BACKGROUND AND OBJECTIVES. Environmental tobacco smoke (ETS) exposure is probably one of the most important public health hazards in our community. Our aim with this article is to (1) review the prevalence of ETS exposure in the United States and how this prevalence is often measured in practice and (2) summarize current thinking concerning the mechanism by which this exposure may cause infections in young children.
METHODS. We conducted a Medline search to obtain data published mainly in peer-reviewed journals.
RESULTS. There is still a very high prevalence of ETS exposure among US children ranging from 35% to 80% depending on the method of measurement used and the population studied. The mechanism by which ETS may be related to these infections is not entirely clear but may be through suppression or modulation of the immune system, enhancement of bacterial adherence factors, or impairment of the mucociliary apparatus of the respiratory tract, or possibly through enhancement of toxicity of low levels of certain toxins that are not easily detected by conventional means.
CONCLUSIONS. The prevalence of ETS exposure in the United States is still very high, and its role in causing infections in children is no longer in doubt even if still poorly understood. Research, therefore, should continue to focus on the various mechanisms of causation of these infections and how to best reduce the exposure levels.
Environmental tobacco smoke (ETS) exposure or passive smoke exposure is one of the most common preventable health hazards in our community. In children, ETS exposure has also been shown to be particularly associated with upper and lower respiratory tract infections such as the common cold, middle-ear disease,1–4 respiratory syncytial virus,5,6 bronchitis,7,8 pneumonia, and other serious bacterial infections.8–13 Sudden infant death syndrome (SIDS) has also been directly linked to ETS exposure by numerous studies.14–18 In children, the literature is replete with studies on the role of ETS exposure on asthma.19–36 During the past decade, ETS exposure is being increasingly associated with behavioral and cognitive problems in children.37–40 Furthermore, ETS exposure has been shown in a number of studies to adversely affect physical growth in young children.41–43 Although ETS exposure is a well-known risk factor for cancer in adults, there is emerging evidence that it may also be associated with childhood cancers.44–48
Despite the overwhelming evidence of the role of ETS exposure on infant health, a very high proportion of children continue to be exposed. Although ETS exposure has been consistently linked to the above-cited infections, to our knowledge almost no recent reviews exist on the mechanisms by which this exposure may cause infections. With this article, therefore, we aim to review the prevalence of ETS exposure and summarize some of the current thinking on how this exposure may cause infections in young children.
Data sources were identified through Medline searches by using various key words including, but not limited to, “ETS,” “passive smoke exposure,” “prevalence of ETS exposure,” “health effects of ETS exposure,” “smoking in pregnancy,” “ETS and SIDS,” “lactation/breastfeeding and smoking,” and “measuring ETS exposure.” Manual searches were also done, and suitable articles were chosen from the references of articles identified from Medline searches. Others sources of articles were directly identified from Web searches. Articles were empirically chosen on the basis of the authors’ assessment of the strength of the design, the uniqueness of the study, and the scientific merit, although population-based studies were preferred when selecting articles on the studies of prevalence of ETS exposure. Most of the studies were deliberately selected from works done in the United States.
Most Common Chemical Toxins of ETS
Tobacco smoke contains >4000 chemical toxins or intoxicants, exposure to which causes various illnesses as discussed above. The most common and well-known tobacco toxins are nicotine, carbon monoxide, formaldehyde, hydrogen cyanide, sulfur dioxide, nitrogen oxide, ammonia, polycyclic aromatic hydrocarbons, and the nitrosamines. These substances produce both irritant and immunologic effects on the respiratory tract.49 Table 1 lists some of the most common toxins and their effects on the respiratory system. The role of nicotine in causing infections will be discussed below.
Prevalence of ETS Exposure
Studies quantifying ETS exposure vary depending on the methodology used and the location. It is interesting to note that smaller studies tend to demonstrate higher exposure levels than larger national studies.
