3
Experimental Studies Relevant to the Pathophysiology of Secondhand Smoke

This chapter discusses pathophysiologic experiments that have investigated the cardiovascular effects of mainstream and sidestream tobacco smoke in cells, in animals, and in humans. It addresses the association between secondhand-smoke exposure and acute coronary events. Specifically it provides information on the biological plausibility of a causal relationship between secondhand smoke exposure and acute coronary events (Question 2, see Box 1-1) and information on the duration of exposure and time following cessation of exposure within which effects might be observed (Questions 3 and 5, see Box 1-1).

The studies reviewed include those with exposure to secondhand smoke and exposure to specific constituents of secondhand smoke. When secondhand smoke was used, the studies were conducted with cigarette smoke, not smoke from cigars, pipes, or hookahs. Typically, reference cigarettes (cigarettes that are manufactured according to a standard formula for research purposes to provide researchers a consistent and uniform test item) or Marlboro cigarettes are used. Studies have not demonstrated much variation in constituents among cigarette brands and types (HHS, 2001), nor in the concentrations of constituents in secondhand smoke (Daisey, 1999).

As discussed by Hatsukami et al. (2006), “several physiological changes involving potential mechanisms of smoking-induced cardiovascular disease have been observed in cigarette smokers compared with nonsmokers” who have not been exposed to secondhand smoke.

Cigarette smoke, either mainstream or secondhand smoke, could produce cardiovascular disease by a number of interrelated modes of action, including oxidative stress, hemodyamic and autonomic effects, endothelial



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 59
3 Experimental Studies Relevant to the Pathophysiology of Secondhand Smoke This chapter discusses pathophysiologic experiments that have inves- tigated the cardiovascular effects of mainstream and sidestream tobacco smoke in cells, in animals, and in humans. It addresses the association be- tween secondhand-smoke exposure and acute coronary events. Specifically it provides information on the biological plausibility of a causal relationship between secondhand smoke exposure and acute coronary events (Question 2, see Box 1-1) and information on the duration of exposure and time following cessation of exposure within which effects might be observed (Questions 3 and 5, see Box 1-1). The studies reviewed include those with exposure to secondhand smoke and exposure to specific constituents of secondhand smoke. When second- hand smoke was used, the studies were conducted with cigarette smoke, not smoke from cigars, pipes, or hookahs. Typically, reference cigarettes (cigarettes that are manufactured according to a standard formula for re- search purposes to provide researchers a consistent and uniform test item) or Marlboro cigarettes are used. Studies have not demonstrated much varia- tion in constituents among cigarette brands and types (HHS, 2001), nor in the concentrations of constituents in secondhand smoke (Daisey, 1999). As discussed by Hatsukami et al. (2006), “several physiological changes involving potential mechanisms of smoking-induced cardiovascular disease have been observed in cigarette smokers compared with nonsmokers” who have not been exposed to secondhand smoke. Cigarette smoke, either mainstream or secondhand smoke, could pro- duce cardiovascular disease by a number of interrelated modes of action, including oxidative stress, hemodyamic and autonomic effects, endothelial 

OCR for page 59
0 SECONDHAND SMOKE EXPOSURE Secondhand Smoke Vapor Phase Vapor Phase Particulate Matter Nicotine Nicotine Acute Subacute and and Effects Chronic Effects Inflammation Endothelial Dysfunction Endothelial Dysfunction and Activation Increased Platelet Aggregation Plaque Progression and Vulnerability Hemodynamic Changes Insulin Resistance Thrombosis Dyslipidemia Vasoconstriction Increased Coagulation Decreased Heart Rate Variability Thrombosis Rhythm Disturbances Neurogenic Inflammation Accelerated Atherogenesis Acute Coronary Syndromes FIGuRE 3-1 Potential mode of action of secondhand smoke. NOTE: Schematic showing cardiovascular effects of secondhand smoke and how they might lead to acute myocardial infarction. dysfunction, thrombosis, inflammation, hyperlipidemia or other effects (see Figure 3-1). Evidence related to those potential actions is discussed below, followed by a discussion of the effects of the individual constituents of sec- ondhand smoke. Although those physiological changes have been observed and used to assess possible modes of action of secondhand smoke, to date most have not been formally validated as clinical tests and there is not a consensus within the scientific community that they are predictive of actual clinical disease (Ledford, 2008; Wang, 2008; WHO, 2007). Furthermore, a lack of specificity of exposure to secondhand smoke for those markers precludes their use as biomarkers that indicate a given case of cardiovascu-

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE lar disease is caused by exposure to secondhand smoke (Hatsukami et al., 2006). In this section, however, the committee uses those effects to examine whether secondhand-smoke exposure causes pathophysiologic changes that would contribute to the biological plausibility that decreasing secondhand- smoke exposure could lead to a decrease in acute myocardial infarctions (MIs). EFFECTS OF CIGARETTE SMOkE Oxidative Stress As discussed in several review articles (for examples, see Armani et al., 2009; Burke and FitzGerald, 2003), oxidative stress could mediate many of the effects of smoke on the cardiovascular system. Such stress, during which endogenous antioxidants are overwhelmed by oxidants such as reac- tive oxygen species and free radicals, results in impaired cellular function. The exact mechanisms whereby oxidative stress leads to cardiovascular disease, such as atherosclerosis, are not clear, but it appears that oxidative stress may play a role in cardiovascular pathophysiology (Ballinger et al., 2002), and it could account for many effects of tobacco-smoke exposure, such as endothelial dysfunction, thrombosis, and inflammation (Raupach et al., 2006; Thomas et al., 2008). Many constituents of mainstream and sidestream smoke are or pro- duce free radicals capable of producing oxidative stress. Those constituents include vapor-phase carbonyl compounds (such as acrolein), oxides of nitrogen, metabolites of polycyclic aromatic hydrocarbons (PAHs), metals, and particulate matter (PM) (NRC, 1986). Mainstream cigarette smoke increases the concentrations of markers of oxidative stress, lipid peroxida- tion, protein oxidation, and DNA modification. Isoprostanes, indicators of lipid peroxidation and in vivo oxidation injury, are higher in smokers than in nonsmokers, and their concentrations decreased after smoking ces- sation for 2 weeks (Morrow et al., 1995). Smokers admitted to a cardiac outpatient center who then quit smoking had decreases in isoprostanes a few days after quitting, and the decreases continued until a steady state was reached 4 weeks after quiting (Pilz et al., 2000). Pignatelli et al. (2001) demonstrated that oxidized plasma proteins, another marker of oxidative stress, are higher in smokers than in nonsmokers. Ahmadzadehfar et al. (2006) reported that exposure to secondhand smoke significantly increased isoprostane 8-epi-PGF2α in nonsmokers. After repeated secondhand-smoke exposure, isoprostane 8-epi-PGF2α in non- smokers reached nearly the same values as in smokers. Probst-Hensch (2008) investigated whether the effects of secondhand smoke on the cardiovascular system are mediated by oxidative stress in a

OCR for page 59
 SECONDHAND SMOKE EXPOSURE sample of 1,122 nonsmoking subjects enrolled in an air-pollution study. Secondhand-smoke exposure was measured based on self-report during an interview as to “how many hours per day they were exposed to other people’s tobacco smoke (a) at home, (b) at the workplace, (c) in bars and restaurants, and (d) elsewhere.” Exposures were categorized as less than or equal to two hours per day, or more than two hours per day. The role of oxidative stress was assessed by looking at the interactions between gluta- thione S-transferase (GST) deficiency, which exhibits antioxidative proper- ties, and the effects of secondhand smoke exposure on heart rate variability (HRV), a measure reflecting autonomic cardiac function. HRV was assessed from a 24-hour electrocardiogram recording, and subjects were genotyped for GSTM1, GSTT1, and GSTP1, GSTM1, GSTT1, and GSTP1 polymor- phisms interacted with secondhand-smoke exposure to affect HRV. For example, the decrease in HRV in people exposed to secondhand smoke for more than two hours per day was greater when the GSTM1 genotype was deleted as compared to not deleted. That suggests a role of oxidative stress in secondhand smoke’s effects on HRV. Furthermore, animal data reviewed in the surgeon general’s report (HHS, 2006) indicate that exposure to secondhand smoke worsens ischemic heart-event outcomes through free-radical activity. Animal data showed that a 30-min exposure to secondhand smoke resulted in oxidative DNA damage in the myocardium as measured by increases in 8-hydroxydeoxy- guanosine. Secondhand-smoke exposure also activates neutrophils, which leads to oxidation and tissue damage. Data in animals also show oxidative effects. Secondhand-smoke expo- sure (30 mg/m3 total suspended particles from cigarette smoke, or equiva- lent to about two cigarettes every 15 minutes, for 6 hours per day, 5 days per week for 3 or 8 weeks) increased mitochondrial DNA damage in aortic tissue, which can be caused by increased reactive oxygen and nitrogen spe- cies, of apoE -/- mice (mice that lack a high-affinity ligand for lipoprotein receptors that result in them developing atherosclerotic plaques similar to those in humans) (Knight-Lozano et al., 2002). Data on apoE -/- mouse and human tissue indicate that mitochondrial DNA damage might be an early event in atherosclerosis (Ballinger et al., 2002). Eaton et al. (2006) examined the effect of acute tobacco-smoke exposure on mitochondrial function and calcium handling of cardiac cells in rats. Mitochondria were isolated after 6 h of secondhand smoke exposure (about 60 mg/m3, with an average nicotine concentration of 6.95 ± 0.62 mg/m3). Mitochondria from smoke-exposed rats had significantly higher adenosine diphosphate–stimu- lated production of adenosine triphosphate, had a more reduced redox state (nicotinamide adenine dinucleotide [NADH] ratio), showed more rapid membrane depolarization in response to calcium, and had significantly

