Research Paper- Ban on Smoking in Public Places

Article

Second-hand tobacco smoke and children

Eman M Al-Sayed 1

and Khadiga Salah Ibrahim 2

Abstract Cigarette smoke contains harmful chemicals with hazardous adverse effects on almost every organ in the body of smokers as well as of nonsmokers exposed to environmental tobacco smoke (ETS). There has been increasing interest in the effects of passive smoking on the health of children. In order to detect the magnitude of passive smoking in children, parental questionnaires, measuring nicotine and cotinine body levels, and evaluating expired carbon monoxide (CO) concentrations, have been used. Passive smoking causes respiratory illness, asthma, poor growth, neurological disorders, and coronary heart diseases. Herein, we focused on the deleterious influences of passive smoking on immunity and liver. Besides, its effects on the concentrations of various biomarker levels related to the oxidant/antioxidant status were considered. Understanding these effects may help clinicians to counsel parents on smoking cessation and smoke exposure elimination. It may also help to develop interventions to improve the health of children. This review potentially demonstrated some nutraceuticals with a promising role in the prevention of smoking-related diseases.

Keywords Passive smoking, children, liver, oxidant, antioxidants

Introduction

Health risks linked to environmental tobacco

smoke (ETS) exposure are being documented

more frequently in nonsmoking population. ETS

is a risk factor for cardiovascular disease, cancer,

and pulmonary diseases that were previously

attributed only to the long-term effects of active

smoking (Glantz and Parmley, 2001). There has

been increasing interest in the effects of passive

smoking on the health of children (Brady et al.,

2007; Hawamdeh et al., 2003). Children spend

much of their early life with their parents who

may smoke, thus exposing them to prolonged

close exposure to ETS. Lighting a cigarette cre-

ates over 4000 harmful chemicals with hazardous

adverse effects on almost every organ in the body

(El-Zayadi, 2006). The mechanism most often

cited as the cause of smoking-related disorders

is oxidant damage from free radicals generated

through cigarette smoke (CS) and from reactive

oxidants created by smoke-induced activation of

the inflammatory immune system (Moszczynski

et al., 2001).

Constituent of CS

Components of smoke are contained in either the

particulate phase or the gas phase. The particulate

phase ingredients include tar, polynuclear hydrocar-

bon phenol, cresol, catechol and trace elements

which are carcinogens; nicotine which is a ganglion

stimulator and depressor; and indol, carbazole

(tumor accelerators) and 4-aminobiphenyl which

cause hepatocellular carcinoma(Wang et al., 1998).

The gas phase contains carbon monoxide, hydrocya-

nic acid, acetaldehyde, acrolein, ammonia, formal-

dehyde and oxides of nitrogen, nitrosamines,

1 Department of Food Science and Nutrition, National Research Center, Dokki, Giza, Egypt 2 Department of Environmental and Occupational Medicine,

National Research Centre, Dokki, Giza, Egypt

Corresponding author: Khadiga Salah Ibrahim, Department of Environmental and Occupational Medicine, National Research Centre, Dokki, Giza 11141, Egypt. Email: [email protected]

Toxicology and Industrial Health 2014, Vol. 30(7) 635–644 © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0748233712462473 tih.sagepub.com

hydrazine, and vinylchloride that have carcinogenic

activity (Burns, 1991).

Measuring exposure to smoke

Considerable work has been undertaken to identify

ways of measuring the extent of tobacco smoke expo-

sure in nonsmokers. Exposure to tobacco smoke can be

measured by subjective and objective methods. To

detect the magnitude of passive smoking, parental

questionnaires have been used extensively. Question-

naires are generally used to measure the history of

exposure to ETS, but it is difficult to estimate the total

exposure from the questionnaire because parents may

change their smoking habits (Butz and Rosenstein,

1992). Also, it has been documented that self-reports

of smoking status may not always be reliable (Ohlin

et al., 1976). Furthermore, in passive smokers the range

of uptake could be influenced by proximity to the

source of smoke, time of exposure, and ventilation in

the environment (Greenberg et al., 1984). It seems nec-

essary to provide an objective measure of tobacco

smoke uptake by passive smoking. Cotinine is a major

metabolite of nicotine and is the most suitable marker

to measure passive exposure to tobacco smoke. Com-

pared with other metabolites, contine is more specific;

and compared with nicotine, it is found in body fluids

for a longer period of time. The half-life of cotinine in

children is between 37 and 160 h (Lynch, 1984) and

that of nicotine is 30 and 110 min (Isaac and Rand,

1972). Thus, the presence of cotinine is evaluated as

an indicator of long-term exposure to tobacco products,

whereas nicotine provides information about recent

exposure (Greenberg et al., 1984). Cotinine has been

demonstrated to be present in plasma, saliva and urine

of exposed individuals. It has been estimated from coti-

nine measurements that the total nicotine dose received

by children whose parents are smokers is equivalent to

the children actively smoking between 60 and 150

cigarettes per year. Salivary cotinine concentrations

measured in school children have been found to corre-

late strongly with the smoking habits of their parents.

