Pets at birth do not increase allergic disease in at-risk children.

BACKGROUND: The literature is contradictory concerning pet exposure and risk of allergic disease in childhood especially among those with a family history of allergy. OBJECTIVE: To investigate the relationship between cat and dog exposure at birth and allergic outcomes over the first 12 years in a birth cohort selected for familial allergy. METHODS: A prospective birth cohort of 620 infants with a family history of allergic diseases was recruited. Data on pet keeping, family demographics and cord blood samples were collected at birth. Information on childhood wheeze, eczema and hay fever was collected 18 times in the first 2 years, at 7 years and at 12 years. Skin prick tests were conducted at 2, 7 and 12 years, and in parents. Regression analyses were used to investigate the relevant associations while adjusting for potential confounders. RESULTS: Exposure to cats or dogs at birth showed a moderate reduction in risk of wheeze (aOR = 0.76; 95% CI 0.53, 1.09) and hay fever (aOR = 0.71; 0.49, 1.02) after 7 years of age. Protective effects were stronger in children of non-sensitized fathers (aOR wheeze 0.55; 0.31, 0.98; aOR hay fever 0.33; 0.15, 0.77 on exposure to cats alone, or cats or dogs at birth). Pet keeping was not related to cord blood IgE or sensitization from 2 to 12 years. CONCLUSIONS AND CLINICAL RELEVANCE: Pets at birth either decreased or had no effect on allergic disease up to age 12. We found no evidence that exposure to cats or dogs at birth increases the risk of allergic disease in high-risk children.

Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial.

BACKGROUND: Probiotic supplementation in early life may be effective for preventing eczema. Previous studies have suggested that prenatal administration may be particularly important for beneficial effects. OBJECTIVE: We examined whether prenatal treatment with the probiotic Lactobacillus rhamnosus GG (LGG) can influence the risk of eczema during infancy. METHODS: We recruited 250 pregnant women carrying infants at high risk of allergic disease to a randomized controlled trial of probiotic supplementation (LGG 1.8 × 10(10) cfu/day) from 36 weeks gestation until delivery. Infants were assessed during their first year for eczema or allergic sensitization. Immunological investigations were performed in a subgroup. Umbilical cord blood was examined for dendritic cell and regulatory T cell numbers and production of TGFß, IL-10, IL-12, IL-13, IFN-γ and TNFα. Maternal breast milk was examined for total IgA, soluble CD14 and TGFß. RESULTS: Prenatal probiotic treatment was not associated with reduced risk of eczema (34% probiotic, 39% placebo; RR 0.88; 95% CI 0.63, 1.22) or IgE-associated eczema (18% probiotic, 19% placebo; RR 0.94; 95% CI 0.53, 1.68). Prenatal probiotic treatment was not associated with any change in cord blood immune markers, but was associated with decreased breast milk soluble CD14 and IgA levels. CONCLUSIONS: Prenatal treatment with Lactobacillus rhamnosus GG was not sufficient for preventing eczema. If probiotics are effective for preventing eczema, then a postnatal component to treatment or possibly an alternative probiotic strain is necessary.

Cholesterol screening in a community health promotion program: epidemiologic results from a biracial population.

The prevalence and interrelationship of high blood cholesterol levels with other cardiovascular disease risk factors were studied in a biracial suburb of New York City. Participants in community-based screenings to determine blood cholesterol levels have been predominantly white women in older age groups, highly educated and nonsmokers. To reach a more representative segment of a local population and promote healthy lifestyle behaviors, cholesterol screenings were conducted within an ongoing health promotion program in Mount Vernon, NY. Plasma cholesterol levels were determined for 5,011 participants, including 2,308 whites and 1,778 blacks. Of the men, 29 percent had high cholesterol levels; among women, it was 27 percent. Of the men with high levels, half had levels greater than 200 milligrams per deciliter, as did 55 percent of the women. After statistical adjustments were made for age and other risk factors for high blood cholesterol, mean cholesterol levels were higher for whites than blacks. The level for white men was 204 milligrams per deciliter; for women, 212. For black men, the level was 199 milligrams per deciliter; for women, 208, P < .10. Hispanic men had levels of 199, P < .10. The levels for Hispanic women (203 milligrams per deciliter) were significantly lower than that of white women. Among whites who smoked more than 1 pack of cigarettes per day, mean cholesterol levels were 11 milligrams per deciliter higher than for those who never smoked or were light smokers (0, 1-20 cigarettes per day, P < .10). There were too few who smoked more than 1 pack to test this association adequately among blacks. The mean cholesterol levels for hypertensive black men were 10 milligrams per deciliter greater than for black men with normal blood pressure (P<.10).

