Exposure of young infants to environmental tobacco smoke: breast-feeding among smoking mothers.

OBJECTIVES: This study examined the degree to which breast-feeding and cigarette smoking by mothers and smoking by other household members contribute to the exposure of infants to the products of tobacco smoke. METHODS: The subjects were 330 mother-infant pairs derived from a cohort of 1000 pairs enrolled in a longitudinal study of the pulmonary effects of prenatal and postnatal smoking. The main outcome measure was corrected urinary cotinine levels. RESULTS: Urinary cotinine levels were 10-fold higher in breast-fed infants of smoking mothers than among bottle-fed infants of smoking mothers. Among infants of nonsmoking mothers, urine cotinine levels were significantly increased in infants living in homes with other smokers; in this group there was no significant difference between bottle-fed and breast-fed infants. Infants whose mothers smoked in the same room as the infant had only nonsignificant increases in cotinine levels compared with infants whose mothers restricted their smoking to other rooms. CONCLUSIONS: Breast-fed infants of smoking mothers have urine cotinine levels 10-fold higher than bottle-fed infants whose mothers smoke, suggesting that breast-feeding, rather than direct inhalation of environmental tobacco smoke, is the primary determinant of cotinine levels in infants whose mothers smoke.

Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes. A prospective cohort study.

BACKGROUND: Most studies of the reproductive consequences of cigarette smoking base exposure on self-reported smoking habits. This study examines the relationship of birth outcomes to the timing and intensity of maternal active and passive smoking estimated both from self-reports and from cotinine concentration in maternal urine during early, middle, and late gestation. METHOD: This cohort study included 740 white and Hispanic women who obtained antenatal care at the East Boston Neighborhood Health Center between 1986 and 1992. At each antenatal visit, information on maternal active and passive smoking was obtained by a detailed questionnaire, and by measurement of urine cotinine concentrations. Infant birth outcomes were obtained from hospital records. Multiple linear regression was used to evaluate antenatal smoking variables on birth outcomes, with adjustment for maternal demographic characteristics, reproductive history, alcohol use, maternal weight and height, and infant gender. RESULTS: The percentage of mothers who ever smoked cigarettes during pregnancy was 55.5% for white and 10.2% for Hispanic women. A significant inverse exposure-response relationship between cotinine concentration in maternal urine and infant size at birth was demonstrated. However, the relationship was less clear between maternal self-reported smoking status and these outcomes. For the entire gestation, a 1000 ng increase in mean urine cotinine concentration was associated with a 59 +/- 9 g reduction in birthweight, a 0.25 +/- 0.05 cm reduction in length, and a 0.12 +/- 0.03 cm reduction in head circumference, respectively. For maternal passive smoking, the much smaller magnitude of effect precludes firm conclusions. CONCLUSIONS: These data suggest that preventing and reducing active maternal smoking during pregnancy may have a beneficial impact on infant size at birth.

Behavior therapy and the transdermal nicotine patch: effects on cessation outcome, affect, and coping.

The process and outcome of a smoking cessation program using behavior therapy alone (BT) or behavior therapy plus the nicotine patch (BTP) was studied in 64 participants. Participants quit smoking on a target date after a period of ad libitum smoking, cognitive-behavior therapy preparing them for cessation, and behavioral rehearsal for high-risk situations, including stress management, and coping with negative affect. Abstinence was significantly higher for the BTP group versus the BT group from the end of behavioral treatment (79% vs. 63%) through the 3-month follow-up (p < .01), with the effects weakening at the 6- (p = .06) and 12-month marks (p = 38% vs. 22%). More general distress was observed among BT versus BTP participants (i.e., increased withdrawal, tension, fatigue, and coping frequency with decreased coping effort; coping-to-urge ratio). The coping behavior of the BTP group may have been more effective than that of the BT group, as indicated by their significantly higher level of self-efficacy.

A placebo-controlled evaluation of the effects of buspirone on smoking cessation: differences between high- and low-anxiety smokers.

