MT, Y-F Li, B Langholz and FD Gilliland. 2003. Early Life
Environmental Risk Factors for Asthma: Findings from the Children's
Health Study. Environmental
Health Perspectives. doi:10.1289/ehp.6662 Online 9 December
US and other industrialized countries are experiencing an asthma
epidemic. The incidence of asthma in Americans has roughly doubled
since 1980. It is now the most common chronic disease in US children.
Many factors are known to provoke asthma attacks, but advances in
scientific understanding of the underlying causes of the increase
in asthma rates have been slow in coming. A number of hypotheses
have been proposed, with exposures during infancy emerging as a
this paper, Salam et al. report significant increases in
asthma risk associated with exposures experienced early in childhood.
Of the several risk factors they studied, the strongest associations
they found were with exposures to herbicides and pesticides in infancy,
and attending daycare before the age of 4 months old. Children
exposed to herbicides before the age of 1 were 10 times more likely
to develop early persistent asthma than controls.
features of their results are inconsistent with the 'hygiene' hypothesis...
that better health care in childhood prevents the immune system
from developing normally.
did they do? Salam et al. conducted a case-control
study of children in southern California. Cases were 279 children
diagnosed with asthma before the age of 5 years. Of the cases, severity
of asthma varied from early transient wheezing (~17% of cases) to
late onset persistent asthma (24%) to early onset persistent asthma
were 412 asthma-free children chosen to match the cases on a series
of variables including grade, sex, community, and whether or not
the child's mother smoked during pregnancy.
child's biological mother was questioned by phone using a structured
interview to obtain information about a range of possibly-relevant
exposures along with demographic information. In the small percentage
of cases where the mother was not present, interviewers questioned
the father or care-giver.
did they find?
basic observations about their study subjects:
of their subjects were white, male and came from middle-income
children were roughly twice as likely to come from families in
which a parent or sibling had asthma.
family income nor the mother's level of education nor access to
health care differed between cases and controls.
with more siblings were less likely to devleop asthma.
types of exposure during infancy and early childhood substantially
increased the risk that a child would develop asthma, based upon
et al. calculated in comparing cases with controls.
strongest association was for exposure to herbicides in the first
year of infancy and early persistent asthma. Infants exposed
to herbicides before the age of 1 were 10 times more likely to develop
early persistent asthma. This result was highly significant,
with 95% confidence intervals running from 2.46
Children exposed to herbicides after their first birthday,in contrast,
were no more likely to develop asthma than controls. The odds ratio
(OR)for all asthma types and exposure before the age of 1 was 4.58
(95% CI 1.36-15.43). In other words, children exposed to herbicides
before the age of 1 were almost 5 times more likely to have asthma
for pesticide exposure were also significant but not as strong.
Children exposed before 1 to pesticides were 3.58 times more likely
to develop early persistent asthma than controls. As with herbicides,
there was no increased risk of asthma if exposure began after the
age of 1.
to farm animal, farm crop or dust exposure also elevated the risk
of early persistent asthma, although the effect was not as pronounced
as for pesticides and herbicides. The strongest of these was for
exposure to farm animals in the first year or later (OR=3.03). The
limits of the confidence intervals
for these were at or above 1, but only marginally.
exposures other than to pesticides, herbicides, and farm exposures
bore a relationship with early persistent asthma. In contrast, the
risk of early transient wheezing was elevated by exposure to "wood/oil
smoke, soot or exhaust" exposure (odds ratio of 5.65 for exposure
in the first year and later), cockroach exposure (with the largest
odds ratio being 5.09, for exposures taking place at ages older
than 1), and attending day care before the age of 4 months (OR=
found no association between asthma risk and whether or not the
family had pets.
does it mean? The most striking aspect of their finding
is the strong association with herbicides and pesticides before
the age of 1. This is the strongest association yet reported in
a body of scientific literature in which there are few studies that
have attempted to quantify early exposures to pesticides or herbicides
and asthma risk in children. The authors observe:
the widespread use of pesticides and herbicides in the home
and farm environments, and the magnitude of the observed risks,
additional studies of the role these exposures in asthma etiology
across childhood are needed."
they found any association is remarkable because of the relatively
crude nature of the survey instrument, a questionnaire. Normally,
faulty recall would introduce statistical noise into the analysis,
and render an association more difficult to find. The exception
to this would be if parents of asthmatic children are more likely
to remember herbicide/pesticide use than parents of controls. Where
this the case, however, one might expect to see the effect on all
asthma types for both ages (starting before age 1 yr, starting after
age 1 yr), instead of only for early persistent asthma with exposure
before age 1. Hence while biased recall can't be ruled out, it would
appear to be unlikely.
strength of the association is also remarkable because "pesticides"
and "herbicides" include many very different compounds,
not all of which would be likely to be increasing asthma risk. These
data raise the possibility instead that there may be a small number
of compounds for which the odds ratio are much greater. Then in
an analysis like this, in which no distinction is made between herbicides
that cause asthma and those that don't, their effect is averaged
with other compounds and the observed OR is lower.
aspects of their findings are inconsistent with the "hygiene
hypothesis,' that better hygiene early in life leads to
fewer challenges to the developing immune system, which then predisposes
the child to asthma:
beginning day care before the age of 4 months are more likely
to develop asthma. The hygiene hypothesis predicts that children
in day care earlier should be less likely to develop asthma, because
they would begin mingling at an earlier age with other children,
would be exposed to more pathogens and hence more immune system
challenges. Instead of supporting the hygiene hypothesis, this
result instead raises questions about pesticide and herbicide
applications in day care settings, questions which can't be answered
with data from the current publication.
exposed to farm animals and dust are more likely to develop asthma.
The hygiene hypothesis predicts the opposite. Again, this raises
questions about chemical exposures, which might co-vary with farm
animals and dust.
with no siblings were at lower risk to asthma than children with
one or two siblings. As above, the hygiene hypothesis would
predict that interactions with more children (in this case, siblings),
would protect against asthma.
contrast, the finding that once there was at least one sibling (as
opposed to none), children with more siblings were less at risk
to asthma is consistent with the hygiene hypothesis: presumably
more siblings means more exposures. Many other factors covary with
sibling number. As the authors point out, at the very least the
finding that early day care attendance is associated with heightened
risk, and that children with no siblings are at lower risk than
those with one or two "suggests the need for a more complex
prevalence of asthma in inner city poverty centers also undermines
chief weaknesses of the study are its dependence upon parent recall
and the lack of specificity about the details of exposure. Under
most circumstances, these factors would make it false
more likely. Hence the strength of the associations discovered should
be taken seriously.
the study falls far short of establishing any causal relationships
between exposures and asthma, it adds significantly to the evidence
that exposures early in life may increase asthma risk and may thus
may be contributing to the burgeoning asthma epidemic. Salam et
al.'s work adds more broadly to the weight of evidence that
exposures to herbicides and pesticides early in life can have adverse
effects and should be avoided in the home and other settings.