[Prevention and treatment of obesity in children].

The prevalence of childhood obesity and its comorbidities is high in Japan. Increasing prevalence of obesity among children emphasizes the importance of focusing on primary prevention to avoid health complications later in life. We emphasize the prevention of obesity by recommending breast-feeding of infants for at least 6 months and advocating that schools provide for 60 min of moderate to vigorous daily exercise in all grades. Treatment interventions include behavioral therapy, reduction in sedentary behavior, and dietary and exercise education. After dietary treatment combined with exercise treatment, the areas of subcutaneous and visceral fat decreased significantly. These data suggest that dietary treatment combined with exercise treatment in obese children normalizes the distribution of abdominal fat and reduces the risk factors for chronic disease.

An 8-year-old boy with hypereosinophilic syndrome.

Hypereosinophilic syndrome (HES) is a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia and tissue eosinophilia, resulting in a wide variety of clinical manifestations. We present the case of an 8-year-old boy with HES. He complained of recurrent abdominal pain, general fatigue, and diarrhea. Laboratory data showed marked eosinophilia, elevated total IgE with positive specific IgE antibodies to common inhalant and food allergens, and elevated serum CCL17/TARC. A chest CT scan revealed central bronchiectasis, bronchial wall thickening, a mosaic attenuation pattern, and multiple small nodules in lung parenchyma; abdominal CT showed a thickened bladder wall. Gastrointestinal endoscopy revealed scarring in the gastric mucosa and mucosal erosion in the duodenum. Immunohistochemical examination demonstrated numerous eosinophil infiltrations with extensive extracellular eosinophil major basic protein deposition in the gastric mucosa. Only high-dose oral steroid was effective and cyclosporine appeared to have a steroid-sparing effect. HES is extraordinary rare in children and the long-term prognosis in pediatric HES is not well known. Comprehensive diagnostic procedures are vital for the early detection and management of complications in pediatric HES.

Serum measurement of thymus and activation-regulated chemokine/CCL17 in children with atopic dermatitis: elevated normal levels in infancy and age-specific analysis in atopic dermatitis.

Elevated blood levels of thymus and activation-regulated chemokine (TARC)/CCL17 have been observed in atopic dermatitis (AD) and may serve as a new biomarker for AD. However, the normal levels, especially in children, have not been well determined. We sought to establish an efficient enzyme-linked immunosorbent assay (ELISA) with a wide range of detection that would be suitable for measurement of serum TARC/CCL17 and to determine the normal ranges of this chemokine in different age groups and its diagnostic usefulness for AD. A sensitive specific ELISA for TARC/CCL17, which we previously reported, was modified to accommodate the wide range of TARC/CCL17 values often found in sera. Twenty-seven children with AD under 6 yr of age and 25 age-matched normal non-atopic controls, and 18 patients with AD and 27 controls who were 6 yr and older were enrolled. The severity of AD was evaluated using the SCORAD index. The serum levels of TARC/CCL17 were measured with the ELISA, and the serum levels of IP-10/CXCL10 were also measured. With the novel ELISA system, the assayable range of TARC/CCL17 was 14-8000 pg/ml, and the coefficient of variation at various concentrations ranged from 2.3% to 5.0%. The serum levels of TARC/CCL17 in normal individuals were significantly higher in young children, especially in the age group of 0-1 yr. The cut-off values of TARC/CCL17 for the diagnosis of AD were 1431 pg/ml for 0-1 yr group, 803 pg/ml for 2-5 yr group and 510 pg/ml for the 6 yr and older group, with high sensitivity and specificity of 0.83 and 0.93, 0.83 and 0.92, 0.85 and 0.96, respectively. The magnitude of the decrease in the SCORAD index after treatment with topical steroids correlated significantly with the decrease in serum TARC/CCL17. There was no difference in the serum levels of IP-10/CXCL10 between AD and the controls. The TARC/CCL17:IP-10/CXCL10 ratio tended to be higher in the control children aged 0-1 yr than in those aged 2-5 yr. The serum level of TARC/CCL17 reflects the severity and therapeutic response in AD. The high normal levels in infants should be taken into account when assaying TARC/CCL17.

High prevalence and young onset of allergic rhinitis in children with bronchial asthma.