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE increased cyclosporin A–sensitive Ca2+ release, although net Ca2+ uptake was unchanged. Autonomic Effects Cigarette smoke could affect the cardiovascular system through the autonomic nervous system, associated hemodynamic effects, or both. Heart rate is regulated by the interaction between the sympathetic and parasym- pathetic nervous systems. Sympathetic nervous system activation reduces heart-rate variability, and decreased heart-rate variability is associated with higher risk of cardiac death and of arrhythmic events after an acute MI (Buccelletti et al., 2009). Smoking can have direct effects on heart rate, and those effects are thought to be mediated by actions on the sympathetic component of the autonomic nervous system. Nicotine acts on nicotinic cholinergic receptors in the brain and adrenal glands to activate the sympathetic nervous system, and this leads to epinephrine release. Nicotine thus acts as a sympathomi- metic drug in increasing heart rate, blood pressure, and cardiac contractil- ity and constricting some blood vessels (Haass and Kubler, 1997). Studies show that cigarette smoking increases a person’s heart rate (Benowitz et al., 1984; Minami et al., 1999). In the study by Minami et al. (1999) heart rate was higher by an average of 7 beats per minute while smoking compared to when not smoking, and smoking cessation for a week decreased heart rate. Although nicotine from cigarette smoke transiently increases blood pressure, cigarette smoke has not been associated with hypertension in epidemiologic studies (HHS, 2004). Nicotine constricts coronary arteries via alpha-adrenergic effects (Winniford et al., 1986), and the coronary vasoconstriction is greater in diseased than in healthy coronary arteries (Nicod et al., 1984). In healthy smokers, coronary blood flow (CBF) in- creases in response to the cigarette smoking- or nicotine-mediated increase in myocardial work. In the absence of nicotine, however, the magnitude of the increase in myocardial work is less in healthy smokers. In people with coronary arterial disease, nicotine and cigarette smoke decrease CBF. Cigarette smoking is a strong risk factor for coronary vasospasm and for inadequacy of response to vasodilator medication (Caralis et al., 1992). Secondhand smoke has been shown to affect heart-rate variability. Dietrich et al. (2007) examined the relationship between exposure to sec- ondhand smoke and reduction in heart-rate variability. The study exam- ined 1,218 nonsmokers ages 50 years and older who were participating in the Swiss Cohort Study on Air Pollution and Lung Disease in Adults (SAPALDIA) in 2001–2003. Those exposed to secondhand smoke for more than 2 h/day had lower heart-rate variability and a 2.7% higher heart rate

OCR for page 59
 SECONDHAND SMOKE EXPOSURE (95% CI, –0.01 to 5.34%) than those not exposed. The effects of second- hand smoke on heart-rate variability are similar to those observed after exposure to PM (Dietrich et al., 2007). Argacha et al. (2008) further examined the vascular effects of second- hand smoke exposure to assess whether the effects are mediated by a non- specific reaction to smoke, or are more unique to tobacco smoke, the role of nicotine in the effects, the persistence of the effects following cessation of exposure, and the effect of secondhand smoke on microvascular function measured by skin blood flow. Using a cross-over design, the researchers ex- posed 11 healthy men to secondhand smoke, smoke from herbal cigarettes, or air (1 h exposure using a hermetic, 1-m3 Plexiglass box over the head of the subject, with a total of 6 cigarettes lit one every 10 minutes). Heart rate and aortic wave reflection increased and transit time decreased follow- ing exposure to secondhand-tobacco smoke, but not smoke from herbal cigarettes or air. None of the exposures affected blood pressure. Skin blood flow at normal temperature was unchanged by any of the treatments but was decreased in response to heating after exposure to secondhand-tobacco smoke. None of the effects of secondhand smoke persisted 20 minutes after exposure. A separate group of 14 men received 2 mg nicotine via a sub- lingual tablet; in those subjects, the effects on aortic wave reflection were related to the serum nicotine concentrations, indicating a possible role of nicotine in these effects seen after exposure to secondhand smoke. Endothelial Dysfunction The vascular endothelium, which lines the arteries, is a semipermeable layer of cells that are involved in the modulation of platelet activation, leukocyte adhesion, thrombosis, and regulation of vascular tone. It plays an important role in the regulation of blood flow, controlling the dilation and constriction of arteries (Hadi et al., 2005). Part of that regulation is through the production of vasoactive substances by the endothelial cells, including nitric oxide (NO), endothelin, prostacyclin, and angiotensinogen (Al-Qaisi et al., 2008). Endothelial dysfunction is one of the key early steps in the pathway to atherosclerosis (Hadi et al., 2005). Oxidant chemicals produce endothelial dysfunction both by injuring endothelial cells and by degrading NO, the latter of which normally has vasodilator and antiplatelet activity (Heiss et al., 2008; Zhang et al., 2006). Impaired endothelial function in smokers, as measured by flow-mediated dilation of the brachial artery, can be reversed, at least in part, by antioxi- dants (de Sousa et al., 2005; Neunteufl et al., 2000; Raitakari et al., 2000; Takase et al., 2004; Young et al., 2006). Nicotine was also reported to impair endothelial function acutely in human smokers. Smokers also have increased markers of endothelial dysfunction (Rocchi et al., 2007).

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE As discussed in the surgeon general’s report on secondhand smoke (HHS, 2006), data from experiments in animals and humans demonstrate that secondhand smoke also disrupts endothelial function by reducing NO. Endothelium-dependent vasodilation in nonsmokers is affected by chronic and acute exposures to secondhand smoke. Mack et al. (2003) examined the effect of chronic exposure to sec- ondhand smoke on arterial wall stiffness in baseline data from 227 never smokers (102 men, 125 women) enrolled in a clinical trial looking at Vita- min E treatment. Ultrasound images were used to measure arterial diameter and carotid artery intima-media thickness (IMT). A carotid stiffness index beta, computed using the change in arterial diameter between maximum and minimum dilation, was used as an indicator of arterial wall stiffness. Smoking and secondhand-smoke exposures (number of smokers and hours per day exposed at home, number of daily exposures at work and outside the home and work) were ascertained through a questionnaire. The stiff- ness index was associated with body mass index, fasting glucose, and IMT. The stiffness index was not related to exposure to secondhand smoke in the overall study population, but did increase with increased number and daily sources of exposure to secondhand smoke in those subjects with a body mass index of 27.1 kg/m2 or higher, ages 55 years or older, or with an IMT of 0.707 mm or higher. No other associations were statistically significant, including separate analyses by sex and age. Heiss et al. (2008) exposed healthy nonsmokers to smoke-free air or secondhand smoke for 30 min on two nonconsecutive days and measured markers of endothelial dysfunction (Heiss et al., 2008). Plasma cotinine con- centrations were unchanged after exposure to smoke-free air and reached about 0.3 ng/mL, a level “commonly observed in passive smokers” after exposure to secondhand smoke. The secondhand-smoke exposure increased endothelial progenitor cells (EPCs) and plasma vascular endothelial growth factor but eliminated EPC chemotaxis and decreased endothelial function as measured by flow-mediated dilation (FMD). The effects on FMD returned to normal after 2.5 h, but the effects on endothelial growth factors were still increased after 24 h. The detection of endothelial-cell damage in the blood as a result of short-term exposure to secondhand smoke suggests endothelial damage. A 30-min exposure to secondhand smoke in a smoking room signifi- cantly reduced the coronary flow-velocity reserve in nonsmokers to a level similar to that seen in smokers before and after exposure to secondhand smoke (Otsuka et al., 2001). A 5-min exposure to secondhand smoke (mean carbon monoxide level in the exposure chamber, 30 parts per mil- lion) significantly reduced aortic distensibility in nonsmokers and smokers (Stefanadis et al., 1998). Arterial stiffness can result in the impairment of the elasticity of the