Most recent research shows that ∼12% of all pregnant women in the United States smoke during pregnancy, although the rates seem to differ according to geographic region, ethnicity, educational status, and age of the mother.50 Teen mothers (20%) are more likely to smoke than their older counterparts; of all racial groups, white (30%) and American Indian (24%) women have higher smoking rates during pregnancy as compared with black women (8.0%).50
Active and passive smoking in pregnancy can also have adverse health effects in the offspring of smoking mothers. Prenatal exposure has been associated with low birth weight, spontaneous abortion, and numerous other causes of morbidity and neonatal mortality.51–56 Unfortunately, in small studies, it is very difficult to tease out the separate health effects of smoking during pregnancy from those occurring only after delivery, because most women who smoke during pregnancy continue to smoke after delivery. On the other hand, most women who stop smoking during pregnancy immediately start smoking again after delivery. Only large prospective studies are able to identify enough women who smoke only during pregnancy or those who smoke only after delivery for meaningful statistical analyses to be done. When smoking occurs throughout pregnancy and also postdelivery, the effects of ETS exposure on various illnesses may be additive. Ey et al2 prospectively followed 1013 children to 1 year of age and showed that there was an increased risk of recurrent middle-ear infections among the children of parents who smoke. However, the authors were unable to distinguish the separate effects of smoking during pregnancy and those effects attributable only to postpartum smoking exposure. In a large prospective study, Wisborg et al14 showed that children of mothers who smoked ≥15 cigarettes per day during pregnancy were more likely to be hospitalized for various illnesses than unexposed children during pregnancy. This was true even after controlling for various confounders including, among others, postpartum maternal and paternal smoking status. A more recent, larger population-based prospective study by Stathis et al51 showed that maternal smoking during pregnancy alone was associated with middle-ear disease and ear surgery in young children. As previously stated, many other studies have also shown that children exposed to ETS during pregnancy alone are more likely to develop asthma, bronchitis, and decreased lung function than their unexposed counterparts.35–38,43 However, the effects of passive maternal smoking exposure during pregnancy may not be as important as active maternal smoking, as has been shown by a number of research findings. Indeed, Fox et al54 showed that maternal active smoking during pregnancy was more predictive of the height of children than maternal passive smoke exposure.
Few studies have been done to demonstrate the contribution of paternal smoking to childhood illnesses. In a recent review article, Anderson and Cook57 reported 3 studies that showed that paternal smoking alone was associated with SIDS even after controlling for various confounders. In Britain, Blair et al58 found that paternal smoking was a predictor of SIDS even after controlling for maternal smoking and other confounders (odds ratio: 2.5; 95% confidence interval: 1.48–4.22). On the other hand, in New Zealand, Mitchell et al18 found that paternal smoking alone was not significant if the mother was not a smoker (odds ratio: 1; 95% confidence interval: 0.64–1.56)
Hopper et al59 showed, by using a questionnaire alone, that 75% of children were exposed to ETS in an area in Detroit, Michigan. In Pittsburgh, Pennsylvania, Cornelius et al60 showed similar findings with both questionnaire and urinary cotinine-level measurement. Chilmonczyk et al61 did a 2-part study in Portland, Maine, in which they initially used a questionnaire, and found that only 40% of asthmatic children were exposed. When urinary cotinine levels were measured in the same group, the exposure rates rose to 64%. Each of these studies was performed in urban areas. Kum-Nji et al62 showed, by using a detailed questionnaire, that 27% of mothers smoked in the presence of their children, but if other household members were included, almost three fourths of the children in a rural southern Mississippi community were exposed to ETS. Large national studies, however, tend to show somewhat lower exposure rates. For instance, Overpeck et al63 found an exposure rate of almost 50%, whereas Schuster et al64 found an exposure rate of 35% in the National Health Interview Survey study. Pirkle et al65 and Gergen et al66 had similar findings when they used Third National Health and Nutrition Examination Survey (NHANES III) data. Table 2 summarizes the findings of the various exposure rates described above. The discrepancy between the large national and small local studies could be explained by the fact that the large national studies are more representative of the population, whereas the smaller studies are often done in at-risk inner-city populations in which exposure rates are more likely to be high. However, the truth probably lies somewhere in between. National studies may underestimate the exposure rates, because the questionnaire may not be as rigorous as in the smaller studies and may fail to take into account ETS exposure outside the home. In addition, most of the earlier large studies often did not use objective validation of the exposure status by measuring body-fluid biomarkers. Overall, these studies showed that validation with biomarkers tended to produce higher exposure prevalence rates than surveys alone.
