Inhalation Of Tobacco Smoke Research Articles

Substance abuse and anaesthesia—Part 2

Tobacco and alcohol remain the most abused substances in South Africa and elsewhere in the western world. Tobacco is commonly smoked, but in South Africa it is also “sniffed” as snuff, and if inhaled causes as much damage as inhaled tobacco smoke. There is also a high incidence of related cancer.1 Likewise people exposed passively to tobacco smoke may acquire smoking-related conditions such as coronary artery disease and asthma.2

Tobacco toxicology revisited.

Worldwide, the diseases caused by inhalation of tobacco smoke represent one of the major health problems of our times. Of particular concern are lung cancer, chronic obstructive pulmonary disease and cardiovascular disease. In the Western World aggressive campaigning and education against tobacco use by both private interest groups and government agencies have slowed down, if not decreased, the incidence of lung cancer, the most lethal disease. Nevertheless, there is some concern that teen smoking might reverse this trend (Wingo et al., 1999). In many other countries tobacco smoking continues to be widespread and it is anticipated that in certain regions of the world, particularly in Asia, the toll on public health eventually will amount to millions of people annually (Liu et al., 1998; Pisani et al., 1999).KeywordsTobacco SmokeLung TumorEnvironmental Tobacco SmokeChemopreventive AgentBeclomethasone DipropionateThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Exposure of mice to tobacco smoke attenuates the toxic effect of methamphetamine on dopamine systems

Methamphetamine treatment of mice rapidly and severely depleted levels of dopamine and its metabolites, homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus. Exposure of mice to cigarette smoke by means of nose-only breathing apparatus for 20 min twice daily over 3 days prior to drug treatment significantly attenuated the neurotoxicity of methamphetamine as judged by a lesser depletion of dopamine, DOPAC and HVA. The lesser effect of methamphetamine upon content of serotonin level was unaltered by prior inhalation of smoke. Results suggest a specific protective effect of inhaled tobacco smoke upon the effects of methamphetamine upon dopaminergic circuitry.

Cigarette smoke inhalation stimulates dopaminergic neurons in rats.

In humans, nicotine is self administered by inhalation of tobacco smoke as opposed to animal models, where nicotine is administered via systemic injection. The aim of the present study was to clarify whether tobacco smoke inhalation would affect dopaminergic projections differently from the reported activation after the systemic administration of nicotine. For this purpose, tobacco smoke from cigarettes containing 1.0 or 0.1 mg nicotine was delivered by inhalation to rats, while recording from antidromically identified nigrostriatal and mesolimbic dopamine neurons. Smoke inhalation from 1.0 mg nicotine cigarettes caused a peculiar abrupt increase of discharge activity of mesolimbic dopamine neurons, while nigrostriatal cells were less responsive. This activation was promptly antagonized by mecamylamine (2.0 mg/kg, i.v.). In contrast, smoke delivered from 0.1 mg nicotine cigarettes was ineffective. These findings suggest that the boosting activation of mesolimbic dopamine neurons by inhaled nicotine might be relevant for the rewarding properties of tobacco smoking and also for the effectiveness of new treatments to stop smoking.

The economic impact of smoking in Germany.

Smoking is a high-risk behaviour affecting health and economic welfare of society. Thus it is important to quantify the economic burden smoking places on social institutions in Germany. Approximately 33.4% of the male and 20.4% of the female population are current smokers. This study investigates the health care costs of smoking based on 1996 figures, focusing on the seven most frequent diseases associated with the inhalation of tobacco smoke: chronic obstructive pulmonary disease (COPD, international classification of diseases (ICD) 490-491); lung cancer (ICD 162); stroke (ICD 434-438); coronary artery disease (ICD 410-414); cancer of the mouth and larynx (ICD 140-149, 161) and artherosclerotic occlusive disease (ICD 440). A data search was carried out on MEDLINE, the German Institute for Medical Documentation and Information, and the Internet as well as in databases of health insurance companies and the German Federal institute of statistics. Direct and indirect costs were calculated separately. The results estimate the total smoking related health care costs (attributable fraction due to smoking) for COPD to be 5.471 billion EURO (73%), for lung cancer 2.593 billion EURO (89%), for cancer of the mouth and larynx 0.996 billion EURO (65%), for stroke 1.774 billion EURO (28%), for coronary artery disease 4.963 billion EURO (35%) and for atherosclerotic occlusive disease 0.761 billion EURO (28%). The economic burden of smoking related health care costs for Germany is 16.6 billion EURO. Smoking is therefore responsible for 47% of the overall costs of these diseases (35.2 billion EURO). In the view of the high costs for smoking, of which almost 50% are due to respiratory disease, pneumologists should enhance their effort in primary, secondary and tertiary prevention.

