- Email: [email protected]
New insights into air pollution and children’s health
SYMPOSIUM: SOCIAL PAEDIATRICS
New insights into air pollution and children’s health
impairment of brain function is unclear. Indeed, the possibility of a confounding variable (e.g. noise) cannot be excluded. However, there are proof-of-concept studies suggesting that airway PM affects brain function. For example, Yokota et al instilled diesel exhaust PM into the nose of 2-week old infant rats once a week for 4 weeks and found that PM-treated animals showed a lower avoidance performance than control animals given sham-instillation. Furthermore, there was a trend for levels of dopamine in the medial mammillary nucleus of the brain to be lower in the PMtreated animals. Histological examination of the brain showed no evidence that PM had penetrated into the nervous system e suggesting that this effect was mediated by indirect mechanisms. The effect of maternal inhalation of traffic-derived pollution on the developing fetus has been identified in recent studies with sufficient power to detect independent effects. In a study of over 70,000 singleton births in Canada, Brauer et al estimated exposure to air pollution at mothers’ residence and found that living within 50 m of a main road was associated with a 22% increase in low-birth weight. When exposure to air pollutants was modelled individually, all air pollutants other than ozone, were associated with small for gestational age. An effect of air pollution on preterm birth was also found e albeit only for PM2.5. Similarly in a US study, Wihelm and Ritz reported an association between modelled exposure of mothers to traffic-derived PM- and risk for preterm birth and term low-birth weight. How PM impacting in the lungs of mothers could influence the developing fetus is unclear. A possible mechanism is that PM alters the pattern of cytokines in the maternal and fetal circulation. Some evidence for this phenomenon was recently provided by Latzin et al who studied a birth cohort of 265 healthy term-born neonates and found that mean PM10 over the last 3 months of pregnancy was associated with increased interleukin-1 beta in cord blood. In summary, although the evidence base is limited these epidemiological associations are of concern and establishing biological plausibility in animal models is urgently needed.
Jonathan Grigg
Abstract Air pollution remains a major threat to children’s health. In high-income countries, most outdoor air pollution is from fossil fuel combustion, and most indoor pollution is from cooking and environmental tobacco smoke (ETS). Outdoor pollution in medium- and low-income countries is a mix of fossil-fuel, solid fuel (e.g. coal) and biomass (wood), and indoor pollution is from biomass smoke, solid fuels and ETS. Over the last decade, new data suggest that both biomass smoke and ETS increases the vulnerability of children to bacterial pneumonia, and that fossil-fuel and biomass smoke impair children’s neurocognitive development. Further research is needed to establish biological plausibility for these associations.
Keywords air pollution; biomass; children; environmental tobacco smoke; fossil-fuel; neurocognitive impairment; pneumonia
Children are especially vulnerable to the adverse effects of environmental pollution. Pollutants are either inhaled, or ingested, or absorbed through the skin. There are many potential environmental threats to children’s health, and for most the evidence base is unclear. For example, teasing out the independent effect of a single chemical amongst thousands of compounds is nearly impossible. For chemicals, regulatory agencies must therefore take a precautionary approach i.e. to not wait for definitive proof to protect children’s health. One area where causal association, is certain, yet exposure of children still occurs, is air pollution. A previous review in this journal of the effects of traffic-derived air pollution, focused on inhalable particulate matter (PM less than 10 microns in aerodynamic diameter; PM10), and addressed lung growth and prevalence of respiratory symptoms. The aim of this review is to focus on new insights into the adverse effects of air pollution, both indoor and outdoor, on children’s health.
Indoor air pollution Indoor air pollutants either penetrate into the home from the outside or are generated within the home. In high-income countries, penetrating indoor pollution is mainly from trafficderived emissions. Thus both PM and vehicular-emitted gases such as nitrogen dioxide (NO2) are higher in homes near main roads than those near to less heavily used roads. For example, Esplugues et al found higher concentrations of NO2 in homes located on streets with a high frequency of vehicle traffic. The major sources of indoor-generated air pollutants are cooking and parental smoking e and both sources produce PM and NO2. PM in homes with smokers is up to 15 mg/m3 higher than nonsmoking homes. Although there is substantial body of evidence showing that exposure of children to passive environmental tobacco smoke (ETS) is associated with increased respiratory symptom prevalence e including cough and wheeze, there has always been the question whether exposure of children to secondhand smoke causes asthma. Strong evidence for a causal link between ETS and asthma has recently been provided by a systematic review of data from eight cohort studies. This metaanalysis showed that the adjusted predicted relative risk for a secondhand smoke effect on incident asthma is 1.33 (95% CI, 1.14e1.56) e an association strongest in school-age children.