Methods of Measuring ETS Exposure
Use of Biomarkers
ETS exposure is measured most commonly either by biomarkers in body fluids/samples or by surveys. Although carbon monoxide is sometimes used, the 2 most frequently used biomarkers are nicotine and its main derivative, cotinine. These 2 substances can be measured from serum plasma, urine, saliva, and hair samples. The obvious advantage of measuring biomarkers is that the method is more objective than surveys, but there are certain disadvantages (also see Table 3). For example, the effective use of biomarkers depends on the half-life of the substance being measured. Because of the invasiveness of this method and because body-fluid samples may need to be collected, many subjects may refuse to participate. Furthermore, there is marked variability among the different laboratories in their ability to detect these biomarkers. Finally, this method is more expensive, which may limit the sample size.
Surveys have the advantage of being less invasive, easily used in large-scale epidemiologic studies, and less expensive. Disadvantages are lack of objective standards, misclassification, or recall bias. Thus, depending on what method is used, the investigator may obtain somewhat different results. However, a correlation of at least 70% has generally been found between the biomarkers and surveys in most studies.
Pathogenesis/Mechanism of Some of the Most Common Infections Associated With ETS Exposure
The Body’s Basic Immune Mechanism
Briefly reviewed, innate immunity consists of physical barriers: skin, mucous membranes, mucociliary epithelium, phagocytic cells such as neutrophils, and the macrophage/monocyte system. Acquired immunity is an inducible, specific immunologic response to a specific antigen or infectious agent. It may be humoral or cellular and consist of specific antibody production derived from B cells. Cellular immunity consists of cellular immune response by activated T cells (CD4 or CD8).
The macrophages engulf or ingest microorganisms, digest them into smaller particles or specific antigens, and subsequently present them to the cell surfaces of the phagocytes. This process of engulfing and killing of the microorganisms is enhanced by peroxides and oxygen (O2) radicals present in the lysosomes of the phagocytes. These surface antigens then interact with T cells (CD4) in the context of major histocompatibility complex II and become activated to subsequently interact with B cells for the latter to produce specific antibody.
The T helper (Th) cells, which include subtypes Th1 (or CD4 killer) and Th2 (CD8), act in consonant with antigen-presenting cells to become activated and subsequently stimulate B lymphocytes to produce specific antibody, which will also kill the microorganisms. It is the CD4 cells that must act in the context of major histocompatibility complex II to restrict the activity of B cells to recognize an antigen as “nonself.” Each B cell only produces 1 specific immunoglobulin G (IgG) subclass. B cells recognize the antigen even many years after initial activation.
ETS Exposure and Phagocytic Function
How can ETS exposure cause infections? Nicotine suppresses or inhibits the phagocytotic activity of the neutrophils or macrocyte/monocyte system through inhibition of the superoxide anion, peroxide, and the production of oxygen radicals.67–76 Harris et al67 found that phagocytic activity of alveolar pulmonary cells was significantly diminished in smokers as compared with nonsmokers. Fogelmark et al68 showed that in experimental hamsters and rats exposed to tobacco smoke under in vivo conditions, a dose-related relationship in the activity of phagocytes could be demonstrated. In vitro studies by Pabst et al69 also demonstrated that nicotine inhibited the phagocytic activity of the neutrophils and the monocytes from the oral mucosa of those who chewed smokeless tobacco. In vivo studies by Numabe et al70 later confirmed these findings in human volunteers. Matulionis74 showed that the macrophages and phagocytes in smoke-exposed mice were more numerous and larger in size than in unexposed subjects.
