The past, present, and future of the medicine in the field of allergic diseases in Japan were reviewed, focusing on the last half-century referring to the author's experiences. Bronchial asthma has been largely controlled with ambulatory care after we experienced two epidemics of mortality increase from this morbidity. Development and change of medication in the last 50 years including β stimulants, theophylline, antiallergic drugs, inhaled steroids, and biologics were also described.

Food allergy was discussed regarding recent prominent increase in prevalence and the related new problems including social and media responses. Regarding pollinosis, a disease for the nation, the usefulness and future of immunotherapy was mainly mentioned. Changes in medical care including topical use of steroids and tacrolimus, barrier function abnormalities, and biological agents were also described with respect to atopic dermatitis. Finally, the progress and future of national policies following the enactment of the BASIC LAW ON MEASURES AGAINST ALLERGIC DISEASES was remarked.

Japan is the only country where a national roll-out of IQOS has occurred, and Japan's worldwide share of IQOS was 96% in October 2016. Unfortunately, Japan became an experimental country for heated tobacco products including IQOS, PloomTECH and glo.

As individuals, as a society, and as a nation, we must come to grips with new tobacco products.

In this paper, after explaining the classification and usage of new tobacco products in Japan, I discussed the health effects of heated tobacco products, suggesting briefly risks on cardiovascular disease, cancer, and allergies. Finally, my idea of how to deal with new tobacco is described.

Allergies are caused by failures in immune function, which is one of the higher functions of the biological system. Immune function is the operation of a complex system consisting of various types of cells. Dysfunction could be caused by a slight abnormality in the behavior of the individual cells that make up the cell society. How can we approach the mechanisms leading to homeostasis and collapse of this complex cell society? An omics approach is expected to introduce a way to tackle this difficult problem. In this review, after summarizing the current status of omics technologies, particularly focusing on proteomic and transcriptomic technologies, we introduce an example of how time-resolved single-cell analysis complements omics analysis to describe the process through which a cell society changes its state. The omics approach together with time-resolved single-cell analysis may reveal new universal principles governing complex biological systems in the future.

Knowledge of allergens is required in order to understand the nature of allergic reactions. Proteins are the major source of allergens, and the specific protein recognized by IgE antibody is designated as the allergen component. The specific point at which IgE antibody binds is known as the epitope. When a common epitope is presented in different proteins, the same antibody binds to all epitopes in a process known as cross-antigenicity. Allergen molecules must be dissolved in water in order to enter the body. Water solubility affects the digestion, absorption and allergenic activity of the molecule. Coagulation of protein molecules is thus an important factor to consider in order to understand a given protein's allergenic activity. The present review describes the molecular structures and functions of ovalbumin and ovomucoid. In addition, the major milk allergen casein is also addressed in terms of the milk presence, structure, and function of four fractions (αs1-, αs2-, β-, and κ-caseins) and IgE epitopes.

Oral allergy syndrome (OAS) is a form of localized IgE-mediated allergy, usually to fruits or vegetables, confined to the lips, mouth, and throat. This syndrome most commonly affects patients who are allergic to pollens, especially birch pollen. So, it's also referred to as pollen-associated food allergy syndrome (PFAS). Because birch pollen allergen, Bet v 1, and the homologous protein of apple, Mal d 1, have 56% identities in amino-acid sequence, these two allergens are cross-reactive through the conserved part which are thought to be conformational epitopes. Accordingly, causal allergens are usually heat-labile. Most common causal foods are raw fruit/vegetables and cooked forms are tolerated.

There are some exceptional cases. Soy protein-containing food items can cause a severe allergic symptom (face swelling, feeling of narrowing of the throat, difficulty swallowing, urticaria, wheezing) in patients with birch pollen allergy, and Bev 1 homologous protein, Gly m 4, is considered as the causal allergen.

In this text, we explain the basic mechanism of PFAS in an easy-to-understand manner, and introduce another hypothesis as to why soymilk cause severe allergy in birch pollen sensitive patients. Recently, the relationship between cypress pollen and peach GRP has been reported overseas, and we report the proportion of positive reactions to peach-GRP in Japanese cedar pollen patients.