Traffic-derived air pollution Recent studies suggest that inhalation of traffic-derived pollutants has non-respiratory effects on the developing nervous system. Franco Suglia et al, estimated the exposure of 202 school-age children to black carbon (i.e. traffic-derived soot) at the home address, and found that black carbon was independently associated with decreases in a range of neurocognitive variables such as vocabulary, and composite intelligence quotient. To date, the mechanism that links deposition of black carbon PM in the lung to
Jonathan Grigg MD is Professor of Paediatric Respiratory and Environmental Medicine at the Centre for Paediatrics in the Blizard Institute, Barts and the London School of Medicine, London, UK. Conflict of interest: none.
PAEDIATRICS AND CHILD HEALTH 22:5
198
Ó 2011 Elsevier Ltd. All rights reserved.
SYMPOSIUM: SOCIAL PAEDIATRICS
The effect of maternal ETS exposure on perinatal outcomes is less obvious. In a recent systematic review and meta-analysis, Salmasi et al identified publications covering 48,439 ETSexposed women and 90,918 unexposed women and found that ETS-exposed infants weigh less, with a trend towards increased low-birth weight. Using a similar approach, Leonardi-Bee et al reported that exposure of non-smoking pregnant women to ETS reduces mean birth weight by at least 33 g, and increases the risk of birth weight below 2500 g by 22%. Since both ETS and trafficderived emissions have components in common, such as carbonaceous PM, these data also provide indirect support for an association between traffic-derived PM and birth weight (discussed above). Another important area on the global scale is the interaction between ETS and vulnerability to infection. In a recent metaanalysis Lee et al assessed the association between ETS and invasive bacterial disease in children. They found a consistent association between invasive meningococcal and Hib disease with the adjusted odds ratio (OR) for meningococcal disease of 1.2 (1.5e2.6). For invasive pneumococcal disease the OR was positive, but not significant. An explanation for this non significant finding is that pneumococcal pneumonia, although the major cause of bacterial pneumonia in children is frequently associated with negative blood cultures. The strongest evidence that ETS is a major vulnerability factor for pneumococcal pneumonia was provided by a study from Vietnam. Suzuki et al assessed hospital admissions for pneumonia among children aged less than 5 years in the previous 12 months in a populationbased cross-sectional survey that included all residents of 33 in a central area of Vietnam. Exposure to ETS was associated with hospital admissions for pneumonia (OR 1.55, 95% CI, 1.25 e1.92). This OR may seem relatively low, but since the prevalence of ETS in Vietnam was 70%, it was estimated that 28% of childhood pneumonia in this community is attributable to ETS with 44,000 excess hospital admissions in young children per year. Biological plausibility for this association was provided by Phipps et al who exposed mice to cigarette smoke for 5 weeks then instilled S. pneumoniae into the airway. Smoke-exposed mice had increased lung bacterial load at both 24 and 48 h after infection, and more clinical illness. Even more important on the global scale, is the association between exposure to biomass and coal smoke (e.g. wood, coal) and infection. Dherani et al in a meta-analysis and systematic review found an overall pooled OR of 1.78 (95% CI, 1.45e2.18) for exposure of children to solid fuel smoke and risk of pneumonia in young children. It is now widely accepted by policy makers that reduction of household indoor air pollution from solid fuels would represent a major contribution to the prevention deaths in young children living in low-income countries. Indeed, these data have contributed to the realization than indoor air pollution is a major environmental cause of death for both women and young children. In response to this, the United Nations Foundation launched the Global Alliance for Clean Cookstoves e which aims for 100 million homes to adopt clean stoves by 2020. In 2011, Hillary Clinton made this initiative a major part of her Global Partnerships Initiative. Since both ETS and indoor solid fuel pollution are associated with pneumonia in young children e could traffic-derived PM also increase vulnerability to infection? Bacterial pneumonia is
PAEDIATRICS AND CHILD HEALTH 22:5
