Early introduction of allergenic foods in infancy is recommended to prevent food allergies because it has been shown that oral intake induces tolerance to foods without causing intestinal sensitization. Based on the results of randomized control trials and meta‒analysis, the guidelines and position papers in some countries recommend the introduction of peanut and hen's egg in early infancy for preventing these allergies since 2015, although there are some differences between these guidelines. However, it is necessary to monitor any possible induced immediate allergic reaction while actually practicing this preventive method. For this reason, position papers of each country recommend that “heated egg” be introduced “from a small amount” in order to reduce the risk of adverse events. However, little guidance is provided on what foods should be introduced early and in which infants, how to increase the quantities eaten afterwards, and whether screening is necessary. Therefore, future studies are needed to provide information regarding these issues.

 Allergic march refers to the natural history or typical progression of allergic diseases that often begin early in life. These include atopic dermatitis (eczema), food allergy, allergic rhinitis (hay fever), and asthma. In most patients, atopic dermatitis is the first clinical manifestation with the highest incidence in the first year of life and those affected develop other allergic diseases such as food allergy, asthma, and allergic rhinitis later in childhood. Several cohort studies have been reported that atopic dermatitis in early infancy increases the risk of food allergy, asthma and allergic rhinitis. We expect that to prevent future allergic march, an appropriate early intervention for atopic dermatitis, which emerges at the first stage of allergic march, is important.

 Beneficial effects of probiotics are long known to mankind. Research is beginning to unravel the true nature of the human microbiome and its interaction with the immune system. The growing prevalence of atopic diseases in the developed world led to the proposition of the “hygiene hypothesis.” Dysbiosis is linked to atopic diseases ; probiotic supplementation is able to alter the microbiome and certain probiotic strains have immunomodulatory effects in favor of a suppression of Th-2 and stimulation of a Th1 profile. To determine whether daily supplementation with specific Lactobacillus gasseri for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis (AR). We conducted a randomized, double-blind, placebo-controlled study on school children (age, 6－12 years) with asthma and AR. Our results showed the pulmonary function and peak expiratory flow rate increased significantly, and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls. Further, there was a significant reduction in the TNF-α, IFN-γ, IL-12, and IL-13 production by the PBMCs following the probiotic treatment. In conclusion, probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR. In the mice model of mite-sensitive allergic asthma, oral administration with L. gasseri can attenuate major characteristics of allergen-induced airway inflammation and IL-17 pro-inflammatory immune response in a mouse model of allergic asthma, which may have clinical implication in the preventive or therapeutic potential in allergic asthma. Moreover, we found the immmuno-regulatory effect of L. gasseri in HDM-induced airway inflammation is through activation of PPARγ in dendritic cells. Hence, using probiotics as complementary treatment options in atopic dermatitis and food allergies seems to be a promising concept although the evidence is of a preliminary nature to date and more convincing trials are needed.

 Since dual allergen exposure hypothesis was proposed, percutaneous sensitization has attracted attention as a principal mechanism involved in the development of food allergy. Several clinical trials have been conducted to prevent food allergy by improving skin barrier function with moisturizers. However, even if suppressing the onset of atopic dermatitis, their preventive effects on the development of food allergy have not been proven. Because not all patients with food allergies have history of atopic dermatitis or impaired skin barrier function, other routes instead of skin may play a role in establishing antigen-sensitization. In pollen-food allergy syndrome, sensitization to pollen antigens, which exhibit cross reactivity with food antigens presumably occurs through respiratory tracts. Therefore, it is difficult to completely prevent the development of food allergy by intervention focusing on percutaneous sensitization. To prevent food allergies, it is necessary to clarify the factors which affect percutaneous sensitization, and the mechanism involved in oral and/or respiratory sensitization.

