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.