Changing patterns of cigarette smoking among teenagers and young adults

Changing patterns of cigarette smoking among teenagers and young adults

PAEDIATRIC RESPIRATORY REVIEWS (2001) 2, 214–221 doi:10.1053/prrv.2001.0143, available online at http://www.idealibrary.com on MINI-SYMPOSIUM: SMOKIN...

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PAEDIATRIC RESPIRATORY REVIEWS (2001) 2, 214–221 doi:10.1053/prrv.2001.0143, available online at http://www.idealibrary.com on

MINI-SYMPOSIUM: SMOKING: EFFECTS ON THE PAEDIATRIC LUNG

Changing patterns of cigarette smoking among teenagers and young adults A. Charlton School of Epidemiology and Health Sciences, The University of Manchester, Manchester, UK KEYWORDS prevalence, smoking, cigarette, young adults, adolescents, children, teenagers.

Summary In Britain at present the highest prevalence of smoking in people aged 16 years and over is among 20- to 24-year-olds. At this age, 42% of men and 39% of women smoke, compared with the overall rates of 28% and 26%. The problem is greatest in the less affluent socio-economic groups. Prevalence of regular smoking among 11- to 15-year-olds has changed little since 1982, although in 1999 it reached one of its lowest points, namely 9%. More girls than boys are smoking, e.g. 25% compared with 21% at age 15 years. Signs of developing nicotine dependence are already evident even in lighter smokers. Smoking behaviour in a country appears to follow a pattern where men start first, followed by boys, women and then girls. In most industrialised countries, prevalence for each group, except teenage girls, has peaked and reversed. Most developing countries are at an earlier stage in the pattern, which must be stopped now if millions of deaths C 2001 Harcourt Publishers Ltd are to be avoided.

INTRODUCTION Tobacco smoking is the most important cause of premature death and much chronic disease. It is a vital issue with regard to children and young people for a number of reasons. It forms part of a “family circle” which can be seen to start with maternal smoking during pregnancy, which adversely affects the fetus, increasing the risk of low birthweight and lung development problems, which are followed by increased risk of respiratory diseases, infections and more minor ailments in infancy and childhood. These children have more time off school, fall behind with their schoolwork and become underachievers who are disenchanted with learning. Consequently they often reject school and its values and fall for the tobacco advertisers’ messages that smoking can give them the qualities

Correspondence to: Professor Anne Charlton, School of Epidemiology and Health Sciences, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, England, UK. Tel: 44 (0)161 275 5663; Fax: 44 (0) 161 275 5612; E-mail: [email protected]

1526–0550/01/030214 + 08 $35.00/0

they cannot achieve otherwise. These young people leave school early, start their family very soon, smoke during pregnancy and start the “family circle” again.1 The earlier regular smoking is started, the greater is the risk of lung cancer and heart diseases later in life. Many respiratory problems in infants and young children are due to passive smoking in the home, or to active smoking by the older child. By knowing who smokes and why, it is easier to pinpoint potential problems and to target interventions in a more meaningful way. In this paper I will: (1) review current smoking patterns in Great Britain; (2) review cigarette smoking among teenagers in Great Britain; (3) give a brief theoretical overview of how and why smoking prevalence patterns change; (4) consider how the smoking patterns in the industrialised world fit into the world pattern; and (5) describe the pressures which influence smoking onset, thus causing the patterns to develop.

C 2001 Harcourt Publishers Ltd

CHANGING PATTERNS OF CIGARETTE SMOKING AMONG TEENAGERS AND YOUNG ADULTS

CIGARETTE SMOKING PREVALENCE IN YOUNG ADULTS AGED 16 YEARS AND OVER From the early 1970s, questions on smoking were included in the General Household Surveys in Great Britain. Data from earlier surveys, such as those of the Tobacco Advisory Council are also available. This has made it possible to follow changes over a long period. The changes in cigarette smoking patterns which have occurred in Great Britain mirror the situation in the industrialised world in general. Prevalence of cigarette smok-

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ing among men was 51% in 1974 and had fallen to 28% in 1998.2 For women over the same period, prevalence of cigarette smoking fell from 41% in 1974, to 26% in 1998. In summary, women’s cigarette smoking prevalence did not rise as high as that of men but has fallen more slowly (Fig. 1). This general picture hides two important trends: (a) the cigarette smoking problem is greatest in younger people; (b) smoking prevalence has fallen least and has remained highest in the less affluent socio-economic groups, the decreases being mainly in the professional and other non-manual groups.