One hundred one smokers were divided into high and low trait anxiety groups on the basis of a normalized score on the Profile of Mood States Anxiety/Tension Scale and were randomly assigned to receive buspirone or placebo in a double-blind fashion. After a 1-week baseline, smokers were exposed to an 8-week drug and behavioral intervention involving buspirone or placebo (up to 60 mg/day) with concurrent group cognitive behavioral intervention. All smokers were to quit smoking on the target date, set at 4 weeks after the program began. Medication was provided for an additional 4 weeks after group treatment ended. The results showed that buspirone had a beneficial effect on smoking abstinence but only among smokers who were already relatively high in anxiety and only for as long as the drug was available. Moreover, when provided to smokers who were relatively low in anxiety, the drug appeared to interfere with abstinence, although these effects also reversed when the drug was withdrawn. These effects were associated with an attenuation of the expected rise in anxiety before the quit date and its actual reversal thereafter, but only in the buspirone high-anxiety group. One-month abstinence averaged 88, 61, 60, and 89% for the buspirone high-anxiety, placebo high-anxiety, buspirone low-anxiety, and placebo low-anxiety groups, respectively. By 12 months, abstinence for the buspirone and placebo high- and low-anxiety groups fell to 12, 23, 41, and 36%, respectively. No differences were observed for measures of self-efficacy, symptoms of withdrawal, medication side effects, or compliance.

The effects of smoking schedules on cessation outcome: can we improve on common methods of gradual and abrupt nicotine withdrawal?

This study compared the efficacy of 2 traditional methods of smoking cessation, gradual reduction and "cold turkey," with a new approach involving variation in the intercigarette interval. One hundred twenty-eight participants quit smoking on a target date, after a 3-week period of (a) scheduled reduced smoking (progressive increase in the intercigarette interval), (b) nonscheduled reduced smoking (gradual reduction, no specific change in the intercigarette interval), (c) scheduled nonreduced smoking (fixed intercigarette interval, no reductions in frequency), or (c) nonscheduled nonreduced smoking (no change in intercigarette interval or smoking frequency). Participants also received cognitive-behavioral relapse prevention training. Abstinence at 1 year averaged 44%, 18%, 32%, and 22% for the 4 groups, respectively. Overall, the scheduled reduced group performed the best and the nonscheduled reduced group performed the worst. Both scheduled groups performed better than nonscheduled ones. Scheduled reduced smoking was associated with reduced tension, fatigue, urges to smoke, withdrawal symptoms, increased coping effort (ratio of coping behavior to urges), and self-efficacy, suggesting an improved adaptation to nonsmoking and reduced vulnerability to relapse.

An evaluation of a multicomponent treatment program involving scheduled smoking and relapse prevention procedures: initial findings.

In the current study, 34 smokers were treated in a smoking cessation program that involved either a scheduled smoking procedure, or a minimal contact self-help treatment control. The interval smoking program consisted of baseline, cessation, and relapse prevention phases. During baseline, subjects self-monitored smoking and the total hours spent awake. During a 3-week cessation period, the scheduled smoking group progressively increased their intercigarette interval, thereby gradually reducing their total daily intake of nicotine. Smokers were expected to quit on a target date set at the end of this period. Cognitive behavioral interventions and relapse prevention training consisted of behavioral rehearsal of nonsmoking skills in a relapse prone environment. Control subjects were given the American Cancer Society "I Quit Kit", and provided subsequent discussion of its use. The results showed that 53% and 41% of the scheduled smoking group was abstinent at the 6- and 12-month follow-up points, respectively. Controls averaged only 6% for the same periods. Scheduled smoking may be a useful addition to a multicomponent treatment program and further study appears warranted to determine the saliency of the treatment features.

The effect of maternal smoking during pregnancy on early infant lung function.

We studied the effect of prenatal maternal cigarette smoking on the pulmonary function (PF) of 80 healthy infants tested shortly after birth (mean, 4.2 +/- 1.9 wk). Mothers' prenatal smoking was measured by: (1) questionnaire reports at each prenatal visit of the number of cigarettes smoked per day, and (2) urine cotinine concentrations (corrected for creatinine) obtained at each visit. Infant PF was assessed by partial expiratory flow-volume curves and helium-dilution measurement of FRC. Forced expiratory flow rates were significantly lower in infants born to smoking mothers, both when unadjusted and after controlling for infant size, age, sex, and passive exposure to environmental tobacco smoke (ETS) between birth and the time of PF testing. Flow at functional residual capacity (VFRC) in infants born to smoking mothers was lower than that found in infants whose mothers did not smoke during pregnancy (74.3 +/- 15.9 versus 150.4 +/- 8.9 ml/s; p = 0.0007). Differences remained significant when flow was corrected for lung size (VFRC/FRC: 0.87 +/- 0.26 versus 1.77 +/- 0.12 s-1; p = 0.013). No differences in pulmonary function were evident among infants exposed and unexposed to ETS in the home after stratifying by prenatal exposure status. We conclude that maternal smoking during pregnancy is associated with significant reductions in forced expiratory flow rates in young infants. The results suggest that maternal smoking during pregnancy may impair in utero airway development and/or alter lung elastic properties. We speculate that these effects of maternal prenatal smoking on early levels of forced expiratory flow may be an important factor predisposing infants to the occurrence of wheezing illness later in childhood.

