SYMPOSIUM: SOCIAL PAEDIATRICS

New insights into airpollution and children’shealthJonathan Grigg

AbstractAir 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 envi-

ronmental pollution. Pollutants are either inhaled, or ingested, or

absorbed through the skin. There are many potential environ-

mental 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 agenciesmust 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 particulatematter (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.

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 associ-

ated 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

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-instil-

lation. Furthermore, therewas a trend for levels of dopamine in the

medial mammillary nucleus of the brain to be lower in the PM-

treated 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

50mof amain roadwas associatedwith a 22%increase in low-birth

weight.Whenexposure to air pollutantswasmodelled individually,

all air pollutants other than ozone, were associated with small for

gestational age. An effect of air pollution on preterm birth was also

founde albeit only for PM2.5. Similarly in a US study, Wihelm and

Ritz reported an association betweenmodelled exposure ofmothers

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 bio-

logical plausibility in animal models is urgently needed.

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 traffic-

derived 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 non-

smoking 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 meta-

analysis 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.

� 2011 Elsevier Ltd. All rights reserved.

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.

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 ETS-

exposed 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 traffic-

derived 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 (dis-

cussed above).

Another important area on the global scale is the interaction

between ETS and vulnerability to infection. In a recent meta-

analysis 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 signifi-

cant 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 pneu-

monia 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 population-

based 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 preva-

lence 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 childrene could traffic-derived PM also

increase vulnerability to infection? Bacterial pneumonia is

PAEDIATRICS AND CHILD HEALTH 22:5 199

relatively uncommon in high-income countries as are, fortunately,

deaths. Since it is difficult to perform adequately powered epide-

miological 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 themechanism

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 receptore and are thenmoved 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 commonmechanisms 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.

� 2011 Elsevier Ltd. All rights reserved.

Practice points

C Exposure of children to air pollution directly affects the lung

and more distant organs.

C Recent data suggest an associationbetween traffic- andbiomass-

derived air pollution and neurocognitive impairment in children.

C Vulnerability to bacterial infection is increased in children

exposed to biomass smoke and to ETS.

C In vitro studies suggest that pollution-mediated vulnerability

to infection is mediated by upregulation of epithelial platelet

activating factor receptor.

SYMPOSIUM: SOCIAL PAEDIATRICS

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 traffic-

associated black carbon and neurocognitive effects in children

mean that wood smoke is also associatedwith effects on the brain?

Some evidence for this was provided by the Randomized Exposure

Study of Pollution Indoors andRespiratory 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 bemeasured

by passivemonitoringe amethod that is both cheap and portable.

During the trial, personal CO measures were collected every

3 months from pregnant mothers. Children underwent neuro-

developmental 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 viral-

infections 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 carbon-

neutral biomass smoke (carbon neutral) but not increase

carbon emissions (e.g. by switching to gas cooking)? A

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� 2011 Elsevier Ltd. All rights reserved.