Environmental Tobacco Smoke Groups Research Articles

Effect of environmental tobacco smoke on COX-2 and SHP-2 expression in a periodontitis rat model.

ObjectivesTo investigate the effects of environmental tobacco smoke (ETS) on the inflammatory process of periodontitis by evaluating bone loss and the expression of cyclooxygenase‐2 (COX‐2) and Src homology phosphotyrosine phosphatase 2 (SHP‐2).Materials and MethodsEighty 6‐month‐old male SD rats were randomized into four groups (10 rats/group/per time point): (a) normal group, (b) ETS group, (c) ligature‐induced periodontitis group, and (d) ligature‐induced periodontitis + ETS group. After treatment with ligature and/or ETS for 8 and 12 weeks, the levels of alveolar bone resorption and the expressions of COX‐2 and SHP‐2 in periodontal tissue were analyzed using histology and immunohistochemistry.ResultsThe ligature‐induced periodontitis group displayed increased bone resorption and elevated expression of COX‐2 and SHP‐2 in periodontal tissues compared to the normal and ETS groups at 8 and 12 weeks. Furthermore, bone resorption and COX‐2 and SHP‐2 levels in the ligature‐induced periodontitis + ETS group were significantly increased compared to those in the normal and ligature‐induced periodontitis groups at both 8 and 12 weeks.ConclusionEnvironmental tobacco smoke increased alveolar bone loss in periodontitis with enhanced expression of COX‐2 and SHP‐2 in periodontal tissues. Further investigation is needed to explore the role of COX‐2 and SHP‐2 in ETS‐associated periodontitis.

Effect of Passive Smoke Exposure on General Anesthesia for Pediatric Dental Patients

The purpose of this study was to test the null hypothesis that children with environmental tobacco smoke (ETS) exposure (also known as passive smoke exposure) do not demonstrate an increased likelihood of adverse respiratory events during or while recovering from general anesthesia administered for treatment of early childhood caries. Parents of children (ages 19 months-12 years) preparing to receive general anesthesia for the purpose of dental restorative procedures were interviewed regarding the child's risk for ETS. Children were observed during and after the procedure by a standardized dentist anesthesiologist and postanesthesia care unit nurse who independently recorded severity of 6 types of adverse respiratory events-coughing, laryngospasm, bronchospasm, breath holding, hypersecretion, and airway obstruction. Data from 99 children were analyzed. The children for whom ETS was reported were significantly older than their ETS-free counterparts (P = .03). If the primary caregiver smoked, there was a significantly higher incidence of smoking by other members of the family (P < .0001) as well as smoking in the house (P < .0005). There were no significant differences between the adverse respiratory outcomes of the ETS (+) and ETS (-) groups. The ETS (+) children did have significantly longer recovery times (P < .0001) despite not having significantly more dental caries (P = .38) or longer procedure times. ETS is a poor indicator of post-general anesthesia respiratory morbidity in children being treated for early childhood caries.

Abstracts of UKEMS/Dutch EMS-Sponsored Workshop on Biomarkers of Exposure and Oxidative DNA Damage and 7th GUM 32P-Postlabelling Workshop. Munster, Germany. March 28-29, 2011

