Monaldi Arch Chest Dis 2001; 56: 6, 545554

TOBACCO POUCH

Health effects of tobacco use and exposure

M. Bartal
ABSTRACT: Health effects of tobacco use and exposure. M. Bartal. Tobacco is still widely consumed in a variety of different ways, mainly as smokeless tobacco and cigarette smoking. Four traits characterize tobacco use whatever the way of using it: 1) addiction linked to nicotine is behind all the tobacco hazards; 2) individual variation in tobacco susceptibility; 3) dose-response relationship; 4) time-lag effect. Smokeless tobacco, chewed or snuffed can lead mainly to inflammation of the oral cavity and oral cancers. Cigarette smoking accounts for 65-85% of global tobacco consumption. Active smoking can cause: 1) respiratory disorders culminating in chronic obstructive pulmonary disease (COPD) and emphysema; 2) cardiovascular hazards by way of increased vascular spasm and atherosclerosis leading to acute and chronic myocardial events, cerebral and peripheral vascular diseases; 3) cancers: twelve types are caused or related to cigarette smoking. Lung cancer is still the leading cause of cancer death in most high-income countries where data are available. An excess mortality is associated with smoking, with a 2-fold greater risk in smokers than in nonsmokers throughout middle age. The exposed pregnant woman subjects herself and her pregnancy to risks, and her fetus to growth retardation and perinatal morbidity and mortality. Passive smoking implicates 20-80% of the whole population. It can be nearly as harmful as active smoking depending upon risk factors, and can lead to short as well as to long-term effects. Children are the most vulnerable population particularly during the first years of life. Passive smoking increases risks for higher and lower respiratory tract illness but a smoke-free environment improves all these disorders. Ischemic heart diseases and lung cancer are the main risks for non smoking adults exposed to cigarette smoke. Tobacco use and exposure is the single most important source of preventable morbidity, disability and premature mortality. But giving up smoking helps at any time, the sooner the better. Health professionals should be the key advocates in tobacco prevention. Monaldi Arch Chest Dis 2001; 56: 6, 545554.

Keywords: Tobacco, smoking, smokeless tobacco, health effects. Department of Respiratory Diseases, IBN Rochd, University Hospital, Casablanca, Morocco Correspondence: Prof. Mohamed Bartal; Department of Respiratory Diseases; CHU Ibnou Rochd; University Hospital; Casablanca, Morocco; e-mail: bartal@iam.net.ma

Evidence of the harmful effects of tobacco has existed for 200 years, at first in relation to oral cancer and then to vascular disease and lung cancer [1]. This evidence was generally ignored, but interest surfaced following the publication in 1950 of 5 case-control studies relating smoking to lung cancer [2-6]. After a long silence, real impetus was given to tobacco as a health issue nearly four decades ago, initiated by the first report of the US Surgeon General in 1964 [7]. Twenty years later the American Thoracic Society issued a position statement which reviewed the health effects of smoking, taking into account scientific data and consensus opinion [8]. Since then our knowledge has markedly expanded and considerable scientific evidence has been published documenting the implications not only of tobacco use but also of tobacco exposure for morbidity and mortality. While tribute should be paid to the individuals and organizations who disseminate knowledge about and increase awareness of the health effects of tobacco use and exposure, the paradox is that those who are well informed about the deleterious effects of tobacco, i.e. health professionals, are not committed enough in the fight against this global epidemic [9, 10]. Tobacco is consumed in a variety of different ways (fig. 1). Evidenced by epidemiologic as well

as experimental studies, the health hazards of tobacco are nowadays a major health concern worldwide not only in industrialized countries but also in low-income countries where the tobacco toll aggravates the burden of transmittable diseases. In this paper we will underline the common features of tobacco use, whatever the kind of tobacco used. We will then sketch briefly the health effects of

Fig. 1. Ways of tobacco use.

M. BARTAL

4. Time-lag effect, i.e. a large interval from 10 to 20 years between the exposure and the main consequences, which is misleading for users. Smokeless tobacco (or unburnt tobacco) The use of smokeless tobacco is limited to some areas in all continents. Tobacco can be chewed or snuffed. In the United States, roughly half of smokeless tobacco users also smoke cigarettes [20]. In Sweden oral snuff was used by 20% of all males in 1996 [21]. Chewing tobacco consists of strips or shreds of tobacco leaf usually mixed with other ingredients. Snuffed tobacco consists commonly of moist particles of tobacco treated with diverse flavours such as mint and menthol and placed between the lip or cheek and the gum [2024]. Dry powdered tobacco can also be snuffed or placed in the nostrils. The deleterious constituents of smokeless tobacco are mainly: 1) nicotine, which is more slowly absorbed than that of smoked tobacco. Its peak and concentration blood levels are similar to that of a cigarette smoker. Nicotine concentration plateaus during and after use. It can lead to nicotine dependence and moreover to dependence on cigarettes in young people [24]; 2) carcinogens which, similar to those of cigarette smoke, are responsible for oral cancers. Reports on health hazards of smokeless tobacco date back to the 18th century and most subsequent studies have evidenced a dose-response relationship. These hazards include local deterioration such as inflammation of the oral cavity with leukoplakia, periodontal tooth and tooth lesions as well as oral cancers, notably of the cheek and gum [25, 26]. Even nasal, esophageal, laryngeal and stomach cancer can be facilitated by smokeless tobacco [25]. Smokeless tobacco also generates systemic alteration such as increase in blood pressure and tachycardia [27]. Addiction is behind all these harmful effects. A recent longitudinal study of more than 100,000 construction workers within a 12-year follow-up in Sweden showed a higher hypertension prevalence in oral snuff users than among non-users and a 2-fold greater relative risk of death due to cardiovascular disease (versus 3fold greater among smokers compared to neverusers of tobacco) (p<0.001) [28]. A 24-hour monitoring of 151 healthy middle- age men showed significantly higher day-time heart rates and blood pressure (p <0.05). The estimated 10-year future risk of cardiovascular events was 4.6% for oral snuff users (p=0.3) versus 13.2% for smokers (p<0.001) compared to 3.4% for never-users of tobacco. But no significant signs of atherosclerosis were observed. The increased risk of cardiovascular stress which could lead to death may be related to the release of sympatho-adrenergic stimuli generated by nicotine. Table 1 shows the high relative risk for oral and oropharyngeal cancers related to smokeless tobacco. Of note, the combination of different kinds of smokeless tobacco or of smokeless tobacco with tobacco smoking increases the relative risk (RR) for oral cancer, e.g. in Pakistan:

