Intestinal microbiota has been implicated in the development of allergic diseases. Colonization by intestinal microbiota suppresses inflammatory and allergic responses by enhancing intestinal epithelial barrier and inducing regulatory T cells. Altered microbial composition is frequently observed in infant patients with allergic diseases. Furthermore, administration of antibiotics early in life may be a causative factor for atopy and asthma. In this review, I highlight current understanding on the microbiota-host interaction that affect the susceptibility to allergic disease.

 Reviewers should make a recommendation for or against publication based on the unbiased independent, critical assessment of the manuscript submitted to journals, and make comments to help authors and editors improve the quality of the manuscript. In this context, scientific papers published in journals are products by cooperation of authors, reviewers and editors. Reviewers are obliged to meet the deadline for reviewing and are responsible for the confidentiality of the contents of the manuscript. COPE Ethical Guidelines for Peer Reviewers, and Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals are useful for us to understand the principles and rules for peer-review.

 Both acquired and innate immune responses are reportedly involved in the development of bronchial asthma in childhood. However, both avoidance of house dust mite antigens and induction of oral tolerance to house dust mite antigens (intervention to acquired immunity) showed only minimal effects. Several studies indicated that patients with asthma have impaired anti-viral immune responses, especially in regard to production of anti-viral interferons which may be the main cause of frequent lower airway infections. Th2 cytokines and epithelial cell-derived cytokines (IL-33 and TSLP) were shown to play predominant roles in that impairment of anti-viral interferon production, suggesting that suppression of these cytokines may be effective. High concentrations of serum Th2 cytokines and epithelial cell-derived cytokines are observed in atopic dermatitis patients. Therefore, primary prevention/appropriate treatment of atopic dermatitis may currently be the best option for preventing childhood asthma.

 Lack G proposed “Dual allergen exposure hypothesis” at 2008. Then, inflammatory skin lesion, “eczema”, has been focused on the place that induces the sensitization to allergen.

 There are close links between eczema/atopic dermatitis and the development of food allergy. We sought to determine the risk factor for food allergy among one-month baby who had eczema at his/her face. At interim analysis, we demonstrated that early-onset eczema is associates food allergy, and persistent eczema and skin barrier dysfunction is risk factors for the development of food allergy.

 These findings suggest that early intervention to early-onset eczema and skin barrier dysfunction could lead to prevention of food allergy from the viewpoint of epicutaneous sensitization and development of food allergy. However, it is also conceivable that there are other routes to develop food allergy. More further research is needed to find the method of prevention of food allergy.

 There has been a paradigm shift from allergenic food avoidance to consumption in early infancy in the prevention of food allergy. This is because it has been revealed that the cause of food allergy is not intestinal sensitization but mainly percutaneous sensitization, and oral consumption has been found to result in immune tolerance. Indeed, it was the first randomized controlled trial in 2015 that clarified that early consumption in infancy prevents the development of food allergy. To date, six randomized controlled trials have been reported on preventing egg allergy. A meta-analysis of these six studies revealed that the onset of egg allergy is prevented by the early consumption of egg. However, it is necessary to pay attention to the possibility of inducing an immediate allergic reaction in actually practicing this preventive method. For this reason, position papers on preventing egg allergy in several countries recommend that “heated egg” be introduced “from a small amount” in order to reduce the risk of adverse events. The timing of starting ingestion etc. is stratified by atopic dermatitis. However, little guidance is provided on how to increase quantities eaten afterwards. Future studies must provide information regarding the rate of increase, frequency, and duration of ingestion.

