Children's Response to Air Pollutants

Authors: Thomas F. Batesona; Joel Schwartzb

Affiliations: a National Center for Environmental Assessment, Office of Research and
Development, U.S. Environmental Protection Agency, Washington, DC, USA
b
Departments of Environmental Health and Epidemiology, Harvard School of
Public Health, and Channing Laboratory, Brigham and Women's Hospital,
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
DOI: 10.1080/15287390701598234
Article Requests: Order Reprints : Request Permissions
Published in: Journal of Toxicology and Environmental Health, Part A, Volume 71, Issue 3
January 2008 , pages 238 - 243
Publication Frequency: 24 issues per year
Previously published as: Journal of Toxicology and Environmental Health (0098-4108) until
1998

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To cite this Article: Bateson, Thomas F. and Schwartz, Joel 'Children's Response to Air
Pollutants', Journal of Toxicology and Environmental Health, Part A, 71:3, 238 - 243

Abstract
It is important to focus on children with respect to air pollution because (1) their lungs are not
completely developed, (2) they can have greater exposures than adults, and (3) those exposures
can deliver higher doses of different composition that may remain in the lung for greater
duration. The undeveloped lung is more vulnerable to assault and less able to fully repair itself
when injury disrupts morphogenesis. Children spend more time outside, where concentrations of
combustion-generated air pollution are generally higher. Children have higher baseline
ventilation rates and are more physically active than adults, thus exposing their lungs to more air
pollution. Nasal breathing in adults reduces some pollution concentrations, but children are more
typically mouth-breathers—suggesting that the composition of the exposure mixture at the
alveolar level may be different. Finally, higher ventilation rates and mouth-breathing may pull
air pollutants deeper into children's lungs, thereby making clearance slower and more difficult.
Children also have immature immune systems, which plays a significant role in asthma. The
observed consequences of early life exposure to adverse levels of air pollutants include
diminished lung function and increased susceptibility to acute respiratory illness and asthma.
Exposure to diesel exhaust, in particular, is an area of concern for multiple endpoints, and
deserves further research.
 compromises postnatal morphogenesis of
tracheobronchial airways (Fanucchi et al.,
2000).

Damage to the lung during periods of

Introduction susceptibility in childhood may result in
airway remodeling that might increase
vulnerability to future insult. Branching
Children are more vulnerable with respect to
morphogenesis is active during lung
air pollution because their lungs are
development and affects how the airways are
significantly undeveloped at birth and are not
ultimately constructed. Plopper and
fully functional until about 6-8 yr of age
coworkers (1994) studied the developmental
(Burri, 1984). Infants are born with only one-
and functional response of neonatal animals,
tenth the number of alveoli of adults and an
including non-human primates, following
under-developed epithelium. Alveolar
pulmonary insult to various components of air
development begins by wk 32-36 of gestation
pollution. In studies of four species and a
(Langston et al., 1984), with approximately
number of different compounds, neonates
24 million alveoli present at birth, and
were always more susceptible to toxicants
experiences a 10-fold growth to 257 million
(Plopper et al., 1994; Fanucchi et al., 1997,
between birth and age 4 (Dunnill, 1962)—
2000, 2004). These authors observed that
although the bulk may be formed by age 2 yr
differentiation and development of the
(Burri, 1997). During this period, the lung
epithelium is changed by a single insult at a
undergoes significant morphogenesis;
very young age (Fanucchi et al., 1997).
respiratory bronchioles develop, as do the
Researchers have observed up to 6 mo after a
epithelium and the immune cell populations.
hit in young animals and not seen repair. In
This process of early growth suggests a
fact, most of the epithelium was at the same
critical exposure period where acute injury to
stage of differentiation as when the injury
the developing lung by air pollutants may
occurred (Smiley-Jewell et al., 1998),
have lasting adverse effects on respiratory
indicating that the lung does not change and
health.