Fig. 2. Addiction as the source of tobacco health risks.

smokeless tobacco and then the main health effects of both active and passive smoking. Common features of tobacco use Whatever the mode in which it is used, tobacco use is characterized by four traits: 1. Addiction or dependence (fig. 2). This refers to the syndrome of drug-seeking behaviour [1115]. Two essential features characterise nicotine dependence: tolerance, despite using substantial amounts of nicotine; and a withdrawal syndrome, which results in the use of nicotine to relieve or avoid withdrawal symptoms. This chronic condition, a real brain disease, is indeed the mother source of health risks. It is well established that multiple nicotinic receptors reside in the central nervous system that are up-regulated upon nicotine intake; hence cigarette smokers have higher levels of brain nicotine receptors than do nonsmokers [15]. Other receptor types mediate the reinforcing effects of nicotine. Nicotine is at least as addicting as heroin, cocaine, or alcohol. Nicotine stimulates dopamine release just like cocaine does. Moreover tobacco use is a gateway for the use of other drugs [15]. In several studies the probability of becoming addicted to nicotine is much higher than that of becoming addicted to other drugs: it is twice as high among ever-users of cigarettes than among ever-users of cocaine [16]. Addiction is the main feature behind all the tobacco hazards leading sooner or later to a poor quality of life as well as to a decrease in life expectancy. Addiction keeps the user compulsively perpetuated in the habit by behavioural and/or physiologic (nicotinic) mechanisms, paving the way to both higher morbidity which spares almost no organ and to premature death. It is estimated that one-third to one-half of people starting to smoke will become addicted. 2. Individual variation in tobacco susceptibility: which can be explained by genetic factors [17, 18] or factors operating in early life or even in utero [19]. 3. A dose-response relationship as well as a duration-response relationship.
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Table 1. Relative risks for oral, pharygeal buccomusol cancers among men by using smokeless tobacco from case-control studies Pakistan Oral Cancer Total cases Total controls Betel quid (1) Tobacco (2) Betel quid + Tobacco Betel quid + smoking Tobacco + smoking (1) + (2) + smoking Smoking
Modified from [23]

India and Sri Lanka Oral Cancer 514 277 1.9 7.6 2.7 11.9 2.1 Oropharyngeal Cancer 81 11.8 6.0 21.5 12.9 28.5

Calcutta Buccomucosal cancer 287 420 0.7 2.7 3.9 5.8 1.2

683 1978 4.2 10.2 8.1 25.0 15.4 23.0 5.7

RR of 4.2 for betel quid alone compared to 25 for betel quid plus smoking [23]. In summary, smokeless tobacco use is widespread in particular areas in all continents. Health effects of smokeless tobacco are mainly local, related to the inflammatory effect of nicotine as well as to the carcinogenic effect of carcinogenic constituents similar to those released by cigarette smoking. Systemic effects in the form of cardiovascular effects are also observed, related to the blood nicotine level [24]. Cigarette smoking Cigarette smoking is the most usual way of smoking, accounting for 65-85% of global tobacco consumption. It is estimated that one in three people smoke worldwide. According to World Health Organization (WHO) estimates there are around 1.1 billion smokers worldwide, 80% of whom live in low-and middle-income countries. If current trends continue the total number of smokers is expected to reach about 1.6 billion by 2025 [29]. Passive smoking involves 20-80% of the worlds population involuntarily exposed to tobacco smoke. Before reviewing the main risks related to cigarette smoking, let us recall the main constituents of tobacco smoke (fig. 3). A smoker puff emits the mainstream smoke directly inhaled whereas sidestream smoke is released into the air from the burning tip of the cigarette between puffs [30]. More than 4,000 compounds are produced in smoke, mainly carbon monoxide, nicotine, diverse irritants as well as more than 40 carcinogens. These chemicals act not only locally but also at a distance as they are absorbed into the blood and thus disseminated throughout the body. These products are the ingredients of a true bomb with a short as well as a long-term effect. An overview of the main health hazards of tobacco use and exposure (environmental tobacco smoke) is shown in figure 4. At the beginning the picture is somewhat benign and thus does not attract attention, but the end is serious with cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and can-

cers. Once again addiction is behind all these hazards, leading sooner or later to a poor quality of life and a premature death. Active smoking Just to give an overview, cigarette smoking has now been associated with some 40 causes of death of which the great majority reflect causality [31]. The relative risk of smoking-related diseases in industrialized countries ranges from two for ischemic heart disease to six for COPD, nine for peripheral vascular disease and ten for lung cancer. The percentage of deaths attributed to smoking ranges from 25% in females to 43% in males for ischemic heart disease and from 75% up to 90% for sudden death heart attack and COPD respectively. Smoking is responsible for 30% of all cancer deaths [3234] (table 2). It is noteworthy that the so-called light, ultra light or mild cigarettes are misleading because addicted people who switch to low tar/nicotine cigarettes smoke more and inhale more deeply to reach the same level of required nicotine.

Fig. 3. Constituents of tobacco smoke.

