Risk factors analysis of attention deficit/hyperactivity disorder and allergic rhinitis in children: a cross-sectional study

Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed disorder found in both children and adults. ADHD is manifested by inattention, hyperactivity, cognitive deficit, and/or impulsivity. It affects approximately 3–5% of youth and 2.5–5% of adults [1]. The incidence of ADHD in China is 6.26% [2]; 9.5% among individuals aged 4 to 17 years old in the United States [3] and 7.2% worldwide [4]. ADHD-related neuropsychological deficits affect academic, social, professional functioning, and impose significant economic burdens on the society [5]. ADHD is associated with many diseases, including cognitive impairment, sleep disorders and allergic diseases. Allergic rhinitis (AR) is one of the most common allergic diseases affecting children. Prevalence of global childhood allergic rhinitis has been reported to be as high as 40% [6]. Allergic rhinitis and ADHD affect children of similar ages [7]. Symptoms of allergic rhinitis may lead to daytime inattention, irritability and hyperactivity, which is commonly observed in ADHD children. Although there have been studies showing that AR has a strong relationship with ADHD [8, 9], the mechanism is still controversial. The prevalence of ADHD and allergic disease has increased worldwide. Both allergy and ADHD rely on gene-environment interaction. At present, there are few studies in this area in China. Our previous research has confirmed that children with AR have higher ADHD-related symptom scores than children without AR [10]. In this study, we therefore investigated the association between the symptom of AR and ADHD in children with AR at different age and gender groups.

The association between ADHD and allergic diseases has been a source of public and clinical concern. The epidemiological research suggests that allergic diseases may increase the risk of ADHD in children, especially allergic rhinitis [22]. Treatment for AR may have a positive effect on behavior [23]. Children with ADHD and allergic disease may have a common biological background [24]. A number of studies have suggested a link between allergies and ADHD, such as food allergies and neuropsychiatric conditions [25] or immune disorder [26].

ADHD symptoms among children with allergic diseases including allergic rhinitis have been reported [27]. Conversely, allergic symptoms in children with ADHD have also been reported [28]. In our cross-sectional study, we demonstrated that AR with ADHD had more severe nasal symptoms than children without ADHD, in accordance with other research [29]. The single factor analysis found that there is no significant correlation between the number of allergens and the symptoms of ADHD, which was similar to a population-based case-control study [30]. The study showed that the association between allergic diseases and ADHD was occurred mostly due to house dust mites only, but not in other types of allergens. Further evaluation and follow-up study are needed for the conclusion. In addition, our study further showed that family history and whether or not combined with other allergic diseases were not significantly associated with ADHD.

Based on these results, we suggest that there is some overlap in the mechanism of action of allergy and ADHD in patients with a comorbid diagnosis. This study also found that the proportion of male patients is significantly higher than that of female children, and the average age of children is younger in IHS > 1.25 group, which suggests that young male children have more severe symptoms associated with ADHD group. Some previous studies in the United States have also found the same trend [3, 31]. To more accurately investigate the association of AR-related factors with ADHD symptoms, we control age and gender factors. Based on the Logistics regression analysis results, we observed that the severity of attention deficits and hyperactivity were significantly associated with multiple factors in AR children. AR children with attention deficit and hyperactivity have a longer duration of symptoms in 1 year compared with AR children without ADHD. This phenomenon exists in different age and gender groups. In addition, we also identified a positive association between ADHD and AR by positive SPT as Yang described [30]. However, in our study, this correlation seems to be mainly reflected in the male AR children, not significant in female children.

The linkage between AR and ADHD may have a different mechanism: allergic has an effect in increasing activity of TH2 cells and the secretion of the anti-inflammatory cytokines IL-4, IL-5, IL-9,IL-10 and IL-13. TH2-derived cytokines play an important role in the inflammatory process inducing the production of allergen-specific IgE production (IL-4), influx of eosinophils into the into the inflammatory sites of allergic tissue (IL-5) [32]. Inflammatory cytokines can activate neuroimmune mechanisms that involve behaviorally and emotionally relevant brain circuits in animals [33] and humans [34], and may influence the neuronal activity of brain structures indirectly by activation of the hypothalamus-pituitary-adrenal axis. Moreover, inflammatory cytokines further lead to altered metabolism of central neurotransmitters such as norepinephrine and dopamine known to be involved in ADHD pathology. Psychological mechanisms of AR-ADHD comorbidity may be associated with an early exposure to stressful life in children. Stress in life can interfere with the development of ADHD- relevant brain structures, affecting cognitive impairment in children, and leading to symptoms of ADHD or ADHD-like.

Sleep problems are common in children with allergic rhinitis. Previous study revealed that the onset of upper airway inflammation due to allergic triggers in subjects under three years of age may be related to the subsequent development of SDB after 8–10 years [35] . Minor sleep restriction can lead to dysfunction of the circuits in specific regions of the brain, especially the prefrontal cortex, and negatively affect cognitive function and behavior [36] .Impaired executive function is common in children with ADHD. Therefore, sleep problems may play an important synergistic role in increasing the risk of ADHD in allergic diseases. There was a viewpoint that allergic diseases and ADHD have a common genetic mechanism. Signal transducers and activators of tranion6 (STAT6) are involved in the regulation of the immune system, cell proliferation and apoptosis, which thought to play a major role in the pathogenesis of ADHD. Previous study showed that it was closely related to allergic diseases [37]. Moreover, AR may affects the quality of sleep and causes daytime fatigue, cognitive, memory deficit and the learning process [38]. Sleep disorder also could lead to cognitive impairment due to the increase of oxidative stress [39].

This study has some limitations as different parental education level may affect their judgments when filling out the questionnaire, which may cause bias data. Besides, our study is a cross-sectional survey that did not cover the whole range of ADHD patients to establish a causal relationship. Further follow-up of this cohort is warranted to elucidate causal associations.

This study demonstrated that attention deficits in children with AR are associated with symptoms severity, duration and skin index, especially in male children. The mechanism of the relationship between AR and ADHD symptoms has not been clarified and needs further studies. Interventions incorporating strategies that focus on allergic disease management and collaborative care for children with ADHD deserve further investigation.