Figure 1 Prevalence of cigarette smoking by sex (men, a; women, b) and age: 1974 to 1988 in Great Britain. Derived from Living in Britain 1998: Results from the 1998 General Household Survey.2 Office for National Statistics. London: The Stationary Office, 1999 (Table 8.1, page 123). Ages: 16–19, –r–; 20–24, –j–; 25–34, –n–; 35–49, ∗; 50–59, –∗–; 60+, –d–; overall, ––.

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Age In 1998 in Great Britain, the highest smoking prevalence for men and women over the age of 16 years was in the 20–24 year age group, with 42% of the men and 39% of the women smoking cigarettes. As Figure 1 shows, in that age group, smoking prevalence fell only from 52% in 1974 to 42% in 1998 and from 44% to 39% in women over the same period, whilst the decreases for men and women overall were from 51% to 28% and 41% to 26% respectively.2 More than two-thirds of smokers say they want to give up smoking. In 1998 in Great Britain 69% of male and 70% of female smokers said they wanted to stop. There was little difference between age groups in this wish to become a non-smoker: 72%, 73%, and 72% of all smokers aged 16–19, 20–34, and 35–49 years respectively said they would like to give up smoking altogether. However, the percentage of ex-regular smokers in the younger age groups was very low in 1998, i.e. 5% of men and 7% of women aged 16–19, 8% of men and women aged 20–24, and 13% of men and 14% of women aged 25–34 said they had been regular smokers but were ex-smokers at the time of the survey.2 The overall percentage of ex-regular smokers was 31% for men and 21% of women. This age gradient is probably, at least in part, due to the length of time older people have had during which to make the repeated attempts to quit smoking which appear to be associated with successful quitting.

Socio-economic status In Great Britain in 1998, 36% of men in manual occupations were cigarette smokers compared with 21% in nonmanual groups.2 For women, smoking prevalence was 31% in manual groups and 21% in non-manual. The decline in smoking prevalence has been slower in manual socioeconomic groups.2 Prevalence of cigarette smoking has decreased from 29% in 1974 to 15% in 1998 among men in professional occupations, but only from 61% to 45% for men in unskilled manual occupations. For women in professional occupations, cigarette smoking prevalence fell from 25% in 1974 to 14% in 1998 and from 43% to 33% over the same period for women in unskilled manual occupations.2 Male smokers in unskilled manual work smoked more cigarettes per week (mean 120) compared with professionals (91), as did female smokers who averaged 100 in unskilled manual occupations and 65 in professions.2 An important issue for young adults and teenagers is that of pregnancy. Not only are young smokers affected personally by their behaviour, but their children also are subjected to serious health risks. In 1995, in England, 26% of mothers in manual socio-economic groups compared with 12% in non-manual groups smoked dur-

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ing pregnancy. Thirty-two per cent of smokers in manual and 46% in non-manual groups gave up smoking during pregnancy.

CIGARETTE CONSUMPTION IN YOUNG ADULTS AGED 16 YEARS AND OVER Taking the United Kingdom as an example, annual consumption of cigarettes rose rapidly among men of all ages from about 800 per smoker in 1905 to its highest point of 4420 per person in 1945, the steepest rises being during the First and Second World Wars. After each of the Wars cigarette consumption fell briefly and then rose again. By 1960, men’s annual cigarette consumption was 4030 per person.3 Since that time it has shown a downward trend. Women took up cigarette smoking later than men did. It was not until about 1920 that their cigarette consumption began to rise steeply. Again, taking the U.K. as an example, women’s annual cigarette consumption was 13 per person in 1921, rising to 1250 in 1945 and to 2630 in 1974.3 In 1998 in Great Britain, average cigarette consumption for male smokers was 109 per week and for women 93 per week. For men, this figure is the continuation of a general downward trend, from 125 per week in 1974 with minor fluctuations. However, for women, average weekly cigarette consumption, although always somewhat lower than that of the men, has remained almost constant, starting at 94 per week in 1974. Women generally smoke fewer cigarettes than male smokers do. In 1974, 49% of male smokers and 67% of female smokers smoked fewer than 20 cigarettes per day. By 1998, 63% of male smokers and 73% of women smokers smoked fewer than 20 cigarettes per day.2 Perhaps surprisingly, on average, young adults smoke fewer cigarettes than older adults. In Great Britain in 1998, 90% and 71% of male smokers aged 16–19 years and 20–24 years, respectively, smoked fewer than 20 cigarettes per day. For women, cigarette consumption was also lower in the two youngest age groups, with 90% of 16–19 year olds and 82% of 20–24 year olds smoking fewer than 20 cigarettes per day.2 However, there is clear evidence that nicotine dependence starts after very few cigarettes and lighter smokers, once hooked, can have great difficulty in stopping. For example, in 1998, more than one in ten lighter smokers (of fewer than ten cigarettes per day) would smoke their first cigarette of the day within half an hour of waking in the morning. Nearly a quarter of smokers of fewer than ten cigarettes per day said they would find it difficult or very difficult to go without smoking for a whole day. These factors can be taken as indicators of dependence.

