Application and dissemination of school life management certificate with allergy guideline in school through collaboration between educators and health care providers is the only way to achieve safe and secure school lives for children with allergic diseases. To be etched in the symposium attendees' minds, we would like to promise Sakiyo-san to promote measures so that a tragic accident will never happen again in any schools in Japan.

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The allergy induced by Glupearl 19S (Katayama Chemical, INC., Osaka, Japan) included in the facial soap Cha no Shizuku (Yuka, Fukuoka, Japan) has been recognized as a major public health problem in Japan. In the literature, cases of allergy to hydrolyzed wheat protein (HWP) started to be reported by European doctors from about 2000. In Japan, the outbreak of HWP-related wheat allergy began in about 2009, and the company started a voluntary recall of the HWP-containing soap on 25th May, 2011. After the voluntary recall, the allergy induced by this soap was widely reported by the media, and in the meantime the problem has come to be recognized by the general population. Studies are in progress to elucidate the reasons why the soap induced such a large-scale allergy problem. In this article, we will review the recent findings published in Europe and Japan regarding the allergy induced by HWP.

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Cochineal extract is a natural red dye produced from the bodies of female insects (Dactilopius coccus or Coccus cacti). The colored principle in this extract is carminic acid. Carmine is a dye of a bright-red color obtained from the aluminium salt of carminic acid, These dyes have been widely used in the manufacture of food (drinks, meat products, dairy products, milk derivatives and confectionery), medicines, and cosmetics as a safe coloring agent. However, several cases of occupational asthma, cheilitis, and food allergy implicating cochineal extract and carmine have been reported. Erythritol is widely used as a food ingredient due to the chemical inertness, sweetness and non-toxicity. The substance is a self-affirmed generally recognized as safe. Some cases of allergic reaction to foods containing erythritol have been reported. The factors and mechanisms of allergic reaction to carminic acid and erythritol, which are substances with low molecular weight, are discussed.

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Oral immunotherapy (OIT) has attracted attention as a treatment for food allergies. OIT appeared to increase response thresholds to food antigens, and to induce desensitization. However, the following issues have also been clarified. 1) Adverse reactions were frequent with OIT, and some cases had severe adverse reactions requiring adrenaline injections. 2) When OIT is given to severe cases, there is a high frequency of symptom induction as compared to moderate cases. 3) Desensitization induced by OIT appeared to have failed after a short time. 4) Clinical tolerance induced by OIT seems to be different from tolerance in the natural course of food allergy. 5) Neither the appropriate amounts of foods nor the treatment period during which patients should ingest foods have been established. Although OIT is widely performed as clinical practice in Japan, clinical research on OIT should be performed by allergic specialists.

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The author who has been serving as an editor of several international journals in the field of allergy explains how peer-review process is carried out. The recent guidelines for clinical studies recommended by International Committee of Medical Journal Editors are also illustrated.

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Aim: Software for biostatistics: STATA is introduced. In addition, as an example, multiple imputations were also introduced.
Methods: A total 1,271 pregnant women were enrolled in this prospective cohort study. Outcome was set for Child behavior check list (CBCL) at 3 years of age. Multiple imputations were used to adjust for missing data.
Results: Longer maternal education years were associated with better CBCL. On the other hand, smoking during pregnancy was associated with worse CBCL even after multi-variate adjustment.
New evidence: STATA is useful in analyses of clinical studies.
The textbook titled [Introduction of clinical data analysis using STATA] will be published in June 2014.

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We surveyed about 5,000 primary school children aged six every year in Himeji-City, Japan, from 1995 to 2010, using the Japanese version of the American Thoracic Society and the Division of Lung Diseases (ATS-DLD) questionnaire. The questionnaire survey showed that the prevalence of atopic dermatitis decreased significantly from 17.5% in 1995 to 9.4% in 2010 (P<0.001). The prevalence of asthma decreased slightly from 17.5% in 1995 to 4.8% in 2010 (P=0.016). However the prevalence of allergic rhinitis, allergic conjunctivitis and Japanese cedar pollinosis increased significantly from 8.6%, 3.6%, 6.7% in 1995 to 11.1%, 4.5%, 8.2% respectively (P<0.001, P<0.001, P<0.001). Decreasing prevalence of atopic dermatitis was associated with decreasing rugs and carpets sales, and with decreasing tatami mats sales in Japan, suggesting that atopic dermatitis was linked to the dust mites. The increasing prevalence of allergic rhinitis, allergic conjunctivitis and Japanese cedar pollinosis was presumably due to a large amount of cedar pollens.