OCR for page 59
 SECONDHAND SMOKE EXPOSURE aorta. Mahmud and Feely (2004) used wave reflection in the aorta as a marker of arterial stiffness to study the effect of exposure to secondhand smoke (15 cigarettes lit in an unventilated room over the course of 1 hour) on healthy nonsmokers (10 men, 11 women). No baseline differences were seen between the controls and treated groups. Following exposure to secondhand smoke brachial and aortic systolic blood pressure increased in males but not females, and an abnormality was observed in the radial and aortic pressure waveforms; no changes were seen in brachial or aortic diastolic blood pressure, heart rate, or left ventricular ejection duration in either sex. No changes were seen in a control group (6 men, 6 women) exposed to air only. Kato et al. (2006) examined FMD in the bronchial artery and 8-iso- prostane levels as indicators of vascular endothelial function and oxidative stress, respectively, in 30 male subjects (15 smokers who had abstained from smoking for at least 12 hours, 15 nonsmokers) exposed to secondhand smoke from 15 cigarettes (in a room 3 meters by 4 meters with a 2.5 meter ceiling with ventilation) for 30 minutes. FMD was lower and the levels of 8-isoprostane were higher at baseline in smokers than nonsmokers; neither changed in smokers. In nonsmokers, however, FMD decreased and the lev- els of 8-isoprostane increased following exposure to secondhand smoke. Giannini et al. (2007) studied the effects of exposure to secondhand smoke (20 minutes in a 60 cubic meter enclosed space with 15 to 20 ciga- rettes smoked, achieving 30–35 ppm carbon monoxide) on vascular reactiv- ity of the brachial artery (measured by FMD) in 18 healthy, nonsmoking volunteers. Carboxyhemaglobin was elevated after exposure to secondhand smoke. FMD was decreased following the exposure, but nitroglycerin- induced vasodilation was not changed significantly. In contrast, in a study of 12 healthy nonsmokers (9 men, 3 women) exposed acutely to secondhand smoke (smoke from three cigarettes for 15 minutes with a clear plastic hood over the participant’s head; air was mixed with the smoke to maintain a carbon monoxide concentration of 20–40 ppm) no effects on vasodilation were seen (Kato et al., 1999). Carboxyhe- moglobin concentrations increased from 0.53 ± 0.05% at baseline to 0.79 ± 0.05% after 30 minutes of exposure and plasma nicotine concentrations increased from 0.46 ± 0.12 ng/ml at baseline to 1.38 ± 0.47 ng/ml after exposure. Forearm vascular resistance, either baseline or its response to an endolethium-dependent vasodilator (acetylcholine) or an endothelium-inde- pendent vasodilator (sodium nitroprusside), was not changed by exposure to secondhand smoke. Hausberg and Somers (2008) also saw no changes in forearm blood flow following exposure of 16 healthy nonsmokers beyond the changes seen in response to administration of vehicle. A significant increase was seen in muscle sympathetic nerve activity following the exposure to secondhand

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE smoke, but changes were not seen in blood pressure, except for the response to the cold pressor test, heart rate, and plasma concentrations of epineph- rine and norepinephrine. Data from animal studies demonstrate that some components of sec- ondhand smoke—1,3-butadiene and PAHs that include 7,12-dimethylbenz [a,h]anthracene and benz[a]pyrene—speed up atherosclerosis development, which results from cell injury and hyperplasia (HHS, 2006). In addition, animal experiments have shown that exposure to secondhand smoke for a few weeks significantly accelerates the atherosclerotic process. Constituents of smoke increase low-density lipoprotein (LDL) cholesterol in the artery lining and bind it to the vessel wall (Roberts et al., 1996). Platelets interact with subendothelial connective tissue, and damaged endothelial cells also play a role in plaque formation. Secondhand-smoke exposure is associated with the build up of glycoaminoglycan and glycopro- tein in animal models, which results in atherogenesis (Latha et al., 1991). Thrombosis Platelets (thrombocytes) are cell derivatives that circulate in the blood and play a role in clot formation. When platelets are activated, they become sticky and adhere to each other (coagulate); platelets also can adhere to damaged vascular endothelium. Adherence of platelets increases thrombus formation, disrupts the coronary artery lining, speeds progression of ath- erosclerotic lesions, and is associated with increased risk of ischemic heart disease (Law and Wald, 2003). The acute cardiovascular effects of ciga- rette smoke result to a substantial degree from thrombosis-related events (Rahman and Laher, 2007). In humans, platelet activation has been studied by measuring urinary excretion of thromboxane (TxM), a metabolite of thromboxane A2, which is released when platelets aggregate in vivo. Smokers have higher concen- trations of TxM than nonsmokers (Modesti et al., 1989). One study found that the decline in TxM after smoking cessation was not found when smok- ers used nicotine patches but was found in those who did not use patches (Saareks et al., 2001). In another study, however, smoking cessation yielded similar decreases in TxM excretion regardless of the use of nicotine patches (Benowitz et al., 1993; Ramachandran et al., 2004). The role of nicotine in that effect, therefore, remains unclear. Experimental research indicates that secondhand-smoke exposure re- sults in increased platelet activation and aggregation. Researchers assayed platelet sensitivity, an indication of platelet aggregation, in human subjects (smokers and nonsmokers). Platelet sensitivity in nonsmokers increased af- ter subjects sat for 20 min in a room where cigarettes had just been smoked (Burghuber et al., 1986) or in a corridor where others were smoking (Davis

OCR for page 59
 SECONDHAND SMOKE EXPOSURE et al., 1989). In addition, data on rabbits receiving a high-cholesterol diet (Sun et al., 1994; Zhu et al., 1993) and rats (Zhu et al., 1994) demonstrate that bleeding time, a measure of platelet aggregation, is shortened on ex- posure to secondhand smoke. Some studies have reported that nicotine in high doses activates platelets in animals (McDonald et al., 1973; Nemr et al., 2003). Inflammation Cigarette smoke produces systemic inflammatory effects. Although those biological effects have not been validated as predicting differences in tobacco-related injury or disease risk in randomized clinical trials, they have been predictors of future cardiovascular events in observational epidemio- logic studies (Lindahl et al., 2000; Packard et al., 2000). High concentra- tions of activated oxygen species found in tobacco smoke could potentially damage heart muscle cells and lead to inflammation, which can result in additional organ injury. Smoking is associated with higher polymorphonuclear (PMN) leuko- cyte counts, fibrinogen, C-reactive protein (CRP), and other inflammatory markers (HHS, 2004). Some in vitro and animal studies report that nicotine is a chemoattractant, enhances leukocyte adhesion, and increases release of some proinflammatory cytokines (Di Luozzo et al., 2005; Heeschen et al., 2003; Lau et al., 2006). Studies of smokers switching to nicotine medica- tions, however, have found that inflammatory biomarkers decline as in those who quit smoking and do not take nicotine; this suggests that the nicotine in smoke is not responsible for the inflammation (Benowitz and Gourlay, 1997). Venn and Britton (2007) examined the relationship between secondhand- smoke exposure, measured as plasma cotinine, and biomarkers of heart- disease risk—including CRP, homocysteine, fibrinogen, and white-cell count—in 7,599 never-smokers in the third National Health and Nutrition Examination Survey (NHANES III). Subjects with detectable but low serum cotinine concentrations (0.05–0.215 ng/mL) had significantly higher con- centrations of fibrinogen (adjusted mean difference, 8.9 mg/dL; 95% CI, 0.9–17.0) and homocysteine (0.8 μmol/L; 95% CI, 0.4–1.1), but not CRP or white-cell count, than subjects with no detectable cotinine. Similar effects were observed in those with high serum cotinine concentrations (more than 0.215 ng/mL). The increased concentrations of fibrinogen and homocyste- ine observed in subjects exposed to secondhand smoke were about 30–45% of the concentrations in smokers. Similarly, Wilkinson et al. (2007) used the NHANES III data to ex- amine the relationship between secondhand-smoke exposure and CRP, focusing on never-smokers ages 6–18 years. An increase in serum cotinine