 Immediate-type of childhood food allergies are likely to resolve with age. We have previously reported the natural history of food allergy against hen's egg, cow's milk, and wheat, based on results of oral food challenge (OFC). We observed that the resolution rates by 6 years of age were as follows : 73% for hen's egg, 85% for cow's milk and 66% for wheat. From a retrospective chart review in USA, 69% of the children outgrew soy allergy by the age of 10 years. On the other hand, 22% of the children outgrew peanut allergy diagnosed at the age of 1 year by OFC, by the age of 4 years. In addition, among food allergies diagnosed at the age of 6 years, 50% or more outgrew hen's egg, cow's milk and wheat allergies by the age of 12 years, whereas approximately 30% outgrew peanut allergy. A history of anaphylaxis, high levels of specific IgE and large wheal diameter of skin prick test were the risk factors of persistent food allergy. Although the natural history of immediate-type of childhood food allergies differs with respect to causative foods, we need to consider performing OFC to confirm the resolution of food allergies in childhood.

 Physicians interviewing patients for diagnosing possible food allergies should focus on the diet of the patient and the amount of food intake as well as on the symptoms manifested. Furthermore, food-specific IgE antibody assessment and skin prick tests could aid the diagnosis. The oral food challenge test is the gold standard for final diagnosis. A diagnosis of food allergy should be made based on the observation of allergic symptoms following the intake of suspected foods. However, sensitization observed on blood test to unsuspected food could lead to erroneous judgment in routine practice. For initial diagnosis, results from the food-specific IgE antibody assessments and skin prick testing could be utilized, following which the diagnosis could be confirmed using the oral food challenge test in appropriate cases. Diagnosis regarding egg, milk, and wheat allergy has been established ; therefore, we will focus on the diagnosis of allergies caused by other allergen.

 Oral food challenge and dietary counseling are the basic skills for management of food allergies. However, there are no unified protocols. In this review, we aimed to introduce our attempts to improve the current methods to be more safe and effective. The dose and intervals of an oral food challenge is optimized for each patient based on the clinical history and IgE titers. Furthermore, reduction of allergenic activity by food processing or cooking is considered when we introduce processed food for food challenge or home intake. In terms of dietary counseling, we discuss the safety and unresolved problem on our “quantitative intake” method.

 According to the Food Allergy Clinical Practice Guideline 2016, the definition of oral immunotherapy (OIT) is as follows : “The antigen is orally administered under the guidance of a doctor after confirming the threshold levels in the oral food challenge test in cases where the achievement of natural tolerance is delayed. It is defined as a therapy that is aimed at acquiring tolerance ultimately after increasing the threshold levels”. OIT has received attention for its potential as an effective treatment of food allergy.

 While OIT is an effective treatment for increasing the threshold, it may possibly cause a severe reaction ; hence, adequate safety measures are necessary while administering OIT. However, since there is not enough evidence regarding the superiority or inferiority of the OIT method itself, there is no unified safety protocol developed yet, and research should be conducted to clarify this.

 Therefore, in this report, we describe a method of OIT that incorporates feasible safety, evaluation of the patient’s risk in advance, and setup necessary to minimize the risk of OIT protocols.

 Oral immunotherapy (OIT) induces desensitization in a majority of patients. However, adverse reactions occur due to full-dose OIT. These reactions are mainly mild or moderate, but at times can be severe. In addition, efficacy and continuation of therapy have been problematic.

 In recent years, some studies on omalizumab combined with OIT, low-dose OIT, sublingual immunotherapy (SLIT) and epicutaneous immunotherapy (EPIT) were performed. Combining omalizumab with OIT was reported to improve safety but not the outcome and long-term efficacy. We performed low-dose OIT (target dose : 1/32 of heated whole hen's egg, 3 mL of cow's milk, 2 g of Udon noodle or 0.5 g of peanut) for children with severe food allergy with low thresholds. Low-dose OIT seems to be relatively safer compared with full-dose OIT and it would be appropriate approach for severe food allergies.

 Further studies are needed to assess the long-term efficacy and safety of omalizumab combined with OIT or low-dose OIT.

 Childhood asthma and respiratory tract infections have been pointed out to be a mutually close relationship with sensitization and exacerbation. Allergic sensitization reduces infective immunity against viruses, and infection promotes antigen sensitization.

 During the period of pandemic influenza A (H1N1) pdm09 infection in 2009 and enterovirus D68 infection in 2015, acute exacerbation of asthma occurred in children who had not been diagnosed with asthma or those with intermittent type.

