Frontiers in allergy最新文献

{"title":"From lockdown to recovery: changing patterns of viral infection severity in a pediatric cohort with asthma.","authors":"Cassidy Jones, Matthew Laws, Shahwar Yousuf, Andrew Delo, Susanna Hartzell, Emma Kinder, Ashton Ingold, Bobby L Boyanton, Dana Frederick, Rachel A Frenner, Erin Hathorn, Peter M Mourani, Joshua L Kennedy","doi":"10.3389/falgy.2025.1645968","DOIUrl":"https://doi.org/10.3389/falgy.2025.1645968","url":null,"abstract":"<p><strong>Background: </strong>Respiratory viruses such as rhinovirus and respiratory syncytial virus (RSV) are common triggers of asthma exacerbations in children. The COVID-19 pandemic introduced non-pharmaceutical interventions (NPIs) that altered viral circulation; however, their long-term effects on pediatric asthma outcomes remain unclear.</p><p><strong>Objective: </strong>To evaluate how the epidemiology and severity of respiratory viral infections in children with asthma changed before, during, and after COVID-19-related NPIs.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis of pediatric asthma patients (ages 4-18) with laboratory-confirmed respiratory viral infections from 2018 to 2024 at Arkansas Children's (AC) and AC Northwest (ACNW). Viral detection was performed using the BioFire® Respiratory Panel. Clinical severity was evaluated using a modified World Health Organization Ordinal Scale for Clinical Improvement (mWHO OSI). Patients were categorized by period (pre-NPI, NPI, post-NPI), viral type, rurality, and Childhood Opportunity Index (COI).</p><p><strong>Results: </strong>This study included 9,391 pediatric asthma patients with laboratory-confirmed viral infections. RV/EV was the most common virus during all periods. Viral incidence decreased during NPIs but rebounded post-NPI with unusual seasonality. mWHO OSI scores declined over time (pre-NPI: 2.98; NPI: 2.49; post-NPI: 2.28), with significant reductions in hospitalizations, PICU admissions, and oxygen use (<i>p</i> < 0.0001). Severe disease (mWHO OSI 6-8) was infrequent. Rural and low-COI patients exhibited higher severity, although disparities narrowed post-NPI.</p><p><strong>Conclusions: </strong>NPIs were associated with sustained reductions in asthma-related illness severity, even with increased viral detection post-pandemic. These findings highlight the long-term impact of public health measures on pediatric asthma outcomes and emphasize the need for ongoing surveillance of respiratory viruses and health disparities.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1645968"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of food extraction techniques and impact of nitrogen fertilization on the potential allergenicity of soybean related to birch pollen-food allergy syndrome.","authors":"Paulien Verscheure, Robin Daelemans, Lieve Coorevits, Laura Van Gerven, Raf Aerts, Rik Schrijvers","doi":"10.3389/falgy.2025.1650232","DOIUrl":"https://doi.org/10.3389/falgy.2025.1650232","url":null,"abstract":"<p><strong>Background: </strong>Birch pollen-food allergy syndrome is triggered by cross-reactive allergens in plant-based foods. Environmental factors such as nitrogen fertilization may influence food allergenicity, but this has not been studied before.</p><p><strong>Methods: </strong>We compared and optimized protein extraction protocols for birch-homologue foods, including apple, carrot, and soybean. Various extraction buffers and mixing methods were tested for consistency and protein yield. We applied this to a pilot study assessing potential changes in the allergenic potential of plant-based foods due to altered nitrogen availability. A greenhouse experiment was conducted in which soybean plants were subjected to different nitrogen fertilization treatments. Allergenicity was evaluated using <i>ex vivo</i> basophil activation testing in five individuals with birch pollen-food allergy syndrome.</p><p><strong>Results: </strong>No major differences were observed between the tested extraction protocols, and key allergens were detectable in all food sources. In the pilot experiment, fertilized soybeans showed visible changes in size, a smaller shape, a different protein profile, and lower basophil reactivity compared to unfertilized soybeans.