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Validation of self reported smoking by serum cotininemeasurement in a community-based study E Vartiainen, T Seppälä, P Lillsunde, P Puska. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
J Epidemiol Community Health 2002;56:167–170 Study objective: The validity of self reported smoking in population surveys remains an importantquestion. An associated question is what would be the value of measuring serum cotinine concentra-tions in such surveys to obtain validated smoking data.
Design: Cross sectional analysis of data on self reported smoking and serum cotinine among a ran- dom population sample of 5846 persons aged 25 to 64 years, who participated in the FINRISK-92 . . . . . . . . . . . . . . . . . . . . . . .
Main results: Among self reported regular smokers, 97.2% of men and 94.9% of women had a coti- nine concentration of 10 ng/ml or higher in serum. Of those participants who reported to have smoked at any time during their life but not during the previous month, 6.3% of men and 5.2% of women had a serum cotinine concentration of at least 10 ng/ml. Among never smokers 2.5% of men and 2.7% of women had detectable level of cotinine in their serum. The validity of self reporting was similar among subjects from different areas, ages, and socioeconomic groups.
Conclusions: In a sample of the general population in Finland the validity of self reported smoking is high, and most of the few self reported non-smokers who had cotinine in their serum had only low or . . . . . . . . . . . . . . . . . . . . . . .
Bothinclinicalandincommunitysettingstherehasbeen smokersandpossiblemisclassificationsbyselfreport.Among a concern about the validity of self reported smoking.1 2 the 547 self reported smokers 12.1% were found to have serum Mainly, three biological measurements have been used to cotinine levels less than 14 ng/ml and were possible misclassi- validate self reported smoking: carbon monoxide, thiocyanate, fications by self report. The cotinine level cut off points to and cotinine.3 The aim of our paper is to study the validity of determine smoking has varied from 3 ng/ml to 40.5 ng/ml self reported smoking in a cardiovascular risk factor popula- among studies.8 The most commonly used cut off points are tion survey by comparing self reports with results of measure- between 10 ng/ml and 20 ng/ml. From the review of 16 stud- ies it was concluded that the maximum sensitivity was near Nicotine metabolises rapidly and extensively, primarily in the cut off point of 8.8 ng/ml.9 The aim of this paper is to the liver. N-oxidation of nicotine to nicotine-1’-N-oxide occurs describe how valid self reported smoking is in an area with a in humans. This metabolite has been shown to convert back to community-based cardiovascular prevention programme and nicotine. In humans, the urinary elimination phase of the in other areas of Finland as well as in different demographic metabolite parallels that of the parent nicotine, indicating a formation rate limited excretion. It has been estimated thatapproximately 4% of the nicotine dose is excreted as nicotine-1’-N-oxide. Furthermore, it has been estimated that the quan- titative disposition of nicotine is as follows: an average of 9% In 1992 the FINRISK survey was carried out to assess cardio- of the dose seems to be excreted as intact nicotine, and about vascular risk factor levels and to assist the monitoring of 70% of nicotine seems to be converted to cotinine. Cotinine is trends in Finland. The survey represents the third and final the major plasma metabolite of nicotine and persists for a FINMONICA survey and is used to evaluate the long term considerable time period in plasma, with a half life of approxi- effects of the North Karelia project.10 The survey was mately 16 hours. Only a minor fraction of the generated coti- conducted in four areas of Finland. In eastern Finland these nine is excreted by the kidneys, but cotinine is further areas were the provinces of North Karelia and Kuopio. The metabolised to more polar water soluble substances. Accord- North Karelia and Kuopio provinces have populations of ing to recent human data the major metabolite found in urine 180 000 and 250 000, respectively. The third survey area in south western Finland encompasses the city of Turku, the In the CARDIA study self reported smoking prevalence was small town of Loimaa, and 12 small rural municipalities with 31%, and the measured prevalence of serum cotinine with 14 a total population of roughly 210 000 people. Two cities in the ng/ml as the cut off point was 32%.6 The proportion of reported Helsinki capital area, Helsinki and Vantaa, were included in non-smokers with a cotinine level of at least 14 ng/ml was the study. Helsinki’s and Vantaa’s populations are 500 000 and 4.2%. The misclassification was larger among subjects who were black, had a high school education or less, or were former In 1992 the sampling frame followed the WHO MONICA smokers. The possible reasons for misclassification were protocol. A random sample of 2000 people from each of the reporting errors, environmental tobacco smoke, or an inappro- survey areas was drawn from the National Population priate cut off point for delineating smoking status.