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE of 0.5 ng/mL was associated with an increase in CRP of 0.96 mg/dL (95% CI, 0.93–1.00). Clark et al. (2008) used serum cotinine concentrations and the NHANES data (1999–2002) to examine the relationship between secondhand-smoke exposure and markers of inflammation in adult workers. Inflammatory markers analyzed included CRP, fibrinogen, homocysteine, and white cells. Serum cotinine concentrations were categorized as below the detection limit, low (above the detection limit but below 0.2 ng/mL), or high (0.2–15 ng/mL). Workers exposed with low and high levels of cotinine had signifi- cantly higher concentrations of homocysteine than unexposed workers. No significant differences were seen in concentrations of CRP, fibrinogen, and white cells. Flouris et al. (2008) explored the sex-specific secondhand-smoke effects on gonadal and thyroid hormones, inflammatory cytokines, and vascular function. After exposing 28 nonsmoking adults (14 men and 14 women) to a simulated bar-restaurant environment for 1 hour, the study found interleukin-1β and systolic blood pressure significantly increased in men but not women. Gonadal hormones, however, were decreased following secondhand smoke exposure in both men and women. Hyperlipidemia Cigarette-smoking is associated with low high-density lipoprotein cho- lesterol (HDL-C), which is a risk factor for atherogenesis. Smoking is believed to exert effects on lipids, at least in part, by the sympathomimetic effects of nicotine (Woodward et al., 2006). Nicotine increases lipolysis and increases free fatty acid concentrations (Hellerstein et al., 1994). Increased fatty acid turnover is associated with overproduction of very-low-density- lipoprotein (VLDL) cholesterol, increased LD cholesterol, and decreased HDL cholesterol. One study reported that nicotine-patch administration prevented the expected normalization of HDL cholesterol after smoking cessation (Moffatt et al., 2000). Studies of smokeless tobacco users have been used to separate effects of nicotine (similar exposure from cigarette smoking and smokeless tobacco use) from the effects of combustion prod- ucts (cigarette smoke only). The data on lipid abnormalities comparing smokeless tobacco to nontobacco users is conflicting, making it difficult to ascertain the role of nicotine (Tucker, 1989; Wallenfeldt et al., 2001). Moffat et al. (2004) assessed the effect of secondhand smoke on blood lipids. Exposure of 12 healthy, male nonsmokers to secondhand smoke (6-hour continuous exposure in a smoking chamber with a volunteer smoker smoking six cigarettes at a rate of one cigarette per hour plus nine other cigarettes burned to attain mean air concentrations of carbon mon- oxide of 12 ppm, and nicotine of 16 μg/m3) reduced HDL-C, increased the

OCR for page 59
 SECONDHAND SMOKE EXPOSURE Andersson, K., and P. Arner. 2001. Systemic nicotine stimulates human adipose tissue lipoly- sis through local cholinergic and catecholaminergic receptors. International Journal of Obesity & Related Metabolic Disorders: Journal of the International Association for the Study of Obesity 25(8):1225-1232. Andersson, K., P. Eneroth, and P. Arner. 1993. Changes in circulating lipid and carbohydrate metabolites following systemic nicotine treatment in healthy men. International Journal of Obesity & Related Metabolic Disorders: Journal of the International Association for the Study of Obesity 17(12):675-680. Andre, E., B. Campi, S. Materazzi, M. Trevisani, S. Amadesi, D. Massi, C. Creminon, N. Vaks- man, R. Nassini, M. Civelli, P. G. Baraldi, D. P. Poole, N. W. Bunnett, P. Geppetti, and R. Patacchini. 2008. Cigarette smoke-induced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents. Journal of Clinical Investigation 118(7):2574-2582. Arabi, Z. 2006. Metabolic and cardiovascular effects of smokeless tobacco. Journal of the Cardiometabolic Syndrome 1(5):345-350. Argacha, J.-F., D. Adamopoulos, M. Gujic, D. Fontaine, N. Amyai, G. Berkenboom, and P. van de Borne. 2008. Acute effects of passive smoking on peripheral vascular function. Hypertension 51(6):1506-1511. Armani, C., L. Landini, Jr., and A. Leone. 2009. Molecular and biochemical changes of the cardiovascular system due to smoking exposure. Current Pharmaceutical Design 15(10):1038-1053. Aronow, W. S. 1978. Effect of passive smoking on angina pectoris. New England Journal of Medicine 299(1):21-24. Badre, R., R. Guillerm, N. Abran, M. Bourdin, and C. Dumas. 1978. [Atmospheric pollution by smoking (author’s transl)]. Annales Pharmaceutiques Françaises 36(9-10):443-452. Balcarova, O., and J. Halik. 1991. Ten-year epidemiological study of ischaemic heart disease (IHD) in workers exposed to carbon disulphide. Science of the Total Environment 101(1-2):97-99. Ballinger, S. W., C. Patterson, C. A. Knight-Lozano, D. L. Burow, C. A. Conklin, Z. Hu, J. Reuf, C. Horaist, R. Lebovitz, G. C. Hunter, K. McIntyre, and M. S. Runge. 2002. Mi- tochondrial integrity and function in atherogenesis. Circulation 106(5):544-549. Benowitz, N. L. 2003. Cigarette smoking and cardiovascular disease: Pathophysiology and implications for treatment. Progress in Cardiovascular Diseases 46(1):91-111. Benowitz, N. L., and S. G. Gourlay. 1997. Cardiovascular toxicity of nicotine: Implica- tions for nicotine replacement therapy. Journal of the American College of Cardiology 29(7):1422-1431. Benowitz, N. L., F. Kuyt, and P. Jacob, 3rd. 1984. Influence of nicotine on cardiovascular and hormonal effects of cigarette smoking. Clinical Pharmacology & Therapeutics 36(1):74-81. Benowitz, N. L., G. A. Fitzgerald, M. Wilson, and Q. Zhang. 1993. Nicotine effects on eicosanoid formation and hemostatic function: Comparison of transdermal nicotine and cigarette smoking. Journal of the American College of Cardiology 22(4):1159-1167. Bernhard, D., A. Rossmann, B. Henderson, M. Kind, A. Seubert, and G. Wick. 2006. Increased serum cadmium and strontium levels in young smokers: Effects on arterial endothelial cell gene transcription. Arteriosclerosis, Thrombosis & Vascular Biology 26(4):833-838. Bhatnagar, A. 2004. Cardiovascular pathophysiology of environmental pollutants. American Journal of Physiology—Heart & Circulatory Physiology 286(2):H479-H485. ———. 2006. Environmental cardiology: Studying mechanistic links between pollution and heart disease. Circulation Research 99(7):692-705. Brook, R. D. 2005. You are what you breathe: Evidence linking air pollution and blood pres- sure. Current Hypertension Reports 7(6):427-434.

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE Brook, R. D., J. R. Brook, and S. Rajagopalan. 2003. Air pollution: The “heart” of the prob- lem. Current Hypertension Reports 5(1):32-39. Brook, R. D., B. Franklin, W. Cascio, Y. Hong, G. Howard, M. Lipsett, R. Luepker, M. Mittleman, J. Samet, S. C. Smith, Jr., and I. Tager. Expert Panel on Population and Prevention Science of the American Heart Association. 2004. Air pollution and car- diovascular disease: A statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association. Circulation 109(21):2655-2671. Brunnemann, K. D., M. R. Kagan, J. E. Cox, and D. Hoffmann. 1990. Analysis of 1,3-butadiene and other selected gas-phase components in cigarette mainstream and sidestream smoke by gas chromatography-mass selective detection. Carcinogenesis 11(10):1863-1868. Buccelletti, E., E. Gilardi, E. Scaini, L. Galiuto, R. Persiani, A. Biondi, F. Basile, and N. G. Silveri. 2009. Heart rate variability and myocardial infarction: Systematic literature review and metanalysis. European Review for Medical and Pharmacological Sciences 13(4):299-307. Burghuber, O. C., C. Punzengruber, H. Sinzinger, P. Haber, and K. Silberbauer. 1986. Platelet sensitivity to prostacyclin in smokers and non-smokers. Chest 90(1):34-38. Burke, A., and G. A. FitzGerald. 2003. Oxidative stress and smoking-induced vascular injury. Progress in Cardiovascular Diseases 46(1):79-90. Burstyn, I., H. Kromhout, T. Partanen, O. Svane, S. Langard, W. Ahrens, T. Kauppinen, I. Stucker, J. Shaham, D. Heederik, G. Ferro, P. Heikkila, M. Hooiveld, C. Johansen, B. G. Randem, and P. Boffetta. 2005. Polycyclic aromatic hydrocarbons and fatal ischemic heart disease. Epidemiology 16(6):744-750. Cal EPA (California Environmental Protection Agency). 1991. Proposed identification of , butadiene as a toxic air contaminant. Sacramento: California Environmental Protection Agency. ———. 2005a. Proposed identification of environmental tobacco smoke as a toxic air con- taminant. Part A: Exposure assessment. Sacramento: California Environmental Protec- tion Agency. ———. 2005b. Proposed identification of environmental tobacco smoke as a toxic air con- taminant. Part B: Health effects. Sacramento: California Environmental Protection Agency. Caralis, D. G., U. Deligonul, M. J. Kern, and J. D. Cohen. 1992. Smoking is a risk factor for coronary spasm in young women. Circulation 85(3):905-909. Cassee, F. R., J. H. Arts, J. P. Groten, and V. J. Feron. 1996. Sensory irritation to mix- tures of formaldehyde, acrolein, and acetaldehyde in rats. Archives of Toxicology 70(6):329-337. Chalon, S., H. Moreno, Jr., N. L. Benowitz, B. B. Hoffman, and T. F. Blaschke. 2000. Nicotine impairs endothelium-dependent dilatation in human veins in vivo. Clinical Pharmacology & Therapeutics 67(4):391-397. Chang, S. J., C. J. Chen, T. S. Shih, T. C. Chou, and F. C. Sung. 2007. Risk for hypertension in workers exposed to carbon disulfide in the viscose rayon industry. American Journal of Industrial Medicine 50(1):22-27. Chelland Campbell, S., R. J. Moffatt, and B. A. Stamford. 2008. Smoking and smoking ces- sation—the relationship between cardiovascular disease and lipoprotein metabolism: A review. Atherosclerosis 201(2):225-235. Chow, J. C., J. G. Watson, J. L. Mauderly, D. L. Costa, R. E. Wyzga, S. Vedal, G. M. Hidy, S. L. Altshuler, D. Marrack, J. M. Heuss, G. T. Wolff, C. A. Pope, and D.W. Dockery. 2006. Health effects of fine particulate matter air pollution: Lines that connect. Journal of the Air & Waste Management Association 56:1368-1380.

