Perspectives | Correspondence
Perspectives | Correspondence
volume 120 | number 9 | September 2012 • Environmental Health Perspectives
C-Reactive Protein Levels in
van den Hooven et al. (2012) found a non
significant association between high levels
of maternal and fetal Creactive protein
(CRP) and exposure to air pollution when
they examined the correlation of CRP levels
with inflammation and obstetric morbidity.
The authors reported that elevated fetal CRP
levels at delivery were associated with higher
longterm average maternal exposure to PM10
(particul ate matter ≤ 10 μm in aero dynamic
diameter) and NO2 (nitrogen dioxide). Other
studies have reported that neither pre eclampsia
(Kristensen et al. 2009) nor pregnancy loss
(Boggess et al. 2005) is associated with a
systemic inflammation as reflected by CRP
levels. However, van den Hooven et al. (2012)
insisted that exposure to air pollution may
lead to systemic inflammation in pregnancy.
Although this statement is defensible, the
confounding results regarding CRP levels
should be clarified.
CRP is accepted as a good marker of
acute inflammation, particularly within
infection, but its value in chronic inflamma
tion depends on the inflammation pathway
involved and the under lying process. In an
examination of auto immune inflammatory
responses triggered by the indoor environ
ment in sick buildings, CRP was < 0.1 mg/dL
(normal range, 0.1–0.5 mg/dL) in 27% of
patients (Blasco 2011). Interestingly, 13% of
patients had suffered miscarriages. CRP may
be low or typically very low during a flareup
of some connective tissue dis orders, such
as systemic lupus erythematosus (SLE) or
undifferen tiated connective tissue disease. The
erythro cyte sedimentation rate more accu
rately reflects SLE disease activity in patients
without associated infection. Therefore, the
presence of normal or low CRP levels does
not guarantee the absence of inflammation
or a positive pregnancy outcome. It would
be interesting to assess possible individual
immune susceptibility markers and other
markers, such as auto antibodies or tumor
necrosis factor α, in future studies of sys
temic inflammation induced by air pollutants
The author declares he has no actual or potential
competing financial interests.
Luis Miguel Blasco
Unidad de Alta Resolución Hospitalaría
Hospital Marqués de Valdecilla
Blasco LM. 2011. Sick building syndrome and autoimmunity
[Letter]. Lupus 20:544–546.
Boggess KA, Lieff S, Murtha AP, Moss K, Jared H, Beck J,
et al. 2005. Maternal serum C-reactive protein concentra-
tion early in pregnancy and subsequent pregnancy loss.
Am J Perinatol 22:299–304.
Kristensen K, Wide-Swensson D, Lindstrom V, Schmidt C,
Grubb A, Strevens H. 2009. Serum amyloid a protein and
C-reactive protein in normal pregnancy and pre eclampsia.
Gynecol Obstet Invest 67:275–280.
van den Hooven EH, de Kluizenaar Y, Pierik FH, Hofman A,
van Ratingen SW, Zandveld PY, et al. 2012. Chronic air
pollution exposure during pregnancy and maternal and
fetal C-reactive protein levels: the Generation R Study.
Environ Health Perspect 120:746–751.
Editor’s note: In accordance with journal
policy, van den Hooven et al. were asked
whether they wanted to respond to this letter,
but they chose not to do so.
Use of Meta-analyses by IARC
In their letter, Kogevinas and Pearce (2012)
suggested that metaanalyses should be more
routinely prepared for the evaluations of the
International Agency for Research on Cancer
(IARC) Monographs program. We concur
that metaanalyses are useful in many cases,
but there are also counter examples where
they have not been useful. For example, when
Kogevinas et al. (1998) reviewed the carcino
genicity of cancer hazards in the rubber
manufacturing industry, they argued against
using metaanalytic techniques because of
the hetero geneity of exposure circumstances
within and between manufacturing plants
and differences of exposure classifications
used in the studies. They concluded that a
single summary risk estimate would be
uninformative. Based on their systematic
narrative review, the authors concluded that
there is an increased risk of neoplasms of
the urinary bladder, lung, and larynx and
an increased risk of leukemia (Kogevinas
et al. (1998). In contrast, Alder et al.
(2006) performed a metaanalysis of cancer
occurrence among workers in the rubber
manufacturing industry. Based on summary
estimates for the entire rubber industry and
two major sectors of this industry, these
authors concluded that excesses other than
for leukemia were not substantiated by their
synthetic metaanalysis (Alder et al. 2006).
After reviewing all the pertinent studies, a
later IARC Working Group concluded that
there is sufficient evidence for an increased
risk of several types of cancer in rubber
manufacturing (Baan et al. 2009).
In contrast, when the IARC Working
Group for Volume 98 reviewed the evidence
on shift work and cancer, a published meta
analysis had reported a statistically signifi
cantly increased risk for breast cancer among
women who regularly worked the night
shift (Megdal et al. 2005). Nevertheless, the
IARC Working Group concluded that there
was only limited evidence for carcino genicity
in humans (IARC 2010).
In the context of the Volume 98
Monographs meeting, the Working Group
performed a metaanalysis and concluded
that there was sufficient evidence for the
carcino genicity of exposures as a painter
(IARC 2010). In preparation for the
Volume 100 series of the IARC Monographs,
this metaanalysis was further developed,
taking into account studies published after
the Volume 98 meeting (Guha et al. 2010).
This metaanalysis and another one (Bachand
et al. 2010) were available to the Working
Group for Volume 100F. Bachand et al.
(2010) did not provide results by duration
of employment or for non smokers, but they
argued that the increased risks could be due
to residual confounding. After reviewing
all published evidence, the IARC Working
Group reconfirmed the carcinogenicity of
exposures as a painter.
In general, during the last two decades
metaanalyses have become more widely used
in epidemiology, and the 2006 amendment of
the IARC Preamble now specifically mentions
the possibility of pre meeting and ad hoc meta
analyses during the course of a Monograph
meeting (IARC 2006). In practice, this has
been done even earlier, for example, when
the Working Group for Volume 83 updated
a published metaanalysis on involuntary
smoking and lung cancer (IARC 2004).
Anticipating scenarios as described above, the
Preamble (IARC 2006) stresses the need “that
the same criteria for data quality be applied
as those that would be applied to individual
Kogevinas and Pearce (2012) referred to
a recently published metaanalysis for asbes
tos and ovarian cancer that we coauthored
(Camargo et al. 2011). Interestingly, another
metaanalysis of this same question was
published by Reid et al. (2011). Whereas
our metaanalysis focused on occupational
cohorts with welldocumented exposure to
asbestos and identified almost twice as many
cases from occupational cohorts, Reid et al.
also included environ mental and household
exposures as well as linkage and case–control
studies. Nevertheless, both metaanalyses
reported increased risks overall and in most
stratified analyses. However, while Reid et al.
(2011) believed that increased risks may be
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