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Table 2. Relative risks of smoking-related diseases. Industrialized world data Non-smokers Disease Ischemic heart disease Sudden death by heart attack (<50 yrs) Peripheral vascular disease Chronic obstructive lung disease Lung cancer All cancer deaths
From [3234]

Smokers Risk 2 5 9 6 10 2

% of deaths attributed to tobacco 25% (F) - 43% (M) 78-80% 90-98% (incidence) 80-90% 80-85% 30%

1 1 1 1 1 1

As to the respiratory risks there is combined action of different compounds of smoke leading to acute as well as chronic inflammatory effects. The consequences are the damaging of the structure and function of the airways including central and peripheral bronchi, alveoli and capillaries. The results are loss of cilia, mucus gland hypertrophy, increased number of globlet cells and macrophages, increased permeability, parenchymal destruction. The early changes in smokers are: bronchiolitis, mucus cell metaplasia, denudation of lining epithelium, mural edema, smooth muscle hypertrophy, peribronchiolar fibrosis and excess of airways < 400 m diameter. In the long-term, cigarette smoke reduces mucociliary function as well as provoking squamous metaplasia paving the way to carcinoma [3537]. The second impact of cigarette smoke is the damaging of the local immune system, as suggested for instance by an increased number of peripheral blood mononuclear phagocytes which appear to be functionally compromised, and higher levels of circulating immunoglobulin (Ig)E. It is also demonstrated that tobacco-exposed B and T lymphocytes exhibit decreased proliferative capacities [38, 39]. As a consequence of these changes, it is no wonder that smokers present with increased risks of infectious diseases in both the upper and lower tract, ranging from bronchitis, pneumonia and tuberculosis, an increase of respiratory symptoms such as chronic cough and phlegm, wheeze and dyspnea, leading in the long-run to a lower level of lung function [40], and an increase of asthma episodes and exacerbations. Cigarette smoke can increase the nonspecific bronchial responsiveness with a synergistic atopy-smoking action [41, 42]. Some studies have demonstrated an increased risk of sensitization to some allergens such as house dust mite but not to cat or grass allergens [43]. And last but not least COPD and emphysema are the highest respiratory toll paid by smokers [44]. These diseases might be coined chronic smoking disease as it is estimated that at least 85% of cases are due to smoking. But they appear with a 10- to 20-year time lag [45]. There is a strong dose-response relationship between the amount smoked and the decline rate of the forced expiratory volume in one second (FEV1) [46]. In general, current smokers have a lower FEV1 and an accelerated decline of FEV1. These changes appear to be more signifi548

cant in females than males [4750]. They are also dependent on individual susceptibility, explaining why airflow limitation clinically occurs only in 1015% of all smokers [49]. On the other hand, TAGER et al. using an autoregressive multiple regression model have estimated that active smoking has more effect on lung function when smoking starts in adolescents [51]. Thus a child beginning to smoke at 15 years of age and continuing to smoke would have 8% less [95% confidence interval (CI)] of his expected FEV1 by 20 years of age. Nevertheless other risk factors than cigarette smoke could be involved in the pathogenesis of COPD: genetic factors, low birth weight, living conditions, airways infection in the early life, air pollution, and airway hyperresponsiveness [19, 52, 53]. In nonsmokers without respiratory disease, FEV1 declines by 25 to 30 ml per year from age 25 to 30 years onwards. In smokers the mean decline is about 45 ml per year, while it declines by up to 200 ml per year in susceptible smokers [54, 55]. Furthermore, smoking has been incriminated as a cause of interstitial lung disease [56]. As to the cardiovascular hazards of tobacco use (fig. 4), these are mainly related to both carbon monoxide and nicotine. Carbon monoxide is responsible for a reduction in systemic transport by way of an increase in the carboxyhemoglobin concentration [57]. Carbon monoxide and nico-

Fig. 4. Health hazards of tobacco use and exposure.

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tine cause deleterious effects on the structure and function of blood vessels, platelets and inflammatory leukocytes, leading to increased vascular spasm and atherosclerosis [5861]. Smokers can have increased circulating levels of catecholamines and free fatty acid, causing increased low-density lipoprotein cholesterol and/or reduced high-density lipoprotein cholesterol [59]. Enhanced coagulation by increased platelet aggregation [58], inhibition of prostacyclin synthesis [61] and stimulation of smooth muscle proliferation combined with injury of the endothelium [21] pave the way to atherosclerosis [60]. It has been demonstrated in young cigarette smokers aged 15 to 35 years who died accidentally a greater risk of atherosclerotic plaques in all vascular beds studied including the right coronary artery and descending aorta, this latter being more implicated in aneurysms in adult smokers [62]. Cardiovascular risks of smoking include acute and chronic myocardial changes with an increase of recurrent heart attacks, an increase of coronary heart disease (CHD) and an increase of sudden death from CHD [6367]. Thirty per cent of all CHD deaths are yearly attributed to tobacco in the United States, where there is a 2- to 4-fold increased incidence for these two last disorders. The incidence of aortic aneurysm is more than 5 times higher in smokers than in nonsmokers [33, 64]. On the other hand factors such as diabetes, hypercholesterolemia, and use of oral contraceptives aggravate all these pathological disorders. Peripheral vascular disease could lead to lower limb gangrene and amputation. More than 90% of patients with this condition are cigarette smokers [68]. Peripheral vascular risks include sexual impotence which increases by 50-80% in smokers compared to never-smokers [69,70]. Smokers were over twice as likely to become impotent (56%) as nonsmokers (21%) in a study of 1,290 men who had received treatment for impotence [71]. Cigarette smoking is also a risk factor for cerebral thrombosis and stroke [72]. One of the most illustrative studies underlying smoking-related diseases is the 40-year follow-up (1951-1991) of a prospective study of the mortality of male British doctors [67]. Excess deaths included: ischemic heart disease, myocardial degeneration, aortic aneurysm, arteriosclerosis, cerebral thrombosis and other cerebrovascular disease. In summary, cardiovascular hazards are among the highest risks of cigarette smoking extending from heart disease to cerebral and peripheral vascular diseases. Heart disease is the most common smoking-related cause of death in high-income countries [29]. In the United States, for instance, smokers are 3-times more likely to die in middle age of vascular diseases [34]. Regarding cancer, at least twelve types are caused by, or related to, cigarette smoking [1] (table 3). As demonstrated in long-term prospective studies such as the American Cancer Societys Second Cancer Prevention study which followed more than 1 million US adults, cancers occur in susceptible people and are dose-dependent as well