CHANGING PATTERNS OF CIGARETTE SMOKING AMONG TEENAGERS AND YOUNG ADULTS

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SMOKING PREVALENCE AMONG TEENAGERS

Cigarette consumption among 11- to 15-year-olds attending secondary schools

Smoking is a behaviour which almost always begins in childhood. Very few smokers take up the habit after the age of 19 years and some start very early in life. In Great Britain in 1998, 43% of men and 31% of women who had ever been regular smokers had started smoking before the age of 16 years.2 Only 14% of men and 22% of women smokers began smoking after the age of 19 years. Several studies in the UK have shown that the age of 9 years is a peak time for experimentation with cigarettes for boys. Girls reach their peak of experimentation just a little later, at 10 years of age. Some children, especially those from smoking households, try their first cigarette very early, perhaps even before starting school. An increased risk of coughs and other respiratory problems has been found in these very young active smokers and it cannot be assumed that such diseases are always caused by passive smoking, although they are exacerbated by it.4

The pattern of cigarette consumption shown in adults appears to become established at secondary schools. Although at that stage more girls than boys are regular smokers, they smoke fewer cigarettes (on average). In 1998, boys who said they were regular smokers had smoked on average 65 cigarettes in the previous week compared with an average of 49 for the girls who smoked.5 It is interesting to compare the findings of the secondary school survey with the adult data. Seventy-one per cent of the regular smokers aged 11 to 15 years indicated in a diary of smoking that they had smoked more than 20 cigarettes during the previous week, and one third of the smokers had smoked an average of 10 cigarettes per day, i.e. more than 70 during the week. There are already signs of dependence developing. Fifty-four per cent of the boys and 60% of the girls who smoked regularly said they would find it difficult to go without smoking for a week. Sixty-seven per cent of the boys and 74% of the girls who smoked regularly said they would find it difficult to give up smoking altogether. However, overall, 38% of the boys and 32% of the girls who smoked regularly said they would like to give up and many of them had tried. Earlier research has indicated that dependency can be established after relatively few cigarettes have been smoked and that young smokers who quit smoking do experience withdrawal symptoms similar to those of adult smokers.8 More than a third of the young people who had been regular smokers for less than a year said they would find it difficult not to smoke for a week and more than half of these early smokers said they would find it difficult to give up smoking altogether, although 57% overall in this group had tried.5

Cigarette smoking prevalence among 11- to 15-year-olds attending secondary schools Regular surveys, mainly on a biennial basis, have been carried out on smoking prevalence in secondary school pupils aged 11 to 15 years in Great Britain by the Office of National Statistics since 1982. Regular smoking in young people under the age of 16 years is defined as smoking at least one cigarette per week on a regular basis. In 1998 in England, 11% of this age group (9% of boys and 12% of girls) were regular smokers and 8% were occasional smokers who smoked on a regular basis but not as much as one per week.5 By 1999, 8% of boys and 10% of girls were regular smokers.6 As Figure 2 shows, there has been relatively little change in general prevalence for this age group since surveys began. The last two surveys have shown a drop in prevalence and this could be good news. However, it has happened before only to be followed by a rise in subsequent surveys. Only time will tell whether or not it is the start of a downward trend. Although data from England are used as an example in this paper, they are fairly representative of the general situation in the industrialised world as a whole. For example, a recent survey of American youth aged 9–21 years, found 9.2% (95% CI : 7.6–10.9) of middle school students, aged 9 to 12 years (in Grades 6, 7 and 8), and 28.5% (95% CI : 25.8–31.2) of high school students, aged 13 to 18 years (in Grades 9, 10, 11 and 12), were currently smokers of cigarettes.7 Smoking prevalence among girls in England overtook that of boys in the mid-1980s and has continued at a higher level ever since. As might be expected, prevalence of regular smoking increases with age. The 1998 survey found 1%, 3%, 7%, 17% and 24% regular smokers of at least one cigarette per week among 11, 12, 13, 14 and 15-year-olds respectively.

