Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Low-dose oral food challenges.

BACKGROUND: Infants aged <1 year with confirmed food allergies generally need to avoid causative foods completely for a certain period. Low-dose oral food challenges (LD-OFCs) may be an effective strategy for safely introducing small amounts of causative foods to individuals with food allergies. This study clarified the safety of LD-OFCs in infants aged <1 year with food allergies. METHODS: We retrospectively analyzed the clinical records of LD-OFCs performed in infants aged <1 year allergic to hen's egg, cow's milk, or wheat between April 2014 and October 2017. Approximately 1/25th-1/20th of the egg white from a heated whole hen's egg, 3 mL heated cow's milk, and 2 g wheat noodles (udon) were used as challenge foods. We examined the LD-OFC results, including the induced symptoms and treatment required for positive LD-OFC results. RESULTS: The LD-Egg, LD-Milk, and LD-Wheat OFC groups comprised 68, 42, and 13 participants, respectively. The positivity rates for the LD-Egg, LD-Milk, and LD-Wheat OFC groups were 7%, 24%, and 0%, respectively. Patients predominantly exhibited skin symptoms, and most were treated with oral antihistamines alone. None of the patients experienced anaphylaxis or required adrenaline injections. CONCLUSIONS: Infants aged <1 year with food allergies can safely undergo LD-OFCs by consuming low doses of causative foods. Avoiding the complete elimination of causative foods is an important strategy for managing infants with food allergies when initially introducing causative foods.

Accidental allergic reactions to immediate-type food allergens in Japanese children: A single-center study.

BACKGROUND: Few studies have assessed the nature of accidental allergic reactions (AAR). We assessed the prevalence and risk factors for AAR in Japanese children. METHODS: This study included children with immediate-type hen's egg (HE), cow's milk (CM), wheat, or peanut allergy who developed allergic reactions within at least 2 years and were followed up regularly at a single national allergy center in Japan. From January to December 2020, low-dose reactivity was defined as allergic reactions to ≤250, ≤102, ≤53, or ≤ 133 mg of HE, CM, wheat, or peanut protein, respectively. The annualized AAR rate showed the number of reactions per patient per year (95% confidence interval). AAR risk factors were analyzed using multiple logistic regression. RESULTS: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. The median (interquartile range) age was 5.0 (2.3-8.6) years, 39% had completely eliminated allergenic food, and 24% had low-dose reactivity. The annualized AAR rate was 0.130 (0.109-0.153) in all sub-cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low-dose reactivity was a significant risk factor for AAR in the overall and CM cohorts, respectively (p < .001 and p = .036). CONCLUSION: In this single-center study in Japan, the annualized AAR rate was relatively low during the COVID-19 pandemic; however, half of the participants with AAR had moderate to severe symptoms. Especially in the case of low-dose reactivity, children would require careful AAR risk management.

Efficacy and safety of sublingual immunotherapy using house dust mite tablet for 1-4 years old children with perennial allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) for perennial allergic rhinitis (AR) has not been extensively studied in preschoolers. We investigated the efficacy and safety of house dust mite (HDM) SLIT-tablet for children aged 1-4 years. METHODS: Children aged 1-4 years with AR were divided into SLIT (n = 22) and control (n = 12) groups based on their guardians' preferences. The SLIT group received a daily dose of 10,000 JAU of HDM SLIT-tablet for 12 months, whereas the control group received symptomatic treatment only. RESULTS: The baseline median age was 41 and 34 months in the SLIT and control groups, respectively, and the median AR symptom score was 4 for both groups. Compared with baseline, the AR symptom score had decreased significantly in the SLIT group after 12 months (score: 3, p = .002), whereas it tended to increase in the control group (score: 6, p = .08). Adverse reactions to SLIT were mild and occurred in eight patients (36%). In the SLIT group, Dermatophagoides (D.) farinae-specific IgE (sIgE) levels increased during the first 6 months and decreased to baseline levels at 12 months. In the control group, D. farinae-sIgE levels had increased significantly at 12 months compared to baseline (p = .01). D. farinae-specific IgG4 and HDM IgE-blocking factor levels were significantly increased at 12 months compared to baseline in the SLIT group only (p < .001). A lower wheezing frequency was seen in the SLIT group (0.3%) compared to the control group (0.7%). CONCLUSION: This pilot study demonstrated the efficacy, safety, and immunomodulatory effects of HDM SLIT-tablet in preschoolers with AR.