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The principle of the treatment of an allergic disease is avoiding the allergen. The people with animal allergy keep a pet, sometimes it starts asthma attack death and an anaphylatic shock. In recent years, we can control symptoms of allergic diseases now by the progress in a pharmacotherapy. Desire to keep a pet is up to persons. Sometimes, priority is given to it from an allergy treatment. If it carries out, how can you keep a pet? I considered pet's sort, the size, the method of a manage, and the probability of a moreover immunotherapy or a pharmacotherapy.

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The purpose of this debate is not to argue about pet keeping for pet allergy children, but about children who have not pet allergy but have the other allergic diseases. In real world, we have been providing consultation to patients with asthma and/or atopic eczema who would like to keep pets in spite of their positive sensitization to pet allergens. Some reports of birth cohort studies showed pet keeping in early life stage had protective effects on onset of allergic diseases later on, although many conflicting results from different papers exist. We also discovered that dog keeping in early infancy had not promote atopic dermatitis in school children even in Japan, but I do not always approve pet keeping for any one at this moment.

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Inhaled corticosteroids (ICSs) are the mainstay of treatment in children with asthma. Recently, the efficacy and safety of intermittent ICS in the management of children with persistent asthma has been receiving a lot of attention. MIST trial suggests the effect of intermittent budesonide in preschool children with recurrent wheezing. TREXA study suggests an effectiveness and safety of intermittent ICS as rescue medication with SABA for children with mild asthma. We can expect the future studies which investigate the possibilities of effect and safety of intermittent ICSs use in the long-term management of mild asthma in children.

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Inhaled corticosteroid (ICS) is the cornerstone of treatment in the long-term management of childhood asthma. Recent studies showed that intermittent use of ICS was as effective as daily use of ICS for treatment of mild asthma, and that long-term usage of ICS resulted in the reduction in growth. From these data, intermittent use of ICS seems an attractive alternative for treatment of mild intermittent asthma.
However, even though the initial decrease in attained height associated with the use of ICS persisted as a reduction in adult height (approximately 1 cm), the decrease was not progress or cumulative. Although there was no significant difference in the rate of asthma exacerbations between intermittent and daily use of ICS, daily ICS was superior to intermittent ICS in increasing asthma-free days. Furthermore, it is hard to distinguish intermittent from persistent asthma only by symptom patterns.
Up to now intermittent use of ICS is not recommended for treatment of children with mild asthma.

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Rush oral immunotherapy (rush OIT) for severe food allergy has several benefits compared with slow OIT since it has ample evidence in efficacy and safety. The factors that determine the effects of allergen immunotherapy are dosing and frequency of allergen administration and length of the course. Several randomized controlled trials (RCTs) have proved that higher and frequent dosing can be employed by utilizing refractory period of IgE-mediated reaction and ultimately result in full desensitization status in short period. On the contrary, there has been little evidence in efficacy of slow OIT since controlled trial is difficult to perform because of long treatment period and natural outgrow process over the long period confounds the study results. In addition, rush OIT may be safer than slow OIT because the former treatment is performed in hospital settings under intensive medical supervision and the latter is done at home without supervision. We have performed RCTs of rush OIT for severe egg and milk allergy and clearly proved the efficacy not only in desensitization/tolerance induction but also in QOL. Therefore rush OIT is indispensable treatment for children with severe food allergy.

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Recently, oral immunotherapy (OIT) is often reported to be effective to treat food allergy.
In our hospital, rush OIT was performed in 81 cases of hen's egg allergy, 109 cases of cow's milk allergy, and 37 cases of wheat, in which serious symptoms are induced. In 63.0% of egg cases, 61.3% of milk cases and 71.0% of wheat cases, patients became capable of taking target amount of allergic foods (status of hyposensitization) after 5 days hospitalization. One year after, in 97.2% of egg cases, 60.1% of milk cases and 93.3% of wheat cases, patients got status of hyposensitization. But the clinical rate of acquiring tolerance remains only 40.5% as to egg cases, 10.8% as to milk cases and 46.7% as to wheat cases.
In many cases, OIT is thought to novel approach to lead patients into the status of hyposensitization in the long term and efficient to treat anaphylaxis. But it may take longer term for patients to acquire tolerance in this way. On the other hand, in rush OIT, strong systemic symptoms may be induced even during the term of sustaining status quo, and risk factors for causing therapeutic response is not clear yet. From the standpoint of effect and safety of the therapy, it seems more important to continue administering treatment for a long term rather than increasing dose in a rush during short-term hospitalization. Therefore, safer and more effective way of therapy replacing rush OIT seems to be needed for the future.