 Many studies had been conducted to elucidate the relationship between allergy and breastfeeding. Breastfeeding is likely to play a protective role against allergy. The European Academy of Allergy and Clinical Immunology recommends exclusive breastfeeding for the first 4-6 months after childbirth, but a recent study on the relationship between the time when cow’s milk formula feeding was introduced and milk allergy revealed that cow’s milk formula introduction before the 14th day after birth decreased the incidence of milk allergy. Another retrospective study that investigated feeding pattern during the newborn and early infantile phases of milk allergy patients demonstrated that continuous feeding of cow’s milk formula was infrequent at early phases after birth. One study investigated the relationship between feeding patterns during the first 3 months after birth and milk allergy in infants with egg allergy. Continuous feeding of cow’s milk formula for the first 3 months promotes milk tolerance. These findings show that early introduction of continuous cow’s milk formula may protect against milk allergy. Breastfeeding reduces the incidence of infections, inflammatory bowel syndrome, sudden infant death syndrome, and several other diseases ; however, the effects and benefits of cow’s milk formula over breastfeeding remains unknown, which warrants further studies.

 Allergen immunotherapy is the only radical treatment for allergic diseases, and in recent years, its effectiveness and clinical significance have been re-acknowledged. In particular, sublingual immunotherapy (SLIT) has become prevalent in recent years ; in light of its safety and convenience, SLIT is expected to form a central part of immunotherapy. Currently, however, due in part to the fact that it is indicated only for those aged 12 years and older and that there are only two types of antigens treated―house dust mites and Japanese cedar―subcutaneous immunotherapy (SCIT) remains a critically important means of treatment. Nonetheless, SCIT also still has numerous issues. In terms of safety, in particular, there is a high incidence of systemic symptoms, and it is hoped that safer formulations can be developed, or safer up-dosing schedules can be established. Another important issue is that far fewer allergen extracts are available for use in Japan as compared to abroad. As one treatment with future potential, our department has been implementing SCIT with birch pollen extract against pollen-food allergy syndrome (PFAS), with favorable results.

 Allergen immunotherapy is the only specific treatment for allergic diseases. Patients attain a therapeutically effective maintenance dose more rapidly with rapid subcutaneous immunotherapy than with a conventional schedule.

 House dust mite (HDM) is one of the most important antigens for bronchial asthma and allergic rhinitis. In the past, only house dust extract could be used in subcutaneous immunotherapy for HDM allergy patients in Japan, but since 2015, standardized mite antigen has been used. Despite its therapeutic effect, problems related to its side effects persist.

 Although an increasing number of facilities provides rapid subcutaneous immunotherapy in children, its use remains limited in Japan.

 The following points must be considered in evaluating the prospects of this treatment :

  (1) selective use of subcutaneous immunotherapy and sublingual immunotherapy

  (2) establishment of a safe protocol

  (3) establishment of a marker for patient selection

  (4) widespread use of this treatment for HDM allergy patients

 Sublingual liquid of Japanese cedar and sublingual tablets of house dust mite were approved as sublingual immunotherapy (SLIT) in Japan, but there are few reports of SLIT to adolescents. Therefore, we share our experience and discuss usefulness of SLIT comparing subcutaneous immunotherapy (SCIT).

 We introduced SCIT for Japanese cedar or house dust mite in 30 cases respectively in 2013-2017. We introduced SLIT for Japanese cedar or house dust mite in 15 cases respectively.

 High efficacy was observed in SLIT for Japanese cedar and both SCIT for Japanese cedar and house dust. We need more cases to confirm the efficacy of SLIT for house dust mite. Adverse drug reactions leading to withdrawal were observed in 0% with both SCIT, but in 9% with SLIT for Japanese cedar, 33% with Actair^® (house dust mite compressed tablet), and 0% with Miticure^® (house dust mite freeze-dried tablet).

 Most patients could continue SLIT for Japanese cedar. Adverse drug reactions with SLIT for house dust mite were often observed in patients who have bronchial asthma or severe allergic rhinitis. In these cases, we recommend SCIT in admission or using house dust mite freeze-dried tablet.