</p><p><strong>Conclusion: </strong>Our findings support the feasibility of standardized extraction methods. Varying nitrogen fertilization in soybeans resulted in altered physical, proteomic, and allergenic characteristics in this pilot study. Our results highlight the need for further research on environmental influences on food allergy.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1650232"},"PeriodicalIF":3.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Real-life effectiveness of once-daily single-inhaler triple therapy (FF-UMEC-VI) after switching from dual therapy (ICS-LABA) in patients with symptomatic asthma: trelegy ellipta for real asthma control study.","authors":"Yoshitomo Kushima, Yasuo Shimizu, Ryo Arai, Kazuyuki Chibana, Yuka Shimizu, Masahiro Amagai, Akihiro Takemasa, Naoya Ikeda, Meitetsu Masawa, Atsushi Kushima, Hiroaki Okutomi, Yusuke Nakamura, Rinna Tei, Yuki Ando, Nana Yazawa, Yuto Goto, Yasuo Haruyama, Tatsuo Yukawa, Seiji Niho","doi":"10.3389/falgy.2025.1683768","DOIUrl":"https://doi.org/10.3389/falgy.2025.1683768","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/falgy.2025.1537501.].</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1683768"},"PeriodicalIF":3.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linear and conformational epitopes of vicilin-buried peptides as a model for improved nut allergy diagnostics.","authors":"Lauren T Swientoniewski, Ian M Rambo, Jacqueline B Nesbit, Hsiaopo Cheng, Stephen A Y Gipson, Stacie M Jones, Dieu T Doan, Stephen C Dreskin, S Shahzad Mustafa, Scott A Smith, Michael D Kulis, Adam R Rivers, Alexander C Y Foo, Geoffrey A Mueller, Soheila J Maleki","doi":"10.3389/falgy.2025.1648262","DOIUrl":"10.3389/falgy.2025.1648262","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals allergic to peanuts (PN) may show IgE cross-reactivity to tree nuts, especially walnuts (WN), which often complicates diagnosis. Vicilin-buried peptides (VBPs), short segments within the N-terminal vicilin leader sequence (LS), contribute to cross-reactivity due to their ubiquitous, highly conserved and stable <i>α</i>-hairpin structures. The binding patterns of cross-reactive IgE to linear and conformational epitopes of PN and WN LSs and constituent VBPs may serve as a model for understanding clinically symptomatic cross-reactivity.</p><p><strong>Methods: </strong>Serum samples (<i>n</i> = 30) from primarily oral food challenge-positive individuals with PN allergy (PNA, 33%), WN allergy (WNA, 47%), and PN and WN allergies (PWA, 20%) were collected. These sera and a monoclonal IgE antibody (6D12) were examined for IgE binding with microarrays of overlapping peptides from native Ara h 1 LS [AH1LS, Ara h 1.0101 (26-84)] and recombinant Jug r 2 LS [JR2LS, Jug r 2.0101 (1-173)] and via direct and competitive inhibition ELISA with intact LSs and constituent VBPs from PN (AH1.1) and WN (JR2.1, JR2.2, JR2.3). A mixed model analysis assessed the contribution of IgE binding patterns to VBPs in relation to PNA, WNA, or PWA status.</p><p><strong>Results: </strong>All three intact WN VBPs bound IgE at similar frequencies, with individual sera showing varying preferences for specific VBPs. AH1.1 was less recognized by WNA individuals but more frequently recognized by PNA and PWA subjects. WN VBPs were recognized by PNA sera samples at rates comparable to AH1.1. Our data indicates that each VBP can bind to one IgE molecule with high affinity. In a competitive inhibition ELISA, combining VBP competitors did not enhance inhibition compared to the dominant VBP, suggesting that both high- and low-affinity VBPs compete for the same monoclonal IgE in serum. This observation was mimicked by 6D12, a monoclonal IgE against JR2.1.</p><p><strong>Discussion: </strong>Cross-reactivity among VBPs most likely arises from monoclonal IgE binding to α-hairpin structures and their overlapping linear amino acid sequences. The combination of linear and conformational IgE binding patterns enabled us to differentiate between the WNA, PNA, and PWA groups in this study and may assist us in using AH1LS and JR2LS to distinguish PN and WN allergies in the future.