Table 3. Cancers caused by or related to cigarette smoking Ratio of mortality rates in male British doctors 1951-91 Lung Larynx Pharynx Oral cavity Esophagus Bladder Kidney Stomach Pancreas Cervix Liver Leukemia (acute myeloid)
Modified from [1]

80-90% 85% 75% 65% 65% 40-60%

14.9

24.0 7.5 2.3 2.2 2.2

as duration-dependent [34]. This is particularly true for lung cancer, which is also dependent on the age of starting to smoke. Thus a 3-fold increase in the duration of smoking or in the amount of cigarettes smoked per day is associated respectively with a 100-fold risk or a 3-fold risk of lung cancer. Teenagers beginning to smoke are at higher risk if they continue to smoke: there is a 3-fold greater risk for those who initiate smoking before age 15 years than those who initiate after age 25 years [73]. The estimated relative risks for current cigarette smokers, for males and females respectively, are 10.5 and 17.8 to have cancer of the larynx, 22.4 and 11.9 to have lung cancer, 27.5 and 5.6 to have oral cavity cancer [34]. In one case-control study we carried out in Casablanca (Morocco) the odds ratio for lung cancer in smokers was 25.9 versus 4.8 in ex-smokers [74]. Lung cancer is still the leading cause of cancer death in most high-income countries where data are available. Ninety per cent of these deaths are caused by cigarette smoking [75]. Moreover simultaneous exposure to other factors increase the risk of cancer. For instance, the two habits of drinking heavily and smoking are responsible for 9 out of 10 cases of larynx cancer [76]. Tobacco and alcohol may act synergistically to generate oral and pharyngeal cancer [77]. A synergistic effect is also invoked for some agents such as radon and asbestos [78] whereas exposure to silica, arsenic, diesel exhaust, and aromatic amines act by additional effect. The estimated percentage of all cancer deaths due to smoking in 1990 is, for females and males respectively, 4 and 21 in low-income countries, 10 and 42 in industrialized countries, the mean prevalence worldwide being 6 and 29 [79, 80]. Without doubt the future will be worse for the poorest countries which will pay the heaviest toll if the trend of smoking remains as it is now.
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Mortality in relation to smoking Many longitudinal studies have underlined an excess mortality associated with smoking [34, 67, 7982]. But the most demonstrative study was the 40-year follow-up related to male British doctors 1951-91 [67]. Taking together the main diseases, mortality was 2-fold greater in smokers than in nonsmokers throughout middle age and was still 30% greater at 85 years of age and above. Half of heavy smokers died under 70 years of age versus 20% of the nonsmokers. Results from the first 20 years of the study (1951-71) underestimated the risks because the trend was 2-times faster in the latter half of the study (1971-91) as mortality was 3-fold greater in middle age smokers than in nonsmokers at ages 45-64 years and 2-fold greater at 65-84 years. Some 40 causes of death have now been positively associated with cigarette smoking whereas 8 or 9 are negatively associated. The great majority reflect causality [31]. The main causes are from cancers of the mouth, esophagus, pharynx, larynx, lung, pancreas and bladder; from COPD and other respiratory diseases; from cardiovascular diseases and from peptic ulcer. Figures 4, 5 and 6 sum up the worldwide death toll. In industrialized countries it is estimated that 35% of deaths in men and 12% in women aged 35-69 years are attributed to smoking. The figures vary according to smoking prevalence. The trend is towards a decrease of this prevalence in industrialized countries and on the contrary towards an increase in low-income countries. By the year 2025 the poorest countries will pay the heaviest death toll with 10 million deaths per year whereas industrialized countries will suffer less than 3 million deaths. This gap is related to both socioeconomic and educational status as tobacco use is associated with poverty and poor education [29]. A statement of the Joint Committee on Smoking and Health developed by six international organizations reported in 1995 that in countries where data on smoking-related deaths are available, representing about one-third of the world population, annual deaths from smoking numbered about 1.7 million in 1985, with an estimated 2.1 million in 1995 and... about 21 million in the decade 1990-99: 5 to 6 million in the European Community, 5 to 6 million in the USA, 5 in former USSR, 3 in Eastern Europe and 2 elsewhere. More than half of these deaths occur in people 35-69 years of age [10]. Appalling though this perspective is, one encouraging reality is that stopping smoking, particularly before middle age, substantially reduces almost all of the excess risk of death [67]. Cigarette smoking and pregnancy Female smoking prevalence differs greatly from country to country depending on education level and cultural traditions. When a pregnant woman smokes, not only does she expose herself to all the risks of smoking, but she also exposes her pregnancy and her fetus to specific risks. Such risks could also be related to passive smoking in pregnant women as for some of these hazards the
550

relative contributions of maternal and passive smoking in pregnancy and early infancy have not been fully elucidated. Among the most frequent risks are miscarriage by spontaneous abortion, placenta previa, placenta abruption, premature rupture of membranes, and fetal intrauterine growth retardation [8387]. Moreover the infant will be up to 200g lighter and 1 cm shorter [64, 83, 84]. Estimates for low-birth weight or intrauterine growth retardation pooled from over 30 studies on nonsmoking pregnant women exposed to environmental tobacco smoke yield a relative risk ranging from 1.2 to 1.4 [88]. There will be an increased perinatal mortality by 25-56% and an increased risk of sudden infant death syndrome [83, 85, 87], as well as an increased perinatal morbidity in terms of deficit in lung function [86], an increased risk of respiratory infection as well as an increased risk of wheezing respiratory illness [89]. Passive smoking (or Environmental tobacco smoke) Active smoking is the mother source of environmental tobacco smoke (ETS), or passive smoking, which exposes nonsmokers to a complex mixture of exhaled mainstream smoke (15% of the ETS) and noninhaled sidestream smoke (85% of the ETS). Sidestream smoke is richer than mainstream smoke in some compounds such as benzopyrene (3 times more), carbon monoxide (5

Fig. 5. Estimated percentage of all cancer deaths due to smoking, 1990. From [7980]

Fig. 6. Annual deaths attributed to tobacco. WHO, 1995 (A48-9, WHO Program on Substance Abuse). From (A48-9, WHO program on substance abuse).