Food allergy in a changing dietary landscape: A focus on the Asia Pacific region.

Recent studies have provided compelling evidence to suggest that various environmental factors play a significant role in the development of food allergies. As our society experiences rapid economic growth, increased urbanization, and a shift towards a more Westernized diet, the incidence of food allergies is also on the rise and the pattern is gradually evolving. This review will delve into the changes in the epidemiology of food allergies within the Asia-Pacific region and the various dietary practices and factors that are postulated to play a role in the rise in food allergies over the years. Although there have been important advancements in the field of food allergies, there are still numerous uncertainties regarding the intricate relationship between diet and food allergies. Specifically, the role of epigenetic factors in influencing the susceptibility to food allergies, as evidenced by studies that assessed the impact of migration and rural-urban dynamics, is not fully understood. Addressing this knowledge gap presents an opportunity to develop more effective prevention and treatment strategies that could greatly benefit individuals living with food allergies.

Recombinant Gad c 1 improves diagnostic efficacy of cod allergy but not horse mackerel allergy.

BACKGROUND: Parvalbumin Gad c1 is a major cod allergen used as a follow-up marker of fish-allergic children. However, the diagnostic efficacy of recombinant Gad c 1 (rGad c 1) for fish allergy diagnosis remains controversial. This study aimed to evaluate the efficacy of rGad c1 for diagnosing cod and horse mackerel allergy. METHODS: This single-centered, retrospective study obtained oral food challenges (OFCs) information performed for cod and horse mackerel. Cod-, horse mackerel-, and rGad c1-specific immunoglobulins (sIgEs) were investigated. Diagnostic performances of these parameters were compared using areas under the curve (AUC). RESULTS: We enrolled 45 and 38 children with suspected cod and horse mackerel allergies, respectively. The median age (interquartile range) of children with suspected cod allergy was 5.7 (0.7-11.7) years and that of children with suspected horse mackerel allergy was 6.0 (1.0-12.3) years. Fourteen and 22 children reacted to OFCs with 25 (10-40) g of cooked pacific cod and 40 (10-40) g of cooked horse mackerel, respectively. The cod sIgE and rGad c 1 sIgE AUCs for cod allergy diagnosis were 0.85 and 0.90, respectively. For horse mackerel allergy diagnosis, AUCs of horse mackerel and rGad c 1 sIgE were 0.76 and 0.72, respectively. Both AUCs for cod and mackerel allergy were significantly different. CONCLUSION: rGad c 1 sIgE is more effective than cod sIgE as a diagnostic marker of cod allergy, but less effective than horse mackerel sIgE as a diagnostic marker of horse mackerel allergy. Further studies are warranted to explore the potential applications of rGad c 1 sIgE in the diagnosis of various fish allergies.

Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy.

BACKGROUND: Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. OBJECTIVES: This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. METHODS: This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. RESULTS: This study enrolled 650 infants and analyzed 640 infants (enhanced [n = 318] or conventional [n = 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P = .0028; risk difference: -10.5%, upper bound of a 1-sided CI: -3.0%), while it lowered body weight (mean difference: -422 g, 95% CI: -553 to -292 g) and height (mean difference: -0.8 cm, 95% CI: -1.22 to -0.33 cm) at 28 weeks of age. CONCLUSIONS: This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs.

Current perspective on allergen immunotherapy for food allergies.