Thromboangiitis Obliterans (Buerger's Disease).

Thromboangiitis obliterans (TAO) is a devastating nonatherosclerotic disease that often leads to digit and limb loss as well as intractable ischemic rest pain. Patients with TAO are uniformly heavy users of tobacco. This disorder is characterized as a miscellaneous form of vasculitis affecting small- and medium-sized arteries and veins. TAO causes painful ischemic ulcers of the digits and unusually painful and inflammatory superficial thrombophlebitis. The key to early diagnosis of TAO is a high clinical index of suspicion in the appropriate patient scenario, exclusion of any other potential cause, abnormal results from an Allen's test, and arteriographic findings of segmental digital arterial occlusions with "corkscrew" collateral vessels. The primary and clearly most effective therapy for TAO is cessation of the use of all tobacco products, with avoidance of any environmental tobacco smoke inhalation. There has been recent enthusiasm for prostaglandin E therapy and the intramuscular injection of angiogenic growth factors. For patients in whom the disease is identified late or for those who are unable to discontinue cigarette smoking, however, a frequent result is multiple limb amputations.

A comparison of the effects of nicotine on dopamine and non-dopamine neurons in the rat ventral tegmental area: an in vitro electrophysiological study

Increased neurotransmission within the mesolimbic dopamine system is considered an essential component for the rewarding and dependence producing properties of nicotine. Nicotinic acetylcholine receptors on dopamine containing neurons in the ventral tegmental area are thought to be a prime target for nicotine’s stimulatory effects. However, there is no evidence regarding the actions of nicotine on ventral tegmental GABAergic interneurons which play an important modulatory role in mesolimbic dopamine neuronal excitability. In the present study we sought to characterize the effects of nicotine on the activity of both dopamine and non-dopamine neurons in the juvenile rat ventral tegmentum. Extracellular recording techniques in rat brain slices and two methods of drug perfusion were used. Nicotine was found to markedly increase the firing rate of both groups, although the dopamine neuronal response pattern was considerably different and more vigorous than that in the non-dopamine neurons. The nicotine-induced excitations were also reversed by mecamylamine. Furthermore, desensitization to nicotine’s stimulatory effects occurred in both neuronal populations, although non-dopamine neurons appeared to desensitize to a greater degree. In fact, the desensitization accompanying sequential uninterrupted applications of nicotine appears to occur at concentrations below that described to produce receptor activation. The low nM concentrations of nicotine used in the present study are comparable to plasma levels of nicotine found after smoking a cigarette or even with passive inhalation of tobacco smoke. Thus, the present results not only confirm that nicotine stimulates the firing rate of ventral tegmental area dopamine neurons, but also that GABAergic neurons may be an important target for nicotine’s central nervous system effects. The less robust response in the non-dopamine presumptive GABAergic population and their more pronounced desensitization could lead to disinhibition of dopamine neurons thereby facilitating a more sustained increase in the response of mesolimbic dopamine neurons to nicotine.

SMOKING AND THE MOLECULAR EPIDEMIOLOGY OF LUNG CANCER

Lung carcinogenesis in humans requires exposure to environmental agents, including the inhalation of tobacco smoke, radioactive compounds, asbestos, heavy metals, and petrochemicals. Tobacco smoking is the risk factor with the highest attributable lung cancer risk worldwide. This article discusses occupational carcinogen exposure and exposure from tobacco use, and the lung-cancer risk associated with these types of exposure.