Portuguese legislation prohibits smoking in most indoor public spaces. However, some restaurants/bars remain, in which smoking is still allowed, representing a potential risk for employees, particularly for chronic respiratory diseases and cancer development. The objectives of this project were to compare the indoor air quality of some restaurants with and without smoking permission and, in their workers, to search for associations between respiratory dysfunctions and biomarkers of exposure, biological effects (DNA and proteome alterations) and susceptibility. Herein, we present data on DNA damage and genetic susceptibility in 37 workers occupationally exposed to environmental tobacco smoke (ETS) and from 44 non-exposed workers. DNA damage was assessed by the comet assay in blood leukocytes and by micronucleus (MN) analysis in buccal cells. DNA repair capacity was evaluated by a challenge of blood cells with EMS (32 μM), preceding the comet assay. Polymorphisms in metabolism (GSTP1, GSTM and GSTT) and DNA-repair genes (hOGG1,XRCC1, XRCC3, and NBS1) were analysed by PCR/RFLP. No significant differences in the MN frequency and in level of DNA damage was observed between ETS and non-ETS groups. However, challenge with EMS resulted in a significantly lower level of DNA breaks in ETS-exposed as compared to non-exposed workers (P<0.0001). Concerning polymorphisms analysis, GSTP1 variant allele carriers showed a decreased frequency of MN in buccal cells, which was not influenced by ETS exposure. No association related to the other polymorphisms was detected. In conclusion, the present data show that blood cells from ETS-exposed workers display a lower mutagenic response to EMS challenge, suggestive of an adaptive response elicited by the previous exposure to low levels of ETS.

Using blood pressure telemetry to assess acute changes in arterial stiffness in rats after nitric oxide synthase inhibition or environmental tobacco smoke exposure

Although environmental tobacco smoke (ETS) exposure has been reported to acutely increase arterial stiffness in humans, understanding of the underlying mechanisms is unclear and few studies have measured these effects in experimental animals. One potential mechanism for the increased arterial stiffness is reduced nitric oxide (NO) bioactivity as a result of oxidative stress. Thus, the objective of this study was to determine whether acute changes in arterial stiffness could be detected using arterial pulse wave dP/dt in blood pressure telemetry implanted rats and to investigate the role of NO in regulating dP/dt. Intravenous injection of acetylcholine (0.91 ng/kg) decreased and norepinephrine (0.02 mg/kg) increased dP/dt compared to saline vehicle (0.5 mL/kg). Injection of the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg) decreased plasma nitrate/nitrite (NOx), but transiently increased dP/dt. ETS at low and high doses had no effect on dP/dt, but increased plasma NOx levels at high ETS exposure and increased plasma nitrotyrosine levels in both ETS groups. In conclusion, acute changes in NO production via acetylcholine or L-NAME alter the arterial pulse wave dP/dt consistently with the predicted changes in arterial stiffness. Although acute ETS appears to biologically inactivate NO, a concomitant increase in NO production at high ETS exposure may explain why dP/dt was not acutely altered by ETS in the current study.

In Utero and Postnatal Exposure to Environmental Tobacco Smoke (ETS) Alters Alveolar and Respiratory Bronchiole (RB) Growth and Development in Infant Monkeys

The direct effect of environmental tobacco smoke (ETS) exposure in utero on the development of the lung parenchyma is not known. We used design-based stereologic methods to evaluate in utero and postnatal ETS exposure on alveolar and respiratory bronchiole (RB) development in the rhesus macaque. Timed-pregnant rhesus macaques and their offspring were exposed to filtered air or various amounts of ETS during the prenatal and postnatal period. The left cranial lobe from necropsied infants was evaluated by design-based stereological methods and general pathological review. Infants in the in utero and six-month ETS groups had an 18% and 17% relative decrease, respectively, in alveolar number and a 57% and 33% increase, respectively, in alveolar size compared to filtered air (FA) monkeys. Lung volume positively correlated with alveolar number in the FA and six-month ETS group and negatively correlated in the in utero ETS group. The distribution of alveolar size was much more variable in the in utero group. Overall, RB volume was significantly increased in the six-month ETS group (p < .04). Taken together, these results indicate that in utero and postnatal ETS exposure is associated with altered parenchymal lung development.