 Further epidemiologically and immunologically investigating the relationship between childhood asthma and respiratory tract infection is surely beneficial for the prevention of both.

 I described asthma management for asthma in preschool children. 1) The phenotype of preschool children asthma was classified into IgE-related asthma (allergen-induced asthma/atopic asthma) and non-IgE related asthma (virus induced asthma etc.). 2) “Diagnostic treatment” was used for the diagnosis of preschool asthma. 3) In preschool asthma, most of IgE-related asthma shifts to “atopic asthma” which is positive for inhalation allergens. On the other hand, a part of non-IgE-related asthma shifts to “atopic asthma” or “non-atopic asthma”. 4) The transition from preschool asthma to refractory asthma is the two phenotypes of multiple antigen positive atopic asthma and neutrophilic asthma with pulmonary function decline. 5) To prevent the transition to intractable asthma, early intervention in preschool asthma is necessary. Salmeterol・fluticasone combination (SFC) is considered effective for prevention of neutrophilic asthma accompanied by decreased pulmonary function at school age. And prevention of multiple antigen positive atopic asthma, Sublingual immunotherapy for cedar and mite is considered useful.

 Long term management for pediatric asthma centered on inhaled corticosteroid and leukotriene receptor antagonist has spread along with the dissemination of the Japanese pediatric guideline for the treatment and management a of asthma. As a result, the number of asthma-related death and hospitalized patients due to asthma attacks has decreased, and the quality of life of many children with asthma has been improved. Despite high-dose inhaled corticosteroid and combined therapy of multiple asthma medications, there are also children with severe asthma that cannot be adequately controlled. Recently, a humanized anti-IgE monoclonal antibody (omalizumab) and a humanized anti-IL-5 monoclonal antibody (mepolizumab) have been approved for use in pediatric severe asthma, and the effectiveness of these biological agents has been reported. On the other hand, some cases show persistent asthmatic symptoms even after the initiation of biological agents, and their pulmonary function or airway inflammatory markers cannot be improved. In addition, there is not enough evidence regarding the methods for tapering or discontinuation of the biological agents. Therefore, development of biomarkers to predict effectiveness as well as guidelines to select biological agents according to the endotypes are desirable for a proper treatment of pediatric severe asthma in the future.

 The incidence of chronic obstructive pulmonary disease (COPD), a refractory and progressive disease, is increasing worldwide. Risk factors for COPD should be eliminated as much as possible because there is no effective prophylaxis against COPD. Recently, childhood asthma has been reported to be an important risk factor for the onset of COPD. Childhood asthma is a common disease and the natural healing of asthma is not often observed. Furthermore, through recent advances in therapy, there are many apparently mild cases and long-term management of asthma may be interrupted in many cases. Taking into account the extremely long-term course of asthmatic children, pediatricians should implement long-term management with lung function testing, and should strictly instruct patients to avoid tobacco use throughout their life. Although COPD is an adult disease, for the prevention of COPD, it is necessary to confirm that the reduction of the pulmonary function starts from the early childhood period in asthmatic patients. Furthermore, in planning the desired transitional medicine, it is important for pediatricians to understand COPD.

 Background : In light of an increasing demand for egg oral food challenges (OFCs) for infants in Japan, this study examined the safety of boiled egg-white OFCs in infants.

 Methods : Infants aged<12 months were administered a 20-minute boiled egg-white OFC (total challenge dose : approximately 1/2 egg white) to obtain definitive diagnoses of hen's egg allergy (DD-OFC) and to determine safe intake quantities and tolerance acquisition (ST-OFC). We assessed the proportion of positive OFCs and the severity of OFC-induced symptoms.

 Results : Sixteen (43.2%) of 37 DD-OFC patients and 29 (80.6%) of 36 ST-OFC patients had positive OFCs. Egg-white sIgE≥3.93Ua/mL and ovomucoid sIgE≥0.42Ua/mL were associated with positive DD-OFCs. Complete avoidance of hen's egg protein was associated with positive ST-OFCs. Grade 2 (moderate) symptoms were observed in 27 (60.0%) of 45 patients with positive OFCs, and were associated with no previous exposure or complete avoidance of hen's egg protein. Anaphylactic reactions were observed in 4 (8.9%) patients, and were associated with no previous exposure to hen's egg protein.

