, at about 18 hours, and it is excreted over a much longer period of time. Whereas nicotine remains in the body for about six hours, cotinine can be detected in the urine for about three days (Dempsey et al. 2004).

Nicotine metabolism is influenced by many factors, including racial origin and physiological status. Black smokers have been found to have higher cotinine levels than white Caucasians, while during pregnancy nicotine metabolite levels increase in the last period of gestation. These variations suggest the metabolism of nicotine is determined physiologically as well as genetically (Messina et al. 1997).

Smoke topography

The smoker’s individual need for nicotine will determine their method of smoking; and this is to some extent governed by their smoke topography. This refers to the frequency and volume of smoke inhaled, the number of puffs, and the individual cigarette duration and inter-puff interval, with the latter being an important predictor of nicotine blood levels (Bridges et al. 1990).

Although the smoke topography is relatively consistent in a given individual, the method of smoking will change if the nicotine or tar content of the cigarette brand varies. Studies have shown that smokers compensate when they change to a low-tar or low-nicotine brand, or smoke fewer cigarettes, so as to extract more nicotine from each one (Hammond et al. 2005). Users of low nicotine yield cigarettes smoke nearly three times more intensively than those of medium or high yielding cigarettes in order to achieve the same level of plasma nicotine (Matsumoto et al. 2013).

It is very difficult to measure nicotine intake because we have to take into account so many different factors: the different cigarette brands available, smoke topography, depth of inhalation and nicotine metabolism.

The main parameters for variation of the smoking dose are:

Number of cigarettes smoked per day

Selection of brand according to nominal smoke yield

Number of puffs per cigarette

Puff interval (puff frequency)

Puff volume

Duration of puff

Flow rate during puffing

Amount of smoking expelled from the mouth (mouth spill)

Depth of inhalation

Duration of inhalation

Butt length

Blocking of filter vents.

Assessing smoking behaviour

Historically, the easiest way to assess smoking habits was simply to ask the smoker about their daily cigarette usage. However, this approach – while providing some useful information – tends to be unreliable and subject to bias. Cigarette smoking is frequently defined as ‘smoking at least one cigarette a day for a year’. But even anonymous questionnaires will record about 5% of cigarette users regarding themselves as non-smokers because they believe that smoking only one or two cigarettes a day (or smoking just at weekends) is not really smoking. These people are called ‘non-identifying smokers’ and they represent about 12% of tobacco consumers (Leas et al. 2015). The percentage of denial increases according to how much pressure the smoker feels under not to smoke, especially if they believe that their medical or surgical treatment may be compromised if they admit to smoking (Payne & Southern 2006).

Nevertheless, sophisticated questionnaires have been developed to assess levels of nicotine addiction. For instance, the Fagerstrom Test for Nicotine Dependence (FTND) includes questions about the time to first cigarette in the morning (TTFC) and the level of difficulty experienced when not being able to smoke (Fagerstrom 1978). Nicotine dependence is recognised by the World Health Organisation (WHO) as a medical condition and such questionnaires are widely acknowledged as the best way of assessing the level of nicotine dependency and the smoker’s ability to abstain from tobacco (Table 1.3).

Table 1.3 Fagerstrom Test for Nicotine Dependence (Heatherton et al. 1991)

Add up the total score to calculate dependence on nicotine:

Although they are widely used, there are still problems with smoking questionnaires because many subjects give false information, due to guilt or embarrassment. An alternative to questioning is the use of biochemical measurements (or biomarkers) to determine the concentration of tobacco products in the breath, blood or other biological fluids.

Biochemical testing

The first biochemical tests for smoking were developed by the physiologist Claude Bernard (1813–1878). He discovered that smokers excreted large amounts of thiocyanate (SCN), a breakdown product of hydrogen cyanide, in their urine.

Many studies have since found a close correlation between daily cigarette consumption and SCN levels (Scherer 2006) and the SCN test has the advantage of measuring smoking habit over about 10–14 days (Bliss & O’Connell 1984). On the other hand, SCN levels have been found to be influenced by body weight and the ingestion of different foodstuffs. For example, people who consume nuts, pulses, brassica vegetables and cow’s milk may end up giving false positive results. Consequently, this biomarker has largely fallen out of favour (Larramendy et al. 2004).

Another (still widely used) biomarker is the concentration of carboxyhaemoglobin (COHg), either in plasma or as carbon monoxide in expired-air (eCO). Carbon monoxide is a gas generated by burning organic material such as tobacco leaves. It is inhaled and permeates through the lining of the lung into the bloodstream. CO has a high affinity for haemoglobin, (approximately 240 times greater than oxygen), so it reduces the oxygen-carrying capacity of the blood. Following circulation, it returns to the lungs where the COHg dissociates, releasing the CO back into the breath, where, using suitable hand-held equipment, it can be measured.

Table 1.4 Different biomarkers for tobacco intake

The presence of CO in expired-air has been used for many years as a means of monitoring smoking (Eymer et al. 1936), and studies have shown that eCO correlates well with plasma levels and cigarette consumption (Andersson & Moller 2010). The most widely used technology to measure eCO is an electrochemical detector in a hand-held monitor. The smoker is instructed to take a deep breath and hold it for a minimum of 15 seconds, after which they should expel all their breath slowly to achieve an end-tidal breath sample, as it is the last air in the lungs and speed of expulsion that is critical to