Man Yui Chong,Weihong Shi,Maja Bulatović-Ćalasan,Rick Gert-Jan Pleijhuis,Ingrid Terreehorst,Philip H Li
{"title":"Improving Beta-Lactam Allergy Risk Stratification Through Digital Decision Support: A Randomized Crossover Study of BLAST-A.","authors":"Man Yui Chong,Weihong Shi,Maja Bulatović-Ćalasan,Rick Gert-Jan Pleijhuis,Ingrid Terreehorst,Philip H Li","doi":"10.1111/all.70147","DOIUrl":"https://doi.org/10.1111/all.70147","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"86 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mi Jeong Kim, Seung Hwa Lee, Su Jung Kim, Ha Eun Song, Hyoyeong Lee, Mi Jin Kang, Song-I Yang, Hyo-Bin Kim, So Yeon Lee, Jeong-Hyun Kim, Hosub Im, Hoon Je Seong, Yong Joo Park, Jeonghun Yeom, Ji-Hye Oh, Eom Ji Choi, Dong In Suh, Kyung Won Kim, Kangmo Ahn, Youn Ho Shin, Soo-Jong Hong, Hyun Ju Yoo
<p>Exposure to environmental factors has been linked to increased asthma risk. However, few studies have investigated the complex relationships among exposome, metabolites, and asthma. Existing research suggests that environmental exposures shape omics profiles associated with respiratory outcomes. A recent study of preschool children found that metabolomic clusters associated with asthma risk varied by neighborhood resources, suggesting that environmental triggers may induce both metabolic and disease severity [<span>1</span>]. The Human Early Life Exposome project linked prenatal and childhood exposures to serum metabolomic shifts potentially predisposing children to asthma [<span>2</span>]. Despite this progress, the interplay among exposome, metabolites, and disease pathogenesis remains insufficiently explored, particularly in childhood asthma. This study aimed to elucidate the integrated relationships among urinary exposome, plasma metabolites, and childhood asthma.</p><p>We analyzed 139 children aged 6–7 years from the general population-based ECHO-COCOA (Exposome and Child Health with Omics–Cohort for Childhood Origin of Asthma and allergic diseases) birth cohort study, 26 children with asthma and 113 children without asthma and atopic dermatitis (Table S1). Informed consent was obtained from all individual participants included in the study.</p><p>Mass spectrometry–based methods were used to quantify 74 urinary exposome components (Table S2) and plasma metabolites (Table S3). Global metabolomic profiling identified asthma-related metabolites, followed by targeted quantification of selected features, mainly glycerophospholipids, amino acids, and derivatives. These target metabolome data were analyzed in relation to urinary exposures and asthma-related outcomes.</p><p>Asthma-associated urinary exposures were initially identified (Figure 1). Then, metabolites related to these asthma-associated exposures were explored. Asthma-associated exposures included arsenic, phenylmercuric acetate, and mono-n-butyl phthalate, which were linked to increased acetylornithine. Phosphatidylcholine (PC) (12:0/12:0), phosphatidylethanolamine (PE) (16:0/16:0), taurine, and spermidine were significantly associated with diethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)) (Figure 2A). Notably, PE (16:0/16:0), taurine, and spermidine also correlated with asthma-related clinical markers. Taurine showed a negative correlation with PC<sub>20</sub> and a positive association with eosinophil count. PE (16:0/16:0) and spermidine positively correlated with eosinophils, while PE (16:0/16:0) also associated with total IgE levels. Mendelian randomization (MR) analysis revealed possible causal relationships between taurine and PC<sub>20</sub>; PE (16:0/16:0) and IgE; and taurine, spermidine, PE (16:0/16:0) and eosinophils (Table S4). These met