Nicotine and cotinine in the cervical mucus of smokers, passive smokers, and nonsmokers.

Although epidemiological studies suggest that cigarette smoking is a risk factor for cervical cancer, further evidence is required to document the biological plausibility of this relationship. This study obtained cervical mucus, using a cervical flush technique, from 50 patients in a neoplasia clinic. Nicotine was detected in the cervical mucus of all 25 smokers and cotinine in the mucus of 84% of the smokers; nicotine and cotinine levels were correlated (P < or = 0.10) with both the number of cigarettes usually smoked and the number smoked in the last 24 h. Nicotine and cotinine levels for passive smokers and nonexposed women were much lower than for women who currently smoked, with little difference found between the nonsmoking women who did and did not report passive smoke exposure. In the one woman who reported smokeless tobacco use, both nicotine and cotinine were detected at much higher levels than for other nonsmoking women. These results indicate that tobacco constituents do indeed reach the uterine cervix, suggesting that they could play a causal role in the development of cervical cancer.

Biochemical validation of self-reported exposure to environmental tobacco smoke.

Biochemical validation of reported exposure to environmental tobacco smoke (ETS) lends credibility to epidemiological studies investigating the association of passive inhalation of smoke to respiratory disease or lung cancer. In the current study, a series of questions regarding ETS exposure was self-administered to nonsmokers and self-reported intensity of exposure was compared with cotinine levels in urine samples obtained on site. The target population of this study was a group of municipal workers who reported exposure in a domestic setting and/or in the workplace. When asked if they were exposed to ETS on social occasions, both males and females who responded positively had higher urinary cotinine levels (P less than 0.02) than those who gave a negative response. Mean urinary cotinine concentrations were found to be elevated in both men and women who reported that they lived with a smoker. Cotinine levels in the urine of those reporting exposure were over twice as high as those in the urine of respondents who denied having been exposed. ETS exposure in the home was the greatest contributor to increased urinary cotinine levels in both men and women. Among individuals who were exposed at work only, the reported degree of exposure agreed well with the mean urinary cotinine values. Those findings emphasize that the validation of exposure status with a biomarker is an essential prerequisite for epidemiological studies investigating passive smoking.

The delivery and uptake of nicotine from an aerosol rod.

Nicotine aerosol rods were assessed for their possible usefulness as substitutes for cigarettes. Under standard FTC conditions, the per puff delivery of the aerosol rod averaged 0.3 micrograms nicotine/puff after 10 puffs and 6.4 micrograms nicotine/puff after 60 puffs. After puffing on the rods, no nicotine was detected in the plasma or urine of seven subjects.

Short-term studies on the in vivo metabolism of N-oxides of nicotine in rats.

This study was designed to examine the in vivo reduction of the N-oxidation products of nicotine metabolism in rats. Male Fischer-344 rats were divided into one control and three experimental groups (n = 20). Each treatment group received either 0.02% trans-nicotine N'-oxide, 0.02% cis-nicotine N'-oxide, or 0.02% nicotine N,N'-dioxide in drinking water for 3 wk. After 7 d of metabolite administration, plasma nicotine levels in the trans-nicotine N'-oxide group rose to twice that of the cis-nicotine N'-oxide or nicotine N,N'-dioxide group. Plasma cotinine [1-methyl-5-(3-pyridinyl)-2-pyrrolidinone] concentrations reached maximum levels during wk 1 in the cis-nicotine N'-oxide and nicotine N,N'-dioxide groups but continued to increase for another 7 d in the trans-nicotine N'-oxide group. At d 15 and again at d 21, rats from each group (n = 10) were placed in metabolism chambers and given 50 ml tap water over a 24-h period. Analysis of urine obtained from a metabolism-chamber study conducted after 15 d of consumption revealed concentrations of nicotine in the trans-nicotine N'-oxide group that were 3 times higher than cis-nicotine N'-oxide-treated animals. Urinary cotinine levels were similar in all three groups. Results from a second chamber study (d 21) showed similar urinary nicotine and cotinine values in all treatment groups. Plasma total triiodothyronine (TT3) concentrations were reduced in all treatment groups during the first week. Plasma total thyronine (TT4) concentrations were reduced (p less than 0.05) in the trans-nicotine N'-oxide and cis-nicotine N'-oxide treatment groups during the first week. Plasma total thyronine (TT4) concentrations cis-nicotine N'-oxide is presented. An analytical method for separation of nicotine, cotinine, and cis- and trans-nicotine N'-oxide, as well as cis- and trans-nicotine N,N'-dioxide, is also outlined.

