This paper describes the phenotypes of pediatric asthma, particularly virus-induced asthma caused by virus infection. Many cases of asthma in preschool children are induced by virus infection and may develop airway remodeling. Therefore, the Japanese Pediatric Guidelines for the Treatment and Management of Asthma 2008(JPGL2008)and the PRACTALL Consensus Report attach importance to respiratory viral infection as one of the risk and precipitating factors for asthma, as well as to allergens. This paper reviews the relationship between bronchiolitis caused by respiratory syncytial virus (RSV) and the occurrence of asthma, mainly describing the results of the author's group. In children with severe bronchiolitis caused by RSV infection, 1) Creola body-positive infants often develop asthma within 5 years; 2) When patients have a genetic impairment in the production of a Th1 cytokine IFN-γ, they often develop asthma; 3) Administration of a humanized anti-RS virus monoclonal antibody, palivizumab, suppresses recurrent wheezing in patients aged 3 years or younger. From the above results, early intervention for virus-induced asthma is considered necessary. Furthermore, attention is being paid to the results whether or not the prevention of severe bronchiolitis caused by RSV infection in children suppresses the occurrence of atopic asthma caused by mites peculiar to Japan.

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Accumulating results from human and mouse studies, intestinal microbiota play critical roles in the development of immune system of the host and the induction of oral tolerance to ingested food antigens. Clinical observations that the smaller numbers of lactobacillus were found in the stool of children with allergic diseases than those of normal children lead to establish the clinical efficacy of the administration of probiotics to high-risk pregnant women in order to prevent the development of atopic dermatitis in their offspring. However, the precise mechanisms of this effect remain uncertain. In addition, the administration of probiotics showed no effects on the IgE production or development of allergic diseases except atopic dermatitis in the offspring. The mechanisms by which intestinal microbiota influence immune system of the host, in particular induction of oral tolerance should be elucidated in the future, and useful probiotics facilitating oral immunotherapy for food allergy patients will be desired.

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Recent advances in neonatal intensive care, especially for extremely low birth weight infants, have drastically improved life prognosis of the infants. However, ‘intact’ survival without sequelae for all babies is still to be achieved and prevalence of severe motor and intellectual disabilities (SMID) secondary to central nervous system damages of any cause in childhood, especially in neonatal period, is increasing. Patients with SMID have complex problems involving multiple organs and multidisciplinary approach is mandatory. However, a lack of evidence in optimal diagnosis and treatment procedures for the complex problems poses a host of issues in daily medical care. Wheeze is one of the most common symptoms in SMID, which can be caused by various pathogenesis not only in the respiratory system but in other organ systems such as the gastrointestinal tract. Bronchial asthma, one of the major causes of wheeze, is a chronic inflammatory disease of the airways and may be present in SMID patients. Once a SMID patient is diagnosed as asthma, he/she has to be properly managed as recommended by asthma guidelines. However, lack of diagnostic criteria for asthma in SMID often results in overtreatment or undertreatment. We retrospectively analyzed 40 SMID patients in our institution. Twenty two patients (55%) had wheeze during the past 12 months. Basic procedures including suction of upper respiratory exudates and saliva and stabilization of the jaw resulted in resolution of wheeze in 18 of them (81.8% of wheeze). The rest, 4 patients (18.2% of wheeze) underwent beta-2 agonist inhalation. Wheeze resolved in 2 out of 4 patients (9.1% of wheeze). We also performed impulse oscillometry (IOS) when they did not have wheeze. Significant reduction in airway resistance with IOS was confirmed in the patients. We diagnosed them as asthma (5% of total patients). The other 2 cases were respectively diagnosed as laryngomalacia and sinusitis. Our experience indicates that prevalence of asthma in SMID is comparable to that in general population and careful diagnostic procedures may allow us to identify those who need anti-inflammatory treatment and those who do not need other type of care. In addition, IOS may be a good tool to measure respiratory function in SMID since no voluntary effort is necessary to perform the test. We reviewed respiratory care in SMID and proposed a diagnostic diagram for wheeze in SMID.