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Fig. 7. Worldwide death toll from tobacco use and esposure. ** years lost per smoker who dies in old age; ** years lost per smoker who dies in middle age. Modified from [79]

times more), and ammonia (50 times more) [89]. No wonder that ETS implicates more people than active smoking: 20-80% of the worlds population with an estimated average of 700 million children, i.e. half of the worlds children [88]. It could be nearly as harmful as active smoking, depending upon risk factors such as number of smokers, rate of smoking, room size, ventilation and duration of exposure [34, 88, 89]. ETS is harmful for any category of exposed people. But children are the most vulnerable, particularly during the first years of life. In over 40 studies all but one demonstrated increased risks for lower respiratory tract illness (e.g. croup, bronchitis, bronchiolitis, pneumonia). This is essentially related to parental smoking, maternal smoking being more harmful than paternal smoking with a respective increase in risk of 1.7 fold (95% CI = 1.6-1.9) and 1.3 fold (95% CI = 1.2-1.4) [88]. Concerning the higher respiratory tract, i.e. outcomes from acute otitis media to surgery for glue ear, the pooled RR for these outcomes ranges from 1.2. to 1.4 and is statistically significant. As to asthma, increased exacerbations more than onsets of asthma have been shown in over 60 studies of school-aged children. The pooled RR for either parent smoking ranges from 1.2 to 1.4. What is remarkable is that a smoke-free environment improves all these morbidities. In non-smoking adults exposed to ETS [9095], a recent meta-analysis of 19 epidemiological studies showed that after adjusting for dietary confounding, ETS caused a 23% increased risk of ischemic heart diseases (95% CI = 14% - 33%) [93]. Another recent meta-analysis of 37 studies on ETS and lung cancer in non-smoking adults who lived with a smoker demonstrated a 26% excess risk of lung cancer (95% CI = 7% - 49%) after adjustment for bias and dietary confounding [92]. A multicentre case-control study conducted in seven European countries since 1988 by the International Agency for Research on Cancer (IARC) determined an odds ratio of 1.25 for subjects exposed to spousal ETS. Exposure to ETS in the workplace

yielded an odds ratio (OR) of 1.17. The risk of lung cancer decreased progressively with time since cessation of exposure. No risk was present after 15 years without exposure [95]. It is estimated that ETS is responsible each year in the United States alone for 3,000 deaths from lung cancer, 35,000 to 62,000 deaths from ischemic heart disease, 150,000 to 300,000 cases of bronchitis and pneumonia in infants and children aged 18 months and younger, 8,000 to 26,000 new cases of asthma, exacerbation of asthma in 400,000 to 1 million children, 700,000 to 1.6 million visits to physician offices for middle ear infection, 9,700 to 18,000 cases of low-birth weight and 1,900 to 2,700 sudden infant deaths [96]. The fact that children are the most vulnerable to ETS has moved national as well as international bodies to promote an international consultation on ETS and child health by WHO: the report concludes that the evidence of this harm to children is consistent and robust. Furthermore, this involuntary and harmful exposure can also be seen as a human rights violation, given the provisions of articles 6 and 24 of the 1989 United Nations Convention on the Rights of the Child [88]. A recent critical review of the health hazards of ETS clearly distinguished among short and long-term effects, those which are established, strongly evidenced or controversial (table 4) [97]. Despite the body of evidence implicating ETS, ladies and gentlemen, dont worry be happy. As Philip Morriss experts put it: ETS is just as risky as drinking milk and eating biscuits [98]. Conclusion Figure 4 sums up again the main health hazards of tobacco use and exposure in terms of morbidity, disability and mortality. The gravest occur with a time-lag of at least 10 to 15 years. But it is noteworthy that giving up smoking helps at any time, the sooner the better [67]. Tobacco use and exposure is the single most important source of preventable morbidity, disability and premature mortality. Health professionals including medical students should be the foremost advocates in tobacco prevention [99]. So they need to be taught and trained to tackle this issue, taking advantage of their privileged position in the community. They must take the lead i) as a role model (the first great gift we can bestow on others is a good example); ii) in implementing not only tertiary prevention, trying to cure or at least to alleviate some health hazards, but also primary prevention by disseminating knowledge, promoting health educational programmes, legislation and regulations aimed at convincing young people not to begin to smoke, and, finally, by contributing to the most advantageous secondary prevention, i.e. smoking cessation programmes. Because once again, giving up smoking helps at any time, the sooner the better [67]. Anti-tobacco promotion should be carried out not only within medical professional settings but also within lay social and educational activities, in partnership with non-governmental organizations
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Table 4. Health hazards of ETS (Environmental Tobacco Smoke) (1) Acute or short-term Established Strong evidence Controversial evidence * Irritation of the eyes/nose, throat and lower respiratory tract * Exacerbation of asthma * Increased lower respiratory infection in children * Increased upper respiratory infection in children * Increased risk of angina in coronary heart disease patients * Increased risk of episodes of phlegm in adults * Acute reduction in lung function in adults (2) Long term Established * Increased respiratory symptoms in children * Increased lung cancer risk in nonsmoking adults * Reduced birth weight in infants * * * * * * * * * Reduced lung growth in children Increased risk for new asthma in children Increased otitits media and middle ear effusion in children Increased respiratory symptoms in adults Increased risk for cardiovascular disease in adults Increased risk for sudden infant death Prematurity Long-term reduction in lung function in adults Increased risk for non respiratory cancers and childhood leukemia

Strong evidence

Controversial evidence

Modified from [97]

as well as religious and political leaders. As a global epidemic fuelled by the tobacco industry, this issue requires a global strategy which is underway. This global strategy requires a large and global partnership and coalition between national health, political, religious authorities and international bodies, the goal being to curb the epidemic and increase the hazards to the tobacco industry. It is an exciting challenge for all of us to contribute to this exalting task of killing the Killer number one.
Acknowledgements: The author thanks Dr El Biaze for his technical assistance, and F. Bartal and A. Kasmi for their skillful assistance.