暴露于环境因素与哮喘风险增加有关。然而，很少有研究调查暴露物、代谢物和哮喘之间的复杂关系。现有的研究表明，环境暴露塑造了与呼吸结果相关的组学特征。最近一项针对学龄前儿童的研究发现，与哮喘风险相关的代谢组学簇因社区资源而异，这表明环境触发因素可能同时诱导代谢和疾病严重程度bbb。人类早期生活暴露项目将产前和童年暴露与血清代谢组学变化联系起来，这些变化可能使儿童易患哮喘。尽管取得了这一进展，但暴露体、代谢物和疾病发病机制之间的相互作用仍未得到充分探讨，特别是在儿童哮喘中。本研究旨在阐明尿暴露、血浆代谢物与儿童哮喘之间的综合关系。我们分析了139名6-7岁的儿童，他们来自基于一般人群的ECHO-COCOA（儿童哮喘和过敏性疾病的暴露和儿童健康组学队列）出生队列研究，26名患有哮喘的儿童和113名没有哮喘和特应性皮炎的儿童（表S1）。所有参与研究的个体都获得了知情同意。采用基于质谱的方法定量74种尿暴露成分（表S2）和血浆代谢物（表S3）。全球代谢组学分析确定了哮喘相关代谢物，随后对选定的特征进行了有针对性的定量分析，主要是甘油磷脂、氨基酸和衍生物。分析这些目标代谢组数据与尿路暴露和哮喘相关结果的关系。最初确定了与哮喘相关的尿暴露（图1）。然后，研究人员探索了与这些哮喘相关暴露相关的代谢物。与哮喘相关的暴露包括砷、醋酸苯汞和邻苯二甲酸单正丁酯，它们与乙酰鸟氨酸的增加有关。磷脂酰胆碱（PC）（12:0/12:0）、磷脂酰乙醇胺（PE）（16:0/16:0）、牛磺酸和亚精胺与邻苯二甲酸二乙酯（DEHP）代谢物（邻苯二甲酸二乙酯单（2-乙基-5-羟基己基）（MEHHP）、邻苯二甲酸二乙酯单（2-乙基-5-氧己基）（MEOHP）、邻苯二甲酸单（2-乙基-5-羧戊基）（MECPP））显著相关（图2A）。值得注意的是，PE（16:0/16:0）、牛磺酸和亚精胺也与哮喘相关的临床指标相关。牛磺酸与PC20呈负相关，与嗜酸性粒细胞计数呈正相关。PE（16:0/16:0）和亚精胺与嗜酸性粒细胞呈正相关，PE（16:0/16:0）也与总IgE水平相关。孟德尔随机化（MR）分析揭示了牛磺酸与PC20之间可能的因果关系；PE（16:0/16:0）和IgE；牛磺酸、亚精胺、PE（16:0/16:0）和嗜酸性粒细胞（表S4）。这些代谢物也与IL-1β有关，IL-1β是哮喘的一种中枢促炎细胞因子。这些发现表明，牛磺酸、亚精胺和PE（16:0/16:0）可能是DEHP暴露背景下哮喘的有希望的候选生物标志物。牛磺酸、亚精胺和pe是公认的自噬调节因子和抗氧化剂，可减轻哮喘中的氧化应激和炎症[3-5]。这些代谢物水平的升高可能反映了代偿反应或表明自噬的调节机制。此外，花生四烯酸代谢与哮喘炎症有关，与牛磺酸外排有关，这可能解释了哮喘患者体内牛磺酸水平升高的原因。在成人哮喘中也观察到亚精胺和PEs升高。然而，DEHP对这些代谢物影响的机制尚不清楚。尽管如此，这些代谢物可能作为dehp相关儿童哮喘的潜在生物标志物（图2B，C）。尽管DEHP的半衰期很短（~1天），但它在消费品中的广泛存在导致了体内慢性、低水平的伪持久性。虽然韩国儿童哮喘在普通人群中的低患病率可能会限制统计效力，但我们的结果通过MR分析和受试者工作特征（ROC）分析得到了加强。这些方法帮助我们最大限度地减少混杂因素的影响，并区分哮喘和非哮喘儿童的代谢物生物标志物。进一步的研究，特别是纵向和扩展队列和机制验证，需要验证我们的结果。多次尿液取样或24小时尿液收集可改善对长期暴露的评估。总的来说，我们的研究结果强调牛磺酸、亚精胺和PE（16:0/16:0）是邻苯二甲酸盐相关儿童哮喘的潜在生物标志物。方法：M. J. Kim， S. J. Kim， H. E. Song， H. Lee，资料：S. H. Lee， M. J. Kang， S. i。杨,H.-B。Kim， S. Y. Lee, j.h。Kim, lim H., seh . J., Park yj ., yej ., Choi E. J., sud . i, Kim K. W., Ahn K., yh .。 Shin和s.j.。洪，数据分析与数据解释：j - h。洪善善、刘海杰，撰稿、评论、编辑：金明杰、李善华、李善杰。洪和刘海杰。作者声明无利益冲突。支持本研究结果的数据可向通讯作者索取。由于隐私或道德限制，这些数据不会公开。
{"title":"Association Between Di-(2-Ethylhexyl) Phthalate and Childhood Asthma Through Plasma Metabolome Alterations","authors":"Mi Jeong Kim, Seung Hwa Lee, Su Jung Kim, Ha Eun Song, Hyoyeong Lee, Mi Jin Kang, Song-I Yang, Hyo-Bin Kim, So Yeon Lee, Jeong-Hyun Kim, Hosub Im, Hoon Je Seong, Yong Joo Park, Jeonghun Yeom, Ji-Hye Oh, Eom Ji Choi, Dong In Suh, Kyung Won Kim, Kangmo Ahn, Youn Ho Shin, Soo-Jong Hong, Hyun Ju Yoo","doi":"10.1111/all.70143","DOIUrl":"10.1111/all.70143","url":null,"abstract":"<p>Exposure to environmental factors has been linked to increased asthma risk. However, few studies have investigated the complex relationships among exposome, metabolites, and asthma. Existing research suggests that environmental exposures shape omics profiles associated with respiratory outcomes. A recent study of preschool children found that metabolomic clusters associated with asthma risk varied by neighborhood resources, suggesting that environmental triggers may induce both metabolic and disease severity [<span>1</span>]. The Human Early Life Exposome project linked prenatal and childhood exposures to serum metabolomic shifts potentially predisposing children to asthma [<span>2</span>]. Despite this progress, the interplay among exposome, metabolites, and disease pathogenesis remains insufficiently explored, particularly in childhood asthma. This study aimed to elucidate the integrated relationships among urinary exposome, plasma metabolites, and childhood asthma.</p><p>We analyzed 139 children aged 6–7 years from the general population-based ECHO-COCOA (Exposome and Child Health with Omics–Cohort for Childhood Origin of Asthma and allergic diseases) birth cohort study, 26 children with asthma and 113 children without asthma and atopic dermatitis (Table S1). Informed consent was obtained from all individual participants included in the study.</p><p>Mass spectrometry–based methods were used to quantify 74 urinary exposome components (Table S2) and plasma metabolites (Table S3). Global metabolomic profiling identified asthma-related metabolites, followed by targeted quantification of selected features, mainly glycerophospholipids, amino acids, and derivatives. These target metabolome data were analyzed in relation to urinary exposures and asthma-related outcomes.