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WORKSHOP: CARBON MONOXIDE AND CVD Gi.rvM fq. ~ /1I p i, b -1 IW Ib lO] Sv~r~.vr.v. l.~a J ' FIG. 4. Cumulative frequency curves for nonsmokers and different smoking catneories. sources of SCN. External sources other than smoking are cyanide-containing products. industrial cyanide in the metal industry, cyanide-producing bacteria,or SCN itself in cabbage, mustard, turnips etc. Cyanide in tobacco smoke and from - other sources is converted mainly by the.liver enzyme sulfur transferase to the nontoxic SCN, which is excreted by urine. These other sources are possible reasons for error with regard to smoking. To increase the accuracy one may use this method in conjunctiorn with a determination of expired CO. _ _ ~ - . . .- - - - - --- --- - - ~ ~ INTERMEDIATE META9OLISM -1 anwy.. I.a.... Ye.. CYANIDEr_ Thav i TNIDCYA ATE rt~.al rt~a pu/rv.y FIG. 5. Uptake. intermediate melabolism. and excretion of Ihiocyanalc._ EYCRETIDN s

I WORKSHOP: CARBON MONOXIDE AND CVD 5ervn.Thixy.uce Iv.'^1- ioa m +-n e-x 01 .-.n Cige,etra Ciqer- PiPa fnmcire~:onI Nonimoten smake,s Ftea2. Median and centra195`,i range of serum thiocyanale values in nunsmokers and smokers wiuh different smoking habits. ( The different levels therefore are due either to different average amounts of rsmoked tobacco or to different absorption of cyanide with regard to smoking habits. Both questionnaire and SCN determination try to assess actual smoking hab-its. ; Actual smoking habits may be reasonably defined as the average amount of ~ cigarettes or other tobacco products smoked during the last week or last month- From experience with a few people who gave up smoking totally at once. w.e could . determine a biologic half-life of about 2 weeks. The SCN level is therefore rcla- tively independent from short-term daily variations of smoking behavior. Our questionnaire asked whether a smoker had smoked within the last 3 hr before blood sampling. Figure 3 shows that, within each class, those who had smoked within the last 3 hr had higher SCN medians than those who did not. However, the difference is nearly absent in the highest class with more than 20 cigarettes. The interpretation of these results is difficult, but can be attributed to questionnaire problems as follows: Within each questionnaire category those who smoked in the last 3 hr before blood sampling are those who smoke more, as recency of smoking is correlated to amount of smoking. This can bc seen from the steadily rising percentage of smokers within each category during the 3 hr before blood sampling from 10% in the lowest to 65`7o in the highest class. Furthermore, F-- -~~~'~0-- - ~

`Tq_'- . ~ . . BORGERS AND JUNGE RESULTS Figure I shows the main results with cigarette smokers as the most important group. Actual smoking was divided into 6ve classes by the questionnaire: nonsmokers, 1-4, 5-10, 11 -20, and more than 20 cigarettes per day. The corre- sponding median serum SCN values are 51 pmoUliter for nonsmokers, rising steadily ily to 174 µmoVliter in smokers of more than 20 cigarettes per day. In addi- tion to the median in each smoking category, the figure shows the central 95`7~ range. One would expect at first that there should be as little overlap as possible between the SCN distributions of the smoking categories, so that persons could be classified by their SCN values into a corresponding questionnaire category with- out error. One must, however, bear in mind that the questionnaire is not an absolute standard and that the overlapping distributions are partially due to "wrong" questionnaire results with regard to true exposure, as well as from errors in the SCN method itself. Figure 2 shows the results with regard to other smoking habits than cigarettes. Cigarette smokers in total have a median of 141 µmoVliter, cigar smokers have a median of 165 µmol/Iiter, pipe smokers have a median of 81 µmoVliter, and smok- ers of two or three types have a median of 130 µmoUliter. The other types (cigar, pipe) are not broken down by amount of smoking because of insufficient numbers. senimTh.v.rure m0 100 ~ .-e ~-rsr 0 1-4 6-10 11-CO _) 20 C/qa.enn'Ozy 1 1 Fto. t. Median and central 95!'c range of serum thiocyanate values in nonsmokers and cigarene smokers with regard to questionnaire category. ~ ICo N rt9~^r ~ Acaa^~t.~ i