SMOKING CESSATION: Techniques and Benefits

Tobacco dependency syndrome is an organic disease caused by chronic use of inhaled tobacco smoke. It is occasionally controlled by willpower alone, but often requires pharmacotherapy in conjunction with various techniques to manage the psychological manifestations. The two effective drugs are bupropion, which is an oral antidepressant, and nicotine, which can be administered by several modalities, including a skin patch, an oral inhalant, a nasal spray, and a chewable oral preparation. Successful therapy may require both drugs, and multiple simultaneous nicotine modalities. High-dose nicotine therapy may achieve an abstinence rate of 80% during therapy, but maintaining drug-free abstinence at such high levels over long periods is less successful, possibly because the tobacco smoke-induced changes in brain structure and function are not easily reversed.

Second-hand smoke increases bronchial hyperreactivity and eosinophilia in a murine model of allergic aspergillosis.

Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af) cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS) on a murine model of allergic bronchopulmonary aspergillosis (ABPA). BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-γ indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia.

Formation of N-(2-Hydroxyethyl)valine Due to Exposure to Ethylene Oxide via Tobacco Smoke: A Risk Factor for Onset of Cancer

Human exposure to ethylene oxide (EtO) occurs mainly through inhalation of occupational polluted air and tobacco smoke. EtO is able to react with DNA and proteins producing some molecular adducts. One of these, resulting from reaction between EtO and valine in hemoglobin, is N-(2-hydroxyethyl) valine (HOEtVal). This adduct represents a biological effective dose marker, the level of which correlates linearly with the alkylating activity occurring in DNA. The aim of the present study was to measure HOEtVal in 146 urbanized adult and healthy subjects, nonoccupationally exposed to EtO, and to correlate it with smoke habits. HOEtVal showed a direct positive relationship to tobacco smoke exposure quantified by questionnaire, urinary cotinine (r=0.64509), and the number of cigarettes (r=0.6308) actively or passively smoked. Results relative to HOEtVal and urinary cotinine in adults distinguish well between active and passive smokers but do not allow distinguishment between passive smokers and nonsmokers. Nevertheless, several authors demonstrated a very good capacity of cotinine to discriminate inside groups of adolescents passive smokers. Therefore, the future objective of the present study is a closer inspection of the two biomarkers with respect to passive exposure to tobacco smoke considering a large group of adolescents. Finally, the correlation between urinary cotinine and HOEtVal increases knowledge about early steps of the carcinogenic process due to active exposure to tobacco smoke.

An experimental study of the influences of tobacco smoke on fertility and reproduction.

1. The aim of this study was to evaluate the toxicological influence of tobacco smoke on fertility and reproduction of Wistar female rats. The influence of tobacco smoke from the Polish 'Popularne' cigarette brand was studied. The experiment was conducted on three generations of animals, each generation having two litters. The initial number of animals of the parent generation F0 was 192 (128 females and 64 males). Animals were passively exposed to tobacco smoke in three different concentrations based on the content of carbon monoxide (500, 1000 and 1500 mg of CO per cubic meter of air). Animals were exposed to tobacco smoke for 6 h a day, 5 days a week, during 11 weeks. 2. The analysis of indices of mating and fertility revealed the decrease in those indices with animals exposed to tobacco smoke. We also observed an increased number of mothers breading among animals exposed to tobacco smoke. In animals exposed to tobacco smoke, the dose-effect or dose-response dependencies for mating, fertility and delivery indices were found. There was no influence of tobacco smoke on the duration of pregnancy. 3. Tobacco smoke inhalation caused increased levels of carboxyhaemoglobin. 4. Tobacco smoke did not change the duration of pregnancy in rats.