Thyroid hormone concentrations in rats after chronic nicotine metabolite administration.

In an attempt to evaluate the observed relationship of chronic cigarette smoking and reduced thyroid hormone activity, the major urinary metabolites of nicotine were administered to rats for 78 weeks. The animals were divided equally into one control (n = 33) and three treatment groups. Treatment group 1 received 0.1% (w/v continine, group 2 received 0.02% pure trans-nicotine-N'-oxide, and group 3 received 0.02% of a trans/cis mixture (64/36%) of nicotine-N'-oxide. Plasma and urinary nicotine and cotinine concentrations were determined as well as a variety of thyroid hormone parameters. Pure trans-nicotine-N'-oxide was more extensively metabolized to its cotinine end product, relative to the diasteromeric N'-oxides, mixture. Serum triiodothyronine (T3) was markedly reduced in animals receiving nicotine-N'-oxides, but was not different in the cotinine treatment group when compared to control values. A reduction in serum thyroxine (T4) values was noted only among those rats receiving the pure trans-nicotine-N'-oxide. The T3/T4 ratio, free T3 index, T3 uptake, and rT3 were altered in animals receiving nicotine-N'-oxides. These findings indicate that specific nicotine metabolites alter thyroid hormone concentrations after chronic low-dose administration and possibly do so through back conversion to the parent compound, nicotine.

Cigarette smoking as a risk for cardiovascular disease V: Biochemical parameters with increased and decreased nicotine content cigarettes.

Cigarette smokers were assessed for customary smoking behavior and then were assigned a cigarette which was 0.4 mg higher or lower in nicotine and after 4 weeks, were returned to their customary brand. Biochemical indices of smoking behavior including blood carboxyhemoglobin (COHb), plasma nicotine, cotinine and thiocyanate (-SCN) were measured every 2 weeks. When nicotine availability was increased, smokers received an increased nicotine bolus per puff as determined by plasma nicotine and did not alter smoking topography or cigarettes per day. Over the 4 weeks, plasma cotinine increased without corresponding increases in COHb and -SCN. The return to standard brand resulted in declining cotinine levels but increasing COHb and -SCN, suggesting altered inhalation patterns. In smokers switched to a low yield cigarette, there was a decrease in the nicotine obtained per cigarette followed by a steady rise in plasma cotinine, -SCN and blood COHb over the 4-week period. A positive correlation was observed between cotinine and the gas phase constituents during the change to lower yield and back to standard brand cigarettes. These results indicate that cigarette smokers compensate for decreased nicotine yield with concomitant increases in gas phase components. In addition, increased nicotine availability results in an increased body burden of nicotine and "tar," but not gas phase constituents. The relative risks of cardiovascular disease under these two situations, which increase exposure to nicotine or gas phase components, deserve careful consideration.

Validation of self-reported smoking behavior: biochemical analyses of cotinine and thiocyanate.

Biochemical determinations of plasma and salivary cotinine and thiocyanate were used to differentiate smokers from non-smokers and to follow daily smoking patterns in smokers. Results indicate that cotinine is better suited than thiocyanate to determine smoking status in large scale epidemiologic studies and to follow alterations in smoking behavior over periods of time. Salivary cotinine is a reliable alternative to plasma for validation of smoking status and for following changes in daily smoking patterns.

Cigarette smoking as a risk for cardiovascular disease III: Biochemical effects with higher nicotine yield cigarettes.

Subjects who smoked a medium range nicotine yield cigarette were given a higher nicotine yield cigarette (an increase of 0.34 mg nicotine) to smoke ad libitum for two weeks. Plasma nicotine, cotinine, thiocyanate and blood carboxyhemoglobin levels were determined as well as various physiological parameters including heart rate and blood pressure. Increases in plasma nicotine were most directly correlated to heart rate when smokers were first challenged with a higher nicotine yield cigarette (r = 0.85); less directly correlated after a two-week acclimatization period (r = 0.42) and poorly related to their customary product (r = 0.23). Interestingly, it was noted that subjects did not compensate for higher nicotine yield by smoking fewer cigarettes per day when incremental nicotine changes were realistic. They did, however, show higher plasma nicotine, thiocyanate and an upward trend in plasma cotinine with the stronger cigarettes. These increases in cigarette constituents present in plasma, coupled with increasing correlation of heart rate and nicotine uptake, lead us to suggest that uptitration of smokers might cause them to establish new baseline levels. These findings have important health implications in light of recent suggestions to increase the nicotine yet decrease the tar of cigarettes in an attempt to overcome smoker compensation phenomena observed with low yield products.