OCR for page 59
 SECONDHAND SMOKE EXPOSURE Clark, J. D., 3rd, J. D. Wilkinson, W. G. LeBlanc, N. A. Dietz, K. L. Arheart, L. E. Fleming, and D. J. Lee. 2008. Inflammatory markers and secondhand tobacco smoke exposure among U.S. Workers. American Journal of Industrial Medicine 51(8):626-632. Conklin, D. J., P. Haberzettl, R. A. Prough, and A. Bhatnagar. 2009. Glutathione S-transfer- S-transfer- ase P protects against endothelial dysfunction induced by exposure to tobacco smoke. American Journal of Physiology—Heart & Circulatory Physiology. Cucina, A., P. Sapienza, V. Borrelli, V. Corvino, G. Foresi, B. Randone, A. Cavallaro, and L. Santoro-D’Angelo. 2000a. Nicotine reorganizes cytoskeleton of vascular endothelial cell through platelet-derived growth factor BB. Journal of Surgical Research 92(2):233-238. Cucina, A., P. Sapienza, V. Corvino, V. Borrelli, V. Mariani, B. Randone, L. Santoro D’Angelo, and A. Cavallaro. 2000b. Nicotine-induced smooth muscle cell proliferation is mediated through bFGF and TGF-beta 1. Surgery 127(3):316-322. Cucina, A., P. Sapienza, V. Corvino, V. Borrelli, B. Randone, L. Santoro-D’Angelo, and A. Cavallaro. 2000c. Nicotine induces platelet-derived growth factor release and cytoskel- etal alteration in aortic smooth muscle cells. Surgery 127(1):72-78. Daisey, J. M. 1999. Tracers for assessing exposure to environmental tobacco smoke: What are they tracing? Environmental Health Perspectives 107 Suppl 2:319-327. Davis, J. W., L. Shelton, I. S. Watanabe, and J. Arnold. 1989. Passive smoking affects endo- thelium and platelets. Archives of Internal Medicine 149(2):386-389. de Sousa, M. G., J. C. Yugar-Toledo, M. Rubira, S. E. Ferreira-Melo, R. Plentz, D. Barbieri, F. Consolim-Colombo, M. C. Irigoyen, and H. Moreno, Jr. 2005. Ascorbic acid improves impaired venous and arterial endothelium-dependent dilation in smokers. Acta Pharma- cologica Sinica 26(4):447-452. Delfino, R. J., C. Sioutas, and S. Malik. 2005. Potential role of ultrafine particles in associa- tions between airborne particle mass and cardiovascular health. Environmental Health Perspectives 113(8):934-946. Di Luozzo, G., S. Pradhan, A. K. Dhadwal, A. Chen, H. Ueno, and B. E. Sumpio. 2005. Nicotine induces mitogen-activated protein kinase dependent vascular smooth muscle cell migration. Atherosclerosis 178(2):271-277. Dietrich, D. F., J. Schwartz, C. Schindler, J.-M. Gaspoz, J.-C. Barthelemy, J.-M. Tschopp, F. Roche, A. von Eckardstein, O. Brandli, P. Leuenberger, D. R. Gold, U. Ackermann- Liebrich, and S. Team. 2007. Effects of passive smoking on heart rate variability, heart rate and blood pressure: An observational study. International Journal of Epidemiology 36(4):834-840. Dong, J. Z., and S. C. Moldoveanu. 2004. Gas chromatography-mass spectrometry of car- bonyl compounds in cigarette mainstream smoke after derivatization with 2,4-dinitro- phenylhydrazine. Journal of Chromatography A 1027(1-2):25-35. Eaton, M., H. Gursahani, Y. Arieli, K. Pinkerton, and S. Schaefer. 2006. Acute tobacco smoke exposure promotes mitochondrial permeability transition in rat heart. Journal of Toxicol- ogy and Environmental Health—Part A: Current Issues 69(15):1497-1510. Egeland, G. M., G. A. Burkhart, T. M. Schnorr, R. W. Hornung, J. M. Fajen, and S. T. Lee. 1992. Effects of exposure to carbon disulphide on low density lipoprotein choles- choles- terol concentration and diastolic blood pressure. British Journal of Industrial Medicine 49(4):287-293. Esterbauer, H., R. J. Schaur, and H. Zollner. 1991. Chemistry and biochemistry of 4- hydroxynonenal, malonaldehyde and related aldehydes. Free Radical Biology & Medi- cine 11(1):81-128. Flouris, A. D., G. S. Metsios, A. Z. Jamurtas, and Y. Koutedakis. 2008. Sexual dimorphism in the acute effects of secondhand smoke on thyroid hormone secretion, inflammatory markers and vascular function. American Journal of Physiology—Endocrinology and Metabolism 294(2).

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE Giannini, D., A. Leone, D. Di Bisceglie, M. Nuti, G. Strata, F. Buttitta, L. Masserini, and A. Balbarini. 2007. The effects of acute passive smoke exposure on endothelium-dependent brachial artery dilation in healthy individuals. Angiology 58(2):211-217. Gonick, H. C., Y. Ding, S. C. Bondy, Z. Ni, and N. D. Vaziri. 1997. Lead-induced hypertension: Interplay of nitric oxide and reactive oxygen species. Hypertension 30(6):1487-1492. Green, M. A., and J. L. Egle, Jr. 1983. Effects of intravenous acetaldehyde, acrolein, form- aldehyde and propionaldehyde on arterial blood pressure following acute guanethi- dine treatment. Research Communications in Chemical Pathology & Pharmacology 40(2):337-340. Guberan, E., and L. Raymond. 1985. Mortality and cancer incidence in the perfumery and flavour industry of geneva. British Journal of Industrial Medicine 42(4):240-245. Haass, M., and W. Kubler. 1997. Nicotine and sympathetic neurotransmission. Cardiovascular Drugs and Therapy 10(6):657-665. Haberzettl, P., E. Vladykovskaya, S. Srivastava, and A. Bhatnagar. 2009. Role of endoplasmic reticulum stress in acrolein-induced endothelial activation. Toxicology & Applied Phar- macology 234(1):14-24. Hadi, H. A., C. S. Carr, and J. Al Suwaidi. 2005. Endothelial dysfunction: Cardiovascular risk factors, therapy, and outcome. Vascular Health and Risk Management 1(3):183-198. Hanna, S. T. 2006. Nicotine effect on cardiovascular system and ion channels. Journal of Cardiovascular Pharmacology 47(3):348-358. Hatsukami, D. K., N. L. Benowitz, S. I. Rennard, C. Oncken, and S. S. Hecht. 2006. Bio- markers to assess the utility of potential reduced exposure tobacco products. Nicotine & Tobacco Research 8(2):169-191. Hausberg, M., and V. K. Somers. 2008. Environmental smoke exposure: A complex cardio- vascular challenge. Hypertension 51(6):1468-1469. Hausberg, M., A. L. Mark, M. D. Winniford, R. E. Brown, and V. K. Somers. 1997. Sympa- thetic and vascular effects of short-term passive smoke exposure in healthy nonsmokers. Circulation 96(1):282-287. Heavner, D., W. T. Morgan, and M. W. Odgen. 1996. Determination of volatile organic compounds and respirable suspended particulate matter in New Jersey and Pennsylvania homes and workplaces. Environment International 22:159-183. Heeschen, C., J. J. Jang, M. Weis, A. Pathak, S. Kaji, R. S. Hu, P. S. Tsao, F. L. Johnson, and J. P. Cooke. 2001. Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. Nature Medicine 7(7):833-839. Heeschen, C., M. Weis, and J. P. Cooke. 2003. Nicotine promotes arteriogenesis. Journal of the American College of Cardiology 41(3):489-496. Heiss, C., N. Amabile, A. C. Lee, W. M. Real, S. F. Schick, D. Lao, M. L. Wong, S. Jahn, F. S. Angeli, P. Minasi, M. L. Springer, S. K. Hammond, S. A. Glantz, W. Grossman, J. R. Balmes, and Y. Yeghiazarians. 2008. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function: Sustained vascular injury and blunted nitric oxide production. Journal of the American College of Cardiology 51(18):1760-1771. Hellerstein, M. K., N. L. Benowitz, R. A. Neese, J. M. Schwartz, R. Hoh, P. Jacob, 3rd, J. Hsieh, and D. Faix. 1994. Effects of cigarette smoking and its cessation on lipid me- tabolism and energy expenditure in heavy smokers. Journal of Clinical Investigation 93(1):265-272. Hergens, M. P., M. Lambe, G. Pershagen, and W. Ye. 2008. Risk of hypertension amongst Swed- ish male snuff users: A prospective study. Journal of Internal Medicine 264(2):187-194. HHS (U.S. Department of Health and Human Services). 2001. Risks associated with smok- ing cigarettes with low machine-measured yields of tar and nicotine. Bethesda, MD: National Institutes of Health, National Cancer Institute.