The effect of cotinine or cigarette smoke co-administration on the formation of O6-methylguanine adducts in the lung and liver of A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, induces lung adenomas in A/J mice, following a single intraperitoneal (i.p.) injection. However, inhalation of tobacco smoke has not induced or promoted tumors in these mice. NNK-induced lung tumorigenesis is thought to involve O6-methylguanine (O6MeG) formation, leading to GC-->AT transitional mispairing and an activation of the K-ras proto-oncogene in the A/J mouse. NNK can be metabolized by several different cytochromes P450, resulting in a number of metabolites. Formation of the promutagenic DNA adduct O6MeG is believed to require metabolic activation of NNK by cytochrome P450-mediated alpha-hydroxylation of the methylene group adjacent to the N-nitroso nitrogen to yield the unstable intermediate, methanediazohydroxide. Nicotine, cotinine (the major metabolite of nicotine), and aqueous cigarette tar extract (ACTE) have all been shown to effectively inhibit metabolic activation of NNK to its mutagenic form, most likely due to competitive inhibition of the cytochrome P450 enzymes involved in alpha-hydroxylation of NNK. The objective of the current study was to monitor the effects of cotinine and cigarette smoke (CS) on the formation of O6MeG in target tissues of mice during the acute phase of NNK treatment. To test the effect of cotinine, mature female A/J mice received a single intraperitoneal injection of NNK (0, 2.5, 5, 7.5, or 10 mumole/mouse) with cotinine administered at a total dose of 50 mumole/mouse in 3 separate i.p. injections, administered 30 min before, immediately after, and 30 min after NNK treatment. To test the effect of whole smoke exposure on NNK-related O6MeG formation, mice were exposed to smoke generated from Kentucky 1R4F reference cigarettes at 0, 0.4, 0.6, or 0.8 mg wet total particulate matter/liter (WTPM/L) for 2 h, with a single i.p. injection of NNK (0, 3.75, or 7.5 mumole/mouse) midway through the exposure. Cigarette smoke alone failed to yield detectable levels of O6MeG. The number of O6MeG adducts following i.p. injection of NNK was significantly (p < 0.05) reduced in both lung and liver by cotinine and by cigarette smoke exposure. Our results demonstrate that NNK-induced O6MeG DNA adducts in A/J mice are significantly reduced when NNK is administered together with either cotinine, the major metabolite of nicotine, or the parental complex mixture, cigarette smoke.

Lung cancer and passive smoking.

The evidence from epidemiological studies, studies of biochemical markers of exposure and toxicological studies, confirm that there is a causal association between the risk of lung cancer and exposure to environmental tobacco smoke. Nonsmokers can inhale and metabolize carcinogens in tobacco smoke and other markers of environmental tobacco smoke inhalation (nicotine and cotinine) are raised in nonsmokers exposed to environmental tobacco smoke. In epidemiological studies of women who are lifelong nonsmokers, there is a statistically significant excess risk of lung cancer (24%, 95% confidence interval 13-36%) from exposure to environmental tobacco smoke from the spouse and this increases with the number of cigarettes smoked and duration of the marriage. Misclassification bias (women who smoke but claim to be lifelong nonsmokers) and dietary confounding are unlikely to explain the association; after adjustment for both, the risk of lung cancer from environmental tobacco smoke exposure was still statistically significant. In any event, their effects on the risk of lung cancer in the epidemiological studies are balanced out by allowing for background exposure to environmental tobacco smoke (that is, other than from the spouse) in the reference group; the excess risk after allowing for all three is an estimated 26% (95% confidence interval 7-47%), similar to the adjusted figure of 24%. In Britain, about one in every six nonsmokers are exposed to tobacco smoke from smokers in the home. Passive smoking is an avoidable cause of mortality and morbidity. Prevention strategies to reduce the amount of cigarette smoking in public places should be part of public health policy.

Formation of DNA adducts in human buccal epithelial cells exposed to acetaldehyde and methylglyoxal in vitro

Acetaldehyde (AA) and methylglyoxal (MG) are reactive, ubiquitous aldehydes, present in the environment and endogenously formed in animals and humans. They have both been shown to readily form DNA adducts under simulated physiological conditions. We report here on the use of cultured normal and SV40T antigen-immortalized human buccal epithelial cells as model systems for aldehyde exposure of the oral epithelium, occurring through the ingestion of alcoholic beverages and brewed coffee, as well as by inhalation of tobacco smoke and automobile exhaust. By the application of recently developed 32P-postlabeling methods, the presence of both endogenous and induced AA and MG DNA adducts was demonstrated in cultured human epithelial cells. Furthermore, these DNA adducts were formed in a dose-dependent manner at aldehyde concentrations that were relatively non-toxic to the cells.