Secondhand Smoke Induces Allergic Sensitization in Mice

Purpose of the Study. Although there is evidence that environmental tobacco smoke (ETS) can exacerbate allergic responses, the role of ETS in primary allergic sensitization remains unclear. The objective of this study was to examine the influence of ETS on allergic sensitization in a mouse model.Study Population. Female BALB/c and C57BL/6 mice.Methods. The investigators exposed mice to either ovalbumin (OVA), saline, ETS, or OVA + ETS by nebulization. Total IgE and OVA-specific immunoglobulin E (IgE), IgG1 and IgG2a were quantified for each of the 4 exposure groups. Mice were reexposed to nebulized OVA 30 days after the initial exposure and cytokine levels in bronchoalveolar lavage (BAL) fluid were measured. Interleukin (IL)-2, IL-4, IL-5, IFN-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured to look for evidence of Th1 or Th2 skewed immune responses. Two strains of mice were studied, BALB/c, a high IgE producer, and C57BL/6, a low IgE producer.Results. An allergic antibody response, as measured by total IgE and OVA-specific IgE and IgG1, was present in C57BL/6 mice exposed to OVA + ETS, but was not detectable in those exposed to saline, OVA alone, or ETS alone. The results were statistically significant. The allergic antibody response in the BALB/c mice was also most pronounced in the group exposed to OVA + ETS. As this strain more readily produces IgE, there was detectable total IgE as well as OVA-specific IgE and IgG1 in the group exposed to OVA alone, but levels of OVA-specific IgE and IgG1 were statistically significantly higher in the OVA + ETS group. BAL fluid was examined for eosinophilia after rechallenge with OVA in C57BL/6 mice. The OVA + ETS group had marked eosonophilia while the saline, OVA and ETS groups had no eosinophils. Cytokines were also quantified in BAL fluid. IFN-γ, a Th1-associated cytokine, was decreased in OVA + ETS mice as compared with the OVA-exposed group (P < .01), while IL-5, a Th2-associated cytokine, was increased as compared with the OVA-exposed group (P < .05).Conclusion. ETS exposure appears to facilitate the primary allergic response in mice as measured by allergic antibody response and BAL cytokine response and eosinophilia.Reviewers’ Comments. Although some evidence has been published regarding ETS and its role in exacerbating allergic responses, this is the first study demonstrating a significant role for ETS in primary allergic sensitization in mice. Future studies will no doubt address the applicability of these findings to humans.

Perinatal exposure to environmental tobacco smoke induces adenylyl cyclase and alters receptor-mediated cell signaling in brain and heart of neonatal rats

Perinatal exposure to environmental tobacco smoke (ETS) has adverse effects on neurobehavioral development. In the current study, rats were exposed to ETS during gestation, during the early neonatal period, or both. Brains and hearts were examined for alterations in adenylyl cyclase (AC) activity and for changes in β-adrenergic and m2-muscarinic cholinergic receptors and their linkage to AC. ETS exposure elicited induction of total AC activity as monitored with the direct enzymatic stimulant, forskolin. In the brain, the specific coupling of β-adrenergic receptors to AC was inhibited in the ETS groups, despite a normal complement of β-receptor binding sites. In the heart, ETS evoked a decrease in m2-receptor expression. In both tissues, the effects of postnatal ETS, mimicking passive smoking, were equivalent to (AC) or greater than (m2-receptors) those seen with prenatal ETS mimicking active smoking; the effects of combined prenatal and postnatal exposure were equivalent to those seen with postnatal exposure alone. These data indicate that ETS exposure evokes changes in cell signaling that recapitulate those caused by developmental nicotine treatment. Since alterations in AC signaling are known to affect cardiorespiratory function, the present results provide a mechanistic link reinforcing the participation of ETS exposure, including postnatal ETS, in disturbances culminating in events like Sudden Infant Death Syndrome.