BORGERS AND 111NGE i I r Nrr S.rvnrTnuy.rw. i tP^^mt txoo 50 lm -- TAO~yavrt ~-_ EaR1rdCO 0 I 1-9 Nvmh. cf Cqr.ne. ps Ory Msn E.qed CO ) IJ M ts tu s t Ffc. 6. Mean expired CO and mean serum lhiocvanale Icvets based on a figure in refercnce 151. I Our study does not have data on CO levels. Therefore. to compare both meth- ods, we used data from a study of Vogt, er al. (5). Figure 6 sho«'s mean expired CO and mean SCN levels with regard to questionnaire responses: nonsmokers, 1-9, t0-20, and more than 20 cigarettes. The curves have the same direction, with a steeper slope for CO. - - Figure 7 shows the correlation coefficients of expired CO, SCN, reported number of cigarettes, and time since last cigarette before the test. The correlation between CO and SCN (r = 0.571) is greater than the correlation between either test and questionnaire responses. The coefficient between time since last cigarette and CO is larger (r = -0.416) than benreen time since last cigarette and SCN (r = -0.255). This is the consequence of the different biologic half-life of CO and SCN. In their study Vogt et rel. (5) demonstrated an increase of accuracy in predicting smoking behavior using both methods simultaneously. 9wm Reponel numG> Time una SCN oi ~Cay v,y,-iry E.ppreECO 0,511 I 0,476 -0416 $e.um SCN _ 0.479 -0.255 ReponM rmmbs of ag.rmn.'daY I Fla 7. Pearson correlation coefi`cienis among smokers based on a Ggure in reference IA. I opy.i3hr .'

rQ110_ _ FEXT BORGERS AND JUNGE 9mot.nq eu,.nq 3 M„n ei9+rerteJO+v GAo.. bleuE-umGhM o~free,r. - el rn. n,.a„n m re. 1 - • 72 98 26 138 - 158) 171 - 1071 .-t1 n-5 5- 10 104 121 17 (41 - 13<1 163 - 1961 e-St n-n 11 - 1U 141 157 16 151 - 274) 187 - 226) n-m n.n ) 70 171 173 - 2 (99-IC01 (109-2<1] 4 n-69 . _ ' p C 0,05 Fic. 3. Median and central 959r range (in brackets) of serum thiocyanate values in relation to smoking before blood sampling unit of measure: pmotrliter. the questionnaire asked whether smoke was inhaled or not. We could not find a significant difference in the SCN level with regard to inhalation. Accuracy and Yalidity of llie Test The accuracy of the SCN method as a measure ofexposure to tobacco smoke - can be tested against questionnaire data only in a relative way. It is possible that SCN gives a better prediction of actual smoking behavior than does the question- naire, as there is a systematic bias towards underreporting in questionnaire re- sponses. If we take questionnaire data as a yardstick, however, and try to classify persons by their SCN values with regard to smoking, a SCN level of 100 µmo6'liter would discriminate in an optimal way. Figure 4 shows the cumulative frequencies of SCN values in each questionnaire category. If we take the smokers of more than 20 cigarettes, we will find 3% erroneously classified as nonsmokers by a level- of 100 µmoVliter as a criterion. The error would be- larger of course in the lower smoking categories. _ From a practical point of view, there are two different situations where one would use the test. (a) An individual therapeutic situation where one could see the "normalization" of the SCN level as a success of smoking cessation; and (b) a mass trial, i.e., an intervention trial in atherosclerosis and coronary heart disease. One would be able to assess objectively the diminishing smoking habits in a population by a reduction of the average level of SCN in the same way as for cholesterol or blood pressure. . The "error" of the SCN test would be critical in the first example; whereas in an epidemiologic situation there-are no other sources of SCN increase. which are as massive as smoking and could influence averages in the general population.- These other external sources can be seen in_ Fig. 5. It shows metabolism and I r.f , '_ - ---------------- I . I..GPIJri3hr

