Gastrointestinal food allergy is a type of food allergy in which gastrointestinal symptoms are caused by non-IgE mediated allergic reactions. Various phenotypes have been reported, based on clinical symptoms, and differences have been observed in phenotypes between the population of Japan and populations outside Japan.

 Three classifications of non-IgE mediated gastrointestinal food allergy are used to categorize allergy types outside Japan. Food protein-induced enterocolitis syndrome is characterized by vomiting and diarrhea. Food protein-induced proctocolitis is characterized by bloody stools as the main symptom. Food protein-induced enteropathy presents with chronic diarrhea, failure to gain weight, and malabsorption. Although peripheral eosinophilia is not listed as one of these phenotypes, there are many cases of peripheral eosinophilia, and cases of eosinophilic inflammation of the gastrointestinal tract in Japan. These conditions share common symptoms with eosinophilic gastrointestinal disease. We believe that eosinophilic gastrointestinal disorders are classified separately from gastrointestinal food allergies outside of Japan, in comparison to how they are classified in Japan.

 Food protein-induced enteropathy is one of non-IgE-mediated food allergies and develops in infants within 1-year-old, with prolonged diarrhea, vomits, bloody stools, abdominal distention, and if severe malnutrition, failure to thrive and developmental retardation. It is often difficult to diagnose as this disease, therefore early diagnosis and early intervention are important.

 Although the food loading test is the basis for the diagnosis of this, as an objective test, the antigen specific lymphocyte stimulation test on the food antigen is useful for identifying the causative antigen. In endoscopic examination of gastrointestinal tract, inflammatory findings are recognized in the duodenum and colonic mucosa. In pathological examination from mucosal biopsy, inflammatory cell infiltration such as eosinophils and lymphocytes is noticed. Furthermore, food protein induced enteropathy that exhibits malabsorption and failure to thrive evaluates villous atrophy and crypt hyperplasia in duodenal mucosa.

 Since many diseases causing chronic diarrhea exist other than food protein-induced enteropathy, confirming the findings of the gastrointestinal mucosa using endoscopic and histopathological examination helps not only diagnosis, but also indicators for starting enteral nutrition. Therefore, it should be considered to perform the endoscopic examination when food protein-induced enteropathy is suspected.

 Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy which is considered to be mediated by allergen-specific T cells. Cow's milk FPIES patients have been reported to show a proliferation of either Th2 cells or IL-9-producing T cells according to the lymphocyte proliferation test using cow's milk allergens. Further studies to clarify whether these allergen-specific T cells in the peripheral bloods are involved in the pathogenesis of FPIES are needed. Although some of the patients have specific IgEs to the allergens, the role of humoral immunity remains unclear. Intestinal mast cells might play a role as effector cells in FPIES, and therefore the factors associated with the induction or activation of intestinal mast cells should be investigated.

 Viral infection induces both development and exacerbations of bronchial asthma. A number of case-control studies following to Tucson Children's Respiratory Study appear to have established at least a statistical connection between RS virus infection in infancy and the development of recurrent wheezing and asthma in young children. In later life, it appears unlikely to be a cause of atopic asthma. Rhinovirus infection is a major cause of acute exacerbations of asthma in both adult and children. Recent report by COAST study showed that the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy. On the other hand, COPSAC birth cohort study suggest that the association between respiratory infections in early life and later asthma is independent of virus type. In this review, the pathophysiology of development of childhood asthma induced by viral infection will be discussed.

 Wheezing illness with viral respiratory infection in infants is one of the important risk factors for developing bronchial asthma. Lower respiratory tract infections, especially with RSV, HRV or both, induce early wheezing. Recurrent wheezing has been reportedly linked to pronounced atopic characterization, environmental factors, and genetics. However, no biomarkers for prediction of recurrent wheezing are available for infants experiencing their first episode of wheezing. Therefore, the biomarkers that could be obtained with noninvasive techniques should be urgently identified. Although TSLP, IL-25, IL-33, and Th2 cytokines were known to play important roles in the pathogenesis of asthma we speculated that another factors, which could induce severe airway inflammation, could be involved in the pathogenesis of recurrent wheezing before developing asthma. We very recently reported that MIP-1α obtained from nasopharyngeal aspirates could be a biomarker for prediction of recurrent wheezing. The efficacy of palivizumab and vaccination to RSV in prevention of asthma development after RSV infection in premature infants have been reported. However, they have not been in practical use yet. Further research would be required to identify biomarkers for predicting development of asthma after viral wheezing illness.

 Pediatricians often meet children with virus-induced asthma attacks, and many reports have shown that viruses, such as rhinovirus, respiratory syncytial virus (RSV), may exacerbate asthma attacks.