Food allergies are an increasing global problem and societal issue. In addition to the potential for severe allergic reactions from accidental ingestion, food allergies impose a significant burden on the quality of life, nutrition, cost of living, and social activities of both those afflicted and their caregivers. Strict avoidance of allergens and use of emergency medications to treat allergic reactions are the traditional management and treatment strategies; however, significant progress has been made in recent years toward better treatment of food allergies. Many clinical trials on food allergen immunotherapy (oral, epicutaneous, and sublingual) have revealed its efficacy in increasing reaction thresholds and desensitization. These positive results led to the first FDA approval of peanut oral immunotherapy (OIT). However, safer and more effective approaches are required, and adjunct treatments and allergen modifications are being considered. More than 100 facilities in Japan conduct OIT, and numerous studies on it have been reported. Unlike in Europe and the US, stepwise oral food challenges with dietary guidance are conducted separately from the OIT. This review describes the current perspectives on allergen immunotherapy for the treatment of food allergies, focusing on evidence from Japan.

Three-year prognosis after low-dose oral food challenge for children with wheat allergy.

BACKGROUND: Low-dose oral food challenge (LD-OFC) is an approach to avoid complete elimination in high-risk patients with wheat allergy (WA). We examined the 3-year prognosis after LD-OFC among patients who passed and failed LD-OFC. METHODS: Children with immediate-type WA aged ≤6 years with a history of reaction to ≤390 mg of wheat protein underwent their first LD-OFC with 52 mg (baseline LD-OFC). After passing the LD-OFC, children stepped up to 390, 1300, and 5200 mg step-by-step every 3-6 months. After failing LD-OFC, children repeated LD-OFC every 6-12 months. We assessed wheat tolerance defined as consuming 5200 mg without symptoms for 3 years after baseline LD-OFC. RESULTS: The median age of 124 children was 2.4 years, and the wheat- and ω-5-gliadin-specific immunoglobulin E (IgE) levels (kUA/L) were 23.6 and 2.1, respectively. Upon baseline LD-OFC, 57% passed (LD-tolerant), whereas 43% failed (LD-reactive). Within 3 years, 38% of the LD-reactive group passed re-administered LD-OFC, and 70% of all participants avoided complete elimination. The percentage of the participants who became capable of consuming 390 mg (87% vs. 18%), 1300 mg (78% vs. 13%), and acquired tolerance (70% vs. 13%) was significantly higher in the LD-tolerant group than in the LD-reactive group (p < 0.001). Predictors of persistent WA in the LD-tolerant group were older age (adjusted odds ratio, 1.63), ω-5-gliadin-specific IgE level (1.62 per 10-fold increase), and other food allergies (1.94). CONCLUSIONS: LD-tolerant patients frequently acquired wheat tolerance within 3 years. Even if once positive, one-third could pass the re-administered LD-OFC within 3 years.

[RECURRENT AND VIRTUAL EDUCATION FOR ALL DISCIPLINES AND OCCUPATIONS IN THE ALLERGY REALM : A SURVEY OF THE PARTICIPANTS FROM THE INITIATIVE 'OUTREACH LECTURES' TO CREATE EDUCATIONAL OPPORTUNITIES].

BACKGROUND: In the enhancement of allergy care involving multidisciplinary and multiple medical departments, there is a perceived need for education that targets not only specialists but also non-specialists. However, research on the need for and methods of such education remains inadequate. OBJECTIVE: To design a remote allergy care education program for all medical practitioners and to validate its necessity and utility. METHODS: The Empowering Next Generation Allergist/immunologist toward Global Excellence Task Force (ENGAGE-TF), supported by the Japanese Society of Allergology, initiated a virtual educational program called 'Outreach Lectures' in collaboration with Keio University and Fukui University. This initiative was widely promoted through social media and various institutions, and a survey was conducted through its mailing list. RESULTS: 1139 responses were obtained. More than half were physicians from non-allergy specialties, representing a diverse range of healthcare professions. Over 70% expressed being 'very satisfied,' and over 60% found the difficulty level 'appropriate.' Free-form feedback revealed differences in learning focus based on profession and learning approach based on years of experience. CONCLUSION: The high participation rate (90%) of non-specialist physicians underscores the demand for addressing allergic conditions in primary care. The effectiveness of virtual / recurrent education, particularly for healthcare professionals with over 11 years of experience, was implied. Further follow-up investigation focusing on quantitative and objective assessment of educational effectiveness is indispensable.