OCR for page 59
 SECONDHAND SMOKE EXPOSURE ———. 2004. The health consequences of smoking: A report of the surgeon general. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. ———. 2006. The health consequences of involuntary exposure to tobacco smoke: A report of the surgeon general. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Of- fice on Smoking and Health. Houston, T. K., S. D. Person, M. J. Pletcher, K. Liu, C. Iribarren, and C. I. Kiefe. 2006. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study. BMJ 332(7549):1064-1069. Ingebrethsen, B. J. 1986. Aerosol studies of cigarette smoke. Recent Advances in Tobacco Science 12: 54-142. Jackson, M. A., H. F. Stack, J. M. Rice, and M. D. Waters. 2000. A review of the ge- netic and related effects of 1,3-butadiene in rodents and humans. Mutation Research 463(3):181-213. Jakab, G. J. 1993. The toxicologic interactions resulting from inhalation of carbon black and acrolein on pulmonary antibacterial and antiviral defenses. Toxicology & Applied Pharmacology 121(2):167-175. Jamall, I. S., and H. Roque. 1989. Cadmium-induced alterations in ocular trace elements. Influence of dietary selenium and copper. Biological Trace Element Research 23:55-63. Jiang, D. J., S. J. Jia, J. Yan, Z. Zhou, Q. Yuan, and Y. J. Li. 2006. Involvement of DDAH/ ADMA/NOS pathway in nicotine-induced endothelial dysfunction. Biochemical & Bio- physical Research Communications 349(2):683-693. Juhasz, A., and N. Bodor. 2000. Cardiovascular studies on different classes of soft drugs. Pharmazie 55(3):228-238. Kato, M., P. Roberts-Thomson, B. G. Phillips, K. Narkiewicz, W. G. Haynes, C. A. Pesek, and V. K. Somers. 1999. The effects of short-term passive smoke exposure on endothelium- dependent and independent vasodilation. Journal of Hypertension 17(10):1395-1401. Kato, T., T. Inoue, T. Morooka, N. Yoshimoto, and K. Node. 2006. Short-term passive smok- ing causes endothelial dysfunction via oxidative stress in nonsmokers. Canadian Journal of Physiology & Pharmacology 84(5):523-529. Kilburn, K. H., and W. N. McKenzie. 1978. Leukocyte recruitment to airways by alde- hyde-carbon combinations that mimic cigarette smoke. Laboratory Investigation 38(2): 134-142. Knight-Lozano, C. A., C. G. Young, D. L. Burow, Z. Y. Hu, D. Uyeminami, K. E. Pinkerton, H. Ischiropoulos, and S. W. Ballinger. 2002. Cigarette smoke exposure and hyper- cholesterolemia increase mitochondrial damage in cardiovascular tissues. Circulation 105(7):849-854. Kotseva, K. P., and D. De Bacquer. 2000. Cardiovascular effects of occupational exposure to carbon disulphide. Occupational Medicine (London) 50(1):43-47. Kotseva, K., and T. Popov. 1998. Study of the cardiovascular effects of occupational exposure to organic solvents. International Archives of Occupational & Environmental Health 71 Suppl:S87-S91. Kuo, H. W., J. S. Lai, M. Lin, and E. S. Su. 1997. Effects of exposure to carbon disulfide (CS2) on electrocardiographic features of ischemic heart disease among viscose rayon factory workers. International Archives of Occupational & Environmental Health 70(1): 61-66.

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE Lane, D., E. A. Gray, R. S. Mathur, and S. P. Mathur. 2005. Up-regulation of vascular en- dothelial growth factor-C by nicotine in cervical cancer cell lines. American Journal of Reproduction Immunology 53(3):153-158. Latha, M. S., P. L. Vijayammal, and P. A. Kurup. 1991. Changes in the glycosaminoglycans and glycoproteins in the tissues in rats exposed to cigarette smoke. Atherosclerosis 86(1):49-54. Lau, P. P., L. Li, A. J. Merched, A. L. Zhang, K. W. Ko, and L. Chan. 2006. Nicotine induces proinflammatory responses in macrophages and the aorta leading to acceleration of ath- erosclerosis in low-density lipoprotein receptor(-/-) mice. Arteriosclerosis, Thrombosis & Vascular Biology 26(1):143-149. Law, M. R., and N. J. Wald. 2003. Environmental tobacco smoke and ischemic heart disease. Progress in Cardiovascular Diseases 46(1):31-38. Ledford, H. 2008. Drug markers questioned. Nature 452(7187):510-511. Lee, P. N. 2007. Circulatory disease and smokeless tobacco in western populations: A review of the evidence. International Journal of Epidemiology 36(4):789-804. Levine, R. J., D. A. Andjelkovich, and L. K. Shaw. 1984. The mortality of Ontario undertak- ers and a review of formaldehyde-related mortality studies. Journal of Occupational Medicine 26(10):740-746. Lindahl, B., H. Toss, A. Siegbahn, P. Venge, and L. Wallentin. 2000. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. New England Journal of Medicine 343(16):1139-1147. Luo, J., B. G. Hill, Y. Gu, J. Cai, S. Srivastava, A. Bhatnagar, and S. D. Prabhu. 2007. Mecha- nisms of acrolein-induced myocardial dysfunction: Implications for environmental and endogenous aldehyde exposure. American Journal of Physiology—Heart & Circulatory Physiology 293(6):H3673-H3684. Lustberg, M., and E. Silbergeld. 2002. Blood lead levels and mortality. Archives of Internal Medicine 162(21):2443-2449. Mack, W. J., T. Islam, Z. Lee, R. H. Selzer, and H. N. Hodis. 2003. Environmental tobacco smoke and carotid arterial stiffness. Preventive Medicine 37(2):148-154. Magos, G. A., M. Lorenzana-Jimenez, and H. Vidrio. 1990. Toluene and benzene inhala- tion influences on ventricular arrhythmias in the rat. Neurotoxicology & Teratology 12(2):119-124. Mahmud, A., and J. Feely. 2004. Effects of passive smoking on blood pressure and aortic pres- sure waveform in healthy young adults—influence of gender. British Journal of Clinical Pharmacology 57(1):37-43. Marques, M., I. Millas, A. Jimenez, E. Garcia-Colis, J. A. Rodriguez-Feo, S. Velasco, A. Barrientos, S. Casado, and A. Lopez-Farre. 2001. Alteration of the soluble guanylate cyclase system in the vascular wall of lead-induced hypertension in rats. Journal of the American Science of Nephrology 12(12):2594-2600. Matanoski, G. M., and X. Tao. 2002. Case-cohort study of styrene exposure and ischemic heart disease. Research Report—Health Effects Institute (108):1-29. McDonald, T. P., D. Woodard, and M. Cottrell. 1973. Effect of nicotine on clot retraction of rat blood platelets. Pharmacology 9(6):357-366. McMurray, R. G., L. L. Hicks, and D. L. Thompson. 1985. The effects of passive inhalation of cigarette smoke on exercise performance. European Journal of Applied Physiology & Occupational Physiology 54(2):196-200. McNabola, A., B. Broderick, P. Johnston, and L. Gill. 2006. Effects of the smoking ban on benzene and 1,3-butadiene levels in pubs in Dublin. Journal of Environmental Sci- ence and Health, Part A Toxic/Hazardous Substances and Environmental Engineering 41(5):799-810.