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1648262"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of a digital rescue inhaler and at-home spirometer among inner-city children with asthma: a real-world experience.","authors":"Neema Izadi, Tanisha D Hill, Amanda Boe, Daisy Yu, Jonathan S Tam","doi":"10.3389/falgy.2025.1641312","DOIUrl":"10.3389/falgy.2025.1641312","url":null,"abstract":"<p><strong>Background: </strong>Across all age groups, asthma disproportionally affects inner-city underserved populations. Studies on the use of at-home spirometry and digital inhalers have limited real-world evaluation in pediatric asthma.</p><p><strong>Objectives: </strong>In this prospective exploratory study, we assessed how an integrated digital rescue inhaler and at-home spirometer would affect proper inhaler use, medication adherence, and asthma outcomes using a minimalistic real-world approach.</p><p><strong>Methods: </strong>In total, 21 pediatric patients with asthma (8-17 years of age) were asked to replace rescue medications with the ProAir Digihaler and perform at-home gamified spirometry daily. Lung function and questionnaires were obtained at baseline and at 3-4 months.</p><p><strong>Results: </strong>The participants were mostly male (81%), Latino/Hispanic (71%), and obese (88th ±16 percentile). Proper rescue inhaler step identification by survey did not change, but inhalation technique based on digital inhaler flow measurements improved for all participants. At-home spirometry was sporadic and reported controller adherence did not change. Younger children (age 8-11) were more severe at baseline [Composite Asthma Severity Index (CASI) of 4.8] compared to older children (CASI of 2.9). For younger children, overall asthma control test scores increased by 3.1, CASI decreased by 0.70, and the Pediatric Quality of Life Inventory scores increased by 14 and 11 for participants and parents, respectively.</p><p><strong>Conclusions: </strong>Proper rescue inhaler step identification by survey did not change, but actual inhalation technique based on digital inhaler flow measurements improved. At-home spirometry was sporadic and reported medication adherence did not change. Younger children used the spirometer more frequently and demonstrated improvements in asthma control, severity, and quality of life. These improvements were not observed in older children.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1641312"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful treatment of glucocorticoid-resistant acute severe urticaria with JAK1 inhibitor: case report.","authors":"Ying Wu, Long-Fei Wang, He-Nian Yang, Chen-Xing Kan, Xuan Guo, Guo-Dong Hao","doi":"10.3389/falgy.2025.1657164","DOIUrl":"10.3389/falgy.2025.1657164","url":null,"abstract":"<p><strong>Objective: </strong>This study analyzes a case with a JAK1 (Janus Kinase 1) inhibitor was successfully employed to treat a patient with glucocorticoid-resistant acute severe urticaria (ASU), with the aim of improving clinical understanding of this condition.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on the clinical data, diagnosis, treatment, and prognosis of a patient with acute severe urticaria, who was admitted to the Allergy Department of Tangshan Workers' Hospital on March 10, 2025.</p><p><strong>Results: </strong>The patient was a 50-year-old female who presented with widespread skin wheals and itching, along with a sensation of throat obstruction for two days. Upon admission, the patient had a body temperature of 38.5°C. Large, irregularly shaped wheals, up to 10 cm in diameter, were observed on the skin. These wheals were bright red with surrounding erythema and increased upon scratching. Laboratory tests indicated elevated levels of white blood cells (WBC), neutrophils percentage, neutrophils absolute value, total IgE, and interleukin-6 (IL-6). A diagnosis of acute severe urticaria was made. Prior to admission, the patient had been administered with betamethasone sodium phosphate, dexamethasone sodium phosphate, methylprednisolone succinate, diphenhydramine, and calcium gluconate at the emergency department without relief in wheals and itching. Upon admission, the patient was treated with glucocorticoids and JAK1 inhibitors, resulting in the complete regression of the rash and normalization of laboratory indicators.