[STATE-OF-THE-ART OF GLOBAL START-UP INVESTMENT FOR ALLERGY AND IMMUNOLOGY 2022].

BACKGROUND: In 2022, the "New Capitalism Grand Design and Implementation Plan" was adopted in Japan, emphasizing the promotion and environmental development of startups. Given this context, an investigation into the startup and investment landscape in the allergy sector, both domestically and internationally, becomes imperative. METHODS: We analyzed 156 allergy-related startups from Japan, the US, and Europe from 2010 to 2021. Data on corporate information and investment trends were extracted from databases and VC websites. RESULTS: The total investment reached approximately 7.2 billion USD, with a ratio of 20:6:1 for the US, Europe, and Japan, respectively. The US showed a decline post its peak from 2016-2018, while Europe and Japan experienced growth. Notably, the US primarily invested in biopharmaceuticals for atopic dermatitis and food allergies, Europe in asthma-related apps, and Japan in healthcare apps and cross-border startups. DISCUSSION AND CONCLUSION: While Japan's investment environment in the allergy sector remains in its nascent stages and has room for development, the US and Europe are evidently ahead. Considering the rise of startups and funding limitations in Japan, external funding from regions like the US becomes a potential avenue. These findings are anticipated to contribute to the strategic activation of startups in allergy research and development.

Natural history of cow's milk allergy in children aged 6-12 years.

BACKGROUND: Approximately 50%-90% of children with immediate-type cow's milk allergy (CMA) acquire tolerance by pre-school age. We aimed to investigate the acquisition rate of CMA tolerance in children aged 6-12 years. METHODS: We included children with CMA who persisted until the age of 6. Tolerance was defined as passing an oral food challenge with 200 mL of unheated cow's milk (CM) or consuming 200 mL of CM without symptoms, whereas persistent CMA was defined as fulfilling neither of these criteria by 12 years old. Children receiving oral immunotherapy (OIT) were excluded from the primary analysis. Risk factors associated with persistent CMA were assessed using Cox regression analysis. RESULTS: Of 80 included children, 30 (38%) had previous CM anaphylaxis, and 40 (50%) had eliminated CM completely from their diet. The median CM-specific immunoglobulin E (sIgE) level at 6 years old was 12.0 kUA /L. Tolerance was acquired by 25 (31%) and 46 (58%) children by the age of 9 and 12 years, respectively. At baseline, persistent CMA was associated with higher CM-sIgE levels (hazard ratio 2.29, 95% confidence interval 1.41-3.73, optimal cutoff level 12.7 kUA /L), previous CM anaphylaxis (2.07, 1.06-4.02), and complete CM elimination (3.12, 1.46-6.67). No children with CMA who had all three risk factors (n = 14) acquired tolerance. CONCLUSION: Except for OIT patients, more than half of children with CMA at 6 years old acquired tolerance by 12 years old. Children with CMA who have the risk factors are less likely to acquire tolerance.

Relationship between serum allergen-specific immunoglobulin E and threshold dose in an oral food challenge.

BACKGROUND: Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose. METHODS: We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis. RESULTS: We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n = 1096), milk (n = 671), wheat (n = 370), peanuts (n = 258), walnuts (n = 65), and cashews (n = 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC. CONCLUSIONS: Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels.

Analysis of drug-induced anaphylaxis cases using the Japanese Adverse Drug Event Report (JADER) database - secondary publication.