Association of intrauterine cigarette smoke exposure with indices of fetal lung maturation.

The timing of fetal lung maturation is regulated, at least in part, by the fetal endocrine milieu, which in turn may be influenced by environmental factors. Infants of smoking mothers are at decreased risk of neonatal respiratory distress syndrome (RDS), a disease of lung immaturity. Therefore, we measured fetal lung maturity and cigarette smoke exposure to determine whether the lungs of smoke-exposed fetuses mature more quickly and whether changes in maturation are associated with alterations in amniotic fluid (AF) cortisol levels. Amniotic fluid lecithin-sphingomyelin ratio (L/S) and saturated phosphatidylcholine levels were used as measures of lung maturity, while smoke exposure was assessed by measuring AF cotinine, a stable nicotine metabolite. Lung maturity was more advanced in smoke-exposed fetuses as measured by saturated phosphatidylcholine (P = .02) and L/S ratio (P = .04). Smoke-exposed fetuses attained sufficient lung maturity to minimize the risk of RDS approximately 1 week earlier than in unexposed fetuses. The AF of smoke-exposed fetuses also had higher levels of free, conjugated, and total cortisol. Acceleration of lung maturation in smoke-exposed fetuses is consistent with the decreased risk of RDS in infants of smoking mothers. Maternal smoking could influence lung maturation by directly or indirectly enhancing the production and/or secretion of cortisol. Despite the decreased risk of RDS, the developmental process by which smoke-exposed fetuses attain early pulmonary maturity is abnormal and may contribute to the decreased lung function and increased respiratory illness noted in infants of smoking mothers.

Radioimmunoassay of nicotine-delta 1'(5')-iminium ion, an intermediate formed during the metabolism of nicotine to cotinine.

Cotinine, one of the major metabolites of nicotine, is formed by two sequential enzyme reactions: [formula: see text] Chemical and immunological methods of analysis are available to quantify these two compounds (I and III). Study of the intermediate (III) is hampered because of its complex chemistry and lack of simple methods for its assay. Generally, (II) is trapped by addition of cyanide and analyzed as the 5'-cyanonicotine adduct. In order to develop an immunoassay for (II), rabbits were immunized with a 3'-succinylmethyl-5'-cyanonicotine-protein conjugate with the expectation that (II) would, after treatment with cyanide, be quantified as 5'-cyanonicotine. Unexpectedly, however, the antibodies recognized the cyano adduct and (II) to the same extent (limit of deletion = 1.2 pmol). Nicotine, cotinine, and several other metabolites do not significantly inhibit the antigen-antibody reaction. Inhibition studies with 5' substituted nicotine analogs indicate that the 5'-hydroxynicotine tautomer (IIb) is the species recognized by the antibodies. Inin vitro metabolic studies, (II) accumulates in the absence of aldehyde oxidase, but in its presence, is converted to cotinine. As judged by serological activity, dilute solutions (under 15 microM) of (II) are stable when allowed to stand for 6 days at pH 7 and 37 degrees C. However, at high concentrations of iminium ion (where NMR studies showed instability and formation of multiple products) serological activity is also lost. Iminium ions are generated during the metabolism of some tertiary amine xenobiotics. The use of alpha-cyanoamine haptens to elicit antibodies specific for iminium ions and/or their cyano adducts may permit development of immunoassays for these compounds.

How should urinary cotinine concentrations be adjusted for urinary creatinine concentration?

The correlation between cotinine concentrations in a single specimen of urine and in serum collected on the same occasion from 279 male smokers was 0.83. This was significantly increased, to 0.91, by adjusting the urinary cotinine levels for urinary creatinine concentration to take account of variations in urinary dilution between people. The adjustment used was based on the observed regression relationship between urinary cotinine and urinary creatinine concentrations. Expressing urinary cotinine values as a ratio to urinary creatinine, which has been used as a method of adjustment by others, did not improve the correlation between serum and urinary cotinine levels. The method of adjusting urinary cotinine for urinary creatinine is, therefore, important. The principle of such adjustment should apply not only to cotinine but also to other urinary biochemical measurements.

The effects of smoking on the mood, cardiovascular and adrenergic reactivity of heavy and light smokers in a non-stressful environment.