8. 9. 10. 11.

12. 13.

References
1. 2. 3. 4. 5. 6. 7. Doll R. Uncovering the effects of smoking: historical perspective. Stat Methods Med Res 1998; 7: 87117. Doll R, Hill AB. Smoking and carcinoma of the lung. Preliminary report. Br Med J 1950; ii: 739748. Wynder EL, Graham EA. Tobacco smoking as a possible etiologic factor in bronchogenic carcinoma. JAMA 1950; 143: 329336. Levin ML, Goldstein H, Gerhardt PR. Cancer and tobacco smoking. JAMA 1950; 143: 336338. Schrek R, Baker LA, Ballard GP, Dolgoff S. Tobacco smoking as an etiologic factor in disease. Cancer Res 1950; 10: 4958. Mills CA, Porter MM. Tobacco smoking habits and cancer of the mouth and respiratory system. Cancer Res 1950; 10: 539542. Surgeon General. Smoking and Health. Report of the Advisory Committee to the Surgeon General of the

14. 15.

16.

17.

Public Health Service. Washington DC: US Government Printing Office, 1964. Mason RJ, Buist AS, Fisher EB, Merchant JA, Samet JM, Welsh CH. Cigarette smoking and health. Am Rev Respir Dis 1985; 132: 11331136. Yernault JC. Smoking and smoking cessation: a major role for the respiratory physician. Eur Respir J 1995; 8: 1633. Smoking and health: a physicians responsibility. A Statement of the Joint Committee on Smoking and Health. Eur Respir J 1995; 8: 18081811. US Department of Health and Human Services. The health benefits of smoking cessation. A report of the Surgeon General. US DHHS Center for Disease Control. Office for Smoking and Health, Rockeville, Maryland, 1990. DHHS Publication (CDC) 90-8416. American Psychiatric Association. Diagnosis and Statistical Manual of Mental Disorders. Revised 4th ed. Washington, DC, 1994. World Health Organization. Mental and behavioural disorders due to use of tobacco. International Classification of Disease. 10th revision, 1996, I-F-17, Geneva. Hemmingfield JE, Jude NR. Prevention of nicotine addiction: neuropsychopharmacological issues. Nicotine & Tobacco Research 1999; 1: S41S48. US Department of Health and Human Services. The health consequences of smoking: nicotine addiction. Surgeon Generals Report. CDC Office on Smoking and Health, Rockeville, Maryland, 1988, DHHS Publication No. (CDC) 888406. Anthony JC, Warner LA, Kessler RC. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances and inhalants: basic findings from the National Comorbidity Survey. Experimental and Clinical Psychopharmacology 1994; 2: 244268. Lynch HT, Lynch PM, Guirgis HA. Host-environmental interaction and carcinogenesis in man. In: Kouri

552

HEALTH EFFECTS OF TOBACCO

18. 19. 20. 21.

22. 23.

24. 25.

26.

27. 28.

29. 30. 31. 32. 33. 34.

35.

36. 37. 38.

39.

RE, ed. Genetic differences in chemical carcinogenesis, CRC Press, Boca Raton, FL, 1980; pp 185209. Hughes RJ. Genetics of smoking: a brief review. Behav Res Ther 1986; 17: 333345. Weiss ST. Early life predictors of adult chronic obstructive lung disease. Eur Respir Rev 1995; 5: 303309. The health consequences of using smokeless tobacco. A report of the Advisory Committee to the US Surgeon General, 1986 (NIH Publication No. 86-2874). Progress and challenge. Tobacco control (Swedish style). National Institute of Public Health, Stockholm Publication for the 11th World Conference on Tobacco or Health, Chicago August 2000. Smokeless tobacco control. Report of a WHO Group, Geneva, Technical Report series 733, 1988. International Agency for Research on Cancer (IARC). Tobacco habits other than smoking: betel-quid and areca-nut chewing; and some related nitrosamines. IARC, Lyon, France, 1985. Benowitz NL. Pharmacologic aspects of cigarette smoking and nicotine addiction. New Engl J Med 1988; 319: 13181330. Muir CS, Zaridze DG. Smokeless tobacco and cancer: an overview. In: Tobacco a major international health hazard. IARC Scientific Publications, No. 74, Lyon, France, 1986; pp 3544. Grady D, Greene J, Daniels TE, Ernster VL, Robertson PB, Hauck W, Greenspan D, Greenspan J, Silverman S Jr. Oral lesions found in smokeless tobacco users. J Am Dent Assoc 1990; 121: 117123. Schroeder KL, Chen MS Jr. Smokeless tobacco and blood pressure. New Engl J Med 1985; 312: 919. Bolinder G. Overview of knowledge of health effects of smokeless tobacco. Increased risk of cardiovascular diseases and mortality because of snuff. Loekartidningen 1997; 94: 37253731. Curbing the epidemic. Governments and the economics of tobacco control. A World Bank Publication. Washington DC, 1999. IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Tobacco Smoking, IARC, Lyon, France, 1986, vol.38. Doll R. Risk from tobacco and potentials for health gains. Int J Tuberc Lung Dis 1999; 3: 9099. Fielding JF. Smoking: health effects and control. New Engl J Med 1985; 313: 491498. Wald NJ, Hackshaw AK. Cigarette smoking: an epidemiological overview. Br Med Bull 1996; 52:3-11. US Department of Health and Human Services. Reducing the health consequences of smoking: 25 years of progress. A report of the Surgeon General. Public Health Service, Centers for Disease Control for Chronic Disease Prevention and Health Promotion, Office of Smoking and Health, 1989, DHHS Publication No. (CDC) 89-8411. Casio MG, Hale KA, Niewoehner DE. Morphologic and morphometric effects of prolonged cigarette smoking on the small airways. Am Rev Respir Dis 1980; 122: 265271. Jeffery PK. Chronic obstructive pulmonary disease and cigarette smoke-induced epithelial damage. Eur Respir Rev 1992; 2: 136143. Holt PG. Immune and inflammatory function in cigarettes smokers. Thorax 1987; 79: 1624. Burrows B. Allergy and its relationship to asthma, airway responsiveness, and chronic airway obstruction: an epidemiological perspective. In: Weiss S, Sparrow D, eds. Airway responsiveness and atopy in the development of chronic lung disease. Raven Press, New York, 1989; pp 241270. Barbour SE, Nakashima K, Zhang JB, Tangada S, Hahn CL, Schenkein HA, Tew JG. Tobacco and smoking environmental factors that modify the host response