L-Arginine decreases infarct size in rats exposed to environmental tobacco smoke

This study examined the effects of l-arginine on myocardial infarct size, hemodynamics, and vascular reactivity in environmental tobacco smoke (ETS)-exposed and non—ETS-exposed rats. We previously demonstrated that exposure to ETS increased myocardial infarct size in a rat model of ischemia and reperfusion. If reduced reperfusion was caused by endothelial cell damage and increased vascular tone, l-arginine (ARG) would increase nitric oxide and better protect the heart. Sixty Sprague-Dawley rats were randomly divided into four groups: ETS or non-ETS (control) with and without ARG (2.25% ARG in drinking water). The ETS groups were exposed to passive smoking (4 Marlboro cigarettes per 15 minutes, 6 hours a day) for 6 weeks. After 6 weeks, all rats were subjected to 35 minutes of left coronary artery occlusion and 120 minutes of reperfusion, with hemodynamic monitoring. Aortic rings were harvested to evaluate vascular reactivity. Average air nicotine, carbon monoxide, and total particulate concentrations were 1304 ± 215 μg/m 3, 78 ± 2.0 ppm, and 31 ± .7 mg/m 3 (mean ± SEM) for the ETS-exposed rats. Infarct size (infarct mass/risk area × 100%) increased with ETS exposure but decreased significantly in the ETS-with-ARG group compared with the ETS-without-ARG group (42% ± 6% vs 64% ± 6%, mean ± SEM; p = 0.043). The benefit of ARG was dependent on ETS exposure (ETS × ARG interaction, p = 0.043). There were no significant differences between groups in heart rate, systolic pressure, and rate-pressure product. ARG significantly decreased myocardial infarct size after ischemia and reperfusion in ETS-exposed rats. Neither the adverse effects of ETS on infarct size nor the blockage of this effect by ARG appears to be the result of ETS-induced alterations in hemodynamics.

972-107 L-Arginine Decreases Infarct Size in Rats Exposed to Environmental Tobacco Smoke

We previously showed that environmental tobacco smoke (ETS) increased myocardial infarct size in a rat model of ischemia and reperfusion. If reduced reperfusion was caused by endothelial cell damage and increased vascular tone, we postulated that L-arginine (ARG) would increase nitric oxide and better protect the heart. 60 rats were randomly divided into 4 groups: ETS or Control (C) with and without ARG (2.25% ARG in drinking water). The ETS groups were exposed (4 Marlboro cigarettes per 15 minutes. 6 hours a day) for 6 weeks. During ETS-exposure, average air nicotine, carbon monoxide and total particulate concentrations were 1304 μg/m 3 , 78 ppm and 31 mg/m 3 , respectively. After 6 weeks, all rats were subjected to 35 min LAD occlusion (0) and 120 min reperfusion, with hemodynamic monitoring via the carotid artery. Aortic rings were harvested to evaluate vascular reactivity. Infarct size (infarct mass/risk area x 100%) decreased significantly in the ETS with ARG group compared to the ETS without ARG group. There were no significant differences among groups in heart rate (HR), systolic pressure (SP), and rate pressure product. Tlere were positive correlations between infarct size and heart rates from baseline to reperfusion 120 min (r = 0.4-0.6. p = 0.01-0.001). There was no relationship between vascular reactivity and infarct size. Group No. of Rats Inf/LV (%) Inf/RA (%) 0-35’HR (beats/m) 0-35'SP (mmHg) Max Relax (%) C 11 25 ± 3 51 ± 6 408 ± 11 120 ± 7 84 ± 11 C+ ARG 10 25 ± 2 52 ± 3 415 ± 10 103 ± 11 112 ± 15 ETS 10 34 ± 4 64 ± 6 427 ± 16 108 ± 8 128 ± 16 ETS + ARG 11 22 ± 3 * 42 ± 6 * 410 ± 17 106 ± 10 127 ± 18 Values are Means ± SEM * p &lt; 0.05, p values from two-way ANOVA L-arginine decreases myocardial infarct size after ischemia and reperfusion in ETS-exposed rats. This effect does not appear to be secondary to alterations in hemodynamics.

Environmental tobacco smoke, low birth weight, and hospitalization for respiratory disease.

