DISCUSSION
This study found that history of wheezing and rhinitis in children were
associated with increased risk of developmental problems, in particular,
that of conduct problems. Previous studies have investigated the
relationship between the presence of allergies and behavioral
characteristics of children. However, unlike previous studies, the
present study analyses included adjustments for potential confounding
factors such as demographic characteristics, parenting stress, and
allergy-related variables. Allergy-related variables included ISAAC
items, clinician’s diagnosis of allergies, and family history of
allergies. To control for the impact of collinearity, which was likely
between the variables that represent similar concepts, we performed
adjustments using propensity scores.
Adjusted estimates indicated an association between history of wheezing
and that of nose symptoms and childhood conduct problems. This result is
consistent with that of previous studies, reporting that rhinitis and
asthma, but not eczema, were associated with increased risk of
ADHD.18 A separate cross-sectional study using SDQ as
an outcome measure and logistic regression analyses adjusted for gender,
age, and primary caregiver’s educational level has shown that children
with current asthma symptoms were more likely to present with conduct
problems than those without.5 This study differed from
ours in that no significant association between conduct problems and
history of asthma or hay fever were observed. This discrepancy might be
due to between-study differences in definition of outcomes and
associated cutoff scores. For example, Hammer-Helmich et al. adopted the
“clinical” value as a cutoff score, whereas we adopted the
“borderline” value as the cutoff score. Goodman suggested that the
“borderline” cutoff score be used in studies of high-risk samples
where false positives are not a major concern20;
however, we believe that using a highly sensitive threshold is
appropriate to reduce the danger of overlooking an association. Another
possible reason for between-study differences in findings is use of
different confounders for adjustment during analysis. The present study
adjusted for different types of confounders, using the propensity score
technique. Following these adjustments, our results indicate an
association between history of wheezing and/or nose symptoms in children
and conduct problems; this finding may inform selection of confounders
and support new perspectives in future studies.
Biologically, allergy-sensitized children have elevated levels of
inflammatory cytokines. Studies in clinical psychiatry have shown that
levels of specific cytokines play a role in signaling the brain to
produce neurochemical, neuroendocrine, and neuroimmune responses that
correspond to behavioral changes. These responses may affect important
brain activities such as sleep, appetite, and neuroendocrine
regulation.25 Depending on the rate and amount at
which cytokines cross the blood brain barrier, diverse neuropsychiatric
symptoms may emerge, including low or depressed mood, anxiety, or
psychosis.26 This is not the case with eczema-related
findings; this study’s findings were consistent with those of previous
studies on allergic symptoms25,26 and behavioral
problems in children.
In the present study, history of wheezing and rhinitis affected the risk
of conduct problems in children after adjustment for potential
confounders. Both wheezing and rhinitis cause respiratory symptoms,
which may lead to sleep disorders. Poor sleep quality can adversely
affect the behavior of children.27 In addition, a
previous systematic review revealed the presence of sleep disorders in
children with ADHD28; a separate review reported that
associations between sleep and psychopathology are complex and likely
bidirectional.29 Therefore, additional studies are
needed to elucidate the association between ADHD-like behavioral
characteristics and sleep.
That is to say, given these findings, we believe that high impulsiveness
can be attributed in part to the psychological effect of elevated levels
of inflammatory cytokines that are triggered by allergic sensitization;
in addition, low quality of sleep is likely to play a role in tendency
toward behavioral irritation. However, further studies are needed to
confirm these associations.
This study has several strengths and limitations. This study is the
first to adjust for confounding factors, including participant
demographic characteristics, parenting stress, and allergy-related
variables. Study limitations are as follows. First, while we adjusted
for multifaceted confounders, we did not control for unmeasured or
residual confounding by factors such as sleep and psychopathological
characteristics. Second, as this was a cross-sectional study, the
presented findings preclude meaningful discussions of causality. Further
studies are warranted to confirm our findings; such studies should
involve a longitudinal design and a representative sample. Third, we did
not control for the impact of medication that could affect sleepiness or
mental health, such as antihistamines. Finally, caregivers may have
reported increased parenting stress due duties associated with care of
children with allergies; however, we could not account for this factor
in this study.
In conclusion, this study revealed that history of wheezing and rhinitis
in children is associated with increased risk of behavioral problems, in
particular, that of conduct problems.
Author contributions:
Chikae Yamaguchi: Conceptualization(lead); Data curation(lead); Formal
analysis(lead); Methodology(equal); Funding acquisition(lead);
Writing-Original Draft Preparation(lead); Writing-review and
editing(lead). Takeshi Ebara: Data curation(equal); Formal
analysis(equal); Methodology(lead); Writing-review and editing(equal).Masaki Futamura: Conceptualization(equal); Writing-review and
editing(equal). Yukihiro Ohya: Writing-review and
editing(equal). Midori Asano: Conceptualization(supporting);
Writing-review and editing(equal).
Acknowledgments: The authors thank all study participants and
their families
Key message: This study revealed an association between
childhood history of wheezing and rhinitis and conduct problems. The
strength of this study is that it adjusted for confounding factors,
including demographic characteristics, parenting stress, and
allergy-related variables. In addition, to control for the impact of
collinearity, we adjusted for these factors using propensity scores,
increasing the reliability and validity of our findings.