Register. The sample included people aged 25–64. The sample Self reported smoking and serum cotinine were compared was stratified by 10 year age groups and by sex. Each cell con- among 743 Mexican American participants in the Hispanic tained 250 people. The participation rates are shown in table 1.
Health and Nutrition Examination Survey.7 Of 189 self The survey included a self administered questionnaire reported non-smokers 6.3% were defined as biochemical (mainly covering questions on socioeconomic factors, medical history, health behaviour, and psychological factors) and a 1 ml of 0.5 M NaOH and 5 ml of dichlormethane with cardiovascular risk factor examination conducted by specially pyribenzamine (5 µg/100 ml) as the internal standard. After centrifugation the organic layer was transferred into a clean Smoking was assessed with a set of questions. Two types of test tube and evaporated. The residue was dissolved in 100 µl indices were used to categorise the smokers. In the first index of ethanol, and 1 µl was injected, into the GC/MS column. A the following questions were used: Have you ever smoked in fused silicone capillary column coated with HP 1 (Hewlett your life? (1) no, (2) yes. Those who answered no were classi- Packard, 12 m×0.2 mm×0.33 mm) was used. The initial oven fied as never smokers. Those, who answered yes were asked temperature was 60°C, maintained for one minute, and then the following question: When was the last time you smoked? raised by 30°C per minute to 300°C and followed by linear pro- (1) Today or yesterday, (2) Between two days and. one month gramming. The injector was maintained at 250°C, and the ago, (3) Between one month and half a year ago, (4) From half detector at 280°C. The carrier gas was helium, with a flow of a year and one year ago, (5) More than one year ago. Based on 0.5–1.0 ml/min. The minimum detectable level was 10 ng/ml.
this the first index contained the following four groups: (1) The principal fragment ions (98 and 176 for cotinine, 91 for those who had smoked today or yesterday (“current smok- pyribenzamine) were monitored. The cotinine’s coefficient of ers”), (2) those who had smoked two days to one month ago, variation (cv) was 6.6% (n=10) at a level of 200 ng/mg and (3) those who had smoked longer than one month ago or (4) 19% at a level of 20 ng/ml. The extraction recovery was 98%.
those who had never smoked. For the second index theparticipants were asked: Do you now smoke (1) regularly? (2) occasionally? (3) not at all? (4) 1 have never smoked. The Among those participants who reported to have smoked today number of daily cigarettes, pipes smoked and cigars consumed or yesterday, 96.4% of men and 92.6% of women had a serum were asked from those who reported to have smoked within cotinine level of 10 ng/ml or higher, which was the minimum the past month. The number of smoking times in a day were detectable level of the method. Most of them had serum coti- nine level higher than 50 ng/ml (table 2). Of these participants Blood samples were taken in the seated position and in a who reported to have smoked today or yesterday (=1489), 77 smoke free place as part of the risk factor examination. Fresh subjects did not have a measurable level of cotinine in serum, serum samples were sent to the laboratory at the National 31 reported that they smoke occasionally, 23 said they smoked Public Health Institute where they were frozen. Cotinine was 10 times or less per day, and 21 reported to smoke more than measured by a Hewlett Packard gas chromatography (5890) 10 times per day. From one area seven of those who reported mass spectometre (5970, GC/MS) with a selected ion to smoke at least 10 cigarettes per day every day, and reported monitoring mode. Half a millilitre of serum was shaken with to smoke regularly were asked to give a new blood sample. Two Self reported last smoking time and serum cotinine level (ng/ml) Smoked 2 days – 1 month Smoked longer time than Self reported smoking and cotinine measurements (had not smoked in the past month) having serumcotinine higher than 10 ng/ml by sociodemographic • Self reported smoking is quite reliable in Finnish population.
• Small proportion of daily smokers do not have cotinine in • Validation by cotinine is needed to asses if self reporting of The differences between the areas in smoking were very similar by using different criteria of self reported smoking or different cut off points in cotinine level (table 4).
Among those who reported to smoke at least once per day, the serum cotinine had a correlation of 0.45 with the number of self reported smoking times in a day. When we recorded non-smokers as 0 the correlation increased to 0.75.