The author examined the effect of exposure to environmental tobacco smoke (ETS) on hospitalization for respiratory illness in low-birth-weight (LBW, less than 2,500 g) infants. This analysis was performed on the combined data of 3,285 infants from the Jing-An and Chang-Ning epidemiologic studies of children's health in Shanghai. Infants were classified into three ETS groups according to the total number of cigarettes smoked daily by household members: none, light (one to 19 cigarettes/d) and heavy (20+ cigarettes/d). There were no mothers who were smokers. Infants might have been hospitalized more than once during their first 18 mo of life. Risk and incidence density of hospitalization for respiratory disease increased with increasing smoking by household members among the LBW infants more rapidly than among the normal-birth-weight (NBW) infants. Compared with the NBW infants who were living in nonsmoking households, the odds ratios for the first episode of hospitalization for respiratory disease were 1.40 in the NBW infants who were living in light smoking households and 1.61 in those who were living in heavy smoking households. In the LBW infants, the odds ratios were 2.91 and 4.48 in light and heavy smoking households respectively, after adjustment for study area, sex, and feeding by simple logistic regression analysis. Ordinal logistic regression analysis for all episodes of respiratory hospitalization showed similar results.

Metoprolol does not attenuate atherosclerosis in lipid-fed rabbits exposed to environmental tobacco smoke.

We previously demonstrated that exposure to environmental tobacco smoke (ETS) increases the development of atherosclerosis in lipid-fed rabbits. Clinical studies have suggested a protective effect of beta-blockers in smokers. Accordingly, we evaluated the effects of metoprolol in this animal model to see whether this beta-blocker would block the atherogenic effects of ETS. Thirty-two New Zealand White male rabbits on a 0.3% cholesterol diet were randomly divided into four groups: ETS-metoprolol (ETS-M), ETS-control (ETS-C), and non-ETS with metoprolol (NETS-M) and without metoprolol (NETS-C). The two metoprolol-treated groups received metoprolol at a dose of 0.4 mg.kg-1.h-1 administered subcutaneously by an osmotic pump. Rabbits in the ETS groups were exposed to sidestream smoke from four Marlboro cigarettes per 15 minutes, 6 hours a day, for 10 weeks. Average air carbon monoxide (CO), nicotine, and total particulates (TP) in the exposure chambers were 67.2 +/- 3.1 (SEM) ppm, 1133.7 +/- 78.4 micrograms/m3, and 37.7 +/- 3.0 mg/m3, respectively. Plasma nicotine was significantly higher in ETS-exposed rabbits than in nonexposed rabbits (7.1 +/- 1.9 versus 0.5 +/- 0.1 ng/mL, P < .01). Blood carbon monoxide hemoglobin (COHb) in the ETS-M group was significantly higher than that in the NETS-M group (4.0 +/- 0.2% versus 1.3 +/- 0.1%, P < .0001). The lipid lesions in the aorta and pulmonary artery were 57.2 +/- 7.6% and 33.1 +/- 6.4% (ETS-M), 62.8 +/- 8.4% and 58.4 +/- 6.1% (ETS-C), 38.7 +/- 9.4% and 24.8 +/- 7.7% (NETS-M), and 49.8 +/- 8.7% and 32.7 +/- 7.1% (NETS-C). There were significant differences in lipid deposits of the arteries between the controls and the ETS-exposed rabbits (37 +/- 1% versus 53 +/- 1%, P = .004) and between the controls and metoprolol-treated rabbits (51 +/- 1% versus 38 +/- 1%, P = .027). The benefit of metoprolol was independent of ETS exposure (ETS x metoprolol interaction, P = .595). Exposure to ETS significantly accelerated and metoprolol decreased the development of atherosclerosis in lipid-fed rabbits, but there was no interaction between the effects of ETS exposure and metoprolol. Metoprolol did not protect against the effects of ETS on atherosclerosis, suggesting that the beta-adrenergic system is not the mechanism of ETS-induced atherosclerosis.