</p><p>Asthma-associated urinary exposures were initially identified (Figure 1). Then, metabolites related to these asthma-associated exposures were explored. Asthma-associated exposures included arsenic, phenylmercuric acetate, and mono-n-butyl phthalate, which were linked to increased acetylornithine. Phosphatidylcholine (PC) (12:0/12:0), phosphatidylethanolamine (PE) (16:0/16:0), taurine, and spermidine were significantly associated with diethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)) (Figure 2A). Notably, PE (16:0/16:0), taurine, and spermidine also correlated with asthma-related clinical markers. Taurine showed a negative correlation with PC<sub>20</sub> and a positive association with eosinophil count. PE (16:0/16:0) and spermidine positively correlated with eosinophils, while PE (16:0/16:0) also associated with total IgE levels. Mendelian randomization (MR) analysis revealed possible causal relationships between taurine and PC<sub>20</sub>; PE (16:0/16:0) and IgE; and taurine, spermidine, PE (16:0/16:0) and eosinophils (Table S4). These met","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 1","pages":"304-306"},"PeriodicalIF":12.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Khezia Asamoah, Freda Yang, Ian M. Adcock, Dragana Vuckovic, Mohib Uddin, Kian Fan Chung, Marc Chadeau-Hyam
<p>Neutrophilic asthma is a subphenotype of asthma that affects 20%–30% of all adult asthma patients and is typically harder to treat [<span>1</span>]. Usually driven by type 1 inflammation and external triggers, it is associated with a complex clinicopathobiology [<span>2, 3</span>]. AZD5069, a selective CXCR2 antagonist developed to block neutrophil trafficking without compromising immunity [<span>4, 5</span>], showed biological effects by lowering neutrophil counts in blood, sputum and bronchial biopsies in severe asthma [<span>6</span>]. However, it failed to improve clinical outcomes [<span>7</span>]. In this study, we reanalysed the data using a trajectory-based clustering approach to identify potential responder subgroups to AZD5069 among patients with presumed neutrophilic asthma.</p><p>The data were obtained from a multicentre, double-blind, placebo-controlled, dose-ranging Phase 2b trial involving 640 patients randomised to four arms: AZD5069 at 5, 15 or 45 mg, or matched placebo. The study was done in accordance with the principles of the Declaration of Helsinki, the International Conference on Harmonisation guidelines for good clinical practice, and applicable regulatory requirements. All patients provided written informed consent before any study-specific assessments were done. 422 participants had complete longitudinal measurements for key variables across required timepoints and their characteristics are reported in Table S1. A broad panel of 22 blood biomarkers was collected. To identify distinct patterns in patient response trajectories, a consensus clustering framework (using dynamic time warping) was used on timepoints from 1 to 6 months. Clustering was based on raw values for: pre-bronchodilator FEV<sub>1</sub> (L), Asthma Control Questionnaire (ACQ)-5 and blood neutrophil count (NEUT).</p><p>Three distinct trajectory clusters were identified based on changes in asthma-related outcomes and inflammatory markers (Figure 1). Cluster 3 was characterised by a higher proportion of female patients, a greater prevalence of high baseline BMI, a higher baseline severe exacerbation rate and a lower FEV1/FVC ratio, together with elevated blood neutrophil counts compared with the other clusters. Each cluster included participants from both placebo and treatment arms. The treatment arm across all three clusters saw a significant reduction in NEUT or neutrophil count as a percentage of leukocytes (NEUTLE) (Figure 1, Table S2). Cluster 2 (green) also showed a significant reduction in ACQ-5 (<i>p</i> = 0.019), with 42% showing a clinically important reduction of ≥ 0.5 in ACQ score (Table S3). In contrast, Cluster 3 (blue) remained relatively refractory regarding FEV<sub>1</sub> change. Trajectory groups differed significantly in several baseline characteristics (Table S4).</p><p>Figure 2 displays log-fold changes in biomarker levels across placebo and treatment arms for each trajectory cluster; however there was no significant difference betwe