develop as it should. While comparisons
made across species are complicated by
Little is known about the physiologic
differences in developmental timing, it is
development of children's lungs under adverse
clear that when early developmental processes
environmental conditions. However, Fanucchi
are disrupted, all further development is
and coworkers (2000) evaluated postnatal
subsequently disrupted, with the alterations
lung morphogenesis and function of infant
persisting throughout adulthood.
monkeys, which have airway structure and
postnatal lung development similar to
Exposure to air pollution in adult humans was
humans. Airway morphology and structure
shown to increase permeability of the
were evaluated at the end of 5 mo of episodic
pulmonary epithelium (Broeckaert et al.,
exposure to 0.5 ppm ozone (O3). Compared to
2000) and related inflammatory responses
controls, O3-exposed animals had (1) fewer
(Salvi et al., 1999). Increased permeability
airway generations, (2) hyperplastic
may allow for the translocation of inhaled
bronchiolar epithelium, and (3) altered
materials into interstitial areas or systemic
smooth muscle in terminal and respiratory
circulation. Damaged pulmonary epithelium
bronchioles. These results suggest that
may also inhibit mucociliary clearance,
episodic exposure to environmental O3
thereby increasing the duration of particle
exposure.
Children also have different patterns of
breathing than adults that may alter the
deposition of inhaled pollutants. The nose
partially filters toxic particles and gases,
making the mode of breathing, oral versus
nasal, an important determinant of toxicant
dose to the lungs (Bennett et al., 2003;
Nikasinovic et al., 2003). Nasal airway size
increases with age (Laine & Warren, 1991) as
does percentage of nasal breathing (Warren et
al., 1990). At rest, adults typically breathe
predominantly through the nose, while
children are more commonly mouth-
breathers. Nasal breathing filters and
conditions the inhaled air in temperature and
relative humidity. This implies that even
children breathing the same air at the same
rate may have different exposures than adults.
Children have a larger lung surface area per
unit of body weight than adults, and under
normal breathing, breathe considerably more
air per unit of body weight than adults—with
the highest rates in the youngest children (Iliff
& Lee, 1952; Poets et al., 1993; Arcus-Arth &
Blaisdell, 2007). In addition, children are
more exposed because they spend more time
outside, particularly in the afternoon and in
summertime when concentrations of O3 and
sulfates are typically higher, or at bus stops or
traveling to school in the morning, when
traffic pollutants are at their maximum. The
U.S. Environmental Protection Agency's
National Exposure Research Laboratory
Consolidated Human Activity Database
contains information on children's daily
outdoor activities (Cohen Hubal et al., 2000).
Figure 1 displays the product of the estimated
number of hours per day that children spend
in various outdoor microenvironments by age
(Cohen Hubal et al., 2000) multiplied by the
body weight-normalized daily breathing rates
(L/kg-d) from a recent analysis of the
statistical distribution of daily breathing rates
in children by Arcus-Arth and Blaisdell
(2007). The estimated volume of outdoor air
per kilogram per day inhaled in proximity to
the home is generally higher for younger
children with peak volumes at ages 4-5 yr.
The volumes of outdoor air per kilogram per
day inhaled during time spent at parks and in
vehicles are highest for infants and diminish
steadily with age. Children generally also
have higher ventilation rates than adolescents
(Ekelund et al., 2004) and teenagers or young
adults (Sigmund et al., 2007) because they are
more active. Deep breathing pulls air
pollutants faster and further into the lung—
bypassing initial areas of deposition. A recent
study has reported that in the pulmonary
region of the lung, particle dose can be two-
to fourfold higher among young children as
compared with adults (Ginsberg et al., 2005).
This part of the lung has slower clearance so
particles remain there longer. As children
typically exercise more frequently than adults,
and for longer periods, children are likely to
also have altered deposition patterns of air
pollutants as well which may alter their
response.