BACKGROUND: The epidemiology of drug-induced anaphylaxis using the Japanese nationwide database has been not reported, even though drugs are a common trigger of anaphylaxis. The aim of this study was to describe the epidemiological profile of cases of drug-induced anaphylaxis, including fatal cases, using the data from the Japanese Adverse Drug Event Report database (JADER). METHODS: We extracted data regarding drug-related adverse events, between April 2004 and February 2018, published in JADER by the Pharmaceuticals and Medical Devices Agency. We analyzed cases of anaphylaxis occurring between January 2005 and December 2017. The drug classification was based on the Japanese Standard Commodity Classification. RESULTS: There were 16,916 cases of anaphylaxis reported during the study period. Among them, 418 fatalities were registered. The incidence of drug-induced anaphylaxis and fatal cases was 1.03 cases/year per 100,000 population and 0.03 cases/year, respectively. The most frequent causes of anaphylaxis were diagnostic agents, including X-ray contrast media (20.3%), and biological preparations, such as human blood preparations (20.1%). In fatal cases, diagnostic agents (28.7%) and antibiotic preparations (23.9%) were the most commonly associated types of drugs. CONCLUSIONS: The frequency of drug-induced anaphylaxis and fatalities in Japan remained unchanged over the 13-year period analyzed in this study. Diagnostic agents and biological preparations were the most frequent causes of anaphylaxis; however, fatalities were most frequently caused by either diagnostic agents or antibiotic preparations.

Current situation of anaphylaxis in Japan: Data from the anaphylaxis registry of training and teaching facilities certified by the Japanese Society of Allergology - secondary publication.

BACKGROUND: Anaphylaxis is a potentially fatal severe systemic hypersensitivity reaction that causes symptoms in multiple organs such as the skin, respiratory tract, and gastrointestinal tract; however, no nationwide epidemiological survey on anaphylaxis has been conducted in Japan. This survey aimed to elucidate the triggers and treatment of anaphylaxis in Japan. METHODS: Between February 2015 and October 2017, we prospectively collected clinical data on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology. RESULTS: This study included 79 of the 451 affiliated facilities (18%), and a total of 767 patients were enrolled; 73% of them were aged <18 years and 7% had in-hospital triggers. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. Intramuscular injection of adrenaline was administered therapeutically to 38% of the patients, with 10% requiring multiple doses. Adrenaline auto-injectors were used in 12% of out-of-hospital patients. CONCLUSIONS: The present survey revealed the most common triggers and treatments for anaphylaxis in Japan. Self-management and adrenaline administration as first-line treatment may not be done sufficiently. Therefore, it is necessary to thoroughly educate and train patients and physicians about anaphylaxis.

Differential patterns of fish sensitization in Asian populations: Implication for precision diagnosis.

BACKGROUND: The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern in fish allergic subjects from two distinct populations in Asia. METHODS: One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients' sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80 °C were evaluated by SDS-PAGE and mass spectrometry. RESULTS: Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens. CONCLUSIONS: Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients' allergic manifestations.

[JAPANESE TRANSLATION AND LINGUISTIC VALIDATION OF THE RECAP OF ATOPIC ECZEMA (RECAP)].

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

Natural History of Allergy to Hen's Egg: A Prospective Study in Children Aged 6 to 12 Years.

INTRODUCTION: There are limited reports on the natural history of hen's egg (HE) allergy (HEA) in children <6 years. We aimed to investigate the natural history of HEA in children aged 6-12 years and the factors affecting its tolerance acquisition. METHODS: Using the database in our hospital, a total of 137 patients diagnosed with a definitive immediate-type reaction to HE when they turned 6 years were enrolled, and the natural course of HEA was prospectively examined until patients turned 12 years. Tolerance was defined as being able to pass an oral food challenge to consume a half or whole heated HE or consume heated HE freely without symptoms. Thirty patients (21.9%) who were enrolled for oral immunotherapy and 21 (15.3%) who discontinued follow-up were considered dropouts. Kaplan-Meier estimation was used to evaluate the rate of tolerance. RESULTS: Fifty-five of the 137 patients (40.1%) had a previous HE anaphylaxis history; 61 (44.5%) patients had acquired tolerance to HE by age 12 years; and 25 (18.2%) continued total or partial HE elimination. The estimated acquired tolerance rates by ages 7, 9, and 12 years were 14.6%, 40.8%, and 60.5%, respectively. A previous history of HE anaphylaxis before 6 years of age, reacting to small amounts of heated HE by 6 years of age, and higher ovomucoid-specific immunoglobulin E values at the same age were associated with persistent HEA. CONCLUSION: This study provides important insights into the natural course of HEA beyond early childhood, with the acquisition of HE tolerance continuing throughout the duration of the study.

