[Measurement of urinary free cotinine. Comparison with the level of expired air carbon monoxide]. / Dosage de la cotinine urinaire libre. Deuxième partie: comparaison avec le taux de monoxyde de carbone dans l'air expiré.

BACKGROUND AND AIM: Cotinine is a very reliable index for the estimation of active or passive smoking. Sampling from a single urine void is well accepted by smokers who are willing to stop. It is not possible to exclude modification of urine cotinine according to beverage intake. The aim of this study was to determine if urine cotinine concentration must necessarily be adjusted to creatinine or not, by making comparison with expired air carbon monoxide. MATERIAL AND METHODS: Carbon monoxide was measured in 53 smokers coming for the first time in a smoking cessation program. Urine cotinine was measured by HPLC-UV. The cut-off value for abstinence is 8ppm and 0.05 mg/L, repectively. Urine creatinine was determined using the Jaffe reaction. RESULTS: Mean CO level was 18.5 +/- 10.6 ppm and mean urine cotine was 1.45 +/- 0.86 mg/L. Eight smokers had CO 8 ppm. They should be considered as abstinent. However, only one of them had a cotinine under the detection limit. Urine creatinine varied in a large range (0.7 - 35 mmol/L). But, cotinine was only weakly correlated to creatinine (r = 0.279, p = 0.037). There was a highly significant correlation between cotinine and CO (0.649, p = 0.0001). The correlation of cotinine/creatinine versus CO was not significant (r = 0.249, p = 0.072). In order to take into account fluid intake, urine cotinine of each sample was adjusted as if creatinine was equal to the mean (8.3 mmol/L) of the group of subjects. The correlation observed with adjusted or non adjusted cotinine and CO (r = 0.640, p < 0.0001) was the same. CONCLUSION: Urine cotinine from a single void is an accurate index of tobacco smoking at the individual level. There is no need to adjust cotinine concentration, taking into account urine creatinine. Measurement of urine cotinine can be useful to manage smokers who deliberately wish to overcome tobacco dependence, offering the opportunity to provide an adequate level of nicotine substitutive therapy. It is also of peculiar importance to follow-up pregnant women and smokers for whom cessation is required after a clinical event. Finally, absence of cotinine in urine can be used to document abstinence from tobacco products.

[Urinary cotinine and nicotine metabolites measurement]. / Dosage urinaire de la cotinine et des métabolites de la nicotine.

UNLABELLED: According to the recent regulations (Circulaire DGS/DH du 3 avril 2000), tobacco dependence must be determined by the measurement of urine nicotine metabolites. Various assay methods are presently available. They were tested in order to evaluate their analytical performances and to determine how they can be used for the clinical management of smoking cessation. MATERIAL AND METHODS: Urine samples from a single void (n = 97) were obtained from active and abstinent smokers (with or without nicotine substitutive therapy). They were all analyzed by the various methods. Cotinine concentration was measured in six laboratories, using HPLC combined with UV detection according to a standardized procedure (Ann Biol Clin 2002 : 60 : 263-72). Immunoassay methods were also tested and the values obtained from urine samples were compared to urine cotinine measured by HPLC-UV. RESULTS: HPLC-UV: Urinary cotinine varied in a range from undetectable to 4 mg/L. An interlaboratory comparison was performed according to the Valtec procedure (calculation of equation of Deming, chart of differences). There was a good accordance between laboratories. Cotinine concentration was only slightly influenced by fluid intake, as shown by a poorly significant correlation between cotinine and creatinine (r = 0.23, p = 0.05). Homogeneous immunoassays: The two homogeneous immunoassays (Cotinine) from Thermo Electron and Cotinine Enzyme Immunoassay commercialized by Microgenics were highly correlated (r = 0.97). The correlation was not so strong with HPLC-UV (r = 0.86). Firstly, values were found higher with immunoassays because antibodies crossreact with 3-hydroxycotinine. Secondly, the ratio of immunoassays values to HPLC-UV values varied according to urine specimens. Finally, there was a highly significant correlation with urine creatinine (r = 0.40, p = 0.0001), thus indicating the influence of fluid intake. Heterogeneous immunoassay: The kit Metabolites of Nicotine commercialized by DPC France was tested on the analyzer Immulite, using a procedure specifically established for urine. Antibodies revealed a large spectrum of nicotine metabolites. Therefore, the values were much higher than those observed for the same urine samples with homogeneous immunoassays. CONCLUSION: HPLC-UV can be recommended for the measurement of urinary cotinine, as it was shown a good accordance between laboratories. The low detection limit is of interest for the diagnosis of Environmental Tobacco Smoking. Homogeneous immunoassays can be easily used for routine analysis as they can be performed directly on urine specimen. The results must be interpreted according to cut-off values specifically established according to homogeneous or heterogeneous immunoassays. Variability induced by fluid intake must be taken into account. The interest of the heterogeneous immunoassay needs to be confirmed for the diagnosis of Environmental Tobacco Smoking.

[Biomarkers of tobacco smoke exposure]. / Les marqueurs spécifiques du tabagisme.