FIG. 1. Body-weight-normalized outdoor
daily breathing rate among children age 0-11
yr by microenvironmental location. Estimated
rates are the product of the time spent
outdoors (Cohen Hubal et al. 2000) and age-
specific breathing rates (Arcus-Arth &
Blaisdell, 2007).
At the same time the child's lung is
developing, the child's immune system,
immature at birth, is also beginning to
develop. Much recent attention in asthma
research was focused on this development,
and in particular on factors that influence the
balance between TH-2 (humoral immunity
dominant) and TH-1 (cellular immunity
dominant) phenotypes (Holt, 1998).
Development of TH-2 phenotype over the
TH-1 may lead one to develop allergy. Diesel
exhaust particles have been shown to induce
immunoglobulin (Ig) E antibodies in
combination with allergens where there is a
much more robust inflammatory response and
sensitization (Diaz-Sanchez et al., 1997,
1999; Nikasinovic et al., 2004).
AIR POLLUTION
EFFECTS OBSERVED IN
CHILDREN
Prenatal Effects
While relatively recent, there is now
considerable evidence that maternal exposure
to air pollution during pregnancy is associated
with adverse birth outcomes. Perhaps the
most unexpected results have been recent
papers reporting that prenatal exposure of
populations to prevailing levels of air
pollution is associated with early fetal loss
(Pereira et al., 1998), preterm delivery (Xu et
al., 1995; Ritz et al., 2000; Lin et al., 2001;
Wilhelm et al., 2004; Sagiv et al., 2005), and
lower birth weight (Wang et al., 1997; Ritz &
Yu, 1999; Dejmek et al., 1999; Bobak &
Leon, 1999; Bobak, 2000; Ha et al., 2001;
Bobak et al., 2001; Parker et al., 2005).
Because birth certificates in most areas have
extensive information on maternal age,
education, and smoking, as well as maternal
medical conditions that may affect the
pregnancy, these studies are generally well
controlled. Moreover, particulate air pollution
from combustion sources shares many
characteristics with sidestream tobacco
smoke, which is rich in particles and
polycyclic aromatic hydrocarbons. A number
of studies (Ahluwalia et al., 1997; Dejin-
Karlsson et al., 1998; Dejmek et al., 2002;
Kharrazi et al., 2004) found that
environmental tobacco smoke was associated
with low birth weight, small-for-gestational
age, and preterm delivery. This provides
support for the plausibility of the reported
association.
Infant Mortality
A number of studies reported that air
pollution was associated with infant mortality.
Approximately 4000 excess deaths occurred
as a result of the great air pollution episode of
December 1-5 in London in 1952 (Her
Majesty's Public Health Service, 1954), and
elevated death rates continued for weeks
afterward (Anderson, 1999), indicating that
there were delayed as well as acute effects.
While most of the deaths were in adults,
infant mortality was doubled during that
period (Schwartz, 1994).
This episode is important because it
establishes causality. More recently,
Woodruff et al. (1997) examined infant deaths
in the United States and levels of PM10 in the
air. They excluded infant deaths in the first
month after birth as likely to reflect
complications of pregnancy and delivery, and
found that PM10 was associated with higher
death rates in the next 11 mo of life. This
excess risk seemed to be principally from
respiratory illnesses, although sudden infant
death syndrome deaths were also elevated.
Bobak and Leon (1992) also examined the
cross-sectional association between air
pollution and infant mortality rates across
towns in the Czech Republic. A significant
association was seen between infant death
rates and particle and SO2 concentration.
Other studies examined day-to-day changes in
air pollution and day-to-day changes in infant
deaths. Saldiva et al. (1994) reported that
infant death from respiratory disease was
associated with air pollution, particularly
from traffic. Two other studies (Loomis et al.,
1999; Ha et al., 2003) similarly found
respiratory deaths in infants associated with
air pollution.
Recent studies from California have identified
increased risks of respiratory deaths and
sudden infant death syndrome with increases
in ambient air pollution. Ritz et al. (2006)
identified increased risk of respiratory deaths
associated with elevated concentrations of
carbon monoxide and PM10 and increased
risks of sudden infant death syndrome (SIDS)
with elevation in concentration of NO 2.