PATTERNS OF SMOKING: AN OVERVIEW When cigarette smoking is first introduced into a country, its uptake appears to follow the pattern postulated by Rogers and Shoemaker for the diffusion of innovations.9 First a small group of individuals, the innovators, take up the new behaviour. In the case of cigarette smoking, these innovators are usually men and are likely to be the professionals or those who are aspiring to reach such a status. Tobacco advertising in countries where the pattern of smoking is at this stage focuses on these men, reinforcing their belief that smoking is an integral part of their status or that it will enable them to reach it. India and some African countries have reached this stage and are moving quickly to the next, which is that of the early adopters of the behaviour. Generally these people are boys and the less affluent men in the case of cigarette smoking. Japan and China are in or about this phase at present. Next follows the early and the late majorities. Women are usually

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Figure 2 Percentage of pupils who were regular smokers by age and gender (boys, a; girls, b): 1982–1999: England. Derived from Drug use and drinking among young teenagers in 1999.6 London: Office for National Statistics, 2000 (Table 6). Age: 11, –r–; 12, –j–; 13, –n–; 14, ∗; 15, –∗–; total, –d–.

predominant in this group in the cigarette smoking pattern. Culturally, smoking is often seen as inappropriate for women and it is part of the emancipation process to break down these barriers and become smokers. Tobacco advertisers target clear messages to women just as they did to the male innovators, about taking control of their own lives and reaching for success in their newly-found careers. Some Southern European countries are reaching this stage. In a way, the onset of smoking in women in a country could be seen as a separate diffusion process, with the first women smokers also being innovators. However, onset of smoking in women has always been part of the larger pattern. Girls follow women in the late adopter group. The cigarette smoking pattern in most in-

dustrialised western countries has reached this stage and the highest smoking prevalence rates are now among girls and young women. Although Great Britain has been taken as the example for the purposes of this paper, The United States of America, Canada, Australia, New Zealand and Northern Europe could equally well have provided the theme and the story would have been similar.

Cigarette smoking patterns in some developing and industrialised countries Based on data from two publications, the State of Health Atlas10 for adults and the WHO Global Youth Tobacco

CHANGING PATTERNS OF CIGARETTE SMOKING AMONG TEENAGERS AND YOUNG ADULTS

Survey,11 it is possible to consider the status of specific countries in the cigarette smoking pattern. For example, Costa Rica is still at a relatively early stage. About 30% of men and 18% of young people aged 13–15 years smoke. Fewer than 25% of women have, as yet, taken up smoking. South Africa is somewhat further on. Although fewer than 25% of women smoke, cigarette smoking prevalence among men is in the region of 50% and 18% of young people are current smokers of cigarettes. Poland has moved quickly through the stages and has about 50% of men, more than 25% of women and 29% of urban and 17% of rural youth currently smoking cigarettes. China has very high smoking prevalence among men (60%) but, as yet, women’s smoking prevalence is still below 25% and measures of current cigarette smoking among the young range from 2.4% to 6.3% at different survey points. In industrialised countries health messages about the health risks of smoking, especially with regard to men at that stage, began in the early 1960s with the publication of the Report of the Royal College of Physicians in London12 and the Surgeon General’s Report in the USA.13 These publications focused on men and, as might be expected, the innovators, namely the men in the professional classes, began the reverse trend by giving up smoking. In the UK, we can clearly see the two patterns, first that of onset of cigarette smoking followed and overlapped by that of quitting smoking. Men’s smoking peaked and plateaued in the 1950s and in the early 1960s the reverse trend began. Boys’ smoking peaked and plateaued in the later 1960s, at which stage a survey in 1966 found very high smoking rates among teenaged boys but so little among girls that they were not included in the study.14 Boys’ smoking prevalence fell quickly in the 1970s, but plateaued out by 1982. Women’s smoking prevalence reached its peak and plateau in the mid-1970s and has fallen slowly since. Cigarette smoking patterns in industrialised countries are now at a much later stage of development than those of developing countries. For example, in the USA, men’s and women’s cigarette smoking prevalence has come down to a little above 20%, whereas for high school youth it is nearly 29%. In the UK men’s and women’s cigarette smoking prevalence are 28% and 26% respectively with 24% of 15 year-olds smoking regularly. Developing countries are now the target for the tobacco industry. They want to move the innovation process on as rapidly as possible and youth is one of their main targets. The Global Youth Tobacco Survey 1999 found early experimentation with smoking in a wide range of countries.11 Particularly alarming was the high prevalence of cigarette smoking among youth aged 13 to 15 years in urban Poland (29.3% current smokers; 69.8% having tried a cigarette even if only one or two puffs), Moscow (33.4% current smokers; 67.2% having tried) and Kiev (33.9%; 73.6% having tried). The earliest start to smoking was found to be in China, where 39.2% in Chongquing and