Practitioners of allergist should also enlighten the appropriate and up-to-date knowledge for the families who have food allergies and for the people around them. To achieve the purpose, it is necessary to build regional cooperation with hospital doctors first, and then with the assistance of childcare and educational organization.

The oral food challenge (OFC) is indispensable to provide appropriate information, such as the extent of food to which individual child needs to remove. I believe that it is sufficient to use a single OFC just once within the same day and check the safety of the amount to eat. After the first load, I experienced that the amount of food consumption was able to increase by repeating OFC once a day.

This article reports on the food allergy multi-occupational collaborative project which has been implemented in Ehime prefecture since 2006, aiming to establish a murti-occupational collaboration, and the experience of OFC, which emphasizes the safety at my clinic.

Oral food challenge tests (OFC) are essential for the management of food allergic patients. However, there are not so enough allergy specialists that we have made OFC manuals safely operated for non-allergy specialists in the Committee of Maternal and Child Health Care in Fukuoka City Medical Association. In this manual, allergens are limited in egg, milk and wheat. And, subjects are limited in patients of complete avoidance whose specific IgE antibody (sIgE) levels are as follows: in case of egg allergy class of egg-white sIgE≤2 and ovamucoid≤2; in case of milk allergy sIgE class of milk≤2; and in case of wheat allergy sIgE class of wheat≤3 and ω5-gliadin≤1. In the case of patients who have already taken some allergens, it is designed to start OFC with half quantities of already taken foods.

Under these conditions, OFC were performed for 42 patients in our clinic. In the patients of complete avoidance, 8 cases of egg allergy, 6 cases of milk allergy, and 6 cases of wheat allergy did not show any reactions. Only one case of wheat allergy showed slight urticaria. In 22 cases of patients who have already taken some allergens, only 1 case of egg allergy showed systemic urticaria.

These results indicate that OFC with these conditions can be performed safely by non-allergy specialists.

Central base hospitals and prefectural base hospitals are being organized under the Basic Law on Measures Against Allergic Diseases. However, ideal functions of the base hospitals are still to be established. We have contracted a model project on functions of prefectural base hospital by the Ministry of Health, Labour and Welfare. Here, I describe our attempts.

First, we initiated a close collaboration with the prefectural medical association and established "the Medical Care Network for Allergic Diseases in Mie". For quality assurance of the network, we recruited clinics and hospitals who declare that their practice is based on EBM-based guidelines for various allergic diseases and we posted the "guideline-qualified" clinics/hospitals in the website, "Allergy Portal Mie", where patients can easily search for suitable clinics/hospitals in vicinity. As the human resource development, we started the training course for medical staff who wish to specialize in patient education for allergic diseases. We aim to develop human resources of community-based teaching staff. Attempts of awareness-raising activities such as lectures at shopping malls.

With the development of medicine, it is estimated that 95.7% of chronic diseases that occur in childhood have reached adulthood. Optimal care must be provided to these adult patients, but the question remains whether pediatricians can fully respond to their mandate. Transitional medicine is a lifelong "process" of personalized medicine for young adult with special health care needs. In our country, Japan Pediatrics Society made a proposal in 2014, and in 2015, the Journal of the Japan Medical Association and the 29^th Annual Meeting of the Japanese Association of Medical Science discussed transitional medicine, and from around this time, it gradually came to be recognized. Support for self-reliance, standardization of management of chronic childhood diseases in adulthood, and team care are essential for smooth progress of transitional care. In the United States, an organization called "Got Transition" takes the lead in supporting transitional care. In our country, following this, the development of guides focusing on support for self-reliance, etc. and medical care guides for adulthood by disease, was started. Public support for transitional care is being provided based on the Child Welfare Law and is being developed little by little.