Also, the measured cotinine levels correlate closely

with atmospheric nicotine levels and with the

results of questionnaires about household smoking

(Hawamdeh et al., 2003). Strachan et al., (1990) also

found significant levels of cotinine in children. This

results from their exposure to ETS as it is the only

source of cotinine in body fluids.

Another alternative marker to estimate the magni-

tude of ETS is carbon monoxide (CO) measurement

in children’s expired air (Gonzalez et al., 1998). CO

is produced in vivo in many tissues of the body by

an enzyme called heme oxygenase which is present

in the pulmonary vascular endothelium and alveolar

macrophages and is upregulated by oxidative stress

(Fukushima et al., 1995) and inflammatory cytokines

(Cantoni et al., 1991). Children with nonsmoking par-

ents had the lowest exhaled CO concentrations (Ece

et al., 2000)

Adverse effects of smoking on children health

Passive smoking may have harmful effects particu-

larly in children compared with adults because chil-

dren’s respiratory and immune systems are not fully

developed (Landrigan et al., 2003). In addition,

children spend more time at home and are, therefore,

likely to experience more intense and prolonged

smoke exposure from parental smoking. Exposure to

second-hand tobacco smoke increases a child’s risk

for many diseases, including lower respiratory infec-

tions (Baker et al., 2006), inflammatory bowl disease

(Mahid et al., 2007), sleep disturbances (Yolton et al.,

2010), bronchitis, pneumonia (Johansson et al., 2003),

otitis media (Ilicali et al., 2001) and leukemia (Chang

et al., 2006). Tobacco smoke is also linked to a variety

of behavioral issues and intellectual impairment in

children (Yolton et al., 2005). Lead (Pb) was proved

to be a component of tobacco. ETS smokers have

higher blood Pb levels than nonsmokers, and also

second-hand smoke (SHS) could be associated with

increased blood Pb level in children (Mannino et al.,

2003). The adverse effects of Pb on children’s intel-

lectual development are well documented (Koller

et al., 2004). Moreover, Nelson and his colleagues

(1999) and Gomes and Seraphim (2010) found that

passive smoking during pregnancy has a role in the

induction of fetal growth retardation. Besides,

Laskowska-Kitta et al. (2001) demonstrated that

passive smoking causes disturbances in postnatal

growth and development.

Adverse effects of passive smoking on children’s immunity

Passive smoking might affect the immune system of

children, thus increasing the risk of getting infected.

Smoking affects both cell-mediated and humoral

immune responses (Sopori and Kozak, 1998).

Nicotine blocks lymphocyte proliferation and differ-

entiation including suppression of antibody-forming

636 Toxicology and Industrial Health 30(7)

cells by inhibiting antigen-mediated signaling in

T-cells (Moszczynski et al., 2001) and ribonucleotide

reductase (McCue et al., 2000). Furthermore, smok-

ing induces apoptosis of lymphocytes by enhancing

the expression of Fas (CD 95) death receptor that

allows them to be killed by other cells expressing a

surface protein called Fas ligand (Fas L). Smoking

induces elevation of CD8 þ T cytotoxic lymphocytes (Watanabe et al., 1995), decreases CD4 þ cells, impairs natural killer cell activity (Zeidel et al.,