{"title":"Trajectory-Based Clustering to Identify Asthma Subgroups Responsive to the Selective CXCR2 Antagonist, AZD5069","authors":"Khezia Asamoah, Freda Yang, Ian M. Adcock, Dragana Vuckovic, Mohib Uddin, Kian Fan Chung, Marc Chadeau-Hyam","doi":"10.1111/all.70140","DOIUrl":"10.1111/all.70140","url":null,"abstract":"<p>Neutrophilic asthma is a subphenotype of asthma that affects 20%–30% of all adult asthma patients and is typically harder to treat [<span>1</span>]. Usually driven by type 1 inflammation and external triggers, it is associated with a complex clinicopathobiology [<span>2, 3</span>]. AZD5069, a selective CXCR2 antagonist developed to block neutrophil trafficking without compromising immunity [<span>4, 5</span>], showed biological effects by lowering neutrophil counts in blood, sputum and bronchial biopsies in severe asthma [<span>6</span>]. However, it failed to improve clinical outcomes [<span>7</span>]. In this study, we reanalysed the data using a trajectory-based clustering approach to identify potential responder subgroups to AZD5069 among patients with presumed neutrophilic asthma.</p><p>The data were obtained from a multicentre, double-blind, placebo-controlled, dose-ranging Phase 2b trial involving 640 patients randomised to four arms: AZD5069 at 5, 15 or 45 mg, or matched placebo. The study was done in accordance with the principles of the Declaration of Helsinki, the International Conference on Harmonisation guidelines for good clinical practice, and applicable regulatory requirements. All patients provided written informed consent before any study-specific assessments were done. 422 participants had complete longitudinal measurements for key variables across required timepoints and their characteristics are reported in Table S1. A broad panel of 22 blood biomarkers was collected. To identify distinct patterns in patient response trajectories, a consensus clustering framework (using dynamic time warping) was used on timepoints from 1 to 6 months. Clustering was based on raw values for: pre-bronchodilator FEV<sub>1</sub> (L), Asthma Control Questionnaire (ACQ)-5 and blood neutrophil count (NEUT).</p><p>Three distinct trajectory clusters were identified based on changes in asthma-related outcomes and inflammatory markers (Figure 1). Cluster 3 was characterised by a higher proportion of female patients, a greater prevalence of high baseline BMI, a higher baseline severe exacerbation rate and a lower FEV1/FVC ratio, together with elevated blood neutrophil counts compared with the other clusters. Each cluster included participants from both placebo and treatment arms. The treatment arm across all three clusters saw a significant reduction in NEUT or neutrophil count as a percentage of leukocytes (NEUTLE) (Figure 1, Table S2). Cluster 2 (green) also showed a significant reduction in ACQ-5 (<i>p</i> = 0.019), with 42% showing a clinically important reduction of ≥ 0.5 in ACQ score (Table S3). In contrast, Cluster 3 (blue) remained relatively refractory regarding FEV<sub>1</sub> change. Trajectory groups differed significantly in several baseline characteristics (Table S4).</p><p>Figure 2 displays log-fold changes in biomarker levels across placebo and treatment arms for each trajectory cluster; however there was no significant difference betwe","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 1","pages":"297-299"},"PeriodicalIF":12.0,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stéphanie Wanin, Rola Abou Taam, Lisa Giovannini Chami, Christophe Marguet, Jocelyne Just, Christele Da Silva, Jérôme Msihid, Olivier Ledanois, Rebecca Gall, Harry J. Sacks, Juby A. Jacob-Nara, Capucine Daridon, Antoine Deschildre