Clinical cross-reactivity of wheat and barley in children with wheat allergy.

BACKGROUND: Several studies have reported in vitro cross-reactivity between wheat and barley. However, evidence regarding the clinical cross-reactivity of wheat and barley is limited. This study examined the clinical cross-reactivity of barley and wheat among children with immediate-type wheat allergies. METHODS: We examined the threshold dose of a wheat oral food challenge for wheat-allergic children. We examined the reactivity of barley, and the oral food challenges of barley tea and barley rice were implemented as needed. We measured the specific immunoglobulin E (sIgE) levels in wheat, ω-5 gliadin, and barley. RESULTS: We evaluated 53 children (39 [74%] boys) with a median age of 6.6 years. Among them, 39 (74%) patients had a history of anaphylaxis to wheat. The median wheat-, barley-, and ω-5 gliadin-sIgE levels were 57.3, 12.1, and 3.2 kUA /L, respectively. Twelve patients reacted to barley tea (1.8 mg), 14 reacted to barley rice (220-440 mg), and 27 were tolerant to barley tea and barley rice. Barley-allergic patients had significantly higher wheat- and ω-5 gliadin- and barley-sIgE levels and significantly lower threshold doses of wheat than barley-tolerant patients. Omega-5 gliadin-sIgE was the most useful predictor of barley allergy among wheat-allergic patients; the ω-5 gliadin-sIgE 95% positive predictive value for barley allergy was 4.6 kUA /L. CONCLUSIONS: Half of wheat-allergic children reacted to barley. A lower threshold dose of wheat is related to cross-reactive barley allergies. Omega-5 gliadin-sIgE predicts cross-reactive barley allergy in children allergic to wheat. Clinical cross-reactivity to barley should be considered in the management of wheat-allergic children.

Macadamia nut-specific IgE levels for predicting anaphylaxis.

BACKGROUND: Despite the high risk of anaphylaxis in patients with a macadamia nut allergy (MdA), little is known about the significance of macadamia nut-specific immunoglobulin E (Md-sIgE). Thus, this study aimed to investigate the utility of Md-sIgE for predicting anaphylaxis. METHODS: Children with suspected MdA who visited our hospital were included. MdA was defined as either failing the 3-g macadamia nut (Md) oral food challenge (OFC) or confirming obvious immediate symptoms following Md ingestion. Non-MdA was defined as passing the 3-g Md OFC. RESULTS: A total of 41 children (29 [71%] males) with a median age of 7.7 years were included. The median Md-sIgE level was 2.23 kUA /L. Among the 21 children diagnosed with MdA, eight and 13 children did (An group) and did not (non-An group) develop anaphylaxis. Twenty children were included in the non-MdA group. The Md-sIgE level was significantly higher in the An group relative to the others (7.97 vs. 1.92 kUA /L, p < .001). Furthermore, the Md-sIgE level was significantly higher in the An group than in the non-An group (7.97 vs. 1.92 kUA /L, p = .02). However, there was no significant difference in the Md-sIgE between the non-An and non-MdA groups (1.92 vs. 1.90 kUA /L, p > .99). The area under the curve for predicting anaphylaxis in Md-sIgE was 0.92 (95% CI: 0.83-1.00), and the optimal cut-off value was 3.76 kUA /L. CONCLUSION: Md-sIgE levels were useful in predicting anaphylaxis. Above the cut-off value, we emphasize paying careful attention to the risk of anaphylaxis.