Fibrinogen as a risk factor for coronary heart disease and mortality in middle-aged men and women. The Scottish Heart Health Study.

Fibrinogen was measured in 5095 men and 4860 men aged 40-59 in a random population sample from 25 districts of Scotland recruited during 1984-87: the Scottish Heart Health Study. Fibrinogen was then related to the chance of fatal and non-fatal coronary events and death from any cause during a subsequent follow-up period of around 8 years. Fibrinogen was measured by the Clauss assay. The effect of fibrinogen on coronary heart disease and death was assessed through age-adjusted means and Cox proportional hazards regression models, accounting for age, cotinine (a measure of tobacco smoke inhalation) and 11 other major coronary risk factors. Fibrinogen was found to be an important risk factor for coronary heart disease in men and women, with and without pre-existing coronary heart disease. There appears to be a threshold effect, with those in the highest fifth of the distribution having a much increased risk. Estimated age-adjusted hazard ratios by sex and pre-existing coronary heart disease group for the highest to lowest fifth of fibrinogen range between 1.93 and 4.86. Fibrinogen is also important as a risk factor for coronary death and all-causes mortality, with a similar threshold effect. Comparing the two extreme fifths, the hazard ratios for coronary death are 3.01 and 3.42, and for all-cause mortality are 2.59 and 2.20, for men and women respectively. Adjustment for cotinine reduces the hazard ratios, but further adjustment for the other 11 risk factors has little effect for coronary heart disease events. After full adjustment there is a remaining significant (P < 0.05) hazard ratio for coronary death and death from any cause and for a coronary heart disease event for those free of coronary heart disease at baseline, amongst men, comparing the highest to the lowest fifth. Fibrinogen is a strong predictor of coronary heart disease, fatal or non-fatal, new or recurrent, and of death from an unspecified cause, for both men and women. Its effect is only partially attributable to other coronary risk factors, the most important of which is smoking.

Pulmonary emphysema induced by passive smoking: an experimental study in rats.

We describe a short time model for inducing experimental emphysema in rats by chronic tobacco smoke inhalation. Three groups of male Wistar rats (6 months old) were studied: controls (N = 8), rats intoxicated for 45 days (s-45, N = 7) or for 90 days (s-90, N = 8). The exposed animals were intoxicated 3 times a day (10 cigarettes per exposure period), 5 days a week. Pulmonary damage was assessed by means of functional tests and quantitative pathological examination of the airways and lung parenchyma. The s-45 and s-90 animals were similar in terms of functional residual capacity (FRC) corrected for body weight (FRC/kg) but both groups of smoking rats exhibited significantly higher FRC/kg values than the controls (s-45 = 6.33; s-90 = 6.46; controls = 3.78; P < 0.05). When the two groups of smoking rats were pooled together and compared to controls, they showed decreased lung elastance (1.6 vs 2.19; P = 0.046) and increased mean linear intercept (Lm) (85.14 vs 66.44; P = 0.025). The s-90 animals presented higher inflammation and muscular hypertrophy at the level of the axial bronchus than the controls (P < 0.05). When smoking groups were pooled and compared to controls, they presented significantly higher inflammation at the lateral level (P = 0.028), as well as airway secretory hyperplasia (P = 0.024) and smooth muscle hypertrophy (P = 0.005) at the axial level. Due to its simplicity, low cost and short duration, this technique may be a useful model to obtain new information about airspace remodeling due to chronic tobacco consumption.