Likewise, Woodruff et al. (2006) identified an
increased risk of respiratory-related post-
neonatal infant mortality and SIDS with
elevated concentrations of PM2.5.
Chay and Greenstone (2003) analyzed the
impact of air pollution on infant mortality
capitalizing on a quasi-natural experiment
concerning the 1980-1982 economic
recession in the United States, which induced
substantial variation in air pollution
reductions across sites. The investigators
found that a 1-μg/m3 reduction in total
suspended particulates (TSP) resulted in 4-7
fewer infant deaths per 100,000 live births.
That is, a 1% decline in TSP resulted in a
0.35% reduction in the infant mortality rate at
the county level. The protective effects of
TSP diminution were greater for deaths
within 24 h after birth and within 28 d of birth
compared to deaths between the second and
twelfth months.
Lung Function
Several large cohort studies assessed how
children's lung function performs in the
presence of particulate and gaseous air
pollutants. A study of the second National
Health And Nutritional Examination Study
examined the effect of air pollution on lung
function in children and youths ages 6-24 yr
(Schwartz, 1989). Forced vital capacity,
forced expiratory volume at 1 s, and peak
expiratory flow all showed statistically
significant negative correlations with annual
concentrations of total suspended particulates,
nitrogen dioxide (NO2), and O3. The Harvard
24-Cities Study collected data from over
13,000 children 8-12 yr old related to lung
function and collected data from air monitors
in all communities, which were selected to
reflect areas with high air pollution of various
kinds (Dockery et al., 1996). The study found
that as PM2.1 concentration increased, the
percentage of children with abnormal lung
function also rose. Similar results were seen
for sulfate particles. Another study of 6
communities in the Netherlands looked at
lung function in school children that lived
within 1 km of a freeway and found that lung
function varied in accordance to the number
of trucks per day on the freeway (Brunekreef
et al., 1997). However, there was no relation
between lung function and number of
commuter autos per day—suggesting that
diesel exhaust plays a role in lung function.
The Southern California Children study
looked at year-to-year growth in lung function
over 4 yr among children in the 4th, 7th, and
10th grades in 12 communities. The
investigators found that the growth of FEV1
was significantly slower in more polluted
(higher PM 2.5) communities (Gauderman et
al., 2000). A follow-up study in 2001 tracked
down the children from the 12 community
studies in California and found that lung
growth decreased or increased depending on
whether children moved to a more or less
polluted area (Avol et al., 2001). This study
confirmed what previous research suggested
—if exposure levels change, lung growth
changes.
Respiratory Effects: Chronic Cough
and Bronchitis
Dockery et al. (1989) reported that chronic
bronchitis and chest illness in children were
associated with exposure to particulate air
pollutants. Subsequent studies in the United
States (McConnell et al., 1999) and elsewhere
confirmed that particulate exposure was
associated with higher rates of chronic cough
and bronchitis symptoms in children. A
similar large study (n = 4470) comparing
school children in 10 communities in
Switzerland reported an adjusted odds ratio
for bronchitis of 2.88 (95% CI 1.69-4.89) for
PM10 exposure between the most and least
polluted community (Braun-Hahrlander et al.,
1997). The Harvard 24-Cities Study also
found that particulate air pollution was
associated with bronchitis episodes across the
communities (Dockery et al., 1996). Chronic
cough was also associated with air pollution
in a number of studies (van Vliet et al., 1997;
Tiittanen et al., 1999; Mar et al., 2004).
A 3-yr study in Utah Valley, in which during
the second year the steel mill in the valley
was on strike, clearly demonstrated that
children's hospital admissions for bronchitis,
asthma, pneumonia, and pleurisy dropped
during the second year when the PM10
dropped and rose again in the third year when
the steel mill reactivated and PM10 increased
again (Pope, 1989). A study looking at eastern
Germany, where there has been a decrease in
pollution since the reunification of Germany,
shows that this reduction was associated with
lowered rates of chronic cough and bronchitis
symptoms in a cohort of children (Heinrich et
al., 2000). This demonstrates not merely an
association, but that an intervention produces
improvements in health. A similar result has
now been reported in Switzerland (Bayer-
Oglesby et al., 2005).