relatively uncommon in high-income countries as are, fortunately, deaths. Since it is difficult to perform adequately powered epidemiological studies into air pollution and infection in high-income countries, studies suggesting biological plausibility become more important. For example, my group recently developed a model for the effect of PM on the adherence of pneumococci to lower airway epithelial cells (Figure 1). Adherence of bacteria to airway lining cells is a prerequisite step for establishing invasive disease, and environmental factors that upregulate adhesion are putative vulnerability factors for bacterial pneumonia. We found that both PM10 from a UK city (where most pollution is from traffic), and from Accra (a city with a mix of traffic-derived and solid fuel PM10), up-regulated pneumococcal adhesion to lower airway epithelial cells in vitro. Furthermore, we found that the mechanism for both fossil-fuel PM and mixed source PM was the same, i.e. upregulation of the ligand for pneumococcal adhesion on the surface of epithelial cells e the platelet activating factor receptor (PAFR). PAFR, by chance, happens to express proteins that interact with proteins in the pneumococcal cell wall. Pneumococci therefore adhere to this receptor e and are then moved into the cell as the receptor is internalized. In vitro studies comparing the effects of ETS, biomass PM and traffic-derived PM may therefore help to clarify whether there are common mechanisms underlying the association between air pollution and bacterial infection. From our data, we hypothesize that children exposed to high levels of air pollution (biomass, fossil-fuel and ETS) constitutively express increased levels of PAFR in their lower airway epithelial cells. By linking in vitro observations to valid markers of vulnerability in vivo (such as PAFR expression) it may be possible to generate sufficient data for policy makers to act on the presumption that traffic-derived PM increases pneumonia vulnerability without waiting for expensive and difficult-to-perform epidemiological studies.
Figure 1 Pneumococci adhering to a monolayer of alveolar epithelial cells imaged by scanning electron microscopy. Bacteria are bead-like structures. Adherence is mediated by epithelial platelet activating factor receptor interacting with ligands in the bacterial cell wall.
199
Ó 2011 Elsevier Ltd. All rights reserved.
SYMPOSIUM: SOCIAL PAEDIATRICS
carbon monoxide, a marker for exposure to woodsmoke. Neurotoxicology 2011. Sep 24th [Epub ahead of print]. Esplugues A, Ballester F, Estarlich M, et al. Indoor and outdoor concentrations and determinants of NO2 in a cohort of 1-year-old children in Valencia, Spain. Indoor Air 2010; 20: 213e23. Kulkarni N, Grigg J. Air pollution and children’s health. Paediatric child health 2008; 18: 287e91. Latzin P, Frey U, Armann J, et al. Exposure to moderate air pollution during late pregnancy and cord blood cytokine secretion in healthy neonates. PLoS One 2011; 6: e23130. Lee CC, Middaugh NA, Howie SR, Ezzati M. Association of secondhand smoke exposure with pediatric invasive bacterial disease and bacterial carriage: a systematic review and meta-analysis. PLoS Med 2010; 7: e1000374. Leonardi-Bee J, Smyth A, Britton J, Coleman T. Environmental tobacco smoke and fetal health: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2008; 93: F351e61. Martin 2nd WJ, Glass RI, Balbus JM, Collins FS. Public health. A major environmental cause of death. Science 2011; 334: 180e1. Mushtaq N, Ezzati M, Hall L, et al. Adhesion of Streptococcus pneumoniae to human airway epithelial cells exposed to urban particulate matter. J Allergy Clin Immunol 2011; 127: 1236e12422. Phipps JC, Aronoff DM, Curtis JL, Goel D, O’Brien E, Mancuso P. Cigarette smoke exposure impairs pulmonary bacterial clearance and alveolar macrophage complement-mediated phagocytosis of Streptococcus pneumoniae. Infect Immun 2010; 78: 1214e20. Salmasi G, Grady R, Jones J, McDonald SD. Environmental tobacco smoke exposure and perinatal outcomes: a systematic review and meta-analyses. Acta Obstet Gynecol Scand 2010; 89: 423e41. Suglia SF, Gryparis A, Wright RO, Schwartz J, Wright RJ. Association of black carbon with cognition among children in a prospective birth cohort study. Am J Epidemiol 2008; 167: 280e6. Suzuki M, Thiem VD, Yanai H, et al. Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam. Thorax 2009; 64: 484e9. Vork KL, Broadwin RL, Blaisdell RJ. Developing asthma in childhood from exposure to secondhand tobacco smoke: insights from a meta-regression. Environ Health Perspect 2007; 115: 1394e400. Wilhelm M, Ritz B. Local variations in CO and particulate air pollution and adverse birth outcomes in Los Angeles County, California, USA. Environ Health Perspect 2005; 113: 1212e21. Yokota S, Takashima H, Ohta R, et al. Nasal instillation of nanoparticlerich diesel exhaust particles slightly affects emotional behavior and learning capability in rats. J Toxicol Sci 2011; 36: 267e76.