<p>In France, the prevalence of asthma in children is 9%–10% [<span>1</span>], with 2%–10% of those having severe asthma [<span>2</span>]. Severe asthma in adolescents (age 12–18 years) is characterized by the precocity and accumulation of sensitizations and allergic comorbidities [<span>3</span>]. The French COBRAPed severe asthma cohort reported allergy in 85% of the patients, with high healthcare resource utilization and impaired quality of life [<span>4</span>]. Biologics have revolutionized the management of severe asthma [<span>2</span>], and accurate phenotyping of severe asthma, through assessment of allergic status and eosinophil counts, for example, enables more personalized treatment [<span>5</span>].</p><p>Dupilumab is a human monoclonal antibody that blocks the shared receptor component for interleukins 4/13, key and central drivers of type 2 inflammation in multiple diseases [<span>6</span>]. It is approved in the European Union for patients aged ≥ 12 years with severe asthma associated with type 2 inflammation and in children aged ≥ 6 years with asthma inadequately controlled with other treatments. However, the characteristics of children who benefit from dupilumab in the real world are not well understood. PEDIASTHMA (NCT05070663) is a 52-week, multicenter, observational, prospective, retrospective, real-world study conducted at 15 sites across metropolitan France. Adolescents (age 12–17 years) who were already treated with or started dupilumab treatment for severe uncontrolled asthma were eligible to enroll (severe asthma in children is defined as asthma that remains uncontrolled despite optimized treatment with high-dose inhaled corticosteroids [ICS]-long-acting beta-agonists [LABA] or requires high-dose ICS-LABA to prevent it from becoming uncontrolled) [<span>7</span>]. After a protocol amendment (October 27, 2022), children (age 6–11 years) were also included in the study. The primary objective of PEDIASTHMA is to describe the characteristics of enrolled children and adolescents, including demographic and disease characteristics, quality of life, medical and asthma history, and treatments for asthma at initiation of dupilumab (including previous treatment with other biologics). This pre-specified interim analysis of PEDIASTHMA describes the characteristics (as defined in the primary endpoint) of the first 50 adolescents (age 12–17 years) enrolled. All data are descriptive and presented as mean (standard deviation [SD]). Detailed information on study background, design, ethical considerations, inclusion and exclusion criteria, secondary endpoints, statistical analysis, and investigators can be found in Appendices I–III, Table S1, and Figure S1.</p><p>At enrollment, 66% (<i>n</i> = 33) of patients were male (Table 1). They were 3.9 (3.9) years old at the diagnosis of severe asthma based on the clinical expertise of the investigator and 14.7 (1.7) years at the first administration of dupilumab. They had 3.2 (2.9) severe exacerba
{"title":"Characteristics of Adolescents With Uncontrolled Severe Asthma Starting Dupilumab: The PEDIASTHMA Registry","authors":"Stéphanie Wanin, Rola Abou Taam, Lisa Giovannini Chami, Christophe Marguet, Jocelyne Just, Christele Da Silva, Jérôme Msihid, Olivier Ledanois, Rebecca Gall, Harry J. Sacks, Juby A. Jacob-Nara, Capucine Daridon, Antoine Deschildre","doi":"10.1111/all.70119","DOIUrl":"10.1111/all.70119","url":null,"abstract":"<p>In France, the prevalence of asthma in children is 9%–10% [<span>1</span>], with 2%–10% of those having severe asthma [<span>2</span>]. Severe asthma in adolescents (age 12–18 years) is characterized by the precocity and accumulation of sensitizations and allergic comorbidities [<span>3</span>]. The French COBRAPed severe asthma cohort reported allergy in 85% of the patients, with high healthcare resource utilization and impaired quality of life [<span>4</span>]. Biologics have revolutionized the management of severe asthma [<span>2</span>], and accurate phenotyping of severe asthma, through assessment of allergic status and eosinophil counts, for example, enables more personalized treatment [<span>5</span>].