Tobacco smoking is a major risk factor for cancer, cardiovascular diseases and respiratory illnesses. Smoking is increasing among children and adolescents with subsequent consequences on the health. Furthermore, maternal tobacco smoking during pregnancy adversely affects prenatal growth. Nicotine, the most important tobacco alkaloid, is responsible for maintaining tobacco addiction. According to a recent Circulaire de la direction générale de la santé, nicotine dependence should be determined through questionnaires and quantitative estimate of nicotine metabolites. Nicotine blood level fluctuates and urinary nicotine excretion is of short duration. Nicotine is intensively metabolized in the liver and oxidized into cotinine. Urinary measurement of cotinine appears to be highly related with the degree of intoxication and to allow the differentiation between non exposed and exposed non-smokers. In order to check the present application of nicotine metabolites measurement, a survey was conducted in 340 smoking cessation units. Forty percent physicians (n = 137) answered the survey. For 17% of them, the quantification of nicotine metabolites is included in their daily practise and for 79%, guidelines about cotinine measurement should be given in France. Sixty-seven biologists answered the survey. Recommendations for immunoassay and HPLC determination of cotinine should be given as reported by 66 and 44% of them respectively. Indeed, urinary cotinine measurement with high performance liquid chromatography is highly sensitive and specific. However, immunoassays are more convenient. These two approaches are presently under investigation in order to provide guidelines for optimal use in various clinical situations. Traditional measures for nicotine dependence are the number of cigarettes smoked per day, nicotine intake expressed as mg per day, Fagerstr m questionnaire, expired air carbon monoxide, thiocyanates and cotinine levels in biological fluids. Urinary cotinine measurement is the most useful for the follow-up of smoking cessation including adjustment of nicotine replacement therapy, especially after a clinical event or for the follow-up of smoking pregnant women. It allows the detection of passive smoke exposure in children who are hospitalized for recurrent respiratory illnesses.

[Tools for the assessment of tobacco dependence: comparison with questionnaires and marker assays]. / Les outils d'évaluation de la dépendance tabagique: comparison des questionnaires et des dosages de marqueurs.

Fagerström Tolerance Questionnaire has been questioned in some respects for the purpose of the evaluation of tobacco dependence. In a sample of 208 smokers attempting to quit, we measured on urinary samples the levels of nicotine metabolites via their thiobarbituric acid derivatives comparatively to the levels of nicotine and cotinine by high performance liquid chromatography. Urinary concentration of nicotine metabolites was 77.1 +/- 50.0 mumol/l. Nicotine and cotinine levels were respectively 8.2 +/- 12.0 mumol/l and 12.9 +/- 9.8 mumol/l. Spearman correlation coefficients were used to examine the relationships among various measures of exposure to cigarette smoke, tobacco markers and tobacco addiction scores obtained through the Fagerström Questionnaire and a Simplified Questionnaire. Nicotine metabolites are correlated with the score obtained with the Simplified Questionnaire (rho = 0.39) better than with the score of Fagerström (rho = 0.28) (p < 0.01). These moderate correlations suggest that the measurement of tobacco markers provide a more valuable information than questionnaires for the appreciation of the depth of tobacco intake. The questionnaires should not serve as a substitute for tobacco markers determination.

[Tobacco dependence: a short evaluation questionnaire]. / Dépendance tabagique: questionnaire réduit d'évaluation.

Two hundred and forty-eight smokers were questioned in order to determine the relation between Fagerström's questionnaire--an indirect test of nicotine-dependence in 8 questions with an 11 points score--and the shorter, and quicker, 6 points score questionnaire of only 2 questions described by Heatherton. The relation was considered satisfactory with 67 percent sensitivity and 90 percent specificity. Discordance was observed in only 6 cases. A 5 to 6 points score on the simplified questionnaire reflects a strong tobacco-dependence and justifies an attempt to facilitate tobacco withdrawal by using a nicotine gum or stamp.

[Spirometric modifications induced by bronchography. Effects of Salbutamol]. / Modifications spirométriques induites par la bronchographie. Effets du Salbutamol.

Bronchography enables an appreciation of the morphology and dynamics of the bronchi inaccessible to the fibroscope. However, this examination may aggravate pulmonary function in patients with chronic airflow obstruction. We have studied the effects of bronchography on forced expiration in order to identify and quantify possible spirometric changes. Thus spirometric tests were done at different times during the examination (V.C., F.E.V., flow-volume curves): before and after anaesthetizing the upper airways with xylocaine, after the introduction of contrast to the bronchi and finally after a Salbutamol aerosol. Spirometric values were unaffected by anaesthesia of the upper airways. On the other hand, the introduction of contrast led to a clear and constant fall in maximum expiratory flow, associated with a fall in forced vital capacity. These changes could not be reversed either after inhalation of Salbutamol or sub-cutaneous Terbutaline. The mechanisms producing the spirometric changes which we report does not seem to involve either the adrenergic system or the irritant receptors. Bronchial obstruction produced by the contrast does not alone appear to explain the changes induced by bronchography. Other mechanisms, not yet identified, probably contribute to the decrease in maximum expiratory flow.