 Allergen immunotherapy is a treatment to induce the protective immune response in patients with allergic diseases such as allergic asthma and rhinoconjunctivitis by administering allergens in order to “normalize” the Th2-biased immune response to harmless environmental allergens. It has disease-modifying potential unlike current pharmacotherapy. In Japan, however, only two standardized allergens, house dust mite and cedar pollen allergen, are available. In contrast, there are much more allergen products for immunotherapy in US and Europe and we need to catch up to the “world standard” as early as possible.

 To bridge the gap, currently we use imported allergens for the therapy as unauthorized drug on personal responsibility of the physicians. We performed rush immunotherapy using grass pollen, cat, dog, and venom allergens and found their efficacy and safety. Further study for pharmaceutical approval is needed.

 Recently, to efficiently induce the protective immune response, novel immunotherapies have been reported. Establishment of allergen immunotherapy with more efficacy and safety is the key for the treatment of allergic diseases.

 Life expectancy of the childhood-onset chronic diseases has become dramatically improved since 1970s in Japan. As a result, adults with special health care needs or “patients in transition” have been increasing in number and their transition care has been of great importance. The Japan Pediatric Society published a recommendation for transition care in 2014 and has made continuous efforts to achieve better transition care in each medical field since then. As for allergic disorders pediatric and adult allergologists can share the same understanding of allergy and smooth transition may be realized on this basis.

 What are necessary to achieve adequate transition are : (1) support to attain health literacy, (2) creation and utilization of support tools, (3) acceleration of medical cooperation, (4) accumulation of experiences with “patients in transition” in adult medical side, and (5) drawing up of clinical guidelines for long-time management of the disorders. It should also be stressed that the goal of transition is not merely a baton pass but better life-span management.

 The proportion of adolescent patients with asthma who undergo medical treatment is one-tenth of the proportion of toddler patients in Japan. The proportion is far lower than expected based on remission rates of childhood asthma demonstrated by studies, indicating that adolescent patients who still require medical management for asthma control might not visit a doctor. This is attributed to the characteristic pathophysiological and/or social features of adolescent asthma. Questionnaires completed by pediatricians in the Gunma prefecture in Japan indicate that few doctors report facing difficulties in the transition from childhood asthma toward adulthood medical care. It might be essential to educate patients on the importance of anti-inflammatory treatment even without exacerbation and lung function testing before they reach puberty, to achieve transitional care of childhood asthma.

 Adolescents with asthma move from the care of pediatricians to the care of adult chest or allergy physician (transition) when continuous care is necessary. The initiative of asthma management in transition switch from guardian to the patients themselves, therefore asthma knowledge including self-management method is required for them. The adult physician is not familiar to treat the patients with asthma in transition. Early education for the patients by the pediatrician is useful for avoiding the patient’s confuse of asthma knowledge in transition. And the adult physician has to make effort to constrict well physician-patient relation while assessing of psychological mature in each patient. The disease severity and recommended inhaled corticosteroids does are different in each child and adult asthma guideline, the management plan is left to the discretion of each adult physician. The cooperation with the several health providers is required for achieving well asthma control in transition.

 Representative food allergies in adults are immediate symptoms (urticaria, anaphylaxis, etc.), food type-dependent exercise-induced anaphylaxis and oral allergy syndrome. All of these develop with an IgE-dependent mechanism, and anaphylaxis and FDEIA are severe. There are both sustained cases of childhood onset and adult onset in adult food allergy, although most of adult food allergic patients who consult medical institutions are the latter. Many of these cases, unlike those of childhood onset, do not have spontaneous remission, with the exception of anaphylaxis by hydrolyzed wheat allergy, usually lasts for the lifetime. Causes of adult food allergies are such as wheat, crustaceans, fish fruits, and parasite (Anisakis) allergy and oral mite anaphylaxis are important to be distinguished. In general, adult is more severe than children in food allergy, and it is important to note the history of chronic diseases such as asthma and cardiovascular disease, and the use of β-adrenergic blockers and ACE inhibitors as therapeutic agents.