</p><p><strong>Conclusion: </strong>This case suggests that JAK1 inhibitors can achieve satisfactory results in treating glucocorticoid-resistant acute severe urticaria.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1657164"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of subcutaneous immunotherapy using a depigmented, polymerized extract of cat epithelium in allergic patients: a retrospective, real-world study.","authors":"María Aránzazu Jiménez-Blanco, María Rosario González-Mendiola, Cosmin Boteanu, Javier Dionicio Elera, Maria Luisa Sánchez-Millán, M Ruíz-García, Jose Julio Laguna","doi":"10.3389/falgy.2025.1642315","DOIUrl":"10.3389/falgy.2025.1642315","url":null,"abstract":"<p><strong>Background: </strong>Allergy to animal epithelium is on the rise with an estimated 26% of European adults presenting to clinics for suspected inhalant allergy are sensitized to cats, and allergen avoidance measures are often difficult to implement and often ineffective.</p><p><strong>Methods: </strong>Real-world, retrospective study to evaluate the effectiveness and safety of subcutaneous immunotherapy (SCIT) with depigmented, polymerized cat epithelium extract (Dpg-pol-cat) in adult patients with moderate to severe allergic rhinitis/rhinoconjunctivitis with or without controlled asthma due to cat epithelium sensitization. The primary endpoint was to evaluate the effectiveness of SCIT with Dpg-pol-cat under real-life conditions, as measured by improvement in health-related quality of life (HRQoL) using the validated ESPRINT-15 questionnaire 24 months after treatment initiation.</p><p><strong>Results: </strong>The study included 28 patients. The median age was 35 years and the median duration of treatment with Dpg-pol-cat was 21.8 months. All patients had a 1-day rush build-up schedule. Significant and sustained improvements in all domains of the ESPRINT-15 questionnaire were observed from month 6 to month 24 of treatment, as well as in reduction of rescue medication use and better asthma control. Specific IgG4 levels increased significantly after 24 months of SCIT, although no significant change was observed in mean anti-Fel d 1 IgG4 levels. Most adverse reactions were local and mild, with systemic reactions, all grade <2 according to the 2010 World Allergy Organization grading system, occurring mainly during the build-up phase.</p><p><strong>Conclusions: </strong>SCIT with Dpg-pol-cat proved to be effective with an excellent safety profile in this real-world study, making it a good treatment option for patients with rhinitis/rhinoconjunctivitis and asthma due to allergy to cat epithelium.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1642315"},"PeriodicalIF":3.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Particulate matter as a possible risk factor for eosinophilic esophagitis.","authors":"Natasha Albaneze, Cary C Cotton, Kristen M Rappazzo, Charles E Gaber, Kate Hoffman, Kevin O Turner, Robert M Genta, Elizabeth T Jensen, Evan S Dellon","doi":"10.3389/falgy.2025.1675928","DOIUrl":"10.3389/falgy.2025.1675928","url":null,"abstract":"<p><strong>Background: </strong>Air pollution, including particulate matter smaller than 10 (PM₁₀) and 2.5 (PM_2.5) µm, increases the risk for heart and lung diseases, including asthma, but has not been extensively studied as a possible etiology in eosinophilic esophagitis (EoE). We aimed to estimate the associations between exposure to PM_2.5 or PM₁₀ and EoE.</p><p><strong>Methods: </strong>In this case-control study, using a large national pathology database of esophageal biopsies, EoE cases were defined by having biopsies with ≥15 eosinophils per high-powered field in the absence of other histopathologic causes. Controls were all other patients with esophageal biopsies. Patient residential addresses were geocoded and exposure to PM_2.5 and PM₁₀ were estimated using National Emissions Inventory data at the county level for a 5-year period including the biopsy. We estimated the odds ratios (OR) for EoE as a function of PM_2.5 or PM₁₀ exposure in tons emitted per year air using mixed logistic regression models adjusted for individual- and census tract-level characteristics.