Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

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.

Prevalence of food allergy increased 1.7 times in the past 10 years among Japanese patients below 6 years of age.

BACKGROUND: While food allergy (FA) has been increasingly recognized as a growing public health burden worldwide, epidemiological studies on FA in Japan are limited. METHODS: This was a noninterventional, observational study using the administrative claims data from 2010 to 2019 (10 years). Patients with physician-diagnosed FA in Japan (prevalent cohort) were divided into high-risk or low-risk cohorts using adrenaline prescription. The high-risk cohort was further divided into anaphylaxis or nonanaphylaxis cohort based on the occurrence of anaphylaxis or a serious allergic reaction (SAR) during 1 year after adrenaline prescription. The primary objective was to examine yearly prevalence of FA. The secondary objectives were to describe demographics/clinical characteristics and healthcare resource utilization (HCRU), to evaluate the number of occurrences of anaphylaxis/SAR in the high-risk cohort, and the impact of anaphylaxis/SAR on HCRU. RESULTS: The overall standardized prevalence rate was 0.325% (95% confidence interval [CI], 0.311-0.339) in 2010 and 0.797% (95% CI, 0.790-0.804) in 2019 and predominant in patients age <6 years (preschool; 3.377% [95% CI, 3.229-3.525] in 2010 and 5.726% [95% CI, 5.663-5.789] in 2019). Majority of FA patients (>80%) were children/adolescent throughout the 10 years. While high-risk cohort was a relatively minor population (8.5% in the prevalent cohort in 2019), the occurrence of anaphylaxis/SAR in the high-risk cohort was 227,690/100,000 patient-years. Multivariate analysis showed a significant increase in HCRU variables in the anaphylaxis versus nonanaphylaxis cohort (e.g., 2.08 [95% CI, 2.05-2.11] times more FA-related outpatient visits). CONCLUSIONS: Prevalence of FA increased in a statistically significant way from 2010 to 2019; 1.7-fold increase was observed in patients <6 years old. Patients in the high-risk cohort appear to have suffered from frequent anaphylaxis/SAR, highlighting an unmet medical need for FA patients at "high-risk," considering the unavailability of approved medications to prevent anaphylaxis/SAR.

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.

Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

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.

Efficacy and safety of dupilumab with concomitant topical corticosteroids in Japanese pediatric patients with moderate-to-severe atopic dermatitis: A randomized, double-blind, placebo-controlled phase 3 study.

BACKGROUND: We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies. METHODS: In this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35]). RESULTS: At Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was -39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: -33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified. CONCLUSIONS: Dupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies.

[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.

Precision allergy molecular diagnosis applications in food allergy.

PURPOSE OF REVIEW: Precision medicine has become important in the diagnosis and management of food allergies. This review summarizes the latest information regarding molecular allergology, an essential component of food allergy managements. RECENT FINDINGS: Component-resolved diagnostics (CRD) can be used to investigate sensitization to allergens based on symptoms and to reveal co-sensitization and/or cross-sensitization in patients with allergies. The following allergen components are known to be associated with symptoms: ovomucoid from eggs, omega-5 gliadin from wheat, and many storage proteins (Gly m 8 from soy, Ara h 2 from peanut, Cor a 14 from hazelnut, Ana o 3 from cashew nut, Jug r 1 from walnut, and Ses i 1 from sesame). Recent studies on allergens of macadamia nuts (Mac i 1 and Mac i 2), almonds (Pru du 6), fish (parvalbumin and collagen), and shrimp (Pem m 1 and Pem m 14) have provided additional information regarding CRD. In addition, Pru p 7 is a risk factor for systemic reactions to peaches and has recently been found to cross-react with cypress and Japanese cedar pollen. SUMMARY: CRD provides information of individualized sensitization profiles related to symptoms and severity of allergies in patients. Clinical practice based on CRD offers many benefits, such as higher diagnostic accuracy and improved management of individual patients.

Management of food allergy based on oral food challenge.