ETS Exposure, T-Cell Function, and Ig Production
Nicotine has been shown to suppress Th1 (responsible for Ig production) but selectively stimulate Th2 cell function to produce various cytokines or interleukins (ILs) such as IL-4, IL-5, IL-10, and IL-13.77–82 These cytokines are also responsible for the clinical manifestations often seen in atopic diseases such as asthma, eczema, allergic rhinitis and other allergic disorders. Furthermore, nicotine not only stimulates eosinophils but also will stimulate the B cells to switch from producing Igs such as IgG1 to producing IgE. On the other hand, the suppression of Th1 by nicotine results in decreased Ig production, particularly IgA and IgG2.82,83 In a study by Zhang and Petro,78 Th2 cells exposed to various concentrations of nicotine produced higher concentrations of cytokines such as IL-4 and IL-10 but less IL-1 and interferon γ. When Seymour et al79 exposed certain species of ova-sensitized mice to ETS, the mice exhibited an exaggerated and prolonged response with respect to IgE, IgG1, eosinophils, and Th2 cytokines, demonstrating that ETS exposure “upregulates” allergic response to certain inhaled antigens. An interesting observation is that nicotine has not been shown to suppress IgM production. It also suppresses cytotoxic cell activity through inhibition of the natural killer cells.84,85
ETS and Bacterial Adherence to Mucosal Epithelium
Colonization and subsequent infection by microorganisms often requires selective adherence to the mucosal cell surfaces of the host. Many studies show that nicotine may not only cause direct toxic injury to the mucociliary epithelium but also may lead to enhanced adherence of pathogenic bacteria on the mucosal cell surface.86–92 This enhanced adherence of bacteria is brought about by passive coating on the mucociliary epithelial surface by nicotine.90–92 Approximately 3 decades ago Fainstein and Musher91 found that the acquisition of pneumococcal pneumonia by smokers and the role of nontypeable Haemophilus species in the lungs may be determined, in part, by bacterial adherence to pharyngeal cells. Raman et al90 had similar findings and concluded that the increased pneumococcal adherence in cigarette smokers may promote oropharyngeal colonization and contribute to the increased risk of respiratory infection in cigarette smokers. Table 4 summarizes the mechanisms through which nicotine exposure may result in depressed immunity.
ETS Exposure and Middle-Ear Disease
Several studies have shown that ETS exposure is associated with increased prevalence of otitis media.1–4,8 Nicotine and other ETS products can make subjects more susceptible to ear infections by at least 4 processes that may enhance the invasion of the middle ear by microorganisms colonizing the nasopharyngeal airways. First, exposure may cause toxic injury of mucosal epithelium and other immune cells, resulting in prolonged inflammation and congestion of these airways.69,74,85–87,89 Second, ETS exposure may lead to impaired mucociliary function of the eustachian tube (ET), resulting in ciliostasis (ie, impaired clearance of the nasopharyngeal airways).87,90 These 2 processes subsequently result in blockage of the ET, further compounded by the fact that in young children the ET is more horizontal than oblique. Third, ETS exposure may enhance the adherence of the microorganisms to the epithelial cell surface of the respiratory tract.90,91 Fourth, it is possible that ETS exposure may also result in depressed local immune function such as IgA production.82,83 A fifth mechanism can also be postulated: because children exposed to ETS are more likely to develop allergic disorders, as stated above, the tendency to have prolonged inflammation and congestion of the upper airways may predispose them to ear infections. Overall, a combination of these factors could result in ET dysfunction, which predisposes toward recurrent middle-ear disease. Similar mechanisms may explain the associations of ETS exposure with other infections such as bronchitis, sinusitis, and pneumonia.