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For the purpose of clarifying the factors influencing on environment control behaviors in pediatric asthma management and the shaping process of the continuation to control environment, semi-structured interviews were individually held with 74 parents with asthmatic children. As a result of analysis with modified grounded-theory-approach, “experience of hospitalization”and “patient education”were influencing on starting action. They had passed though “conflict and burden”, thereafter “moderators”and“mediators” caused the maintenance to control environment. Categories included “moderators”of kept on trigger reduction behaviors were ‹use of resources›, ‹custom›, ‹trigger-related knowledge›, etc. and “mediators” of motivate to behavior change, or psychosocial influences were ‹self-efficacy›, ‹outcome expectation›.
To better understanding of the process through which nurses lead patient education cause a changes in environmental behaviors, information on theoretical concepts that moderate and mediate behavior change in trigger control(i.e. self-efficacy, outcome expectation, family support, coping) is needed. In relation to this process, need of the continual support for the shaping the maintenance to control environment was suggested.

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A post-marketing surveillance study was carried out to investigate the safety and efficacy of long-term administration of Onon Dry Syrup 10% (Pranlukast hydrate) in actual clinical settings in patients who were traceable among those eligible for the former prospective survey. A total of 55 cases were collected from 33 medical institutions all over Japan. Thirty four patients were under the medication for more than 1 year.
Among 55 patients included in the safety analysis population, an adverse drug reaction occurred in 1 case (incidence of 1.82%), which was a non-serious case of liver function disorder.
Among 50 patients included in the efficacy analysis population, 46 showed improvement (improvement rate of 92.0%). The result of the analysis by patient background factors showed no special concern with the effectiveness of the drug.
In conclusion, it was confirmed that Onon Dry Syrup is a highly safe and effective medication for bronchial asthma when administered in infants aged less than 1 year for a long-time of period.

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There are few validated questionnaires for epidemiological study of asthma in preschool children. In the present study, parental assessments of asthma among their children aged 0-5 years in the response to an International Study of Asthma and Allergies in Childhood (ISAAC)-based and a newly-developed Japanese Pediatric Guideline (JPGL)-based questionnaire were compared with doctors' diagnosis. Out of 369 children recruited from the children who visited their family doctors in 4 hospitals and 3 clinics during November and December 2007, data of 353 children were analyzed. In the children aged 0-2 years, positive predictive values (PPV) of JPGL-based questionnaire for prevalence rate was 0.70, whereas PVV of ISAAC-based questionnaire was only 0.50. Contrary, in the children aged 3-5 years, PPVs of both questionnaires were 0.68 and 0.74, respectively. We suggest that for the purpose of epidemiological study of asthma, JPGL-based questionnaire could be feasible in children aged 0-2 years, and both questionnaires are acceptable for children aged 3-5 years.

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A 14-year-old boy presented with stomachache and nausea. Blood tests showed eosinophilia (WBC 9200/microl, Eos 29.0%) and increase in ECP (Eosinophil Cationic Protein). Computed tomography revealed wall thickening ranging from pylorus to jejunum, and scirrhous gastric cancer was initially suspected. Endoscopic and histological study showed mucosal redness and edema with eosinophilic infiltration, which led to a diagnosis of eosinophilic gastroenteritis.After oral prednisolone (1 mg/kg per day) was started, eosinophlia and ECP were soon improved, but gastric outlet obstruction remained. Methylprednisolone pulse therapy (30 mg/kg per day, 3 days) was started, then he gained appetite.
Gastric outlet obstruction is a rare complication of eosinophilic gastroenteritis, most commonly treated surgically. We report a case of eosinophilic gastric outlet obstruction in a child that responded to conservative medical management.

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To investigate the pathophysiology of elevated FENO in three children of 11 to 13 years of age with well controlled asthma, assessment of airflow reversibility after prednisolone treatment for 7 days were underwent.
All cases were also suffering from allergic rhinitis and dermatitis and their blood examination revealed increase in serum IgE and blood eosiophils.
Case 1 showed no remarkable airflow reversibility after prednisolone therapy inspite of significant decreased in FENO. Case 2 and 3 showed apparant airflow reversibility in distal airway after prednisolone therapy along with decrease in FENO.
One of the reason for discrepancy between well controlled asthma and high FENO may be derived from distal airway narrowing caused by persistent eosinophilic inflammation.
Assessment of airflow reversibility after prednisolone therapy is considered one of usefull tools for investigating the pathophysiology of high FENO in asymptomatic asthma children with normal pulmonary function.