Bronchial asthma and allergic rhinitis often co-exist, and rhinitis is a major risk factor for the development of asthma. However, the reported incidence of allergic rhinitis in asthmatic children varies widely. The aim of this study was to elucidate the incidence of allergic rhinitis, the onset age of chronic upper and lower airway symptoms, and the correlation of these two symptoms in asthmatic children. A cohort of 130 consecutive children (ages 2-10) with asthma was evaluated. A questionnaire regarding upper and lower airway symptoms was filled out by the parents. Objective diagnosis of allergic rhinitis was also made on the basis of rhinoscopy, nasal cytology, nasal challenge, and specific serum IgE (CAP-RAST). Persistent nasal symptoms were present in 83.8% of the asthmatic children. The incidence of allergic rhinitis was 77.7% based on the objective findings. The mean onset age of asthma was 2.8 yr, and that of rhinitis was 2.9 yr. Nasal symptoms started as early as the first year of life in 8.9% of the children. In children with comorbid asthma and allergic rhinitis, rhinitis preceded in 33.7%, asthma preceded in 31.7%, and both started in the same year in 26.7%. In 7.9%, rhinitis was asymptomatic. Concomitant exacerbation of the upper and lower airways occurred in 34.6% of the total 130 children. These results demonstrate that allergic rhinitis manifested early in life in the majority of the asthmatic children. Persistent nasal symptoms in infancy may point to subsequent development of asthma and possible early intervention.

Clinical Epidemiology and Treatment of Febrile and Afebrile Convulsions With Mild Gastroenteritis: A Multicenter Study.

BACKGROUND: We investigated features and responses to treatment in patients with febrile and afebrile convulsions with mild gastroenteritis and characterized convulsions with rotavirus and norovirus gastroenteritis. METHODS: We conducted a prospective, observational study to evaluate patients with febrile and afebrile convulsions with mild gastroenteritis who were hospitalized between November 2011 and March 2014 at 13 facilities in the National Hospital Organization. We classified the patients into two groups: presence or absence of fever. We investigated the background, clinical and laboratory characteristics, viral antigen in stool, and efficacy of anticonvulsant drugs. RESULTS: Of 126 patients enrolled in this study, 50 were febrile (Fc group) and 76 were afebrile (aFc group). A family history of febrile seizures was significantly more frequent in the Fc group than in the aFc group (28.0% vs 9.2%, P = 0.005). Clinical characteristics were similar between the rotavirus and norovirus groups, but fever was significantly more frequent in the rotavirus group (46.2% vs 8.3%, P < 0.001). Serum sodium levels were significantly negatively related to the number of seizures in the aFc group (ß = -0.13; 95% confidence interval, -0.24, -0.03; P = 0.01). Carbamazepine was significantly more efficacious than diazepam suppositories in the aFc group (odds ratio = 49.3, 95% confidence interval, 2.35, 1037; P = 0.01). CONCLUSION: Febrile convulsions with mild gastroenteritis show characteristics of both febrile seizures and convulsions with mild gastroenteritis. Carbamazepine is optimal for convulsions with mild gastroenteritis. Clinical features of convulsions with rotavirus and norovirus gastroenteritis are similar, except for fever. Serum sodium levels may play a major role in the onset of convulsions with mild gastroenteritis.

[Prevalence of sensitization of Japanese cedar pollen in children from infancy to adolescence].

BACKGROUND: In Japan, morbidity of Japanese cedar pollinosis has dramatically increased, especially in children. However, little is known about the prevalence of pollinosis and sensitization to Japanese cedar pollen (JCP) in young children. OBJECTIVE: The aim of this study is to investigate the prevalence of sensitization to JCP in allergic and non-allergic children from infancy to adolescence. METHODS: Two hundred forty three children with allergic diseases (age 8 months-16 years, mean 5 years) and 137 children without allergic diseases (age 1 month-15 years, mean 4 years) were recruited. Their specific IgE to JCP, house dust mite, orchard grass pollen, egg white, and milk were measured with the CAP-RAST system. A questionnaire was filled out by their parents. RESULTS: The percentage of positive (> or = 2) CAP-RAST to JCP was 47.1% in children with allergic diseases and 19.9% in children without allergic diseases. In children with allergic diseases, the ratio had risen rapidly from 3 to 5 years old. In children without allergic diseases, the ratio of JCP sensitization has gradually increased from the infancy to adolescence. The youngest child who had been sensitized to JCP was 23-month-old boy with atopic dermatitis. The proportion of children who were born from January to march was significantly higher in JCP sensitized group than JCP non-sensitized group. The ratio of house dust mite and orchard grass pollen sensitization was higher in JCP sensitized group than those in JCP non-sensitized group. CONCLUSION: Large number of children acquire sensitization to JCP in their preschool age. We need to develop the way how to protect JCP sensitization in the early stage of life.