OCR for page 59
0 SECONDHAND SMOKE EXPOSURE Metsios, G. S., A. D. Flouris, A. Z. Jamurtas, A. E. Carrillo, D. Kouretas, A. E. Germenis, K. Gourgoulianis, T. Kiropoulos, M. N. Tzatzarakis, A. M. Tsatsakis, and Y. Koutedakis. 2007. Brief report: A brief exposure to moderate passive smoke increases metabolism and thyroid hormone secretion. Journal of Clinical Endocrinology and Metabolism 92(1):208-211. Minami, J., T. Ishimitsu, and H. Matsuoka. 1999. Effects of smoking cessation on blood pres- sure and heart rate variability in habitual smokers. Hypertension 33(1 Pt 2):586-590. Modesti, P. A., R. Abbate, G. F. Gensini, A. Colella, and G. G. Neri Serneri. 1989. Platelet thromboxane A2 receptors in habitual smokers. Thrombosis Research 55(2):195-201. Moffatt, R. J., K. D. Biggerstaff, and B. A. Stamford. 2000. Effects of the transdermal nico- tine patch on normalization of HDL-C and its subfractions. Preventive Medicine 31(2 Pt 1):148-152. Moffatt, R. J., S. A. Chelland, D. L. Pecott, and B. A. Stamford. 2004. Acute exposure to environmental tobacco smoke reduces HDL-C and HDL2-C. Preventive Medicine 38(5):637-641. Morrow, J. D., B. Frei, A. W. Longmire, J. M. Gaziano, S. M. Lynch, Y. Shyr, W. E. Strauss, J. A. Oates, and L. J. Roberts, 2nd. 1995. Increase in circulating products of lipid per- oxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. New England Journal of Medicine 332(18):1198-1203. Morvai, V., A. Hudak, G. Ungvary, and B. Varga. 1976. ECG changes in benzene, toluene and xylene poisoned rats. Acta Medica Academiae Scientarium Hungaricae 33(3):275-286. Morvai, V., E. Szakmary, and G. Ungvary. 2005. The effects of carbon disulfide and ethanol on the circulatory system of rats. Journal of Toxicology & Environmental Health Part A 68(10):797-809. Moskowitz, W. B., M. Mosteller, R. M. Schieken, R. Bossano, J. K. Hewitt, J. N. Bodurtha, and J. P. Segrest. 1990. Lipoprotein and oxygen transport alterations in passive smoking preadolescent children. The MCV Twin Study. Circulation 81(2):586-592. Navas-Acien, A., E. Selvin, A. R. Sharrett, E. Calderon-Aranda, E. Silbergeld, and E. Guallar. 2004. Lead, cadmium, smoking, and increased risk of peripheral arterial disease. Circula- tion 109(25):3196-3201. Nawrot, T. S., L. Thijs, E. M. Den Hond, H. A. Roels, and J. A. Staessen. 2002. An epide- miological re-appraisal of the association between blood pressure and blood lead: A meta-analysis. Journal of Human Hypertension 16(2):123-131. Nemr, R., B. Lasserre, and R. Chahine. 2003. Effects of nicotine on thromboxane/prostacyclin balance in myocardial ischemia. Prostaglandins Leukotrienes & Essential Fatty Acids 68(3):191-195. Neunteufl, T., U. Priglinger, S. Heher, M. Zehetgruber, G. Soregi, S. Lehr, K. Huber, G. Maurer, F. Weidinger, and K. Kostner. 2000. Effects of vitamin E on chronic and acute endothelial dysfunction in smokers. Journal of the American College of Cardiology 35(2):277-283. Nicod, P., R. Rehr, M. D. Winniford, W. B. Campbell, B. G. Firth, and L. D. Hillis. 1984. Acute systemic and coronary hemodynamic and serologic responses to cigarette smok- ing in long-term smokers with atherosclerotic coronary artery disease. Journal of the American College of Cardiology 4(5):964-971. Nowack, R., D. Fliser, J. Richter, C. Horne, E. Mutschler, and E. Ritz. 1993. Effects of angio- angio- tensin-converting enzyme inhibition on renal sodium handling after furosemide injection. The Clinical Investigator 71(8):622-627. NRC (National Research Council). 1986. Environmental tobacco smoke: Measuring expo- sures and assessing health effects. Washington, DC: National Academy Press.

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE Omae, K., T. Takebayashi, T. Nomiyama, C. Ishizuka, H. Nakashima, T. Uemura, S. Tanaka, T. Yamauchi, T. O’Uchi, Y. Horichi, and H. Sakurai. 1998. Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing workers. Occupational & Environmental Medicine 55(7):468-472. O’Toole, T. E., Y. T. Zheng, J. Hellmann, D. J. Conklin, O. Barski, and A. Bhatnagar. 2009. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages. Toxicology and Applied Pharmacology 236(2):194-201. Otsuka, R., H. Watanabe, K. Hirata, K. Tokai, T. Muro, M. Yoshiyama, K. Takeuchi, and J. Yoshikawa. 2001. Acute effects of passive smoking on the coronary circulation in healthy young adults. JAMA 286(4):436-441. Packard, C. J., D. S. O’Reilly, M. J. Caslake, A. D. McMahon, I. Ford, J. Cooney, C. H. Macphee, K. E. Suckling, M. Krishna, F. E. Wilkinson, A. Rumley, and G. D. Lowe. 2000. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland coronary prevention study group. New England Journal of Medicine 343(16):1148-1155. Partanen, T., S. Hernberg, C. H. Nordman, and P. Sumari. 1970. Coronary heart disease among workers exposed to carbon disulphide. British Journal of Industrial Medicine 27(4):313-325. Penn, A., and C. A. Snyder. 1996. Butadiene inhalation accelerates arteriosclerotic plaque development in cockerels. Toxicology 113(1-3):351-354. Pilz, H., A. Oguogho, F. Chehne, G. Lupattelli, B. Palumbo, and H. Sinzinger. 2000. Quitting cigarette smoking results in a fast improvement of in vivo oxidation injury (determined via plasma, serum and urinary isoprostane). Thrombosis Research 99(3):209-221. Pope, C. A., 3rd, R. T. Burnett, G. D. Thurston, M. J. Thun, E. E. Calle, D. Krewski, and J. J. Godleski. 2004. Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Circulation 109(1):71-77. Probst-Hensch, N. M., M. Imboden, D. Felber Dietrich, J. C. Barthelemy, U. Ackermann- Liebrich, W. Berger, J. M. Gaspoz, and J. Schwartz. 2008. Glutathione S-transferase polymorphisms, passive smoking, obesity, and heart rate variability in nonsmokers. Environmental Health Perspectives 116(11):1494-1499. Rahman, M. M., and I. Laher. 2007. Structural and functional alteration of blood vessels caused by cigarette smoking: An overview of molecular mechanisms. Current Vascular Pharmacology 5(4):276-292. Raitakari, O. T., M. R. Adams, R. J. McCredie, K. A. Griffiths, R. Stocker, and D. S. Celermajer. 2000. Oral vitamin C and endothelial function in smokers: Short-term improvement, but no sustained beneficial effect. Journal of the American College of Cardiology 35(6):1616-1621. Ramachandran, J., D. Rubenstein, D. Bluestein, and J. Jesty. 2004. Activation of platelets exposed to shear stress in the presence of smoke extracts of low-nicotine and zero- nicotine cigarettes: The protective effect of nicotine. Nicotine & Tobacco Research 6(5):835-841. Ramos, K. S., and B. Moorthy. 2005. Bioactivation of polycyclic aromatic hydrocarbon carcinogens within the vascular wall: Implications for human atherogenesis. Drug Me- tabolism Reviews 37(4):595-610. Raupach, T., K. Schafer, S. Konstantinides, and S. Andreas. 2006. Secondhand smoke as an acute threat for the cardiovascular system: A change in paradigm. European Heart Journal 27(4):386-392. Revis, N. W., A. R. Zinsmeister, and R. Bull. 1981. Atherosclerosis and hypertension induc- tion by lead and cadmium ions: An effect prevented by calcium ion. Proceedings of the National Academy of Sciences of the United States of America 78(10):6494-6498.