40. 41.

42.

43.

44.

45. 46.

47.

48. 49.

50. 51.

52.

53. 54. 55.

56. 57. 58. 59.

(immune system) and have an impact on periondontal health. Crit Rev Oral Biol Med 1997; 8: 437460. Paoletti P, Viegi G, Carrozzi L, Sapigni T, Baldacci S, et al. Cigarette smoking, indoor pollution and obstructive lung disease. Eur Respir Rev 1995; 5: 315322. OConnor GT, Sparrow D, Seagal MR, Weiss ST. Smoking, atopy and methacholine airway responsiveness among middle-aged and elderly men. Am Rev Respir Dis 1989; 140: 15201526. Lozewicz S, Davison AG, Hopkirk A, Burge PS, Boldy DA, Riordan JF, McGivern DV, Platts BW, Davies D, Newman Taylor AJ. Occupational asthma due to methyl methacrylate and cyanoacrylates. Thorax 1985; 40: 836839. Jarvis D, Chinn S, Luczynska C, Burney P. The association of smoking with sensitization to common environmental allergens. Results from the European Community Respiratory Health Survey. J Allergy Clin Immunol 1999; 104: 934940. US Department of Health and Human Services. The health consequences of smoking: chronic obstructive lung disease. Washington DC, US Governmental Printing Office, 1984; Dl-HIS (PHS) 84-50205. Holland WW. Chronic obstructive pulmonary disease prevention. Br J Dis Chest 1988; 82:32- 44. Burrows B, Knudson RJ, Cline MG, Lebowitz MD. Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis 1977; 115: 195205. Prescott E, Bjerg AM, Andersen PK, Lange P, Vestbo J. Gender difference in smoking effects on lung function and risk of hospitalization for COPD: results from a Danish longitudinal population study. Eur Respir J 1997; 10: 822827. American Thoracic Society. Cigarette smoking and health. Am J Respir Crit Care Med 1996; 153: 861865. Xu X, Weiss ST, Rijcken B, Schouten JP. Smoking, changes in smoking habits, and rate of decline in FEV1: new insight in gender differences. Eur Respir J 1994; 7: 10561061. Tager IB, Speizer FE. Risk estimates for chronic bronchitis in smoking: a study of male-female differences. Am Rev Respir Dis 1976; 113: 619625. Tager IB, Munoz A, Rosner B, Weiss ST, Carey V, Speizer FE. Effect of cigarette smoking on the pulmonary function of children and adolescents. Am Rev Respir Dis 1985; 131: 752759. Camilli AE, Burrows B, Knudson RF, Lyle SK, Lebowitz NM. Longitudinal changes in FEV1 in adults: effects of smoking and smoking cessation. Am Rev Respir Dis 1987; 135: 794799. Buist AS. Risk factors for COPD. Eur Respir Rev 1996; 6: 253258. Burrows B. Predictors of loss of lung function and mortality in obstructive lung diseases. Eur Respir Rev 1991; 1: 340345. Postma DS, Vermeire P. The natural history of chronic obstructive pulmonary disease. ERS Monograph: Management of chronic obstructive pulmonary disease. 1998; 3: 7483. Ryu JH Colby TV, Hartman TE, Vassallo R. Smoking-related interstitial lung diseases: a concise review. Eur Respir J 2001; 17: 122132. Wasserman LR. Cigarette smoking and secondary polycythemia. JAMA 1973; 224: 1654-1657. Glantz SA, Parmley WW. Passive smoking and heart disease: epidemiology, physiology, and biochemistry. Circulation 1991; 83: 112. Craig WY, Palomaki GE, Johnson AM, Haddou JE. Cigarette smoking-associated changes in blood lipid and lipoprotein levels in the 8- to 19-year-old age group: a meta-analysis. Pediatrics 1990; 85: 155158. 553

M. BARTAL

60. 61.

62.

63. 64.

65. 66.

67. 68. 69. 70. 71.

72. 73. 74.

75. 76.

77.

78. 79. 80.