2002) and increases the production of proinflamma-

tory cytokines tumor necrosis factor-a, interleukin (IL)-1 and IL-6 (Moszczynski et al., 2001). Exposure

to tobacco smoke leads to alterations in the epithelial

function, such as reduced mucociliary activity,

decreased clearance of inhaled substances, and abnor-

mal vascular and epithelial permeability (Kum-Nji

et al., 2006). Furthermore, smoking can change the

amount, consistency and permeability of the mucous

(Arcavi and Benowitz, 2004). The number of alveolar

macrophages increases because of tobacco smoke

exposure, but their ability to phagocytose and/or kill

bacteria decreases (Behnia et al., 2000). As a result,

the innate immunity of the lung is compromised, and

it is easier for the infectious agents to reach the alveo-

lar tissue. T-cells are highly susceptible to CS, which

could impair their cytotoxic capacity to fight infec-

tions (Glader et al., 2006). Furthermore, smoking is

associated with reductions in serum immunoglobu-

lins, T-lymphocyte helper/suppressor cell ratios and

natural killer cytotoxic activity (Sopori, 2002), which,

in turn, may result in a decreased immune response of

the body to infections. Passive smoking increases the

susceptibility of children to mycobacterium tubercu-

losis infection (den-Boon et al., 2007). This associa-

tion is a cause for great concern, considering the

high prevalence of smoking and tuberculosis in most

of the developing countries.

Adverse effects of smoking on the liver

Smoking causes a variety of adverse effects on organs

that have no direct contact with the smoke itself such

as liver. It induces three major adverse effects on the

liver: direct toxic effects, immunological effects and

oncogenic effects (El-Zayadi, 2006). Basic and clini-

cal research had demonstrated that smoking alters

enzymatic and inflammatory pathways in liver phy-

siology. Mice exposed to SHS during 1 year in lab

showed fat accumulation in liver cells. Two key reg-

ulators of lipid metabolism are sterol regulatory

element binding protein (SREBP) that stimulates

synthesis of fatty acids in the liver, and adenosine

monophosphate kinase (AMPK) that turns SREBP

on and off. It was found that SHS exposure inhibits

AMPK activity, which, in turn, causes an increase

in SREBP activity and hence, more fatty acids get

synthesized. The result is nonalcoholic fatty liver

disease (NAFLD) induced by SHS (Ponciano-

Rodriguez and Mendez-Sanchez, 2010; Yuan et al.,

2009). Moreover, chemical substances created by

smoking have cyrotoxic potentials via induction of

oxidative stress associated with lipid peroxidation

(Florek et al., 2010) which leads to activation of

stellate cells and development of fibrosis.

In addition, liver cell injury is the result of proin-

flammatory cytokine production by CS(Moszczynski

et al., 2001).

An indirect toxic influence of smoking is hypoxia

that results from increased carboxyhemoglobin level

and decreased oxygen carrying capacity of red blood

cells. Hypoxia stimulates erythropoietin production

which induces hyperplasia of the bone marrow. The

latter contributes to the development of polycythemia

and in turn to increased red cell mass and turnover

(Young and Moss, 1989). Consequently increases

catabolic iron. Also, erythropoietin stimulates absorp-

tion of iron from intestine. Excess iron ultimately

leads to its accumulation in macrophages and subse-

quently in hepatocytes promoting oxidative stress

(Gutteridge and Halliwell, 1989). Increased iron level

in prepubertal and pubertal children has been demon-

strated to be implicated in increased alanine amino-

transferase activity (Okuda et al., 2011).

There is well-known link between smoking either

active or passive and lung cancer. However, epide-

miological studies have shown a relationship between

smoking and cancers of other organs and liver. Sora-

han and Lancashire (2004) reported that parental

smoking increases the risk of hepatoblastoma in their

children. The risk was doubled if both parents

smoked. Much evidence demonstrates that carcino-

genic DNA adducts are useful markers of tobacco

smoke exposure (Lodovici and Bigagli, 2009).

Smoking yields chemicals with oncogenic poten-

tials such as hydrocarbons, nitrosamine, tar,

vinylchoride and 4-amino biphenyl. In an animal

study, exposure of mice to mainstream CS for 120

days started immediately after birth resulted in an

early and potent carcinogenic response manifested

by the appearance of preneoplastic lesions in lung and

parenchymatous degeneration in liver (D’Agostini

Al-Sayed and Ibrahim 637

et al., 2008). Tobacco smoking is associated with

reduction of P53, the tumor suppressor gene (Wang

et al., 2004), consequently increases hepatocarcino-

genesis. Moreover, suppression of T-cell responses

by nicotine and tar is associated with decreased

surveillance of tumor cells (McCue et al., 2000).