The main concern in the validity of self reported smoking has been the possible under reporting. This has been of particular concern in a situation where there is a strong social pressure against smoking like in community-based disease prevention and health promotion programmes, smoking cessation trials,or clinical settings.11 12 In Finland a long term, community- based cardiovascular disease prevention programme has beencarried out in North Karelia,13 one of the four districts thatparticipated in this FINRISK-92 survey.
subjects did not come to the survey, one had stopped smoking, The differences between areas were very similar when two current daily smokers had cotinine in serum, and two assessed either by self reports in a questionnaire or by cotinine others did not have cotinine in serum although they reported concentration in serum. This indicates that a more intensive programme in one area does not affect self reporting. The The percentage of people who had a serum cotinine level of social pressure for people not to smoke is probably lower in at least 10 ng/ml and reported not to have smoked in the pastmonth was 3.9%. Out of these 159 persons 12 had used nico- community-based programmes with cross sectional random tine chewing gum or a transdermal patch. Most of those who samples than in clinical settings where cotinine measure- reported not smoking but had cotinine in serum only ments may be more important. In their report, Jarvis et al2 exhibited a low or moderate level (between 10 ng/ml and 50 found that 19% of smoking hospital patients reported themselves to be non-smokers. When those people were added The validity of self reported smoking was analysed in to the number of smokers the smoking prevalence increased different demographic and socioeconomic groups (table 3) There were no statistically significant differences between age, Our data indicated that 6.3% (78 of 1713) of self reported sex, marital status, or educational groups in the percentage of male non-smokers had cotinine in serum al least 10 ng/ml. lf subjects who reported not to have smoked in the past month we assume that all these men smoke regularly or occasionally but still had a measurable level of cotinine in serum. This per- the percentage of smokers increases from 32% to 34%. In the centage was similar in different areas.
CARDIA study 4% of self reported non-smokers had more Percentage of smokers by different smoking criteria (regular smokers, smoked today or yesterday) and by different cut off points in serum cotinine level than 14 ng/ml of cotinine, and the respective increase in and all age groups, and use of snuff is common only among young men in Finland. Thus, it is very likely that most of these Among Mexican Americans in the Hispanic Health and people are underreporting their smoking. The small number of Nutrition Examination Survey 12% of the self reported smok- these people shows that self reported smoking is very reliable.
ers had a serum cotinine level lower than 14 ng/ml.7 In a com- Other studies have come to similar conclusions.6 7 This raises mercially run community survey, Piers and his colleagues the question of whether costly biochemical validation found that 12% of smokers had a cotinine level lower than 25 procedures are needed in population-based surveys. Cotinine ng/ml. The possible explanations proposed in the discussion measurement describes only one aspect of smoking: exposure have been low or occasional smoking, errors in the laboratory to nicotine within the past few days. Questionnaires must or with completing the questionnaire. In our study 5% of those inquire about the complete smoking history of people, with who reported to have smoked “today or yesterday” did not have cotinine in serum. Most of this was explained by the fact The main conclusion is that in a general population survey that they were occasional smokers who may have smoked with self administered questionnaires the validity of self “today or yesterday” in relation to the time of completing the reported smoking is high in Finland and attempts to validate questionnaire but did not smoke on the day of or day before that by general measurement of cotinine is probably not worth the examination. There is also intraindividual variation how the costs entailed. However, it may be useful to repeat the vali- well serum cotinine is describing nicotine intake. Different dation to a subsample of participants in the future surveys to people convert different percent of nicotine to cotinine.
assess if the self reporting is changing overtime.
Usually this varied between 55% and 92% and also thecotinine clearance varied from 19 to 75 ml/min.14 In their . . . . . . . . . . . . . . . . . . . . .
report Benowitz and colleagues reported a person with deficient c-oxidation of nicotine.5 This is associated with a E Vartiainen, T Seppälä, P Lillsunde, P Puska, National Public Health long half time of nicotine and low level of cotinine in plasma compared with nicotine. It is unknown whether this or othersimilar conditions could explain the very low cotinine values of some smokers observed in many large epidemiological 1 Pierce JP, Dwyer T, DiGiusto E, et al and Quit for Life Steering Committee. Cotinine validation of self-reported smoking in commercially run community surveys. J Chron Dis 1987;40:689–95.