Ross R. The pathogenesis of atherosclerosis: an update. New Engl J Med 1986; 314: 488500. Nowark J, Murray JJ, Outes JA, Fitzgerald GA. Biochemical evidence of a chronic abnormality in platelet and vascular function in healthy individuals who smoke cigarettes. Circulation 1987; 76: 614. Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking: preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA 1990; 264:3018-3024. Jeremy JY, Mikhailidis DP, Pittilo RM. Cigarette smoking and cardiovascular disease. J R Soc Health 1995; l15: 289295. US Department of Health and Human Services. The health benefits of smoking cessation. A report of the Surgeon General. US DHHS, Centers for Disease Control Office of Smoking and Health, Rockeville, Maryland, 1990. DHHS Publication (CDC) 90-8416. Anderson KM, Wilson PW, Odell PM, Kannel WD. An updated coronary risk profile: a statement for health professionals. Circulation 1991; 83: 356362. Ockene IS, Miller NH. Cigarette smoking, cardiovascular disease, and stroke. A statement for health care professionals from the American Heart Association. Circulation 1997; 96: 32433247. Doll R, Peto R, Wheatley K, Gray R, Sutherland L. Mortality in relation to smoking: 40 years observation on male British doctors. Br Med J 1994; 309: 901911. Verhaghe R. Epidemiology and prognosis of peripheral obliterative arteriopathy. Drugs 1998; 56: 110. Mannino DM, Klevens RM, Flanders WD. Cigarette smoking: an independent risk factor for impotence? Am J Epidemiol 1994; 140: 10031008. Mikhailidis DP, Jeremy JY. Smoking and erectile impotence. Int Angiol 1993; 12: 297298. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychological correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 5461. Wolf PA, DAgostino RB, Kannel WB, Bonita R, Belanger AJ. Cigarette smoking as a risk factor for stroke: the Framinghan study. JAMA 1988; 259: 10251029. WHO/IARC. Pollution. In: Tomatis L, ed. Cancer: Causes, Occurrence and control. IARC Scientific Publications, Lyon, France, 1990; 100: 229239. Sasco AJ, Bartal M, Dari I, Carriot F, Benhaim-Luzon V. Smoking and lung cancer in Casablanca, Morocco. Proceedings of the 11th World Conference on Tobacco or Health. Chicago, August 6-11, 2000. Boyle P, Maisonneuve P. Lung cancer and tobacco smoking. Lung Cancer 1995; 12: 167181. Franceschi S, Talamini R, Barra S, Baron AE, Negri E, Bidoli E, Serraino D, La Vecchia C. Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy. Cancer Res 1990; 50: 65026507. Guenel P, Chastang JF, Luce D, Leclerc A, Brugere J. A study of the interaction of alcohol drinking and tobacco smoking among French cases of laryngeal cancer. J Epidemiol Commun Health 1988; 42: 350354. Erren TC, Jacobsen M, Piekarski C. Synergy between asbestos and smoking on lung cancer risks. Epidemiology 1999; 10: 405411. Peto R, Lopez AD, Borcham J, Thun M, Health C Jr. Mortality from smoking in developed countries 19502000. Oxford, UK. Oxford University Press, 1994: A22. Murray CJ, Lopez AD. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected 2020. Harvard School of Public Health, Cambridge, Mass, 1996.

81.

82.

83. 84.

85.

86.

87. 88. 89. 90. 91. 92.

93.

94. 95.

96.

97. 98. 99.

Hammond EC. Smoking in relation to the death rates of one million men and women. In: Heanszel W, ed. Epidemiological approaches to the study of cancer and other chronic diseases. US DEEW National Cancer Institute, Bethesda, Maryland. Monograph 19, 1966; pp 127204. Garfinkel L. Selection, follow-up, and analysis in the American Cancer Society prospective studies. In: Garfinkel L, Ochs O, M. Mushinski, eds. Selection, follow-up, and analysis in prospective studies. National Cancer Institute, Bethesda, Maryland. Monograph 67, 1985; pp 4952. The health consequences of smoking for women. A report of the Surgeon General. Rockeville, Maryland: US Department of Health and Human Services; 1980. Peacock JL, Bland TM, Anderson HR. Effects on birthweight of alcohol and caffeine consumption in smoking women. J Epidemiol Community Health 1991; 45: 159163. Kleinman JC, Pierre MB Jr, Madans JH, Land GH, Schramm WF. The effect of maternal smoking on fetal and infant mortality. Am J Epidemiol 1988; 128: 4655. Hanrahan JP, Tager IB, Segal MR, Castile RG, Van Vunakis H, Weiss ST, Speizer FE. The effect of maternal smoking during pregnancy on early infant lung function. Am Rev Respir Dis 1992; 145: 11291135. Haglund B, Cnathingus S. Cigarette smoking as a risk factor for sudden infant death syndrome: a population based study. Am J Public Health 1990; 80: 2932. International Consultation on Environmental Tobacco Smoke (FTS) and Child Health. WHO/NCD/TFI, 1999, Geneva. Respiratory Health Effects of Passive Smoking: Lung Cancer and other Disorders. US Environmental Protection Agency; Washington DC EPA/600/006F, 1992. Robbins AS, Abbey DE, Lebowitz MD. Passive smoking and chronic respiratory disease symptoms in nonsmoking adults. Int J Epidemiol 1993; 22: 809817. Leaderer BP, Samet JM. Passive smoking and adults: new evidence of adverse effects. Am J Respir Crit Care Med 1994; 150: 12161218. Hole DJ, Gillis CR, Chopra C, Hawthorne VM. Passive smoking and cardiorespiratory health in a general population in the west of Scotland. Br Med J 1989; 299: 423427. Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence. Br Med J 1997; 315: 973980. Hackshaw AK, Law M, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke. Br Med J 1997; 315: 980988. Boffetta P, Agudo A, Ahrens W, et al. Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe. J Nat Cancer Inst 1998; 90: 14401450. California Environmental Protection Agency, Office of Environmental Health Hazard Assessment. Health effects of exposure to environmental tobacco smoke. Sacremento, California, Environmental Protection Agency, 1999 (http://www.calepa;cahwnet.gov/oehha/docs/finalets.htm). Jaakkola MS, Jaakkola JJ. Assessment of exposure to environmental tobacco smoke. Eur Respir J 1997; 10: 23842397. Davey Smith G, Philips AN. Passive smoking and health: should we believe Philip Morriss experts. Br J Med 1996; 313: 929933. Simpson D. Medicines big challenge: doctors and tobacco. Tobacco Control Resource Centre. BMA, Shine G, ed. Waddingham A-2000, ISBNO-7279-1491-X: 1452; (TCRC web site: www.tobacco.control.org).

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