 Severe respiratory issues including pneumonia, atelectasis and severe asthma attack have been reported to occur in hospitalized children with A (H1N1) pdm09 infection. Bronchial asthma increases the risk of hospital admission and intensive care in A (H1N1) pdm09-infected children. The hospitalized children with A (H1N1) pdm09-induced pulmonary complications did not receive long term management for bronchial asthma.

 In this study, we report clinical features in the children with A (H1N1) pdm09-induced asthma attacks and cytokine profiles of bronchoalveolar lavage fluids in a mouse model of bronchial asthma during A (H1N1) pdm09. These results suggest that A (H1N1) pdm09 infection can induce more severe pulmonary inflammation in the settings of bronchial asthma than seasonal H1N1 infection, based on the excessive production of inflammatory cytokines and the reciprocal depression of anti-viral cytokines, along with high viral loads in a mouse model of bronchial asthma.

 Enterovirus D68 is a RNA virus that does not have envelope belonging to picorna viridae enterovirus. Its infection increases in summer to autumn, and presents various findings, such as cold, lower respiratory infection, wheezing, etc.

 In September 2015, during the endemic of enterovirus D68, unusual increases in acute asthma, severe respiratory diseases and acute flaccid paralysis were experienced in many pediatric hospitals in Japan. A retrospective nation-wide monthly surveillance focused on acute asthma exacerbation for children, which was performed for the first time in the world by the Japanese Society of Pediatric Allergy and Clinical Immunology, indicated that enterovirus D68 was an important virus for epidemic of acute asthma exacerbation.

 This experience will develop into research that contributes to the advancement of both allergology and microbiology.

 In our epidemiological studies at 14-year interval, there was no increase in the prevalence of FDEIA in junior-high school students. In the recent study all cases were diagnosed clinically as FDEIA, and at the school nurses the familiarity of FDEIA was improved significantly. However, there was no decrease in the recurrence rate of FDEIA cases. Furthermore, we noticed an emergence of secondary FDEIA cases who had been treated with oral immunotherapy (OIT).

 Recently, OIT is often applied to refractory food allergy patients. And desensitization but not tolerance to the causative food is achieved in many cases. Therefore, once they would acquire the desensitization they could eat the food without problems. However, they still might develop anaphylaxis after taking the desensitized food followed by exercise.

 In the Japanese Pediatric Guideline for food allergy 2016 the definition of FDEIA was revised partially for excluding secondary FDEIA.

 Finally, there are a lot of issues to be resolved in near future. That is, a dissemination of adequate knowledge and direction to reduce the recurrence and the over-diagnosis, an improvement of the provocation test to increase a positivity rate, and an establishment of medicine to prevent the onset should be achieved.

 Food-dependent exercise-induced anaphylaxis (FDEIA) has many unresolved problems from diagnosis to treatment. In this review, we aimed to show a clinical course and practical diagnostic points of FDEIA based on our experience.

 An exercise-provocation test is essential for diagnosis and patient and parents'understanding of the pathophysiology of FDEIA. However, due to its low reproducibility, it is difficult to deny the diagnosis completely even if it is negative. Aspirin is sometimes used when exercise-provocation test is negative, but it should be carried out under sufficient preparation because it increases the risk of inducing anaphylaxis.

 Specific IgE to ω-5 gliadin is useful for a diagnosis of wheat-dependent exercise-induced anaphylaxis in adult patients, but there are no identified components predictive of symptoms in children. A skin prick test using heated peach is useful in the diagnosis of peach FDEIA, and Pru p 7 (peamaclein) could be a component related to systemic reactions to peach.

 In Japanese Pediatric Guideline for Food Allergy 2016, detailed interview, general blood tests and various allergy tests are useful for diagnosis of food-dependent exercise-induced anaphylaxis (FDEIA). And the exercise-induced oral food challenge is preferable for definitive diagnosis.

 However, the reproducibility of the exercise-induced oral food challenge is not always high. Then allergen components have attracted attention as one of new diagnostic tools, and will consider to be useful for diagnosis of FDEIA in recent years.

 Allergen components were measured against pediatric wheat-dependent exercise-induced anaphylaxis (WDEIA) and pediatric peach-dependent exercise-induced anaphylaxis experienced in our department. These results suggested that the combination of Tri a 19, Tri a 21, Tri a 26 and Tri a 37, may be useful for diagnosing pediatric WDEIA, unlike adult patterns. In addition, Pru p 7 of pediatric peach FDEIA was useful as well as previously reported for adult peach immediate allergy, and Pru p 3 was also related. Then, Pru p 7 and Pru p 3 may be useful for the diagnosis of pediatric peach FDEIA.

 At present, there are few studies on allergen components except for some foods, and detailed examination is required continuously.