Discovering common mechanisms underlying the effects of air pollution from different sources is a major research challenge for the next decade. For example, does the association between trafficassociated black carbon and neurocognitive effects in children mean that wood smoke is also associated with effects on the brain? Some evidence for this was provided by the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial in San Marcos, Guatemala e one of the most important studies in the field of indoor air pollution. As part of this stove intervention study, Dix-Cooper et al estimated early life exposure to solid fuel smoke using carbon monoxide (CO) as marker of exposure. The advantage of CO is that it can be measured by passive monitoring e a method that is both cheap and portable. During the trial, personal CO measures were collected every 3 months from pregnant mothers. Children underwent neurodevelopmental assessment when they reached 6e7 years of age. The study showed an inverse association between personal CO exposure of mothers during their third trimesters and their child’s neuropsychological performance. Clearly, further research is needed to confirm these data, but the signal for an association between air pollution and neurocognitive function is concerning.
Future research We are just beginning to understand the true burden of air pollution on children’s health. From what we know to date, it is very likely that the health burden of air pollution exceeds the burden from threats from manufactured chemicals such as endocrine disruptors. What is clear is that current environmental policy does not sufficiently protect children from the adverse health effects of air pollution. For example, London consistently exceeds the current EU air quality standards. Questions that still need further basic and epidemiological research include; (i) what is the effect of air pollution (both indoor and outdoor) on viralinfections and viral-triggered bacterial interactions?, (ii) how does individual behaviour influence individual exposure of children e.g. does travelling to school on a heavily used road significantly increase personal exposure to traffic-derived PM10?, (iii) how can we protect families from the effects of carbonneutral biomass smoke (carbon neutral) but not increase carbon emissions (e.g. by switching to gas cooking)? A
FURTHER READING BeruBe KA, Sexton KJ, Jones TP, Moreno T, Anderson S, Richards RJ. The spatial and temporal variations in PM10 mass from six UK homes. Sci Total Environ 2004; 324: 41e53. Brauer M, Lencar C, Tamburic L, Koehoorn M, Demers P, Karr C. A cohort study of traffic-related air pollution impacts on birth outcomes. Environ Health Perspect 2008; 116: 680e6. Dherani M, Pope D, Mascarenhas M, Smith KR, Weber M, Bruce N. Indoor air pollution from unprocessed solid fuel use and pneumonia risk in children aged under five years: a systematic review and meta-analysis. Bull World Health Organ 2008; 86: 390e8. Dix-Cooper L, Eskenazi B, Romero C, Balmes J, Smith KR. Neurodevelopmental performance among school age children in rural Guatemala is associated with prenatal and postnatal exposure to
PAEDIATRICS AND CHILD HEALTH 22:5
Practice points C
C
C
C
200
Exposure of children to air pollution directly affects the lung and more distant organs. Recent data suggest an association between traffic- and biomassderived air pollution and neurocognitive impairment in children. Vulnerability to bacterial infection is increased in children exposed to biomass smoke and to ETS. In vitro studies suggest that pollution-mediated vulnerability to infection is mediated by upregulation of epithelial platelet activating factor receptor.