Allergic diseases often begin in childhood and develop into adults over a chronic course. Children who become adults with chronic diseases need to understand their illness and to be able to lead their independent lives. However, children who develop symptoms in early childhood and are taking medication and care continuously may grow up with an unclear understanding of the disease, medication and care. They may face problems such as interruption of treatment or inadequate care. We discuss self-reliance support for children and families with allergic diseases in the context of patient education toward the transition to adult medical care, with the view of growth and development.

The transition of pediatric allergic disease to internal medicine has not been satisfactorily achieved. Patients receiving treatment at a general hospital do not think that they should move to internal medicine at the same facility, and usually want to refer to the internal medicine of a nearby medical institution where they have relocated after entering college or finding employment. In addition, they want a clinic that is available on Saturdays, rather than a general hospital, so that they do not take a break from college or work after moving to another medical institution. Regarding bronchial asthma, a relatively large number of allergists are engaged in the treatment of pediatric asthma and adult asthma. Similarly, patients with atopic dermatitis transition smoothly from pediatric to dermatology. In addition, patients with allergic rhinitis (perennial and seasonal) have had no problems since they have been consulting otolaryngology since childhood. After all, the problem is food allergies. It is not because the causal food changes during the transition period, but because of the shortage of internal medicine doctors involved in treating food allergies. Among internal medicine doctors having a certification of allergy specialist, doctors who work mainly for allergic diseases are under 10%. It is hoped that policies based on laws relating to measures against allergic diseases will be realized.

When a patient with an allergic disease that developed in childhood goes to adulthood, it is necessary to shift the practice from pediatrics to adult care appropriate for the individual patient. In other words, transition support is an important issue. To that end, it is necessary to practice "transitional medicine" in a planned and individual manner. Specifically, support for patient's independence and education for understanding of their disease will be the center. A medical roadmap and checkpoints will be useful tools as a method and evaluation for support and education. During the actual transition period, re-evaluation of medical conditions, re-education of patients and parents, and review of treatment policy should be performed. Also, it is necessary to carefully explain the division of roles of adult medical departments. This article also introduced a part of the guide for transition support of bronchial asthma.

Health insurance treatment is medical treatment to which a public medical insurance system such as health insurance is applied. The Japanese medical insurance system was enacted in 1961 with the universal health insurance system. It is based on Article 25 of the Universal Declaration of Human Rights of 1948, "Everyone has the right to a sufficient standard of living for health and well-being and the right to security through medical care and necessary social facilities." However, not all countries have insurance systems in place, and the funding systems for that purpose are diverse, and the reality is that there are various problems. And in such a situation, various distortions have occurred not only in the side receiving medical treatment but also in the side performing medical treatment, and in reality the behavior for our healthy medical treatment activities has been absurdly restricted. It is true that we are facing.

It is essential to obtain enough medical fees to introduce and provide high-quality medical care and spread it to the local community. According to a web survey for the re-evaluation of the asthma treatment instruction management fee (ATIMF) No.2, 239 (35%) of the respondents reported an inhaled corticosteroid (ICS) introduction rate of 20%-39%, whereas more than 20% reported it to be 40%-59%. For the question on ATIMF No.2 claims, the most common answer was "not at all" and after combining it with the category "infrequently", the response rate reached 55%. Further, 14% of the respondents chose "did not know ATIMF No.2," with the reasons for not making a claim being "forgotten" in 37% of the respondents, "no subject to be managed" in 25%, and "insurance score set low" in 20%. The frequency of perceived insufficiency in inhalation technique instruction during the evaluation of children younger than 6 years, who have already been introduced to ICS inhalation, was rated as "common" in 261 respondents (44%) and "present" 317 (53%). Therefore, we propose to add 140 points per teaching session, increase frequency to twice a year for continuous instruction, and add 280 points at the first time. It is important to implement revision measures in cooperation with other academic societies and engage in multiprofessional collaborations to ensure an efficient healthcare system.