Besides, excess iron in hepatocytes by smoking med-

iates fibrosis and favors development of hepatocellu-

larcarcinomas (El-Zayadi, 2006). On the other hand,

tobacco smoke contains toxic compounds such as

acrolein, acetaldehyde, acrylonitrile, and formalde-

hyde, that induce reactive oxygen species (ROS) such

as NO, NO2, peroxynitrite, and nitrosamines (Church

and Pryor, 1985). Acrolein has a highest hazard index

and causes oxidative stress by reacting with sulfhy-

dryl groups (Esterbauer et al., 1991). Children who

exposed to passive smoking are at high risk of cancer

due to free radicals (Kosecik et al., 2005). ROS can

cause cellular damage either directly by oxidizing

DNA thus inducing cancer or by oxidizing critical

regulatory proteins, lipids, and other cellular mole-

cules enable them to play a major role in cancerogeni-

city (Halliwell, 2007).

Changes in antioxidants levels in children exposed to second-hand tobacco smoke

Antioxidants neutralize free radicals through an array

of mechanisms and variety of methods, and while

they are produced endogenously. The body requires

exogenous supplementation from dietary sources for

antioxidants’ production (Anderson, 2007). Antioxi-

dant micronutrients include vitamins C, E and the

carotenoids. While vitamin B is not generally an anti-

oxidant, B2 does have some antioxidant properties

(Loscalzo, 1996). Folate is involved in many critical

physiological processes, including maintenance of red

blood cell function, DNA repair, and metabolism of

homocysteine which is an oxidative stressor (Matsui

and Matsui, 2009).

Vitamin C (ascorbic acid) is an effective free radi-

cal scavenger and is among the strongest determinants

of plasma antioxidant defense (Lykkesfeldt et al.,

2000). Also, passive smoking caused a decrease in

blood ascorbate with a resultant breakdown of the

plasma antioxidant defense system, with concomitant

increase in plasma lipid peroxide concentrations

(Valkonen and Kuusi, 1998). The magnitude of the

adverse effect of ETS exposure on vitamin C status

in children is largely dependent on the amount of

smoke exposure, the greater the concentration of

ambient smoke, the greater its effect will be on vita-

min C status. Consequently, a strong association is

found between children vitamin C blood levels and

their urinary cotinine concentrations (Preston et al.,

2003; Wilson et al., 2011). Children exposed to ETS

should be encouraged to consume increased amounts

of foods rich in vitamin C or should be given the

equivalent amount of this vitamin as a supplement.

The association between SHS exposure and lower

blood levels of b-Carotene, vitamin E and folate in children was demonstrated (Brady et al., 2007; Preston

et al., 2003; Wilson et al., 2011). Meanwhile the levels

of the nonantioxidant vitamins B6, B12 and D did not

differ, vitamin A is likely decreased in SHS-exposed

children due to a decrease in the levels of its precursor,

b-carotene (Wilson et al., 2011). Similar findings of decreased levels of b-carotene (Farchi et al., 2001), vitamin E and folate (Ford et al., 2003) were found

in studies of adults who smoke. The difference in anti-

oxidant status is not merely due to differences in chil-

dren nutritional status between smoke-exposed and

non-exposed children. Brady et al. (2007) and Alberg

(2002) have confirmed this finding as they showed that

ETS-exposed children have lower levels of aforemen-

tioned vitamins independently of their dietary intake.

Also, there is a dose–response relationship between

smoke exposure and antioxidant micronutrient levels

where the antioxidant levels differ by cotinine level

(Wilson et al., 2011).

Uric acid acts as an endogenous radical scavenger

and a nonnutrient antioxidant. When compared to

other antioxidants, uric acid has the highest concen-

tration of all antioxidants in the blood and provides

about half of the total antioxidant capacity of the

human body. It is a main contributor of total radical

trapping antioxidant parameter (TRAP) (Glantzounis

et al., 2005). It is well documented that uric acid

plasma level was extremely elevated in newborns and

in their active smoking mothers (Fayol et al., 2005).

This elevation of uric acid concentration may be a

defense mechanism against oxidative stress induced

by tobacco smoking or may result from increased red

cell mass and turnover by smoking which are associ-

ated with increased purine catabolism (El-Zayadi,

2006).

Promising nutraceuticals against smoking adverse effects

Although it is unclear how much the SHS exposure

related reduction in antioxidants, contributes to the

638 Toxicology and Industrial Health 30(7)

adverse health outcomes seen in children exposed to

tobacco smoke. Understanding these relationships

may help clinicians counsel parents on smoking ces-

sation and smoke exposure elimination and develop

interventions to improve the health of children who

continue to be exposed.

A significant decreased antioxidant levels was

observed even at very moderate exposure (serum coti-

nine level, 0.015–2.0 ng/ml) (Wilson et al., 2011).