</p><p><strong>Results: </strong>Among 12,062 EoE cases and 229,397 non-EoE controls, the unadjusted OR for PM_2.5 was 1.12 (0.99-1.25) and the adjusted OR was 1.10 (95% CI, 0.99-1.23). The unadjusted OR for PM₁₀ was 1.04 (1.00-1.07) and the adjusted odds ratio was 1.02 (95% CI, 0.99-1.06).</p><p><strong>Discussion: </strong>Exposure to higher levels of PM₂₅ and PM₁₀ was modestly associated with EoE case status but the association was attenuated by adjusting for potential confounders. The findings suggest any etiologic role for these particulates in EoE would be of small magnitude.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1675928"},"PeriodicalIF":3.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Gut microbiota-metabolome crosstalk in allergic diseases: mechanistic insights and translational opportunities.","authors":"HanBin Qin, Jiaxin Sui, Shuang Wang, Xiaojing Lv, Zile Zhang, Xinhua Lin, Xuexia Liu, Hua Zhang","doi":"10.3389/falgy.2025.1669427","DOIUrl":"https://doi.org/10.3389/falgy.2025.1669427","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/falgy.2025.1631479.].</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1669427"},"PeriodicalIF":3.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of a 4-step versus a 5-step egg ladder in children with IgE-mediated hen's egg protein allergy: protocol for an open-label randomized controlled trial.","authors":"Andrea Horvath, Anna Bujnowska, Agata Stróżyk, Maria Zemła, Anna Nowak-Węgrzyn, Katarzyna Grzela, Joanna Jerzyńska, Hania Szajewska","doi":"10.3389/falgy.2025.1658186","DOIUrl":"10.3389/falgy.2025.1658186","url":null,"abstract":"<p><strong>Background: </strong>Introducing baked egg into the diet of children with hen's egg allergy (HEA) has been shown to potentially accelerate the development of tolerance to non-heated egg. However, there is no standardized egg ladder (EL) protocol, and different scientific societies across countries recommend varying versions. This study aims to assess the efficacy and safety of the four-step EL (4-EL) compared with the five-step EL (5-EL) in children with IgE-mediated HEA.</p><p><strong>Methods: </strong>We will perform an open-label randomized trial with two-parallel arms in two departments if the same academic hospital. A total of 84 children with IgE-mediated HEA will be allocated in 1:1 ratio to introduce hen's egg allergy into their diet according to either 4-EL or 5-EL with 4-week break period between subsequent steps. Oral food challenge (OFC) with tested products at each subsequent step of the EL will be conducted in hospital settings. The primary outcome will be the percentage of children with tolerance to non-heated hen's egg proteins defined as non-allergic reaction to raw hen's egg (0.5-1 egg, depending on the age of the patient) during the last OFC; measured at the end of the 18-week observation period for the 4-EL and 24-week observation period for the 5-EL. Secondary outcomes will include the percentage of children with negative OFC to each EL step; the percentage of children with anaphylaxis (including the percentage of those who were treated with epinephrine); the percentage of children with exacerbation of atopic dermatitis; growth; compliance; and quality of life of the caregivers and parents anxiety about adverse events during their child's OFC.</p><p><strong>Discussion: </strong>This rigorously designed RCT will provide evidence on the efficacy and safety of the 4-EL in children with IgE-mediated HEA. The findings will inform guideline development groups and further confirmatory trials.</p><p><strong>Trial registration number: </strong>NCT07040111, date of registration: 27 June 2025.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1658186"},"PeriodicalIF":3.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}