ETS and Serious Bacterial Infections
Sepsis and meningitis have been associated with ETS exposure. Nuorti et al13 showed that cigarette smoking was the strongest independent risk factor for invasive pneumococcal disease among immunocompetent, nonelderly adults. O’Dempsey et al10 and Lipsky et al11 had similar findings, whereas Stanwell-Smith et al12 showed that ETS exposure was highly predictive of meningococcal disease. ETS exposure may cause serious bacterial infections through a series of mechanisms, as demonstrated by many in vitro experimental studies and using several animal models. In the late 1960s Green and Carolin92 showed the depressant effect of tobacco smoke on the in vitro antibacterial activity of alveolar macrophages. As shown by several experimental animal studies, cigarette smoke depresses phagocytosis, impairs mucociliary clearance, enhances bacterial adherence, disrupts the respiratory epithelium, and decreases the serum Ig levels by ∼10% to 20% lower than those of nonsmokers.82,83 Also, the children of smokers and those exposed to smoke may have a higher frequency of other respiratory infections such as tuberculosis than the unexposed children.93–95
ETS Exposure and SIDS
With more and more parents following the American Academy of Pediatrics recommendation of the “back-to-sleep” position, ETS exposure in the home is emerging as probably the most significant predictor of SIDS. In a recent review, DiFranza et al96 showed that the odds ratios of predicting SIDS from ETS exposure were much higher in recent studies than in those done before the late 1990s before the back-to-sleep position was adopted by most parents in developed countries.14–18,97 A dose-response relationship was also consistently demonstrated in most SIDS studies, suggesting that the relationship was probably causal. However, the jury is still out on how ETS exposure can cause SIDS. Can some of these cases be caused by infections? There is at least some evidence that SIDS may be caused by sublethal doses of bacterial toxins. Sayers et al98,99 have demonstrated that very minute doses of nicotine can interact with very small sublethal doses of certain bacterial toxins to produce lethal effects in certain animal models. Thus, when they injected a mixture of minute doses of nicotine (as can be obtained from smoking 0.05% of cigarette) and sublethal doses of bacteria toxins of Staphylococcus aureus, Streptococcus pyogenes, and clostridia into rats, mice, or hamsters, these animals unexpectedly died. However, when these toxins at the same doses were injected alone, they failed to produce any lethal effects in these animal models. The authors therefore suggested that the potentiation of sublethal doses of bacterial toxins by nicotine found in tobacco smoke might be one mechanism through which certain cases of SIDS may be caused. The levels of these toxins are so low that they cannot be easily detected by our current conventional laboratory techniques. Other ways by which ETS may cause SIDS have been postulated but are beyond the scope of this article. Because of the high prevalence of ETS exposure, all health care providers involved in the care of mothers and young children should routinely counsel parents on the dangers (particularly of SIDS) of exposing their offspring to ETS during and after pregnancy. Indeed, in a recent meta-analysis Rushton et al100 showed that up to 11% of all SIDS cases in the population could be attributable to postdelivery ETS exposure by the mother.
ETS exposure may also be a significant risk factor for periodontal disease (POD). Arbes et al,101 using data from the NHANES III study, found that POD was more likely to occur in exposed than in unexposed individuals. How ETS exposure may enhance POD is not exactly clear. Experimental evidence suggests that tobacco products may cause POD not only by inhibiting the growth of human periodontal fibroblast102 but also through the enhancement of the effects of toxins produced by putative periodontal pathogens such as Prevotella intermedia, Prevotella nigrescens, and Porphyromonas gingivalis.103
Conservative estimates of ETS exposure rates of young children in the United States are at least 50%, although the rates may vary from region to region, with the highest rate being in the Midwest and South and the lowest rates in the Northeast and West.104 Exposure rates also vary by ethnicity. Although more white than black mothers smoke during pregnancy,49,50 ETS exposure rates are higher among black children, as demonstrated by several recent studies using both questionnaires and biomarkers.105–107 Mean cotinine levels were consistently highest for black children than for other racial groups. This apparent disconnect is probably explained by the fact that black parents are more likely to allow other family members or friends to smoke at their homes even when they themselves are nonsmokers.64
Exposure rates may be closely linked to morbidity and mortality of certain diseases such as asthma, middle-ear disease, and SIDS. It is our view that enough information already exists on the prevalence of ETS. The consistency of well-conducted epidemiologic findings linking ETS exposure to various illnesses supports the theory of causality even if at this stage we do not fully understand all aspects of the pathogenesis of some of the diseases. For instance, we do not fully understand how prenatal ETS exposure can cause SIDS or asthma. Research is ongoing and indeed should continue in these areas. Few studies quantitatively determine the contribution of ETS exposure to these common diseases. Rushton et al100 recently showed that the population attributable risk (PAR) for SIDS attributable to postdelivery maternal smoking alone was 11%. This suggests that the PAR would be much higher if ETS during pregnancy and the smoking status of other house members such as fathers and other frequent visitors was taken into account. More such studies are needed for diseases such as asthma, middle-ear disease, and other illnesses that are important causes of morbidity and mortality in children.