Parents should be counseled that there is a health risk

at any level of SHS exposure and that the only way to

completely protect their children is to ensure they are

never exposed to tobacco smoke (Moritsugu, 2007).

Vitamin E or a-tocopherol is a lipid-soluble antiox- idant that represents the principal defense against

oxidant-induced membrane injury in man (Burton

et al., 1983). Selenium (Se) via its incorporation into

cytosolic glutathione peroxidase, an enzyme contain-

ing four selenium atoms bound as selenocysteine moi-

eties that confers the catalytic activity, appears to

control excessive production of peroxidative sub-

strates (Hayes et al., 2005). Vitamin E and selenium

have additive protective effects against CS hazards

on animals exposed to SHS. Vitamin E also has a pro-

tective effect on DNA against oxidation. Both vitamin

E and Se showed a significant protective effect on

changing activity of catechol-o-methyl transferase

(COMT) in liver which increased by smoking. They

also extremely protect the cell membrane by inhibit-

ing lipid peroxidation induced by smoking (Fiskin

et al., 2006) and by supporting the antioxidant enzy-

matic activities of superoxide dismutase (Cay et al.,

2009).

Cadmium (Cd) from CS accumulates in the human

prostate where it interacts with Se in a manner sug-

gesting the formation of a 1:1 Cd-Se-protein complex.

At low Cd exposures and adequate Se status, this

interaction may be beneficial as it results in detoxifi-

cation of Cd. At higher exposures, Cd may weaken or

abolish the anticarcinogenic effects of Se and increase

prostate cancer risk (Schopfer et al., 2010). Also, diet-

ary selenium inhibits pulmonary cell proliferation in

both control and CS exposed mice and this inhibition

may be related to Se concentration and glutathione

peroxidase activity (Li et al., 2009). Se in smokers

may be due to induction of immunity via enhancing

antibody response (Nquyen Van Binh et al., 2004).

Conflicting data on the relationship between dietary

supplementation of b-carotene and oxidative DNA damage have been reported in smokers. b-carotene has unexpectedly appeared to increase lung cancer risk

among smokers (Kleinjans et al., 2005) via activating

phase 1 carcinogen-bioactivating enzymes. Mean-

while, high plasma carotenoids were found to modulate

smoking-related hepatocellular carcinoma (HCC) risk

(Yu et al., 1999).

However, the results of clinical trials of antioxidants

supplementation in preventing oxidative stress-related

diseases have been mixed (Albanes, 2009). Also, most

studies have shown inconsistent effect of micronutrient

supplementation in smokers. Thus, a diet rich in a vari-

ety of fruits and vegetables, which has all antioxidant

vitamins, is considered the best way to supply smoker

with antioxidants (Wilson et al., 2011).

Probiotics are live microorganisms of human ori-

gin and their use may favorably influence human

health and ameliorate or prevent disease. Also, they

may protect the detoxification function of the kidney

and liver. Furthermore, they may help in adaptation to

tobacco smoking. Consumption of probiotic foods

reduces the risk of cancer in humans. Probiotics may

restore natural killer cell activity which is lowered in

smokers. It was observed that a diet supplemented

with Lactobacillus plantarum could be also useful

in the prevention of cardiovascular disease in smokers

(Hozyasz, 2008).

N-acetylcystein (NAC) is a thiol-containing com-

pound that nonenzymatically detoxifies reactive

electrophiles and free radicals. It is an analogue of the

naturally occurring scavenger glutathione (GSH). It has

GSH-replenishing properties that can be due to both its

role as a stable precursor of cysteine and its GSH-

sparing effect because of its antioxidant properties

(Fiordaliso et al., 2004). NAC has protective influences

on liver and lung of rats exposed to CS and fed low pro-

tein diet via protecting cell membranes from oxidation

and enhancing GSH concentrations (Alhamdan, 2005).

Flavonoids form a class of benzo-gamma-pyrone

derivatives, which are ubiquitous in photosynthesiz-

ing cells. A great interest in these substances has been

stimulated by the potential health benefits arising

from the antioxidant activity of these polyphenolic

compounds (Diplock et al., 1998).

Supplementation of epigallocatechin gallate

(EGCG) reverted the cardiac injury markers, abnorm-

alities of lipid profile, and lipid metabolizig enzymes

in serum and myocardium of rats exposed to CS .