[A questionnaire survey of asthma in children with co-morbid allergic rhinitis].

BACKGROUND: Bronchial asthma is often complicated with allergic rhinitis (AR). OBJECTIVE: To investigate the relationship between the upper and lower airway diseases in children with asthma, we performed a questionnaire survey at 6 centers in Kinki area in Japan. METHODS: A questionnaire was filled out by parents of 333 asthmatic children (0-16 years, median age 7). It included questions concerning nasal symptoms, onset ages of rhinitis and asthma, correlation between nasal symptoms and asthma symptoms, and family history of allergic diseases. RESULTS: One hundred and fifty five (46.5%) subjects answered to have any nasal diseases; 20 with sinusitis, 46 with seasonal AR, and 119 (35.7%) with perennial AR. To further clarify the relationship of asthma and concomitant AR, we focused on patients with perennial AR and compared the clinical characteristics with patients with no nasal diseases. Percentage of non-atopic asthma was significantly lower in patients with comorbid AR than those without. Severity of asthma tended to be milder and family history of perennial AR was more often in the former than the latter group. Interestingly, asthmatic children with comorbid AR were more likely to have cold air-induced asthma exacerbations. In the subjects with comorbid AR, concomitant exacerbation of the upper and lower airways occurred in 38.7%. The median age of onset of asthma and nasal symptoms was 2 and 4 years, respectively. In 43.9% of them, upper airway symptoms started either before or simultaneously with asthma. CONCLUSION: The attention should be paid to the nasal symptoms in children with asthma, especially they have atopic asthma and positive family history of perennial allergic rhinitis. It is important that an appropriate diagnosis and treatment of nasal symptoms to better control asthma in children.

Leukotriene D4 induces production of transforming growth factor-beta1 by eosinophils.

Eosinophils may play an important role in the pathogenesis of airway remodeling in asthma through the production of various fibrogenic cytokines such as transforming growth factor-beta1 (TGF-beta1). Cysteinyl leukotrienes are also suggested to be involved in remodeling with their potential to induce proliferation of airway smooth muscle cells. Since massive eosinophil infiltration and the release of cysteinyl leukotrienes in airway secretions are often seen in asthma, we hypothesized that cysteinyl leukotrienes may be involved in airway remodeling through induction of TGF-beta1 from eosinophils. Peripheral blood eosinophils were cultured with leukotriene D(4) (LTD(4)) and/or interleukin-5 (IL-5) or granulocyte colony-stimulating factor (GM-CSF) for 16 h and gene expression of TGF-beta1 was quantified with real-time PCR. A combination of LTD(4) and IL-5 or LTD(4) and GM-CSF synergistically induced TGF-beta1 expression in eosinophils although stimulation with single factor, LTD(4), IL-5 or GM-CSF did not induce the gene expression. LTD(4) also induced significant gene expression in eosinophils cultured in an intercellular adhesion molecule-1-coated plate. The results suggested that CysLTs stimulate eosinophils to induce TGF-beta1 production in allergic inflammation where IL-5 and GM-CSF are abundant and may be involved in the pathogenesis of airway remodeling.

Synergistic effect of theophylline and procaterol on interleukin-5-induced degranulation from human eosinophils.

Inhibiting the release of toxic granule proteins from eosinophils is a possible means of treating allergic inflammation. This study was performed to examine whether procaterol and theophylline, commonly used bronchodilators in asthma, inhibit eosinophil degranulation induced by interleukin (IL)-5. Purified eosinophils from patients with asthma were incubated with IL-5 for 24 hr in the presence of theophylline, procaterol, combinations of theophylline and procaterol, or dexamethasone. Levels of eosinophil-derived neurotoxin (EDN) in the supernatants were measured with radioimmunoassay. Theophylline inhibited IL-5-induced release of EDN in a concentration-dependent manner. Procaterol inhibited degranulation only at high concentrations. However, procaterol at 10(-9) M and 10(-8) M, which are physiologic concentrations, together with theophylline at 10(-5) M, which is a concentration commonly found in the serum of patients receiving low-dose theophylline, inhibited degranulation by 43.8%. This finding indicates that theophylline and procaterol have synergistic effects. The inhibition was comparable to that with dexamethasone at 10(-9) M. Our results suggest that a combination of low-dose theophylline and procaterol exhibits antiinflammatory effects in asthma by inhibiting eosinophil-effector functions.