Despite the overwhelming epidemiologic evidence, it is still not quite clear how ETS exposure can cause infections in children. Most of the conclusions have been arrived at by using animal models, although the results are convincing. It is our opinion that early exposure of the fetus to tobacco smoke may result in the stimulation of the transformation of the Th0 cell (from which Th1 and Th2 subtypes derive) to the Th2 cell. The lack of early stimulation of Th1 may result in early predisposition to frequent infections postdelivery. On the other hand, the selective stimulation of Th2 in utero may result in the development of allergic disorders soon after birth. If this hypothesis is plausible, then it could be possible to demonstrate, for instance, that sepsis and/or meningitis in neonates may be significantly higher in exposed versus unexposed infants. We still await such studies.
An area of fruitful research is the basis for the lack of collaboration between health care providers such as between pediatricians and obstetricians. The American Academy of Pediatrics has long recommended the prenatal pediatric visit for pregnant women.108 Such visits would enable new mothers to meet their pediatricians, who would educate them on health issues that are likely to affect their children. Such discussions would include smoking and other pertinent health issues. Currently few women, particularly in the low-income group, see a pediatrician before delivery, and the obstetrician alone is responsible for educating the new mother on preventive health issues (eg, ETS exposure) concerning the health of her infant. Unfortunately, the pediatrician only meets the new mother for the first time soon after delivery and has only a few minutes to discuss the above-mentioned health issues. Collaboration between the obstetricians and pediatricians would ensure that there is effective education on tobacco use and other risk-taking behaviors by young mothers before delivery. In fact, in most states, most insurance companies will not even pay for the prenatal pediatric visit, and pediatricians often see these pregnant mothers as a means of recruiting new patients. Although the health department clinics may be doing a great job educating pregnant women on the dangers of ETS, we still believe that pediatricians should have initial contact with all pregnant women before delivery. Many of these women value the pediatrician’s advice on risky behaviors that affect their child’s health. It is our opinion, therefore, that obstetricians should make more formal referrals of all pregnant women to a pediatrician for continued counseling before delivery.
CONCLUSIONS AND RECOMMENDATIONS
ETS exposure among children in the United States is still very high, and this exposure is often measured by prepared questionnaires. However, objective validation by measurement of biomarkers in bodily fluids is often necessary to determine the true extent of the exposure. ETS exposure predisposes children to infection through direct toxic injury of the epithelial cells and also through suppression of the immune system. Very low levels of tobacco components may also potentiate extremely low levels of bacterial toxins that are not easily measured by our conventional laboratory techniques. Studies on PAR for common diseases attributable to ETS exposure are in dire need. Studies on the mechanisms of causation of the various infections are also highly desirable. Because the relationship between ETS exposure and various illnesses is now known to be causal, it is urgent that effective methods to decrease the high prevalence of exposure be found.
- Accepted October 3, 2005.