Furthermore, it significantly decreased the protein

expression levels of nuclear factor kappa-B (NF-

KB), cyclooxygenase 2, tumor necrosis factor-a, and inducible nitric oxide synthase through its antioxidant

effects (Gokulakrishnan et al., 2011). Moreover,

Al-Sayed and Ibrahim 639

Gokulakrishnan and Ali (2010) divulge that EGCG

attenuated perturbations in human erythrocytes by

CS. Also, tea polyphenols can antagonize CS-

induced airway epithelial cell apoptosis through the

effective removal of ROS, promoting BCL-2 mRNA

expression and inhibiting the expression of Bax

mRNA (Qing et al., 2010). Besides; the polyphenols

from walnut (Juglans regia L) kernel modulate CS

acute inflammation, oxidative stress and lung injury

in rats (Qamar and Sultana, 2011).

Caffeic acid phenethyl ester (CAPE) is a flavonoid-

like compound and is one of the major components of

honeybee propolis. It exerts several biological and

pharmacological properties such as antioxidant,

anti-inflammatory, anticarcinogenic and immunomo-

dulatory activities. It is documented that CAPE

administration to CS exposed rats significantly restored

liver functions and partially attenuated liver histologi-

cal changes associated with cigarette exposure, thus the

damage inflicted by cigarette in rat liver can be

partially prevented by CAPE administration (Pekmez

et al. 2007).

Ubiquinone or coenzyme Q (CoQ) has a pivotal

role as a redox link between flavoproteins and cyto-

chromes in the mitochondrial respiratory chain, also

being involved as an essential component of extrami-

tochondrial redox chains. Except in brain and lung,

coenzyme Q appears mostly in its reduced form, ubi-

quinol. It is the only lipid-soluble antioxidant that can

be synthesized de novo by animal cells and regener-

ated by enzymatic mechanisms from its oxidized form

ubiquinone. Ubiquinol inhibits lipid peroxidation by

scavenging free radicals in biological membranes and

lipoproteins. Ubiquinol and vitamin C can regenerate

vitamin E from a-tocopheroxyl radical (Ingold et al., 1993). Therefore, ubiquinone acts as a lipid antioxi-

dant either directly in its reduced form, ubiquinol,

or in recycling of radical form of vitamin E. Plasma

ubiquinol was found to be reduced among smokers

than in nonsmokers (Kontush et al., 1997). Dietary

supplementation of CoQ10 mitigated atherosclerosis

in CS-exposed mice (Gairola et al., 2010).

DL-a-lipoic acid (LA), a dithiol compound, is recognized as a universal antioxidant due to its high

singlet oxygen-quenching constant. It acts as a

potent chelator of redox active metals and combats

the accumulation of lipid peroxidation products

(Holmquist et al., 2007). Acrolein present in CS is

of particular concern as health risk. Acrolein is a

mitochondrial toxicant and induces oxidative mito-

chondrial dysfunction. LA has protective effects

against acrolein-induced toxicity (Jia et al., 2007)

via its mitochondria-targeted antioxidant (Packer

et al., 1997) and mitochondrial nutrient (Liu and

Ames, 2005).

Conclusion

Children who are exposed to passive smoking are sub-

jected to oxidative stress, which has been implicated

in the etiopathogenesis of many disorders. Some of

which occur in organs that have no direct contact with

the smoke itself such as the liver. Smoking induces

three major adverse effects on the liver, immunologi-

cal, toxic, and oncogenic effects. ETS exposure is

associated with physiologic evidence of systemic bio-

chemical alterations in children. They have lower

plasma levels of antioxidants such as vitamins C and

E, B-carotene, folate and uric acid. Meanwhile, they

have higher plasma levels of some pro-oxidants such

as iron. The relationship between SHS exposure and

markers of oxidative stress in children strengthens the

proposed relationship between SHS, oxidative stress,

inflammation, and diseases. It provides evidence sug-

gesting that these pathways are integrally associated

with SHS-exposure-related mechanisms of harm.

Understanding these pathways may improve preven-

tion and treatment of SHS-exposure-related diseases.

A diet rich in antioxidants is important for children

exposed to SHS such as those containing excess vege-

tables and fruits. Supplementation of antioxidants

may be warranted in SHS-exposed children, but more

studies are necessary to determine the optimal doses

and clinical impact of the supplements. Our article

provides additional evidence that children need to

be protected from SHS exposure, both through vigor-

ous efforts to encourage smoking cessation among

family members and through policies that eliminate

smoking in places where children exist.

Funding

This research received no specific grant from any funding

agency in the public, commercial, or not-for-profit sectors.

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