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[Objective] To determine the safety and efficacy of 54-week treatment with a budesonide dry powder inhaler (Turbuhaler^®) (BUD), compared with conventional therapy, in Japanese children with bronchial asthma.
[Method] Patients aged 5 to 15 years old; required treatment with inhaled corticosteroids; with mild persistent, moderate persistent, or severe persistent bronchial asthma; able to use the Turbuhaler^® appropriately, were included. They were treated with either inhaled BUD 100-800μg/day or conventional therapy (CONV : according to the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2005) for 54 weeks (including 6 weeks in the preceding phase III comparative study). The primary endpoint was adverse events (AEs).
[Results] A total of 241 patients (BUD:121) were included in the safety/efficacy analysis. AEs occurred in 118 (97.5%) patients in the BUD group and in 116 (96.7%) patients in the CONV group. The AEs with high incidence (more than 25% in both groups) were upper respiratory tract infection, bronchitis, and gastroenteritis. Serious AEs occurred in 10 (8.3%) patients in the BUD group and in 11 (9.2%) patients in the CONV group. In the BUD group, improvements from baseline in pulmonary function parameters and asthma control parameters were maintained for 54 weeks. At the end of the treatment period, improvements in pulmonary function parameters and asthma control parameters were comparable in both groups.
[Conclusion] Treatment of 100-800μg/day of budesonide dry powder using the Turbuhaler^® for 54 weeks was well tolerated and effective in Japanese children aged 5 to 15 years with bronchial asthma requiring inhaled corticosteroids.

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‹Objective›
The Japanese Pediatric Asthma Control (JPAC) questionnaire is a convenient tool to assess asthma control in children aged 4-15 years. We modified the JPAC questionnaire to evaluate asthma severity and asthma control in children under 4 years of age. The aim of this study is to validate this modified JPAC questionnaire in children aged less than 4 years.
‹Method›
In all, 167 participants aged 5 months to 4 years were diagnosed with asthma by physicians from 6 participating centres. We assessed asthma control by using the modified JPAC questionnaire and determined whether the relationship between total scores and asthma severity was similar in the modified and original JPAC questionnaires. Multiple linear regression models were used, with the total score as an objective variable and age group, asthma severity, and interaction between age group and severity as factors.
‹Results›
An increase apparent severity was significantly associated with a decrease in the total score on the modified JPAC questionnaire (P < 0.0001, Jonckheere-Terpstra trend test). No significant differences were detected between the 2 questionnaires, and the regression slopes of both questionnaires were similar.
‹Conclusion›
The modified JPAC questionnaire can be used to determine asthma severity and asthma control in children under 4 years of age and will facilitate guideline-based care for childhood asthma.

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Children with bronchial asthma sometimes retain nocturnal symptoms of asthma despite treatment with medications for intermittent or mild persistent asthma, other than inhaled corticosteroids and inhaled disodium cromoglycate (DSCG). To evaluate the effects of add-on therapy with budesonide inhalation suspension (BIS) on nocturnal sleep disturbance and caregivers' quality of life (QOL) as compared to DSCG, we conducted a multicenter, open-label, randomized, parallel-group comparative study of such children aged 6 months to <5 years. Of 34 children enrolled, 7 were ineligible for reasons including the absence of nocturnal sleep disturbance during the last week of the observation period. The remaining 27 were randomized and 26 of them were included in the analysis. After 4 weeks of treatment, BIS produced a significantly greater improvement than DSCG in the nocturnal sleep disturbance score, the primary endpoint of the study, as well as in the asthma symptom score. Caregivers of children treated with BIS also experienced substantial improvements in QOL. There was a good correlation between the nocturnal sleep disturbance scores and caregivers' QOL scores. These results indicate that add-on therapy with BIS improves nocturnal sleep disturbance in children who remain symptomatic despite treatment and thereby also improves QOL of their caregivers.

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The causes of asthma death were analyzed on 202 children (3 children in 2009)from 1988 to 1999. The number of asthma death decreased both in children and adults recently. The severity of asthma prior to death were mild(28%), moderate(29%) and severe(43%). The history of aggravating factors to asthma were previous admission in 52%, but the incidence of severe attack with unconsciousness, intubation and use of isoproterenol were low and can not be the risk factors. The main contributing factors were unexpected sudden exacerbation, delayed decision on medical help by the patients and families, low compliance and overuse of drugs of pressurized metered dose inhaler (pMDI) and motor nebulizer (MoNe)
Comparing medications given in 1988 to 1997 and in 1998 to 2009, oral theophylline and β2 stimulants, β2 stimulants by pMDI and MoNe were used less frequently but steroid inhalation were given to 31% of cases in 1998 to 2009. Twelve children died at school, in the toilets, on the way to the hospital, during school activities and on the way home.

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