PURPOSE OF REVIEW: Food allergy is a growing health problem that affects both patients and society in multiple ways. Despite the emergence of novel diagnostic tools, such as component-resolved diagnostics (CRD) and basophil activation tests (BAT), oral food challenge (OFC) still plays an indispensable role in the management of food allergies. This review aimed to highlight the indications and safety concerns of conducting an OFC and to provide insights into post-OFC management based on recent findings. RECENT FINDINGS: Standardized OFC protocols have regional diversification, especially in Japan and Western countries. Recent studies suggested that the interval between doses should be at least more than an hour. Furthermore, applying a stepwise method tailored to the patient's specific immunoglobulin E level and history of anaphylaxis seems to mitigate these risks. Recent surveys have shown that, following a positive OFC, options other than strict avoidance are also selected. SUMMARY: OFC serves diverse purposes, yet the risks it carries warrant caution. The stepwise protocol appears promising for its safety. Subthreshold consumption following OFC shows potential; however, further research on its efficacy and safety is required. Management following OFC should be tailored and well discussed between clinicians and patients.

Fenugreek allergy caused by cross-reactivity with peanut: An in vitro analysis.

Fenugreek is often hidden in processed foods, where it is included in the generic term spice on food labels. Cross-reactivity of peanut and fenugreek should be considered in the management of peanut allergy.

Reaching Communities Through Food Allergy Advocacy, Research, and Education: A Comprehensive Analysis.

This article explores the multifaceted approach of food allergy (FA) advocacy, research, and education to address the diverse challenges associated with FA, such as disparities in socioeconomic status, food security, quality of life, and the overall burden of the disease. Advocacy initiatives are instrumental in driving policy changes, raising public awareness, and directing substantial research funding, with a focus on reducing disparities. They have influenced allergen labeling regulations and improved access to epinephrine, emphasizing the importance of school-based management plans, especially in underserved communities. Research in FA informs medical practices and offers them hope for improved treatments. Recent breakthroughs in peanut allergy prevention and oral immunotherapy trials exemplify the potential for advancements while highlighting the need to address disparities in health care access. Education is a critical tool for prevention, raising awareness, and reducing the risk of allergic reactions. Efforts should be tailored to reach marginalized communities, particularly in schools where education on FA management is essential. Collaborating directly with communities is imperative to ensure inclusivity and address disparities. Barriers such as mistrust, language and cultural differences, and lack of diversity among researchers must be overcome to encourage diverse participation in research studies. This article concludes by emphasizing the significance of a comprehensive approach to FA research that prioritizes equity and inclusivity. The call to action highlights the need for global initiatives to reshape the landscape of FA care and address disparities in health care access and outcomes.

Timing of initial symptom onset during milk and wheat challenges: A retrospective study.

BACKGROUND: Allergic reactions to milk appear sooner than those to hen's eggs, irrespective of the total dose of the oral food challenges (OFCs) and type of matrices. The reported median times for the first symptom occurrence are 20-30 min with milk and 50-60 min with eggs. However, allergic reactions due to wheat have not yet been fully investigated. METHODS: This study retrospectively collected data from OFC for milk and wheat conducted at Sagamihara National Hospital and Sendai Medical Center from 2009 to 2023. The time from the start of the OFC to the onset of symptoms was compared between children with cow's milk and wheat allergy. RESULTS: Twenty-five and 13 children reacted to single-dose OFCs with milk products equivalent to 25 mL of raw cow's milk or 15 g of udon noodles, respectively. The median ages of patients with positive challenges were 1.4 and 2.8 years for milk and wheat, respectively, and the median times for the first symptom occurrence were 20 min and 53 min, respectively (p = .006). CONCLUSION: This multicenter study was the first to examine the time of symptom appearance during single-medium-dose milk and wheat challenges. Allergic reactions to wheat appear later than those for milk during OFC. For multiadministration OFC for wheat, the dosing interval should be longer than 60 min. Our findings can help improve the safety of OFCs.

Updated grading system for systemic allergic reactions: Joint Statement of the World Allergy Organization Anaphylaxis Committee and Allergen Immunotherapy Committee.

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.