Ó 2011 Elsevier Ltd. All rights reserved.
New insights into air pollution and children’s health
impairment of brain function is unclear. Indeed, the possibility of a confounding variable (e.g. noise) cannot be excluded. However, there are proof-of-concept studies suggesting that airway PM affects brain function. For example, Yokota et al instilled diesel exhaust PM into the nose of 2-week old infant rats once a week for 4 weeks and found that PM-treated animals showed a lower avoidance performance than control animals given sham-instillation. Furthermore, there was a trend for levels of dopamine in the medial mammillary nucleus of the brain to be lower in the PMtreated animals. Histological examination of the brain showed no evidence that PM had penetrated into the nervous system e suggesting that this effect was mediated by indirect mechanisms. The effect of maternal inhalation of traffic-derived pollution on the developing fetus has been identified in recent studies with sufficient power to detect independent effects. In a study of over 70,000 singleton births in Canada, Brauer et al estimated exposure to air pollution at mothers’ residence and found that living within 50 m of a main road was associated with a 22% increase in low-birth weight. When exposure to air pollutants was modelled individually, all air pollutants other than ozone, were associated with small for gestational age. An effect of air pollution on preterm birth was also found e albeit only for PM2.5. Similarly in a US study, Wihelm and Ritz reported an association between modelled exposure of mothers to traffic-derived PM- and risk for preterm birth and term low-birth weight. How PM impacting in the lungs of mothers could influence the developing fetus is unclear. A possible mechanism is that PM alters the pattern of cytokines in the maternal and fetal circulation. Some evidence for this phenomenon was recently provided by Latzin et al who studied a birth cohort of 265 healthy term-born neonates and found that mean PM10 over the last 3 months of pregnancy was associated with increased interleukin-1 beta in cord blood. In summary, although the evidence base is limited these epidemiological associations are of concern and establishing biological plausibility in animal models is urgently needed.
Jonathan Grigg
Abstract Air pollution remains a major threat to children’s health. In high-income countries, most outdoor air pollution is from fossil fuel combustion, and most indoor pollution is from cooking and environmental tobacco smoke (ETS). Outdoor pollution in medium- and low-income countries is a mix of fossil-fuel, solid fuel (e.g. coal) and biomass (wood), and indoor pollution is from biomass smoke, solid fuels and ETS. Over the last decade, new data suggest that both biomass smoke and ETS increases the vulnerability of children to bacterial pneumonia, and that fossil-fuel and biomass smoke impair children’s neurocognitive development. Further research is needed to establish biological plausibility for these associations.
Keywords air pollution; biomass; children; environmental tobacco smoke; fossil-fuel; neurocognitive impairment; pneumonia
Children are especially vulnerable to the adverse effects of environmental pollution. Pollutants are either inhaled, or ingested, or absorbed through the skin. There are many potential environmental threats to children’s health, and for most the evidence base is unclear. For example, teasing out the independent effect of a single chemical amongst thousands of compounds is nearly impossible. For chemicals, regulatory agencies must therefore take a precautionary approach i.e. to not wait for definitive proof to protect children’s health. One area where causal association, is certain, yet exposure of children still occurs, is air pollution. A previous review in this journal of the effects of traffic-derived air pollution, focused on inhalable particulate matter (PM less than 10 microns in aerodynamic diameter; PM10), and addressed lung growth and prevalence of respiratory symptoms. The aim of this review is to focus on new insights into the adverse effects of air pollution, both indoor and outdoor, on children’s health.
Indoor air pollution Indoor air pollutants either penetrate into the home from the outside or are generated within the home. In high-income countries, penetrating indoor pollution is mainly from trafficderived emissions. Thus both PM and vehicular-emitted gases such as nitrogen dioxide (NO2) are higher in homes near main roads than those near to less heavily used roads. For example, Esplugues et al found higher concentrations of NO2 in homes located on streets with a high frequency of vehicle traffic. The major sources of indoor-generated air pollutants are cooking and parental smoking e and both sources produce PM and NO2. PM in homes with smokers is up to 15 mg/m3 higher than nonsmoking homes. Although there is substantial body of evidence showing that exposure of children to passive environmental tobacco smoke (ETS) is associated with increased respiratory symptom prevalence e including cough and wheeze, there has always been the question whether exposure of children to secondhand smoke causes asthma. Strong evidence for a causal link between ETS and asthma has recently been provided by a systematic review of data from eight cohort studies. This metaanalysis showed that the adjusted predicted relative risk for a secondhand smoke effect on incident asthma is 1.33 (95% CI, 1.14e1.56) e an association strongest in school-age children.