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37.7% in Guandong had smoked their first whole cigarette before the age of 10 years. In all the countries surveyed, cigarette smoking was not the only form of tobacco use by young people. They appear to be repeating the pattern which took place earlier in the 20th Century in the westernised world and unless its progress is halted, they will experience the same epidemic of smoking-related disease on a larger scale in due course. If present trends continue, the current 4 million deaths per year from tobacco smoking worldwide will rise to 8.4 million by 2020. Seventy per cent of these tobacco-related deaths will be in developing countries, unless trends are reversed immediately.11

PRESSURES TO SMOKE What is causing these patterns of smoking onset? Young people are subjected to a wide range of social influences and pressures to smoke4 and, whether or not they are willing to admit it, soon become dependent on the nicotine in the tobacco smoke.

Social influences Very close to the young person are the influences of home, friends, school and social life. Parents and family are responsible for the child’s primary socialisation. If smoking is the norm in the home, the child will accept this as part of life. Children whose parents smoke are twice as likely to become smokers as those with non-smoking parents.4 Siblings’ smoking is also very strongly related to children’s smoking behaviour. When a child goes to school, friends become the most important influence and remain so. It seems to be a process of peer-bonding rather than the young person being pressured to smoke against his or her will. Young people smoke because they want to belong to a particular social group. Role-models such as pop-stars, film-stars and fashion models reinforce the image the young person wishes to project. Teachers who smoke can appear to be endorsing smoking as safe and acceptable. School policy which prohibits smoking among teachers as well as among pupils has been shown to be associated with the lowest smoking prevalence and lowest cigarette consumption among students.

Personal beliefs and knowledge Many young people believe that smoking does something positive for them, for example that it gives them confidence, makes them appear adult, calms their nerves, helps them to cope in times of stress, controls their weight, improves their appearance, enhances their social status or defines their personality. Films, television and advertising reinforce these beliefs in a number of ways. Young people who see themselves as underachievers academically or badly behaved (perhaps from choice!) are at increased

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risk of becoming smokers. Girls who are unhappy with their physical appearance or self-worth are at increased risk of taking up smoking because they believe it boosts their self-image.15 Some young smokers try cigarettes just to satisfy their curiosity, whilst others smoke to help them to cope with boredom, anxiety, unhappiness or trauma. Knowledge of health risks of smoking seems to have very little influence on a young person’s smoking decision.

National influences A young person is not making their decision about smoking on a purely individual basis. As well as the social influences already discussed, national policies on tobacco advertising, cigarette price and availability of cigarettes to young people and smoke-free areas all play an important part in creating the environment in which a child makes the decision.