Following a period of overnight deprivation, 58 smokers participated in a 90-min laboratory assessment in which they viewed a non-stressful movie and smoked two 0.5-mg nicotine-containing cigarettes. The first cigarette was given to all subjects following 25 min of adaptation and baseline. The next cigarette was provided at their request, which occurred 9-12 min later. "Heavy" and "light" smokers were grouped according to their average morning cotinine values, which fell above or below 250 ng/ml, respectively. The results showed that, relative to their baseline, heavy and light smokers experienced about the same level of post-smoking change in blood nicotine, heart rate and blood pressure. However, heavy smokers showed a significantly greater delta from baseline in post-smoking measures of epinephrine, norepinephrine, tension reduction and increase in vigor enhancement. A strong and consistent correlation was observed between post-smoking increases in epinephrine, tension reduction and increased vigor.

Antibodies and radioimmunoassays for phosphoserine, phosphothreonine and phosphotyrosine. Serologic specificities and levels of the phosphoamino acids in cytoplasmic fractions of rat tissues.

For antibody production, the O-phosphorylated derivative of tyrosine, threonine, or serine was covalently linked to succinylated bovine albumin via the carbodiimide reaction. Each conjugate was then complexed with methylated bovine albumin for immunization of rabbits. To determine binding, the corresponding O-phosphorylated [3H]amino acids were chemically synthesized. In addition, these 3H-phosphorylated derivatives were acylated (with succinic or acetic anhydride) to obtain ligands whose structures resemble those present in the immunogen. The acylated ligands bound to their respective antibodies more effectively: in some cases binding was about three orders of magnitude greater than their non-acylated counterparts. Radioimmunoassays were therefore developed using the N-succinyl-[3H]phosphoamino acids. When the unlabeled N-succinyl-phosphorylated amino acids were used as inhibitors in the homologous immune systems, 50% displacement of the labeled ligand was found with 0.06, 0.27 or 0.8 pmol of the tyrosine, threonine, or serine derivative, respectively. The antibodies were highly specific for the homologous hapten; the requirement for the phosphate group on the acylated amino acid was essentially absolute. Antibody content (expressed as mg/ml serum) and apparent binding constants for the N-succinyl derivatives in individual bleedings of immune sera were 1.9 and 1 X 10(10) M-1 for phosphotyrosine, 0.825 and 6 X 10(8) M-1 for phosphothreonine, and 0.150 and 2 X 10(8) M-1 for phosphoserine. The radioimmunoassays were used to quantitate the phosphoamino acids in cytoplasmic fractions of rat tissue extracts. The production of antibodies to phosphorylated O-tyrosine has been reported previously, but to our knowledge, this represents the first report of antibodies specific for O-phosphorylated serine and threonine residues.

Nicotine regulation among heavy and light smokers in a non-stressful environment.

The purpose of this study was to assess nicotine regulation among "heavy" and "light" smokers. Previous studies supporting the nicotine regulation model of smoking behavior have suggested that smokers compensate for a reduction in the amount of nicotine available in their cigarette by altering smoking frequency, puff volume, or other aspects of smoking topography. However, little is known about a smoker's decision to smoke a specific cigarette, and the concurrent changes in their blood nicotine. Manipulation of nicotine levels in the blood could play a critical role in smoking maintenance, by regulating the extent and quality of the CNS effects of smoking. In this study, 24 heavy and light smokers (cotinine above or below 260 ng/ml) smoked high- (1.0 mg) or low- (0.5 mg) dose nicotine cigarettes while watching non-stressful movies. Blood nicotine was assessed before and after smoking a preload and free operant cigarette. The results showed that blood nicotine levels after smoking the free operant cigarette were significantly more consistent (lower standard error) for the heavy smokers, following a low dose, as opposed to a high-dose preload. Light smokers showed a non-significant trend towards being more consistent when the high-dose nicotine preload was used. This suggests that heavy smokers may have maximized their dose of nicotine whenever available nicotine was in relatively short supply (low dose condition). However, light smokers may have minimized their exposure when available nicotine was relatively more plentiful (high dose condition).

Relative sensitivity and specificity of salivary and serum cotinine in identifying tobacco-smoking status of self-reported nonsmokers and smokers of tobacco and/or marijuana.