Medical care should be provided to the public fairly based on patient needs, not market principles. In the area of pediatric allergy, we have been focusing on patient-centered medical care. However, there was no basic data showing this fact, and no medical fees were appropriate for this work. Last year, the Social Insurance Committee of the Japanese Society of Pediatric Allergy and Clinical Immunology conducted an Internet survey of the society members, revealing the fact that many members spend a lot of time on managing atopic dermatitis and food allergy patients. With the growing evidence of an allergy march prevention strategy, the Commission has recently filed a new application for a "Management fee for pediatric allergic patients". If approved, this fee will contribute to the education of allergic patients in many healthcare institutions.

Towards the insurance-provided medical service revision scheduled in 2020, the social insurance committee has conducted a web survey concerning the items scheduled for application.

According to the survey, 40% of the society members thought that oral food challenge (OFC) needed to be done over 3 times per patient per year.

Furthermore, the number of food allergic patients receiving outpatient treatment was 105 thousand at maximum, and the number of conducted OFC was 90 thousand at maximum.

When further limiting the age of the patients to 9 and above to under 16, the number of treatments were 21 thousand at maximum, and the number of OFC 10 thousand at maximum.

Using this data, it became apparent that when alleviating the limitations of OFC from 2 to 3 times it would result in an estimated 600 million yen of additional expense at maximum.

When alleviating the age limitation to under 16, the estimated additional expense would be 150 million yen at maximum.

Hence for a successful application, it is expected that its application results in speculation of medical fee increase or decrease done under evidence, and if possible, a medical fee cutback effect.

Our understanding of the pathology of atopic dermatitis (AD) is progressing gradually, in relation to both barrier function and the immune system. In recent years, significant progress has been made in methods to both prevent and manage AD. Especially in adults, more targeted therapies are emerging, including biological agents. The analysis of patient-specific endotypes is also progressing, and these findings provide new insights that will guide further development of novel molecular-targeted drugs. With the increasing complexity of emerging treatment strategies, the era has come for pediatricians to better understand the pathology of AD.

One of the most widely studied topics in recent years is the relationship of the microbiome to disease onset and modification. In addition to the gut microbiome, knowledge related to the skin microbiome in children has been increasing. With regard to the prevention of AD onset, the 2014 reports on disease prevention by application of emollients from Japan and the UK caused a paradigm shift around the world. Even now, this safe and medically economical intervention remains an area of great interest, and large-scale clinical researchs are ongoing globally.

The early introduction of food allergens to the diet of infants for the prevention of food allergies and the usefulness of immunotherapy for food allergies have been reported, and research on food allergy has attracted considerable attention.

Although investigation into the true prevalence of food allergies is difficult, epidemiological data from large population cohorts and cross-sectional studies have been reported. Specific IgE testing for novel allergen components has been useful for the diagnosis of food allergies. Moreover, the stepwise oral food challenge (OFC) and the baked milk OFC have been considered for the safe introduction of causative foods. Systematic reviews have confirmed that oral immunotherapy has a higher risk of anaphylaxis than food elimination. Novel studies improving safety and immunotherapy with different routes of administration have proceeded. With regard to the prevention of food allergies, reports regarding the timing of milk introduction and microbiome have also increased.

This article provides the latest topics that are useful for daily medical care in five categories: epidemiology, diagnosis, oral food challenge, treatment, and prevention of food allergy.

There were more than 700 pediatric bronchial asthma papers reported between 2018 and May 2019, searched on PubMed. The area with the largest number of articles was the etiology-pathophysiology area, followed by treatment, investigation, diagnosis, and long-term course. In the etiology and pathophysiology area, the papers that showed how home microbiota and skin barrier dysfunction were involved in the pathogenesis of bronchial asthma were impressive. The most frequently published journal related to pediatric bronchial asthma was Pediatr Allergy Immunol, followed by Ann Allergy Ashma Immunol, J Asthma. Among the searched pediatric bronchial asthma-related articles, 4% were written by Japanese.

Asthma is an allergic disease and should be treated with environmental control as well as with medication. Environmental factors related to the onset and exacerbation of asthma include antigens such as house dust mites, pet dander, and mold. Environmental control has been reported to reduce emergency hospital attendance with acute exacerbations and to reduce dust mite allergen level, a major antigen of asthma. Environmental control is also effective for patients who had no sensitization to dust mites. A systematic review of environmental control concluded that a combination of measures for environmental control improved asthma outcomes. Some studies support the therapeutic effect of environmental control on pet dander and mold antigens. In terms of prevention of asthma, some data indicated the possibility that environmental control could prevent asthma onset, although we could not find any interventional study which directly evaluated asthma onset.