- Address correspondence to Philip Kum-Nji, MD, Children’s Medical Center, Virginia Commonwealth University School of Medicine, 1001 E Marshall St, Richmond, VA 23298. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
- ↵Teele DW, Klein JO, Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective cohort study. J Infect Dis.1989;160 :83– 94
- ↵Ey JL, Holberg CJ, Aldous MB, Wright AL, Martinez FD, Taussig LM. Passive smoking exposure and otitis media in the first year of life. Pediatrics.1995;95 :670– 677
- ↵Lanari M, Giovannini M, Giuffre L, et al. Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity. Pediatr Pulmonol.2002;33 :458– 465
- ↵Law BJ, Carbonell-Estrany X, Simoes EA. An update on respiratory syncytial virus epidemiology: a developed country perspective. Respir Med.2002;96(suppl B) :S1– S7
- ↵Colley JR, Holland WW, Corkhill RT. Influence of passive smoking and parental phlegm on pneumonia and bronchitis in early childhood. Lancet.1974;2(7888) :1031– 1034
- ↵Strachan DP, Cook DG. Health effects of passive smoking. 1. Parental smoking and lower respiratory illness in infancy and early childhood. Thorax.1997;52 :905– 914
- ↵O’Dempsey TJ, McArdle TF, Morris J, et al. A study of risk factors for pneumococcal disease among children in a rural area of West Africa. Int J Epidemiol.1996;25 :885– 693
- ↵Wisborg K, Kesmodel U, Henriksen TB, Olsen SF, Secher NJ. A prospective study of smoking during pregnancy and SIDS [published correction appears in Arch Dis Child. 2001;84:93]. Arch Dis Child.2000;83 :203– 206
- Haglund B, Cnattingius S, Otterblad-Olausson P. Sudden infant death syndrome in Sweden, 1983–1990: season at death, age at death, and maternal smoking. Am J Epidemiol.1995;142 :619– 624
- Scragg R, Mitchell EA, Taylor BJ, et al. Bed sharing, smoking, and alcohol in the sudden infant death syndrome. New Zealand Cot Death Study Group. BMJ.1993;307 :1312– 1318
- ↵Mitchell EA, Ford RP, Stewart AW, et al. Smoking and the sudden infant death syndrome. Pediatrics.1993;91 :893– 896
- Cook DG, Strachan DP. Parental smoking, bronchial reactivity and peak flow variability in children. Thorax.1998;53 :295– 301
- Strachan DP, Cook DG. Health effects of passive smoking. 5. Parental smoking and allergic desensitization in children [published correction appears in Thorax. 1999;54:366]. Thorax.1998;53 :117– 123
- ↵Stein RT, Holberg CJ, Sherrill D, et al. Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children’s Respiratory Study. Am J Epidemiol.1999;149 :1030– 1037
- ↵Eskenazi B, Trupin LS. Passive and active maternal smoking during pregnancy, as measured by serum cotinine, and postnatal smoke exposure. II. Effects on neurodevelopment at age 5 years. Am J Epidemiol.1995;142(9 suppl) :S19– S29
- Weitzman M, Gortmaker S, Sobol A. Maternal smoking and behavior problems of children. Pediatrics.1992;90 :342– 349
- ↵Kleinman JC, Madans JH. The effects of maternal smoking, physical stature, and educational attainment on the outcome of low birthweight. Am J Epidemiol.1985;121 :843– 845
- Sasco AJ, Vainio H. From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action. Hum Exp Toxicol.1999;18 :192– 201
- Filippini G, Maisonneuve P, McCredie M, et al. Relation of childhood brain tumors to exposure of parents and children to tobacco smoke: the SEARCH international case-control study. Surveillance of Environmental Aspects Related to Cancer in Humans. Int J Cancer.2002;100 :206– 213
- ↵Krajinovic M, Richer C, Sinnett H, Labuda D, Sinnett D. Genetic polymorphisms of N-acetyltransferases 1 and 2 and gene-gene interaction in the susceptibility to childhood acute lymphoblastic leukemia. Cancer Epidemiol Biomarkers Prev.2000;9 :557– 562
- ↵Office of health and Environmental Assessment. Respiratory health effects of passive smoking: lung cancers and other disorders. Washington, DC: Office of Research and Development, US Environmental Protection Agency; 1992. Environmental Protection Agency Publication No. 600/6-90/0061
- ↵Mathews TJ. Smoking during pregnancy in the 1990s. Natl Vital Stat Rep.2001;49(9) :1– 14