 Aspirin is known to enhance the both of food allergy and food-dependent, exercise-induced anaphylaxis (FDEIA) symptom in adult cases. But, it is not conclusive in children. The 3-days challenge tests were performed in patients suspected of having FDEIA. The patients were examined with a causal food and exercise on the first day, with aspirin and the causal food on the second day, and with aspirin, the causal food, and exercise on the third day. We defined a positive reaction as the appearance of symptoms or a 180% increase in the plasma histamine level. Finally, after the test pretreated with aspirin before the food and exercise challenge, positive results in response to causal foods were successfully provoked. Positive results were induced by food and exercise challenges in only half patients. In the absence of an exercise challenge, aspirin and food provoked a reaction in only about 10%. Aspirin enhanced the frequency of positive reactions during challenge tests with a causal food and exercise by two-fold. In children, the exercise may be indispensable factor in mechanism of aspirin which enhances food allergy.

 Background : Egg yolk oral food challenges (OFCs) are frequently conducted as a replacement for small-amount egg white OFC. However, limited information is available regarding the amount of egg white remaining in egg yolk.

 Purpose : We evaluated the amount of residual hen's egg white in a raw egg yolk and investigated whether or not patients with an egg white allergy with a low threshold dose could consume one egg yolk.

 Methods : We separated an egg yolk using an egg separator and boiled it. Then, we weighed the egg white and vitelline membrane on the surface of the yolk. We selected 11 patients who tolerated 1.0 g of heated egg white based on the results of a heated egg white OFC from September 2014 to February 2015 and performed an egg yolk OFC.

 Results : The amount of egg white and vitelline membrane on the surface of egg yolk was 0.7 g (0.6-1.0 g, n=6). Of 11 egg-yolk OFCs, 9 showed negative results, 1 had local erythema, and 1 had multiple erythema.

 Conclusion : Eighty% of Patients who tolerated 1.0 g of heated egg white appeared to be able to consume one heated egg yolk.

 Objective : To investigate inhalation technique in patients using pressurized metered-dose inhalers (pMDIs) from residual quantities in long-term management for childhood asthma.

 Method : From July 2013 to May 2014, salmeterol and fluticasone combination pMDIs with dose counters were prescribed to 5- to 15-year-old patients with childhood asthma. The residual drug quantities were measured, and pMDI handlers were confirmed. The factors affecting the hand-strength and shaking of the child and adult models were investigated.

 Result : Of 2,793 prescribed pMDIs, 769 were collected from 188 patients. At 5 years of age, 17% patients had operated the pMDIs themselves. Contrastingly, 93% had operated pMDIs at 10 years of age. Furthermore, 35 and 58% of children with asthma and parents, respectively, operated the pMDIs 95% out of 120 times compared to a mean expected actuation of 9.0 g based on the canister weights (p<0.05). The assessment of the child and adult-model indicated that weak hand-strength and deficient shaking contributed to causing reduced pMDI actuation.

 Conclusion : Less than half of 6- to 13-year-old patients were able to operate pMIDs appropriately, and the proper use of pMIDs was not dependent on the age of the patient.

 Background : According to the increase of children with food allergies, the situation of using adrenaline auto injector (EpiPen^®) by school personnel is also increasing.

 Objective : The aim of this study was to examine school personnel's technique of EpiPen^® objectively.

 Methods : We visited all elementary schools and junior high schools in Yamato-city, and performed role-playing type lecture of EpiPen^® in 2013 and 2015. In 2015, before the lecture we performed a technical test of EpiPen^® for the school personnel (n=678), and evaluated five major points.

 Results : The average score was 2.9 point in all participants. The correct answer rate of how to hold EpiPen^®, and the duration time of injection was low. Participants who checked the label on EpiPen^® were able to use it correctly, even when they had no experience of EpiPen^® lecture. The correct answer rate was higher at schools where the head teacher's answer rate was high.

 Conclusions : Informing the importance of checking the label on EpiPen^®, may be effective for teachers to use EpiPen^® correctly at school. In order to improve the ability of management of food allergies at schools, head teachers are expected to show strong leadership.

 The content of a clinical guideline recommends to be based on the evidence like systematic reviews which are located the highest level. A systematic review is conducted with an explicit methodology including an exhaustive search. The eligible studies are filtered from searched references by a well-designed search strategy. The conclusion is comprehensively drawn with the data from eligible studies with meta-analysis if possible. The recommendation to clinical questions (CQs) is provided on guidelines after assessment of the validity of evidences. In revising the Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL), the JPGL committee proposed eight CQs. The SR team, including 24 pediatricians, conducted systematic reviews with including randomized controlled trials relevant to CQs and evaluated the risk of bias. Recommendations to the CQs were finally fixed by the JPGL committee and the SR team with considering clinical situation in Japan.