Transient increases in albumin and hyaluronan in bronchoalveolar lavage fluid after quitting smoking: possible signs of reparative mechanisms

Inhalation of tobacco smoke results in an accumulation of cells in the lower respiratory tract. The inflammatory response in the alveoli and lung interstitium may also be reflected by increased bronchoalveolar lavage (BAL) fluid concentrations of extracellular matrix components. The present study investigated the influence of smoking on the BAL fluid concentrations of albumin (ALB), hyaluronan (HA) and fibronectin (FN). Lavage fluids from 18 smokers were analysed before and at 1, 3, 6, 9 and 15 months after smoking cessation. Never-smokers ( n=112) served as a reference group. The total cell concentration and the concentrations of macrophages, lymphocytes, neutrophils and eosinophils were higher ( P<0·001–0·01) in smokers' BAL fluid than in never-smokers', but the values returned to normal within 9 months of smoking cessation. The HA concentration was higher ( P<0·001) in smokers' than in never-smokers' BAL fluid, but FN and ALB did not differ. Transient increases in the concentrations of ALB and HA ( P<0·01 for both) was observed within 6 months of smoking cessation. These findings indicate a temporary heightened alveolar-capillary permeability and an increased production and/or degradation of HA, being enhanced following smoking cessation. The findings probably reflect an initiation of a reparative process.

Effect of Probucol, An Oral Hypocholesterolaemic Agent, on Acute Tobacco Smoke Inhalation in Rats

1. We hypothesized that probucol, an oral hypocholesterolaemic agent, can suppress the oxidant stress induced by acute tobacco smoke inhalation in rats. We determined lung tissue glutathione (reduced and oxidized), lipid peroxide, tocopherol and plasma elastase inhibitory capacity, ferroxidase activity and lipid peroxide in rats after inhalation of tobacco smoke. 2. Rats treated with the probucol diet for 3 days or 4 weeks equally showed no suppression of plasma elastase inhibitory capacity and ferroxidase activity compared with control rats after acute tobacco smoke inhalation, although both animals treated with probucol for 3 days or 4 weeks had pharmacologically effective concentrations of probucol to lower plasma cholesterol but plasma cholesterol in rats treated with probucol for 3 days was still in the normal range. 3. Probucol treatment for 4 weeks lessened tobacco smoke-induced suppression of lung tissue glutathione, attenuated tobacco smoke-induced increases in lung tissue lipid peroxide and did not alter lung tissue tocopherol compared with control (lungs). 4. These findings demonstrate that probucol, via its antioxidant ability, confers a protective effect on lung exposed to acute tobacco smoke inhalation.

Effects of tobacco smoke inhalation on the developing mouse embryo and fetus

Pregnant C57BL or mutant curly tail mice were exposed to tobacco smoke in a smoking machine for 10 min, three times a day, either on the day of conception (day 0) and days 1 and 2, or on days 3, 4, and 5, or from day 0 through day 17. In the first two cases, the embryonic development was subsequently assessed on day 9. Both periods of exposure were associated with a dose-related retardation in embryonic growth, but it was more marked with exposure on days 0, 1, and 2. It would seem, therefore, that even brief episodes of maternal smoking are detrimental to the very early embryo, and even if smoking is stopped, the effects persist at least for some days and there is no immediate catch-up growth. In the mice exposed continuously for 17 days, the fetuses were studied on day 18: there was a significant reduction in fetal body weight in both types of mice. There was also a reduction in the number of skeletal ossification centres, showing that additionally, there was developmental delay. In C57BL mice, one rib abnormality occurred, but no major congenital malformations; however, in the curly tail mutants, 60% of which normally have a curly tail or an open neural tube defect, there was a modest increase in the frequency of open spina bifida and exencephaly. A few minor rib abnormalities also occurred, and one case of cleft lip with cleft palate. These results indicate that tobacco smoke, while detrimental to the developing fetus, is not a potent teratogen in the mouse, but that it may have minor effects in those individuals genetically predisposed to an abnormality. This may have implications for humans, and may explain the generally inconclusive findings regarding congenital malformations in the children of women who smoke during pregnancy. In all experiments, the detrimental effects were seen with both higher tar cigarettes (tar and nicotine yields: 12.9 and 1.19 mg/cigarette, respectively) and lower tar cigarettes (4.8 and 0.54 mg/cigarette respectively), so tobacco modification is not really beneficial to the developing fetus.