Traffic-derived air pollution Recent studies suggest that inhalation of traffic-derived pollutants has non-respiratory effects on the developing nervous system. Franco Suglia et al, estimated the exposure of 202 school-age children to black carbon (i.e. traffic-derived soot) at the home address, and found that black carbon was independently associated with decreases in a range of neurocognitive variables such as vocabulary, and composite intelligence quotient. To date, the mechanism that links deposition of black carbon PM in the lung to
Jonathan Grigg MD is Professor of Paediatric Respiratory and Environmental Medicine at the Centre for Paediatrics in the Blizard Institute, Barts and the London School of Medicine, London, UK. Conflict of interest: none.
PAEDIATRICS AND CHILD HEALTH 22:5
198
Ó 2011 Elsevier Ltd. All rights reserved.
SYMPOSIUM: SOCIAL PAEDIATRICS
The effect of maternal ETS exposure on perinatal outcomes is less obvious. In a recent systematic review and meta-analysis, Salmasi et al identified publications covering 48,439 ETSexposed women and 90,918 unexposed women and found that ETS-exposed infants weigh less, with a trend towards increased low-birth weight. Using a similar approach, Leonardi-Bee et al reported that exposure of non-smoking pregnant women to ETS reduces mean birth weight by at least 33 g, and increases the risk of birth weight below 2500 g by 22%. Since both ETS and trafficderived emissions have components in common, such as carbonaceous PM, these data also provide indirect support for an association between traffic-derived PM and birth weight (discussed above). Another important area on the global scale is the interaction between ETS and vulnerability to infection. In a recent metaanalysis Lee et al assessed the association between ETS and invasive bacterial disease in children. They found a consistent association between invasive meningococcal and Hib disease with the adjusted odds ratio (OR) for meningococcal disease of 1.2 (1.5e2.6). For invasive pneumococcal disease the OR was positive, but not significant. An explanation for this non significant finding is that pneumococcal pneumonia, although the major cause of bacterial pneumonia in children is frequently associated with negative blood cultures. The strongest evidence that ETS is a major vulnerability factor for pneumococcal pneumonia was provided by a study from Vietnam. Suzuki et al assessed hospital admissions for pneumonia among children aged less than 5 years in the previous 12 months in a populationbased cross-sectional survey that included all residents of 33 in a central area of Vietnam. Exposure to ETS was associated with hospital admissions for pneumonia (OR 1.55, 95% CI, 1.25 e1.92). This OR may seem relatively low, but since the prevalence of ETS in Vietnam was 70%, it was estimated that 28% of childhood pneumonia in this community is attributable to ETS with 44,000 excess hospital admissions in young children per year. Biological plausibility for this association was provided by Phipps et al who exposed mice to cigarette smoke for 5 weeks then instilled S. pneumoniae into the airway. Smoke-exposed mice had increased lung bacterial load at both 24 and 48 h after infection, and more clinical illness. Even more important on the global scale, is the association between exposure to biomass and coal smoke (e.g. wood, coal) and infection. Dherani et al in a meta-analysis and systematic review found an overall pooled OR of 1.78 (95% CI, 1.45e2.18) for exposure of children to solid fuel smoke and risk of pneumonia in young children. It is now widely accepted by policy makers that reduction of household indoor air pollution from solid fuels would represent a major contribution to the prevention deaths in young children living in low-income countries. Indeed, these data have contributed to the realization than indoor air pollution is a major environmental cause of death for both women and young children. In response to this, the United Nations Foundation launched the Global Alliance for Clean Cookstoves e which aims for 100 million homes to adopt clean stoves by 2020. In 2011, Hillary Clinton made this initiative a major part of her Global Partnerships Initiative. Since both ETS and indoor solid fuel pollution are associated with pneumonia in young children e could traffic-derived PM also increase vulnerability to infection? Bacterial pneumonia is
PAEDIATRICS AND CHILD HEALTH 22:5