- ↵Stathis SL, O’Callaghan DM, Williams GM, et al. Maternal cigarette smoking during pregnancy is an independent predictor for symptoms of middle ear disease at five years’ postdelivery. Pediatrics.1999;104(2) . Available at: www.pediatrics.org/cgi/content/full/104/2/e16
- Lowe CR. Effect of mothers’ smoking habits on birth weight of their children. Br Med J.1959;(5153) :673– 676
- ↵Fox NL, Sexton M, Hebel JR. Prenatal exposure to tobacco: I. Effects on physical growth at age three. Int J Epidemiol.1990;19 :66– 71
- ↵Taylor B, Wadsworth J. Maternal smoking during pregnancy and lower respiratory tract illness in early life. Arch Dis Child.1987;62 :786– 791
- ↵Anderson HR, Cook DG. Passive smoking and sudden infant death syndrome: review of the epidemiological evidence. Thorax.1997;52 :1003– 1009
- ↵Blair PS, Fleming PJ, Bensley D, et al. Smoking and the sudden infant death syndrome: results from 1993–5 case-control study for confidential inquiry into stillbirths and deaths in infancy. Confidential Enquiry Into Stillbirths and Deaths Regional Coordinators and Researchers. BMJ.1996;313 :195– 198
- ↵Hopper JA, Craig KA. Environmental tobacco smoke exposure among urban children. Pediatrics.2000;106(4) . Available at: www.pediatrics.org/cgi/content/full/106/4/e47
- ↵Overpeck MD, Moss AJ. Children’s exposure to environmental cigarette smoke before and after: health of our nation’s children, United States, 1988. Adv Data1991;(202) :1– 11
- ↵Gergen PJ, Fowler JA, Maurer KR, Davis WW, Overpeck MD. The burden of environmental tobacco smoke exposure on the respiratory health of children 2 months through 5 years of age in the United States: Third National Health and Nutrition Examination Survey, 1988 to 1994. Pediatrics.1998;101 (2). Available at: www.pediatrics.org/cgi/content/full/101/2/e8
- Skold CM, Andersson K, Hed J, Eklund A. Short-term in vivo exposure to cigarette-smoke increases the fluorescence in rat alveolar macrophages. Eur Respir J.1993;6 :1169– 1172
- ↵Matulionis DH. Effects of cigarette smoke generated by different smoking machines on pulmonary macrophages of mice and rats. J Anal Toxicol.1984;8 :187– 191
- ↵Seymour BW, Pinkerton KE, Friebertshauser KE, Coffman RL, Gershwin LJ. Second-hand smoke is an adjuvant for T helper-2 responses in a murine model of allergy. J Immunol.1997;159 :6169– 6175
- Frazer-Abel AA, Baksh S, Fosmire SP, et al. Nicotine activates nuclear factor of activated T cells c2 (NFATc2) and prevents cell cycle entry in T cells. J Pharmacol Exp Ther.2004;311 :758– 769
- ↵Holt PG. Immune and inflammatory function in cigarette smokers. Thorax. 7;42 :241– 249
- ↵Dye JA, Adler KB. Effects of cigarette smoke on epithelial cells of the respiratory tract. Thorax.1994;49 :825– 834
- ↵Fainstein V, Musher D. Bacterial adherence to pharyngeal cells in smokers, nonsmokers, and chronic bronchitics. Infect Immun.1979;26 :178– 182
- ↵Singh M, Mynak ML, Kumar L, Mathew JL, Jindal SK. Prevalence and risk factors for transmission of infection among children in household contact with adults having pulmonary tuberculosis. Arch Dis Child.2005;90 :624– 628
- ↵DiFranza JR, Aligne CA, Weitzman M. Prenatal and postnatal environmental tobacco smoke exposure and children’s health. Pediatrics.2004;113(4 suppl) :1007– 1015
- ↵Mitchell EA, Tuohy PG, Brunt JM, et al. Risk factors for sudden infant death syndrome following the prevention campaign in New Zealand: a prospective study. Pediatrics.1997;100 :835– 840
- ↵Sayers NM, Drucker DB. Animal models used to test the interactions between infectious agents and products of cigarette smoked implicated in sudden infant death syndrome. FEMS Immunol Med Microbiol.1999;25 :115– 123
- ↵Sayers NM, Drucker DB, Telford DR, Morris JA. Effects of nicotine on bacterial toxins associated with cot death. Arch Dis Child.1995;73 :549– 551
- ↵Hagan JF Jr, Coleman WL, Foy JM, et al. The prenatal visit. Pediatrics.2001;107 :1456– 1458
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