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There has been an outstanding progress of pharmaceutical treatment for bronchial asthma in these decades, which makes the control of asthma very easy. However, the effects of drug therapy are transient, and subside immediately after cessation of the therapy.
The clinical benefit of allergen immunotherapy is evident for pollen allergy or bee venom allergy. As for asthma, the symptom is not simply the result of IgE-allergen interaction, rather formed by complicated interaction of chronic inflammation of airway, viral infection, weather condition, exercise, psychological stress, etc. But the effect of immunotherapy for asthma is scientifically approved. Though the intensity to reduce asthmatic symptoms in short term is not prominent, the effects to reduce the dose of inhaled corticosteroid, or to prevent the progress from seasonal rhinitis to asthma are meaningful, especially in pediatric area. There is a tendency to avoid immunotherapy due to its risk to induce allergic reaction, and not popular especially in Japan, but we should keep interests in immunotherapy as the only radical treatment for allergic diseases.

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Allergen-specific immunotherapy has been considered as only one treatment to change the natural course of allergic diseases. For the management of childhood asthma, however, the indication of immunotherapy is limited to small numbers of well-controlled patients and its therapeutic effects could be little, if any, under treatment with asthma controllers, including inhaled corticosteroid. Commencement of immunotherapy from early childhood is indispensable to prevent the development of asthma. Although the current allergen-specific immunotherapy seems useful for the treatment of pollinosis, considering the risk of severe systemic side effects, it is not essential for the management of childhood asthma.

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Background: MostGraph, an instrument used for measuring respiratory resistance and reactance by forced oscillation methods, has recently been developed in Japan. Although the reference values of respiratory resistance and reactance in childhood had been reported, the ranges of these values vary. Respiratory resistance and reactance depend on the frequency of the impulse used in children; therefore, there is a need to evaluate the changes in these values in each patient. Objective: The aim of this study was to evaluate the correlation between the changes in Mostgraph parameters and those in the spirometric assessments in medicated asthmatic children. Subjects and Methods: 63 patients with asthma, between 6 to 17 years of age, were evaluated by MostGraph and spirometry. We evaluated the correlations between the changes in Mostgraph parameters and those in the spirometry by Spearman coefficient statistical analysis. Results: The difference of average R5 correlated with ⩒₅₀ (ρ=-0.501, p<0.001) and FEF_25-75 (ρ=-0.472, p<0.001). The difference of inspiratory R5 correlated mostly with that in ⩒₅₀ (ρ=-0.524, p<0.001). The ratio of change in inspiratory R5 correlated with that in ⩒₅₀ (ρ=-0.515, p<0.001). The correlations between the changes in MostGraph parameters and those in the spirometry at expiratory phase did not differ from those at inspiratory phase. Conclusion: MostGraph could detect the different changes that occurred in the peripheral respiratory tracts. Future studies should aim to assess the manner in which MostGraph can be best utilized for the management of asthma.

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Atopic dermatitis (AD) is an eczematous disease with repeated exacerbations and remissions. The Severity Scoring of Atopic Dermatitis (SCORAD), a well-known objective assessment index, uses complicated methods. There is reportedly a correlation between the disease activity of AD and serum thymus and activation-regulated chemokine/CCL17 (TARC). We examined the differences in SCORAD results among individual physicians, TARC, immunoglobulin E, eosinophils, and Lactate dehydrogenase in 7 infants with AD. There was variability among the SCORAD results as scored by each physician. There was a tendency for a correlation between TARC and SCORAD results for experienced physicians and a significant correlation for allergists. Serum TARC was considered to contribute meaningfully to AD assessment.

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In order to clarify the current status of children who need hospitalized treatment for asthma, we gathered and analyzed the information on pediatric patients aged 15 or under who received hospitalized treatment due to acute exacerbation during 2 months, OCT-2011 and NOV-2011, obtained from 49 hospitals in the Kinki region which provided cooperation for this survey.
The subjects were 397 patients, and 66.9% were children aged 5 or under (median age: 4 years). Among them, 17.7% were considered to have been hospitalized for initial attacks. Fever over 37.5°C was noted in 48.1% of the patients, and younger patients had fever more frequently. The duration of hospitalization was 6.0±3.0 days, and fever tended to prolong the duration. Among all patients, 27.0% had a history of hospitalization in the past year, and a few patients experienced recurrent hospitalization. Only 38.8% of the patients were receiving treatment at the hospitals, and 49.7% received no long-term controller therapy. These results suggest that appropriate intervention based on early diagnosis of asthma and accurate understanding of disease control condition, as well as deeper regional medical cooperation would be required for further improvement of the management condition of childhood asthma.

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