- WORKSHOP: CARBON MONOXIDD. AND CVD DISCUSSION The determination of serum SCN and the determination of CO in expired air are both valid methods to assess personal smoking habits. The serum SCN method can be used either alone or, if more accuracy is needed, in conjunction with expired CO. The sources of error (analytical, other sources of SCN) are small enough to permit the use in an epidemiologic study of smoking exposure and smoking reduction. - REFERENCES I. Butts. W. C.. Kuehneman, M., and Widdowson, G. h:. Automated method for determining serum thiocyanate, to distinguish smokers from nonsmokers. Cfin. Clvm. 20. 1344 (1974) - 2- lones. R. H., Ellicolt, M. R-, Cadigan. J. B., and Gacnsler. E. A. The relationship bels.een alveolar and blood carbon monoxide concentrations during breath-holding: Simple estimation of COHb-saluraiions. J. Lab. C71n. M1led. 51, 553 (1958). 3- lunge, B., Borgers. D., Berkholz. M.-B.,Thefeld, W., and Hotfineisier. H. Thiocyanat im Serum als Indikator fur die Schadstoftbelaslung durch Tabakrauch. Arbeirnmed SocinhnrJ. Prurrn- lirnrel. 13, 13 (1978). 4. Ringold, A., Goldsmith, 1. R., H<Iwig, H. L., Finn, R., and Schuette. F. Estimating recent carbon monozide exposures: A rapid method. Arch. Emiron. Health 5, 308 (1962). 5. Vogt, T. M., Selvin, S., Widdowson, O., and Hulley, S. B. Expired air carbon monoside and serum thiocyanate as objective measures of cigarette exposure. Amer-J. Pnblir Henlrh 67, 545 (1977). ~

PREyE{tTIV E MEDICItiE 8, t7W-Un0 ( 1979) r ~ _ ~-~' e C_ i - t2?3 ocy felas n!nd cator of Tobacco Smoking' DIETER BORGERS AND BURCXHARD JOSGE //UIi1bK of Socinl Nedirinr and fpidtniio7ogy. Frderul f/entth Offlrr. Berlin. ISerr Germnn_v `- This study demonstrates the suitability of serum ihiocyanarn as an indicator of tobacco smoke. The median serum level of smokers rises smadil,v from 51 pmot liier in nonsmoken to 174 pmoUliter in smokers of more than 20 cigarettesdav. The method can be used in epidemiologic studies of smoking behavior and smoking cessation. To increase the accuracy' of predicting smoking habits, this test can be used in conjunction .ciih a determinaiion of expired carbon monoxide. - INTRODUCTION Smoking is the main source of carbon monoxide (CO) uptake in the general population. This is shown either by determination of carboxyhenioglobin in the blood or, more conveniently for epidemiologic studies, by analysis of CO in ex- pired air (4). The expired air method is_rapid, inexpensive, and does not have the technical problems-involved in analyzing blood for carboxyhemoglobin. The CO level in the expired air is related directly to the blood carboxyhemogiobin concen- tration (2). A disadvantage of this method is the short biologic half-life of about 4 hr. Recency of exposure is therefore a critical variable-in epidemiologic studies using this method. The concordance of CO levels to smoking is so close that in the general popula- tion one can use it as a test of habitual smoking. It can be used to assess smoking objectively as compared with the questionnaire as a subjective method. Aside from the measurement of CO,there is a second biochemical test available which is the determination of thiocyanate (SCN). The serum level for SCN derived from cyanide components in tobacco smoke is also a specific, simple, and cheap method to assess smoking habits. The following data and analysis show the suitability of this method in an epidemiologic context. METHODS A smoking questionnaire with eight questions concerning smoking history scas administered to about i200 persons, who came in mainly for preemployment examinations (3). The population included both sexes and all ages from 15 to 70 years. Blood was taken and analyzed for the serum SCN IeveL The determination was done with a photometric method, described by Butts ef a!. 11), together.with other clinical parameters on a multichannel autoanalyzer. The method is cheap, efficient, and fulfills clinical standards of precision, validity, and linearity for an automatic method (3). - ' Presented at a Workshop on Carbon Sfono.ide and Cardiovascular Disr3se. sponsored by the American Health Foundation and the Federal Health OfTice. Federal Republic of Germany. Berlin, Oetober 10-1?. 1978. _ - 0091-7435l79.0083 0000502.000 ,/ ~v/ ^ AOn{huortcC~~ ` anrGrm nrJ.