Respiratory Effects: Asthma
Air pollution, including particulate matter, O3,
NO2, and sulfur dioxides, has long been
known to exacerbate asthma (Dockery et al.,
1989; Schwartz et al., 1993; Sheppard et al.,
1999; Ostro et al., 2001; Lin et al., 2002; Gent
et al., 2003; Mar et al., 2004; Barnett et al.,
2005), including (1) increased symptoms, (2)
need for bronchodilator medication, (3)
decreased lung function, and (4) emergency
visits for attacks. Unlike bronchitis and other
respiratory symptoms, asthma prevalence did
not increase with pollution levels in the
Harvard 24-Cities Study (Dockery et al.,
1989). Research shows that the number of
hospital asthma admissions has increased
since 1968, but the levels of NOx and CO2
have fallen (Schwartz, 1997). Further studies
suggested that air pollution, particularly
traffic-related pollution, is associated with the
development of asthma and atopy. For
example, Studnicka et al. (1997) examined 8
small rural communities and found a strong
association between asthma prevalence and
NO2 levels, with odds ratios reaching 5.81
(95% CI 1.27-26.5) contrasting the highest
and lowest exposures. Kramer et al. (2000)
examined 317 children in three German
communities. NO2 measurements outside each
child's home were significant predictors of
hay fever, symptoms of allergic rhinitis,
wheezing, and sensitization against pollen,
house dust mites, or cats, while indoor NO2
was not, indicating that outdoor NO 2 was
serving as a surrogate for other traffic-related
pollutants.
In the Netherlands, residence on a high-traffic
street was associated with more than a
twofold increase in the risk of wheezing after
control for confounders (Oosterlee et al.,
1996). Another Dutch study of schoolchildren
found that asthma was reported significantly
more often among those living within 100 m
from a freeway than among those living
further away and that truck traffic intensity
was significantly associated with chronic
respiratory symptoms (van Vliet et al., 1997)
—even after controlling for potential
confounders related to socioeconomic status.
Subsequent research, including a study in
California in which increased freeway density
was related to increased asthma prevalence in
children, provided more support for diesel
exhaust as a cause of asthma. Similar results
are seen in other studies of traffic-related
pollution (Brunekreef et al., 1997; Kim et al.,
2004; Gauderman et al., 2005). Overall, diesel
exhaust was shown to be a powerful adjuvant
for atopic sensitization (Diaz-Sanchez et al.,
2003), and also seems the most important
traffic indicator in predicting asthma and
atopy.
CONCLUSIONS
Studies of air pollution-related adverse health
effects have focused on children because (1)
their exposure history is easier to ascertain,
(2) their exposure is likely greater at the same
ambient concentrations, and (3) their
developmental state suggests greater
susceptibility than for adults. While recent
studies highlighted the elderly as another
susceptible group, particularly for
cardiovascular effects, the arguments for
increased susceptibility among children have
also generally been found to be valid. Air
pollutants may affect children prenatally, with
interesting new results on birth outcomes and,
most provocatively, on infant mortality. Air
pollutants certainly seem to affect pulmonary
development and development of bronchitic
symptoms. There is increasing evidence for
atopic sensitization and the development of
asthma. The specific pollutants involved in
the prenatal effects seem less clear. However,
exposure to diesel exhaust is a particular area
of concern for multiple endpoints, and
deserves further research, particularly as
diesel engines are often cited as a potential
way to achieve greater energy efficiency.
Acknowledgments
The views expressed in this article are those
of the authors and do not necessarily reflect
the views or policies of the U.S.
Environmental Protection Agency.
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