Exposure to environmental tobacco smoke increases myocardial infarct size in rats.

Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. In this study, we evaluated the influence of 3 days, 3 weeks, and 6 weeks of ETS exposure on myocardial infarct size in a rat ischemia/reperfusion model. Sprague-Dawley rats exposed to ETS (four Marlboro cigarettes per 15 minutes, 6 hours per day, 5 days per week) for 3 days (n = 24), 3 weeks (n = 21), or 6 weeks (n = 12) and control rats (n = 24, n = 21, and n = 12, respectively) were subjected to 35 minutes of left coronary artery occlusion and 2 hours of reperfusion. Infarct size and risk area were determined by triphenyltetrazolium chloride and phthalocyanine blue staining, respectively. Air nicotine, carbon monoxide, and total particulates were measured during ETS exposure. Serum lipids, plasma carbon monoxide hemoglobin (COHb), nicotine, and cotinine concentrations were measured in additional groups (6 to 13 rats each) exposed to 3 days, 3 weeks, or 6 weeks of ETS and controls. Average air nicotine, carbon monoxide, and total particulate concentrations were 1103 micrograms/m3, 92 ppm, and 60 mg/m3 for the ETS-exposed rats. Infarct size (infarct mass/risk area x 100%) increased significantly in the ETS groups compared with the control groups in a dose-dependent manner (P = .023), with longer exposure associated with larger infarct size. Infarct size nearly doubled with 6 weeks of ETS exposure (61 +/- 5% versus 34 +/- 3% for control, mean +/- SEM). Plasma COHb, nicotine, and cotinine levels increased significantly in the ETS groups in a dose-dependent manner (all P < .001). Exposure to passive smoking increases myocardial infarct size in a rat model of ischemia and reperfusion. This increase of infarct size exhibited a dose-response relation. These results are consistent with epidemiological studies demonstrating that ETS increases the risk of heart death.

Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits

Objectives. We evaluated the influence of passive smoking on experimental atherosclerosis in cholesterol-fed rabbits.Background. Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers.Methods. New Zealand male rabbits were randomly divided into three groups after 2 weeks of a 0.3% cholesterol diet. Sixteen rabbits were exposed to a high and 16 rabbits to a low dose of ETS; 32 rabbits located in another room served as an unexposed control group. After 10 weeks of ETS exposure, all rabbits were killed, and the percent of aortic and pulmonary artery endothelial surfaces covered by lipid lesions was measured by staining and planimetry.Results. Average air nicotine, carbon monoxide and total pariculate concentrations were 1,040 μg/m3, 60.2 ppm and 32.8 mg/m3for the high dose ETS group, 30 μg/m3, 18.8 ppm and 4.0 mg/m3for the low dose ETS group and <1 μg/m3, 3.1 ppm and 0.13 mg/m3for the control group. The percent atherosclerotic involvement of the aorta and pulmonary artery increassd significantly with ETS exposure (for the aorta, 30 ± 19% [mean ± SD] for the control group, 36 ± 14% for the low dose ETS group and 52 ± 11% for the high dose ETS group, p < 0.001; for the pulmonary artery, 22 ± 15% for the control group, 29 ± 25% for the low dose ETS group, and 45 ± 12% for the high dose ETS group, p < 6.031). Bleeding time was significantly shorter in the two ETS groups than in the control group (86 ± 17 vs. 68 ± 15, 68 ± 18 s, p < 0.001). There were no significant differences in serum triglycerides, cholesterol and high density lipoprotein cholesterol at the end of the study.Conclusions. Environmental tobacco smoke affects platelet function and increases aortic and palmonary artery atherosclerosis. This increase of atherosclerosis was independent of changes in serum lipids and exhibited a dose-response relation. These results are consistent with data from epidemiologic studies demonstrating that ETS increases the risk of death due to heart disease.