relatively uncommon in high-income countries as are, fortunately, deaths. Since it is difficult to perform adequately powered epidemiological studies into air pollution and infection in high-income countries, studies suggesting biological plausibility become more important. For example, my group recently developed a model for the effect of PM on the adherence of pneumococci to lower airway epithelial cells (Figure 1). Adherence of bacteria to airway lining cells is a prerequisite step for establishing invasive disease, and environmental factors that upregulate adhesion are putative vulnerability factors for bacterial pneumonia. We found that both PM10 from a UK city (where most pollution is from traffic), and from Accra (a city with a mix of traffic-derived and solid fuel PM10), up-regulated pneumococcal adhesion to lower airway epithelial cells in vitro. Furthermore, we found that the mechanism for both fossil-fuel PM and mixed source PM was the same, i.e. upregulation of the ligand for pneumococcal adhesion on the surface of epithelial cells e the platelet activating factor receptor (PAFR). PAFR, by chance, happens to express proteins that interact with proteins in the pneumococcal cell wall. Pneumococci therefore adhere to this receptor e and are then moved into the cell as the receptor is internalized. In vitro studies comparing the effects of ETS, biomass PM and traffic-derived PM may therefore help to clarify whether there are common mechanisms underlying the association between air pollution and bacterial infection. From our data, we hypothesize that children exposed to high levels of air pollution (biomass, fossil-fuel and ETS) constitutively express increased levels of PAFR in their lower airway epithelial cells. By linking in vitro observations to valid markers of vulnerability in vivo (such as PAFR expression) it may be possible to generate sufficient data for policy makers to act on the presumption that traffic-derived PM increases pneumonia vulnerability without waiting for expensive and difficult-to-perform epidemiological studies.
Figure 1 Pneumococci adhering to a monolayer of alveolar epithelial cells imaged by scanning electron microscopy. Bacteria are bead-like structures. Adherence is mediated by epithelial platelet activating factor receptor interacting with ligands in the bacterial cell wall.
199
Ó 2011 Elsevier Ltd. All rights reserved.
SYMPOSIUM: SOCIAL PAEDIATRICS
carbon monoxide, a marker for exposure to woodsmoke. Neurotoxicology 2011. Sep 24th [Epub ahead of print]. Esplugues A, Ballester F, Estarlich M, et al. Indoor and outdoor concentrations and determinants of NO2 in a cohort of 1-year-old children in Valencia, Spain. Indoor Air 2010; 20: 213e23. Kulkarni N, Grigg J. Air pollution and children’s health. Paediatric child health 2008; 18: 287e91. Latzin P, Frey U, Armann J, et al. Exposure to moderate air pollution during late pregnancy and cord blood cytokine secretion in healthy neonates. PLoS One 2011; 6: e23130. Lee CC, Middaugh NA, Howie SR, Ezzati M. Association of secondhand smoke exposure with pediatric invasive bacterial disease and bacterial carriage: a systematic review and meta-analysis. PLoS Med 2010; 7: e1000374. Leonardi-Bee J, Smyth A, Britton J, Coleman T. Environmental tobacco smoke and fetal health: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2008; 93: F351e61. Martin 2nd WJ, Glass RI, Balbus JM, Collins FS. Public health. A major environmental cause of death. Science 2011; 334: 180e1. Mushtaq N, Ezzati M, Hall L, et al. Adhesion of Streptococcus pneumoniae to human airway epithelial cells exposed to urban particulate matter. J Allergy Clin Immunol 2011; 127: 1236e12422. Phipps JC, Aronoff DM, Curtis JL, Goel D, O’Brien E, Mancuso P. Cigarette smoke exposure impairs pulmonary bacterial clearance and alveolar macrophage complement-mediated phagocytosis of Streptococcus pneumoniae. Infect Immun 2010; 78: 1214e20. Salmasi G, Grady R, Jones J, McDonald SD. Environmental tobacco smoke exposure and perinatal outcomes: a systematic review and meta-analyses. Acta Obstet Gynecol Scand 2010; 89: 423e41. Suglia SF, Gryparis A, Wright RO, Schwartz J, Wright RJ. Association of black carbon with cognition among children in a prospective birth cohort study. Am J Epidemiol 2008; 167: 280e6. Suzuki M, Thiem VD, Yanai H, et al. Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam. Thorax 2009; 64: 484e9. Vork KL, Broadwin RL, Blaisdell RJ. Developing asthma in childhood from exposure to secondhand tobacco smoke: insights from a meta-regression. Environ Health Perspect 2007; 115: 1394e400. Wilhelm M, Ritz B. Local variations in CO and particulate air pollution and adverse birth outcomes in Los Angeles County, California, USA. Environ Health Perspect 2005; 113: 1212e21. Yokota S, Takashima H, Ohta R, et al. Nasal instillation of nanoparticlerich diesel exhaust particles slightly affects emotional behavior and learning capability in rats. J Toxicol Sci 2011; 36: 267e76.