OCR for page 59
 SECONDHAND SMOKE EXPOSURE Roberts, K. A., A. A. Rezai, K. E. Pinkerton, and J. C. Rutledge. 1996. Effect of environmental tobacco smoke on LDL accumulation in the artery wall. Circulation 94(9):2248-2253. Rocchi, E., F. Bursi, P. Ventura, A. Ronzoni, C. Gozzi, G. Casalgrandi, L. Marri, R. Rossi, and M. G. Modena. 2007. Anti- and pro-oxidant factors and endothelial dysfunction in chronic cigarette smokers with coronary heart disease. European Journal of Internal Medicine 18(4):314-320. Saareks, V., P. Ylitalo, J. Alanko, I. Mucha, and A. Riutta. 2001. Effects of smoking cessation and nicotine substitution on systemic eicosanoid production in man. Naunyn-Schmiede- bergs Archives of Pharmacology 363(5):556-561. Sklar, J. L., P. G. Anderson, and P. J. Boor. 1991. Allylamine and acrolein toxicity in perfused rat hearts. Toxicology & Applied Pharmacology 107(3):535-544. Smith, C. J., and T. H. Fischer. 2001. Particulate and vapor phase constituents of cigarette mainstream smoke and risk of myocardial infarction. Atherosclerosis 158(2):257-267. Smith, C. J., T. A. Perfetti, M. A. Mullens, A. Rodgman, and D. J. Doolittle. 2000a. “IARC Group 2B carcinogens” reported in cigarette mainstream smoke. Food & Chemical Toxicology 38(9):825-848. Smith, C. J., T. A. Perfetti, M. A. Rumple, A. Rodgman, and D. J. Doolittle. 2000b. “IARC Group 2A carcinogens” reported in cigarette mainstream smoke. Food & Chemical Toxicology 38(4):371-383. Stefanadis, C., C. Vlachopoulos, E. Tsiamis, L. Diamantopoulos, K. Toutouzas, N. Giatrakos, S. Vaina, D. Tsekoura, and P. Toutouzas. 1998. Unfavorable effects of passive smoking on aortic function in men. Annals of Internal Medicine 128(6):426-434. Stewart, P. A., C. Schairer, and A. Blair. 1990. Comparison of jobs, exposures, and mor- tality risks for short-term and long-term workers. Journal of Occupational Medicine 32(8):703-708. Stone, P. H., and J. J. Godleski. 1999. First steps toward understanding the pathophysiologic link between air pollution and cardiac mortality. American Heart Journal 138(5 Pt 1):804-807. Subramanyam, G., M. Bhaskar, and S. Govindappa. 1992. The role of cadmium in induction of atherosclerosis in rabbits. Indian Heart Journal 44(3):177-180. Sun, Y. P., B. Q. Zhu, R. E. Sievers, S. A. Glantz, and W. W. Parmley. 1994. Metoprolol does not attenuate atherosclerosis in lipid-fed rabbits exposed to environmental tobacco smoke. Circulation 89(5):2260-2265. Sweetnam, P. M., S. W. Taylor, and P. C. Elwood. 1987. Exposure to carbon disulphide and ischaemic heart disease in a viscose rayon factory. British Journal of Industrial Medicine 44(4):220-227. Sztalryd, C., J. Hamilton, B. A. Horwitz, P. Johnson, and F. B. Kraemer. 1996. Alterations of lipolysis and lipoprotein lipase in chronically nicotine-treated rats. American Journal of Physiology 270(2 Pt 1):E215-E223. Takase, B., H. Etsuda, Y. Matsushima, M. Ayaori, H. Kusano, A. Hamabe, A. Uehata, F. Ohsuzu, M. Ishihara, and A. Kurita. 2004. Effect of chronic oral supplementation with vitamins on the endothelial function in chronic smokers. Angiology 55(6):653-660. Therond, P. 2009. Catabolism of lipoproteins and metabolic syndrome. Current Opinion in Clinical Nutrition and Metabolic Care 12(4):366-371. Thomas, S. R., P. K. Witting, and G. R. Drummond. 2008. Redox control of endothelial func- tion and dysfunction: Molecular mechanisms and therapeutic opportunities. Antioxidants & Redox Signaling 10(10):1713-1765. Tripathi, R. M., and G. P. Thomas. 1986. A simple method for the production of ven- tricular tachycardia in the rat and guinea pig. Journal of Pharmacological Methods 15(3):279-282.

OCR for page 59
 PATHOPHYSIOLOGY OF SECONDHAND SMOKE Tucker, L. A. 1989. Use of smokeless tobacco, cigarette smoking, and hypercholesterolemia. American Journal of Public Health 79(8):1048-1050. Venn, A., and J. Britton. 2007. Exposure to secondhand smoke and biomarkers of cardiovas- cular disease risk in never-smoking adults. Circulation 115(8):990-995. von Klot, S., A. Peters, P. Aalto, T. Bellander, N. Berglind, D. D’Ippoliti, R. Elosua, A. Hormann, M. Kulmala, T. Lanki, H. Lowel, J. Pekkanen, S. Picciotto, J. Sunyer, and F. Forastiere. 2005. Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five european cities. Circula- tion 112(20):3073-3079. Wallenfeldt, K., J. Hulthe, L. Bokemark, J. Wikstrand, and B. Fagerberg. 2001. Carotid and femoral atherosclerosis, cardiovascular risk factors and C-reactive protein in relation to smokeless tobacco use or smoking in 58-year-old men. Journal of Internal Medicine 250(6):492-501. Walrath, J., and J. F. Fraumeni, Jr. 1984. Cancer and other causes of death among embalmers. Cancer Research 44(10):4638-4641. Wang, T. J. 2008. New cardiovascular risk factors exist, but are they clinically useful? Euro- pean Heart Journal 29(4):441-444. Weitzman, M., S. Cook, P. Auinger, T. A. Florin, S. Daniels, M. Nguyen, and J. P. Winickoff. 2005. Tobacco smoke exposure is associated with the metabolic syndrome in adolescents. Circulation 112(6):862-869. WHO (World Health Organization). 2007. The scientific basis of tobacco product regulation: Report of a WHO study group. Geneva, Switzerland: World Health Organization. Wilkinson, J. D., D. J. Lee, and K. L. Arheart. 2007. Secondhand smoke exposure and C- reactive protein levels in youth. Nicotine and Tobacco Research 9(2):305-307. Winniford, M. D., K. R. Wheelan, M. S. Kremers, V. Ugolini, E. van den Berg, Jr., E. H. Niggemann, D. E. Jansen, and L. D. Hillis. 1986. Smoking-induced coronary vasocon- striction in patients with atherosclerotic coronary artery disease: Evidence for adrenergi- cally mediated alterations in coronary artery tone. Circulation 73(4):662-667. Woodward, M., A. Rumley, C. Rumley, S. Lewington, C. E. Morrison, and G. D. Lowe. 2006. The association between homocysteine and myocardial infarction is independent of age, sex, blood pressure, cholesterol, smoking and markers of inflammation: The Glasgow Myocardial Infarction Study. Blood Coagulation & Fibrinolysis 17(1):1-5. Young, J. M., B. I. Shand, P. M. McGregor, R. S. Scott, and C. M. Frampton. 2006. Com- parative effects of enzogenol and vitamin C supplementation versus vitamin C alone on endothelial function and biochemical markers of oxidative stress and inflammation in chronic smokers. Free Radical Research 40(1):85-94. Yuan, H., L. S. Wong, M. Bhattacharya, C. Ma, M. Zafarani, M. Yao, M. Schneider, R. E. Pitas, and M. Martins-Green. 2007. The effects of second-hand smoke on biological processes important in atherogenesis. BMC Cardiovascular Disorders 7(1). Zhang, S., I. Day, and S. Ye. 2001. Nicotine induced changes in gene expression by human coronary artery endothelial cells. Atherosclerosis 154(2):277-283. Zhang, W. Z., K. Venardos, J. Chin-Dusting, and D. M. Kaye. 2006. Adverse effects of cigarette smoke on no bioavailability: Role of arginine metabolism and oxidative stress. Hypertension 48(2):278-285. Zhu, B. Q., Y. P. Sun, R. E. Sievers, W. M. Isenberg, S. A. Glantz, and W. W. Parmley. 1993. Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits. Journal of the American College of Cardiology 21(1):225-232. Zhu, B. Q., Y. P. Sun, R. E. Sievers, S. A. Glantz, W. W. Parmley, and C. L. Wolfe. 1994. Exposure to environmental tobacco smoke increases myocardial infarct size in rats. Circulation 89(3):1282-1290. Zoloth, S. R., D. M. Michaels, J. R. Villalbi, and M. Lacher. 1986. Patterns of mortality among commercial pressmen. Journal of the National Cancer Institute 76(6):1047-1051.

OCR for page 59