 Conclusions : Egg-white OFCs in infants produced a high proportion of positive OFCs, including moderate-to-severe reactions. More appropriate OFC protocols are needed to improve patient safety.

 Background : Mugwort and birch pollen allergies are frequently associated with immunoglobulin E (IgE) -mediated hypersensitivity to celery and spices. The phenomenon is known as the celery-birch-mugwort-spice syndrome and is well documented in Europe, but rare in Japan.

 Patient : A 14-year-old girl with a history of seasonal rhinoconjunctivitis and runny nose in the spring experienced pruritus of the tongue and mouth when she consumed spaghetti bolognese with celery. She also developed coughs, wheezing, and a squeaky voice after consuming a curry and rice. We performed detailed questioning, measurement of specific IgE antibodies, a skin prick test, and an oral challenge test.

 Result : Serum-specific IgE antibodies to Japanese cedar, cypress, birch, alder pollen, celery, and birch PR-10 (Bet v 1) were detected. On the other hand, serum-specific IgE antibodies to mugwort pollen and birch profilin (Bet v 2) were not detected. She showed positive reactions to several Apiaceous spices in the skin prick test. She also showed positive reactions to coriander and celery in the oral challenge test.

 Conclusion : According to these results, we suspected an apiaceous spice allergy caused by cross-reactions with a Betulaceae pollen allergy in this case. Although it is well known that celery and mugwort profilin can generate cross-reactions with birch profilin (Bet v 2), Bet v 2 was not detected in this case. Thus, we suspect that there are unknown cross-reactive proteins between celery, Betulaceae pollen, and apiaceous spices. Since more children have Betulaceae pollen allergies, we should pay attention to spice allergies.

 Immediate-type buckwheat allergy is not rare attaining the school-going age among children in Japan. Compared with other allergies, buckwheat allergy easily causes anaphylaxis and is hard to outgrow. However, there is still no report on oral immunotherapy (OIT) for buckwheat allergy. We conducted an oral food challenge test using buckwheat noodles in two patients with buckwheat-induced anaphylactic episode after obtaining informed consent to determine the safe amount of buckwheat noodles required to initiate OIT. Both patients consumed buckwheat noodles daily at their homes, and their dosage was increased from 20% to 50% at an outpatient hospital every month. Case 1 : An 8-year-old boy who had an anaphylactic episode after inhaling buckwheat powder at 7 years of age. Case 2 : An 11-year-old boy who had an anaphylactic episode after consuming one serving of buckwheat noodles at 5 years of age. Each patient underwent OIT until reaching the dosage of one serving of buckwheat noodles (150 g, 200 g) at 1 and 3 years after treatment initiation. No patient presented with anaphylaxis during OIT. In conclusion, OIT with buckwheat can be considered as an optional treatment for buckwheat allergy.

 Purpose : The present study aimed to assess the safety of a stepwise oral food challenge (OFC) using udon noodles.

 Subjects and Methods : This retrospective analysis reviewed the OFC and laboratory test results as well as the participants' history of food allergies from the medical records of participants who underwent an OFC using udon noodles at Miyagi Children's Hospital between September 2012 and April 2018. The total food dose classifications were as follows : step 1, 1 g of udon noodles ; step 2, 10 g of udon noodles ; step 3, 50 g of udon noodles ; and step 4, 100 g of udon noodles.

 Results : Five hundred twenty‒one participants were included in the analysis. OFC‒positive rates were 16% (step 1), 34% (step 2), 21% (step 3), and 18% (step 4). An intramuscular adrenaline injection was administered to 0.5% and 1.5% of the participants during steps 1 and 2, respectively, whereas no patients underwent intramuscular adrenaline injections during steps 3 or 4.

 Conclusions : The stepwise OFC with udon noodles is safe, as indicated by the low OFC‒positive and adrenaline treatment rates.