Discovering common mechanisms underlying the effects of air pollution from different sources is a major research challenge for the next decade. For example, does the association between trafficassociated black carbon and neurocognitive effects in children mean that wood smoke is also associated with effects on the brain? Some evidence for this was provided by the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial in San Marcos, Guatemala e one of the most important studies in the field of indoor air pollution. As part of this stove intervention study, Dix-Cooper et al estimated early life exposure to solid fuel smoke using carbon monoxide (CO) as marker of exposure. The advantage of CO is that it can be measured by passive monitoring e a method that is both cheap and portable. During the trial, personal CO measures were collected every 3 months from pregnant mothers. Children underwent neurodevelopmental assessment when they reached 6e7 years of age. The study showed an inverse association between personal CO exposure of mothers during their third trimesters and their child’s neuropsychological performance. Clearly, further research is needed to confirm these data, but the signal for an association between air pollution and neurocognitive function is concerning.
Future research We are just beginning to understand the true burden of air pollution on children’s health. From what we know to date, it is very likely that the health burden of air pollution exceeds the burden from threats from manufactured chemicals such as endocrine disruptors. What is clear is that current environmental policy does not sufficiently protect children from the adverse health effects of air pollution. For example, London consistently exceeds the current EU air quality standards. Questions that still need further basic and epidemiological research include; (i) what is the effect of air pollution (both indoor and outdoor) on viralinfections and viral-triggered bacterial interactions?, (ii) how does individual behaviour influence individual exposure of children e.g. does travelling to school on a heavily used road significantly increase personal exposure to traffic-derived PM10?, (iii) how can we protect families from the effects of carbonneutral biomass smoke (carbon neutral) but not increase carbon emissions (e.g. by switching to gas cooking)? A
FURTHER READING BeruBe KA, Sexton KJ, Jones TP, Moreno T, Anderson S, Richards RJ. The spatial and temporal variations in PM10 mass from six UK homes. Sci Total Environ 2004; 324: 41e53. Brauer M, Lencar C, Tamburic L, Koehoorn M, Demers P, Karr C. A cohort study of traffic-related air pollution impacts on birth outcomes. Environ Health Perspect 2008; 116: 680e6. Dherani M, Pope D, Mascarenhas M, Smith KR, Weber M, Bruce N. Indoor air pollution from unprocessed solid fuel use and pneumonia risk in children aged under five years: a systematic review and meta-analysis. Bull World Health Organ 2008; 86: 390e8. Dix-Cooper L, Eskenazi B, Romero C, Balmes J, Smith KR. Neurodevelopmental performance among school age children in rural Guatemala is associated with prenatal and postnatal exposure to
PAEDIATRICS AND CHILD HEALTH 22:5
Practice points C
C
C
C
200
Exposure of children to air pollution directly affects the lung and more distant organs. Recent data suggest an association between traffic- and biomassderived air pollution and neurocognitive impairment in children. Vulnerability to bacterial infection is increased in children exposed to biomass smoke and to ETS. In vitro studies suggest that pollution-mediated vulnerability to infection is mediated by upregulation of epithelial platelet activating factor receptor.
Ó 2011 Elsevier Ltd. All rights reserved.