A special survey was done to assess the demographic factors 2 Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, et al. Comparison of tests and health behaviour of non-participants by a short postal used to distinguish smokers from nonsmokers. Am J Public Health1987;77:1435–8.
questionnaire and by phone if they did not respond to the 3 Suadicani P, Hein HO, Gyntelberg F. Serum validated tobacco use and mailed questionnaire. About 50% of non-respondents were social inequalities in risk of ischaemic heart disease. Int J Epidemiol contacted. There were more non-participants in younger men 4 Pechacek TF, Fox BH, Murray DM, et al. Review of techniques for and in cities. Smoking was slightly more prevalent among measurement of smoking behavior. In: Matarazzo JD, Weiss SM, Herd non-participants. No differences were observed in other JA, et al, eds. Behavioral health. A handbook of health enhancement and health behaviours. Participants were not directly informed disease prevention. Chichester: Wiley, 1984:729–54.
5 Benowitz NL, Jacob III P, Sachs DPL. Deficient C-oxidation of nicotine.
that self reported smoking will be validated by cotinine.
Clin Pharmacol Ther 1995;57:590–4.
Hence, the results reflect the general situation how people are 6 Wagenknecht LE, Burke GL, Perkins LL, et al. Misclassification of reporting smoking. However, the self reporting may change smoking status in the CARDIA Study: A comparison of self-report withserum cotinine levels. Am J Public Health 1992;82:33–6.
over time when the norms in the society are changing. This 7 Pérez-Stable EJ, Marin G, Marin BV, et al. Misclassification of smoking survey was done in 1992, it may be useful to repeat the valida- status by self-reported cigarette consumption. Am Rev Respir Dis tion in future surveys to assess if the self reporting is chang- 8 Patrick DL, Cheadle A, Thompson DC, et al. The validity of self-reported smoking: a review and meta-analysis. Am J Public Health The actual percentage of smokers depends on the cotinine cut off point, on the formulation of questions in the question- 9 Etzel RA. A review of the use of saliva cotinine as a marker of tobacco naire, and on the subsequent definition of a smoker. A smoking exposure. Prev Med 1990;19:190–7.
10 Vartiainen E, Puska P, Jousilahti P, et. al. Twenty-year trends in coronary relatively large proportion of smokers report that they smok- risk factors in North Karelia and in other areas of Finland. Int J Epidemiol Years ago, smoking used to be a more clearly defined habit: 11 Murray RP, Connett JE, Lauger GG, et al for the Lung Health Study Research Group. Error in smoking measures: effects of intervention on people were either smokers or non-smokers. This seems to be relations of cotinine and carbon monoxide to self-reported smoking. Am J changing. About 20% of male smokers and 30% of female smokers reported in our survey that they smoking occasion- 12 Glasgow RE, Mullooly JP, Vogt TM, et al. Biochemical validation of smoking status: Pros, cons, and data from four low-intensity intervention ally. About half of the self reported occasional smokers did not trials. Addict Behav 1993;18:511–27.
have cotinine in serum, and most of the rest had only moder- 13 Puska P, Tuomilehto J, Nissinen A, et al, eds. The North Karelia Project.
ate levels. If this will change over time requires a new survey 20 year results and experiences. Helsinki: Helsinki University PrintingHouse, 1995.
in the future. This also means that classic calculations of sen- 14 Benowitz NL. Biomarkers of environmental tobacco smoke exposure.
sitivity and specificity are not as appropriate as they were Environ Health Perspect 1999;107:349–55.
when people were more clearly classified as smokers or 15 Emmons KM, Abrams DB, Marshall R, et al. An evaluation of the relationship between self-report and biochemical measures ofenvironmental tobacco smoke exposure. Prev Med 1994;23:35–9.
The effect of passive smoking on cotinine level is small, the 16 Tunstall-Pedoe H, Brown CA, Woodward M, et al. Passive smoking by usual level being between 0.5 ng/ml to 10 ng/ml.15–18 Thus, it is self report and serum cotinine and the prevalence of respiratory and not likely that passive smoking could explain the high coronary heart disease in the Scottish heart health study. J EpidemiolCommunity Health 1995;49:139–43.
cotinine level among some self reported non-smokers.
17 Coultas DB, Howard CA, Peake GT, et al. Salivary cotinine levels and Nicotine replacement therapy explained a few of those high involuntary tobacco smoke exposure in children and adults in New values. Use of smokeless tobacco was not included in the Mexico. Am Rev Respir Dis 1987;136:305–9.
18 Delfino RJ, Ernst P, Jaakkola MS, et al. Questionnaire assessments of questionnaire, which may be one explanation for this discrep- recent exposure to environmental tobacco smoking in relation to salivary ancy. On the other hand, these people were from both sexes cotinine. Eur Respir J 1993;6:1104–8.

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