 Montelukast, a leukotriene receptor antagonist (LTRA), is widely used alone or in combination with inhaled corticosteroids in treating bronchial asthma. LTRA is considered a drug with fewer side effects. However, parasomnias, including sleepwalking, sleep talking, and other neuropsychiatric symptoms, are mentioned as the side effects in the medical package insert of a LTRA, montelukast, although the incidence is very low. We encountered a case of a 7-year-old boy who has been monitored for food allergy for 2 years and sleepwalked after taking montelukast. He visited our outpatient clinic with a complaint of prolonged severe dry cough before dawn in September. Our clinical diagnosis was bronchial asthma based on his allergic history, sensitization to environmental allergens, and characteristics of cough, and montelukast was subsequently prescribed. A day after starting montelukast administration, a strange behavior similar to somnambulism was observed for the next 2 days. After stopping montelukast intake based on our instruction, the behavior disappeared. Therefore, somnambulism-like behavior was likely associated with montelukast. Although few previous cases have been reported parasomnia after taking montelukast, neuropsychiatric adverse effects should be noted when prescribing montelukast for the first time.

 Object : This study evaluated the usefulness of environmental intervention by home visits for asthmatic children with house dust mite allergy.

 Subject : The intervention group (A group) consisted of 10 children and their family members ; the control group (C group) consisted of 12 children and their family members.

 Methods : We visited homes of the A group at the beginning of the study and at 1, 2, 3, 4, 6, 9, and 12 months after the start. We measured the allergen levels of house dust mites in several parts of their houses using a handy measurement kit, and explained how to clean up the home environment based on the allergen levels. In order to measure house dust mite levels by ELISA, we also took house dust from the futons of the patients and the floors of their bedrooms, etc.

 Their bronchial asthma was treated following JPGL2012. We checked the number of emergency department visits and hospital admissions they made for asthma attacks. We also measured house dust mite-IgE levels and lung function before and after the study.

 Results : We were unable to continue home visits for 3 families of the A group. House dust mite levels were decreased after 1-year intervention in the houses where mite allergen levels were very high in their futons and in their bedrooms.

 Asthma treatment was stepped down for 4 children of the A group and 2 children of the C group ; unchanged for 6 children of the A group and 6 children of the C group ; stepped up for 4 children of the C group ; which was statistically significant between the two groups (likelihood ratio test ; p=0.049). There was no significant difference between the A and C groups in the number of hospital admissions, emergency department visits, and the change of house dust mite-specific IgE levels and the ratio of forced expiratory volume in 1 second to forced vital capacity.

 Conclusion : Environmental intervention by home visits is useful.

 Objective : We aimed to examine the effect of introducing egg yolk in diets of infants.

 Methods : Patients aged<3 years who underwent the egg white oral food challenge (OFC) were divided into two groups according to preceding consumption of egg yolk : egg avoidance group (84 cases) and egg yolk consumption group (50 cases). The results of OFC, egg white- and ovomucoid-specific immunoglobulin E (IgE), and dietary instruction after OFC were compared between both the groups.

 Results : The positive rate of OFC results (p<0.01) and rate of “continuous elimination of egg white” after OFC (p<0.05) were significantly lower in the egg yolk consumption group than in the egg avoidance group. No significant differences in egg white- and ovomucoid-specific IgE were observed between the two groups. In addition, regardless of the reasons for egg avoidance (“histories of immediate reactions” or “other reasons”), the positive rate of OFC and “continuous elimination of egg white” were lower in the egg yolk consumption group than in the egg avoidance group.

 Conclusion : Early introduction of egg yolk may accelerate the introduction process of egg white.