Bronchial asthma is one of the most common allergic diseases. To improve bronchial asthma, an "environmental adjustment" is commonly recommended, to reduce the amount of inhaled allergens. However, there is insufficient evidence to support such a recommendation.

The following two points are central to the question of whether adjusting the environment can improve bronchial asthma:

(1) It is necessary to examine 'Whether the environment is contaminated with the allergen that causes asthma'.

A meta-analysis has shown that there are a number of cases where environmental recommendations were not effective for all sensitized families. However, there is no convenient method to examine the allergen concentration to which a person is exposed from day to day.

(2) Allergen levels should be reduced to a level that does not aggravate disease.

Adjusting a subject's environment has proven to be complex, usually requiring a multifactorial approach. However, performing and maintaining multiple methods simultaneously is challenging.We believe that these points require further investigation in order to improve environmental adjustments.

Many immunological studies have revealed a critical role of the gut microflora in the maintenance of systematic immunity. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host". Most corresponding microorganisms are of the Bifidobacterium and Lactobacillus species. Probiotic bacteria may have a direct ability to alter the human immune system, because not only live bacteria, but also dead bacteria, can effectively promote the acquisition of oral tolerance.

Recent studies have focused on the effects of short chain fatty acids produced by the gut microflora on the development of regulatory T cells and oral tolerance. The dominant microbiota is classified into Clostridium species, which might have different activity from classical probiotic bacteria.

Prebiotics is defined as "a substrate that is selectively utilized by host microorganisms conferring a health benefit". Typical materials include dietary fiber and non-digestible oligosaccharides. Some prebiotics increase the amount of short chain fatty acid in the gut, and are expected to be effective for preventing allergic diseases.

Accumulating evidences on the immunological mechanisms of probiotics and prebiotics suggest their potential effects for prevention of allergic diseases. Meta-analysis and systematic reviews of interventional studies revealed that probiotics reduced the risk of eczema but not other allergic conditions, whereas prebiotics decreased the risk of developing food allergies and wheeze/asthma. The certainty in the evidences is very low due to the risk of publishing bias, inconsistency and imprecision of the results. Therefore, major guidelines don't actively recommend probiotics and prebiotics for prevention of allergic diseases. Because of the diminution of regulatory T cell inducing ability of probiotics and prebiotics after their discontinuation and the refractoriness of some high-risk infants, probiotics and prebiotics are not recommended without the establishment of measures to identify suitable subjects and the intervention procedures.

Aim: The present study aimed to elucidate the long-term efficacy of oral immunotherapy (OIT) for different food allergies in children.

Methods: A questionnaire-based survey was conducted among individuals with hen's egg, cow's milk, or wheat allergies who initiated OIT and achieved the maintenance OIT dose at Miyagi Children's Hospital between January 2010 and January 2016.

Results: A total of 77 participants (52%) responded to the survey; of these, 32 were allergic to hen's egg, 28 to cow's milk, and 17 to wheat. The survey was conducted over a median period of 6.4 years after the participants achieved the maintenance OIT dose. Moreover, the continuation rate of the maintenance OIT dose was 90%, without differences in terms of the offending food. Overall, 34 participants (44%) experienced allergic symptoms after the third year of the maintenance phase, without differences in terms of the offending food. The rate of severe symptoms was 5%, without differences in terms of the offending food, which necessitated the use of an adrenaline auto-injector, as recommended by the Japanese Society of Pediatric Allergy and Clinical Immunology.

Conclusion: Out findings indicate the long-term efficacy of OIT. In this study, approximately 50% of the participants experienced allergic symptoms and 5% experienced severe symptoms after the third year of the maintenance phase; thus, individuals receiving OIT should be carefully followed up.