CONCLUSIONS • Patterns of cigarette smoking are similar throughout the industrialised world. • Men’s smoking prevalence has decreased in these countries over the past three decades. • Women’s smoking prevalence has also decreased, but not as steeply as that of men. • The highest smoking prevalence is currently among young adults. • More people in manual than in non-manual occupations are smokers and the decrease in smoking prevalence in the manual groups has been less. • More than a quarter of mothers in manual socio-economic group smoked during pregnancy as compared with 12% of mothers in non-manual groups. • Many younger lighter smokers show signs of nicotine dependence even after 1 year of smoking. • Although overall three quarters of regular smokers want to give up, there are relatively few ex-regular smokers among young adults. • Most adult regular smokers start before the age of 19 years, smokers in manual occupations in general start the earliest. • Eight percent of boys and 10% of girls aged 11 to 15 years were regular smokers of at least one cigarette per week in 1999 in England. • There are many pressures on young people to become smokers at social, individual and national levels. • Onset of smoking and quitting of smoking in a country appears to follow the pattern of diffusion of innovations. • Developing countries are now following this pattern of onset and unless trends are reversed will suffer a

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major epidemic of smoking-related diseases in years to come. Dependence can develop very quickly and a behaviour which begins as experimentation with a few cigarettes can develop into a lifetime’s dependence which is very hard to break. It is beyond the scope of this paper to discuss this aspect further. However, paediatricians are in a very good position to help to prevent smoking and its associated health problems and always need to take smoking into account with every patient both in industrialised and most especially in developing countries.

PRACTICE POINTS • Prevalence of smoking is high among young women especially in less affluent socio-economic groups and must be taken into account with regard to mothers of patients. • Even a young child can be a smoker and this might be a factor in his or her disease and treatment. • Advice and help to the mother, the child or other member of the family to help them stop smoking if necessary could be especially effective from a paediatrician. • Paediatricians’ influence is strong and could help the national and community lobbies to provide an environment as free as possible of pressures on young people to smoke especially in developing countries.

RESEARCH DIRECTIONS • Studies on the effectiveness of paediatricians’ advice to smoking mothers and other relatives on their smoking behaviour and the subsequent health of their children. • Evaluations of various help and advice methods provided by paediatricians for smoking mothers of children with respiratory problems in order to determine the most effective in both behaviour and health terms.

ACKNOWLEDGEMENTS The author sincerely thanks the Cancer Research Campaign for having supported all her research into young people and smoking.

REFERENCES 1. Charlton A. Children and smoking: the family circle. Brit Med Bull 1996; 52: 90–107.

CHANGING PATTERNS OF CIGARETTE SMOKING AMONG TEENAGERS AND YOUNG ADULTS

2. Bridgwood A, Lilly R, Thomas M, Bacon J, Sykes W, Morris S. Living in Britain 1998. Results from the 1998 General Household Survey. Office for National Statistics, Social Survey Division. London: The Stationery Office, 2000. 3. Wald N, Kiryluk S, Darby S, Doll R, Pike M, Peto R. UK Smoking Statistics. Oxford: Oxford University Press, 1988. 4. Royal College of Physicians. Smoking and the Young. London: Royal College of Physicians,1992. 5. Goddard E, Higgins V. Smoking, Drinking and Drug Use among Teenagers in 1998. Volume 1: England. Office for National Statistics. London: the Stationery Office, 1999. 6. Government Statistical Service. Drug Use, Smoking and Drinking among Young Teenagers in 1999: England. Government Statistical Service. London: Office for National Statistics, 2000. 7. American Legacy Foundation. Legacy First Look Report 4. The Relationship between Cigarette Use and Other Tobacco Products: Results from the 1999 National Youth Tobacco Survey. Washington: American Legacy Foundation, 2000.

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8. McNeill AD. The development of dependence on smoking in children. Br J Addict 1991; 86: 589–592. 9. Rogers EM. Diffusion of Innovations. Fourth Edition. New York: Free Press, 1995. 10. Mackay J. The State of Health Atlas. London: Simon and Schuster, 1993. 11. Warren CW, Riley L, Asma S, Erikson MP et al. Tobacco use by youth: a surveillance report from the Global Youth Tobacco Survey project. B World Health Organ 2000; 78: 868–875. 12. Royal College of Physicians. Smoking and Health. Tunbridge Wells: Pitman Medical, 1962. 13. US Public Health Service. Smoking and Health. Public Health Service Publication No. 1103. Washington: Surgeon General’s Advisory Committee on Smoking and Health, 1964. 14. Bynner JM. The Young Smoker. London: Her Majesty’s Stationery Office, 1969. 15. Minagawa K, While D, Charlton A. Smoking and self-perception in secondary school students. Tob Control 1993; 2: 215–221.