 Based on the specific IgE (sIgE) class of mite and cedar pollen in 70 asthmatic patiens aged 12 to 16 years were classified into 4 phenotypes of low sensitization, mite predominant, cedar pollen predominant and high sensitization. Age, sex, respiratory function, biomarkers of exhaled NO (eNO), total IgE and blood eosinophil count, dose of inhaled corticosteroids (ICS) and sIgE class of dog and cat were compared among 4 phenotypes. Furthermore, the correlation between each biomarker and between respiratory function and biomarkers were investigated in each phenotype. There was no significant difference of age, sex and respiratory function in 4 phenotypes. Exhaled NO, total IgE and blood eosinophil count were low, in order of low sensitization, cedar pollen predominant, mite predominant and high sensitization, and significant difference was observed between low sensitization and others (p<0.05). Exhaled NO and total IgE of mite predominant and eNO and eosinophil count of cedar pollen predominant showed positive relationship. The number of eosinophils/total IgE ratio was significantly high in the cedar pollen predominant compared to mite predominant. There was negative correlation between eNO and %V50 in mite predominant (p<0.05), but no significant relationship was found in the other phenotypes. These results suggest that there are pathological differences among these 4 phenotypes.

 The chance to repeatedly attend lectures on food allergies is increasing. However, there is limited evidence whether or not these attendances improve understanding of food allergies. We recruited 225 teachers and compared the effectiveness of the lecture to improve understanding against the number of times the lecture was attended. The results indicated that the more lectures attended, the better the understanding of food allergies and epinephrine auto injectors. On the other hand, repeated attendance at the lecture did not improve recognition of the severity of airway and abdominal symptoms. For example, even immediately after the lecture less than 70% of participants selected “call an ambulance” for some severe airway and abdominal symptoms. The understanding of correspondence on anaphylaxis was also lower despite attending the lecture. The important issues in the lectures regarding food allergies may be to emphasize correct recognition of the severity of airway and abdominal symptoms, and continuity of understanding of this recognition. To solve these issues, repeated lectures should focus on airway and abdominal symptoms and the necessity of an emergency action plan.

 Objectives : This study investigated the association of intervention by a Pediatric Allergy Educator (PAE) and demographic/clinical factors with appropriate management of the epinephrine auto-injector (EpiPen^®) by pediatric patients and their families in order to develop better intervention methods. Methods : Ninety-seven pediatric patients with food allergies were prescribed the EpiPen from June 2015 to January 2016. Inappropriate management was defined as the child or a family member handling the EpiPen improperly, including accidental injection, (n=7) or not renewing the EpiPen when it expired (n=19). We compared intervention by the PAE and clinical variables between the 26 patients with inappropriate management of the EpiPen and the 71 patients with correct management. Results : Intervention by the PAE was more frequently performed in the 71 patients with correct management of the EpiPen. The median delay in renewal of the EpiPen was two months. Six of the 7 cases of inappropriate handling by children occurred in various situations due to the child’s curiosity about the EpiPen. In multiple logistic regression analysis, intervention by the PAE, multiple prescription of the EpiPen were independently related to a lower risk of inappropriate use of the EpiPen, and a history of repeated anaphylaxis was independently related to a more risk of it. Conclusion : Intervention by the PAE was suggested to decrease the risk of inappropriat EpiPen use by pediatric patients and their family members. Healthcare staff sharing detailed information about inappropriate use with patients may lessen the occurrence of inappropriate handling of the EpiPen in the future.

 Soy sauce is a traditional fermented seasoning of Japan and is available throughout the world. The two main raw ingredients of soy sauce are soybean and wheat, both of which are established food allergens. By several immunological methods, it was clearly demonstrated that wheat allergens were completely degraded into amino acids and peptides that lose the IgE-binding ability during the fermentation process. In contrast, soybean allergens were gradually degraded during the fermentation process, but were not completely degraded in raw soy sauce. The residual soluble soybean allergens in raw soy sauce were denatured to insoluble allergens by the heat-treatment process, and subsequently completely removed from soy sauce by the sedimentation and filtration processes. Therefore, to reduce the allergenicity of soy sauce, the heat-treatment, sedimentation and filtration are very important processes in addition to the enzymatic degradation during the fermentation of soy sauce.