Serum and salivary cotinine levels were measured in 327 smoking and nonsmoking participants in a study of the health effects of marijuana with and without tobacco. These individuals had no reason to misrepresent their current tobacco-smoking status. The sensitivity, specificity, and predictive values positive and negative of the cotinine levels in distinguishing self-reported current tobacco smokers from nonsmokers was high (88-100%) and essentially the same for both fluids. Agreement between self-report and cotinine levels was not influenced by the presence or absence of marijuana smoking. A good correlation was found between serum and salivary cotinine levels in self-reported tobacco smokers (r = 0.84, p less than 0.001). Mean average levels were 279 +/- 144 ( +/- standard deviation) ng/ml for serum and 360 +/- 195 ng/ml for saliva. In a separate group of seven tobacco smokers, cotinine levels in saliva were found to be essentially independent of salivary flow rate. An analogous relationship has been observed by others for various compounds that are filtered to saliva from the blood. This may explain the close relationship observed between serum and salivary cotinine levels, and the observation made by others that the half-life of salivary cotinine is similar to that of serum cotinine.

A radioimmunoassay for the teleocidins using 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2 as hapten.

A teleocidin A-2 derivative, 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2, induced ornithine decarboxylase in mouse skin and inhibited the specific binding of [3H]12-O-tetradecanoyl-phorbol-13-acetate to a mouse skin particulate fraction with a potency that was weaker than that of teleocidin A-2 and stronger than that of (-)-indolactam-V. To obtain antibodies, 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2 was covalently linked to bovine albumin with a carbodiimide and the resulting conjugate used for immunization of rabbits. Antibodies directed toward teleocidin were produced as measured by neutralization of teleocidin's capacity to stimulate arachidonic acid metabolism in rat liver cells (the C-9 cell line). An 125I-labeled ligand was prepared by reaction of the same derivative with radiolabeled Bolton-Hunter reagent. The antibodies bound this radiolabeled hapten, and the binding increased progressively with repeated immunizations. After absorption of the rabbit IgG with a goat anti-rabbit IgG, binding was reduced greater than 95%. The binding of the 125I-labeled ligand to the antibodies of one rabbit had an apparent average association constant of 2.84 x 10(9) M-1 at 0 degrees C. The serologic specificity of the antiserum was characterized by measuring the inhibition of binding by several teleocidins of varying structure as well as by other tumor promoters and toxins. The rank order of inhibitory activity expressed as concentration required for 50% inhibition (IC50) was for 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2'(0.56 pmol) greater than teleocidin A-1 (6.5 pmol) greater than or equal to teleocidin A-2 (7.3 pmol) greater than (-)-indolactam-V (3.7 nmol) greater than teleocidin B-4 (13 nmol). Maitotoxin, aplysiatoxin, palytoxin, mezerein, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate did not inhibit at the levels tested.

Decreased serum cotinine levels in smokers of both tobacco and marijuana as compared with smokers of tobacco only.

Serum and salivary cotinine levels were determined in tobacco smokers (n = 125) who smoked only tobacco (n = 47) or who smoked both marijuana and tobacco (n = 78) as part of a field study of the pulmonary effects of heavy, habitual use of marijuana alone or with tobacco. After adjustment for current daily amount of tobacco use and time since the last tobacco cigarette was smoked, the smokers of both marijuana and tobacco were found to have lower levels of cotinine than those who smoked only tobacco, in serum [258 +/- 113 ng/ml (S.D.) and 332 +/- 109, respectively; p = 0.003] and in saliva (331 +/- 170 and 395 +/- 170, respectively; p = 0.058). Serum cotinine showed a significantly negative relationship to the daily amount of marijuana currently smoked (p = 0.026). Possible explanations include inhibition by marijuana component(s) of the enzymes that participate in the conversion of nicotine to cotinine, differences in nicotine absorption patterns between the two groups of tobacco smokers, and acceleration of cotinine metabolism by marijuana smoking. Carefully controlled pharmacokinetic studies, not possible in a large-scale survey such as this one, are required both to confirm the differences in blood cotinine levels observed between the dual smokers and smokers of tobacco only and to define more clearly nicotine-marijuana interactions.

The effect of nicotine on the delay of gastric emptying.

The effect of cigarette smoking and its active component, nicotine, on the gastric emptying of solid food was assessed in a randomized double-blind crossover design. Ten regular smokers were studied after a 6 h fast and least 18 h after their last cigarette. Subjects smoked a total of three high (1.91 mg) or low (0.17 mg) nicotine cigarettes, before and after a technetium-labelled solid meal and were scanned by gamma camera periodically over a 2-h period. All calculations of gastric emptying revealed a significant delay after smoking high versus low nicotine cigarettes in: mean per cent isotope remaining in the stomach at each measurement point from 90-120 min; amount of meal remaining in the stomach at 2 h; and mean time at which 50% of the meal had emptied (T1/2). Delay in gastric emptying was significantly correlated with increase in serum nicotine concentration on the high nicotine day.