</p><p>Dupilumab is a human monoclonal antibody that blocks the shared receptor component for interleukins 4/13, key and central drivers of type 2 inflammation in multiple diseases [<span>6</span>]. It is approved in the European Union for patients aged ≥ 12 years with severe asthma associated with type 2 inflammation and in children aged ≥ 6 years with asthma inadequately controlled with other treatments. However, the characteristics of children who benefit from dupilumab in the real world are not well understood. PEDIASTHMA (NCT05070663) is a 52-week, multicenter, observational, prospective, retrospective, real-world study conducted at 15 sites across metropolitan France. Adolescents (age 12–17 years) who were already treated with or started dupilumab treatment for severe uncontrolled asthma were eligible to enroll (severe asthma in children is defined as asthma that remains uncontrolled despite optimized treatment with high-dose inhaled corticosteroids [ICS]-long-acting beta-agonists [LABA] or requires high-dose ICS-LABA to prevent it from becoming uncontrolled) [<span>7</span>]. After a protocol amendment (October 27, 2022), children (age 6–11 years) were also included in the study. The primary objective of PEDIASTHMA is to describe the characteristics of enrolled children and adolescents, including demographic and disease characteristics, quality of life, medical and asthma history, and treatments for asthma at initiation of dupilumab (including previous treatment with other biologics). This pre-specified interim analysis of PEDIASTHMA describes the characteristics (as defined in the primary endpoint) of the first 50 adolescents (age 12–17 years) enrolled. All data are descriptive and presented as mean (standard deviation [SD]). Detailed information on study background, design, ethical considerations, inclusion and exclusion criteria, secondary endpoints, statistical analysis, and investigators can be found in Appendices I–III, Table S1, and Figure S1.</p><p>At enrollment, 66% (<i>n</i> = 33) of patients were male (Table 1). They were 3.9 (3.9) years old at the diagnosis of severe asthma based on the clinical expertise of the investigator and 14.7 (1.7) years at the first administration of dupilumab. They had 3.2 (2.9) severe exacerba","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 1","pages":"292-296"},"PeriodicalIF":12.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marlena Tynecka, Agnieszka Tarasik, Bartosz Hanczaruk, Adrian Janucik, Krystian Czolpinski, Alicja Walewska, Arkadiusz Zbikowski, Anna Zeller, Agnieszka Kulczynska-Przybik, Magdalena Niemira, Joanna Reszec-Gielazyn, Barbara Mroczko, Adam Kretowski, Cezmi A. Akdis, Milena Sokolowska, Marcin Moniuszko, Cagatay Karaaslan, Andrzej Eljaszewicz
Asthma is a complex airway disorder driven by diverse immunological pathways. While type 2 (T2)-mediated inflammation is well characterized, the mechanisms underlying T2-low (also referred to as mixed inflammatory phenotype) or non-T2-mediated asthma, often associated with Th1/Th17-driven immune responses and high pulmonary neutrophilic inflammation, remain poorly understood. This study investigates airway remodeling in acute and chronic experimental asthma models induced by house dust mite extract to elucidate inflammatory and structural changes. Two acute T2-low models demonstrated pronounced airway inflammation characterized by goblet cell hyperplasia, collagen deposition, and significant upregulation of extracellular matrix remodeling and fibroblast activation. In contrast, the chronic Th17-mediated model exhibited reduced ECM deposition, increased matrix metalloproteinase (MMP) activity, and a distinct molecular signature dominated by IL-17A-driven pathways, indicative of ECM degradation and structural instability. Furthermore, the acute models showed immune cell apoptosis as the predominant cell death mechanism. In contrast, the chronic inflammation model was marked by necroptosis localized to structural lung cells, contributing to persistent inflammation and remodeling. Our findings provide new insights into the distinct immunopathological mechanisms underlying airway remodeling and fibrosis in T2-low and Th17-mediated asthma phenotypes. The study emphasizes the need for advanced preclinical models and targeted therapeutic strategies to address ECM dysregulation and chronic inflammation to progress in airway remodeling treatment in asthma.
{"title":"Dynamic Regulation of Collagens, Proteases, Their Inhibitors, and Cell Death in Experimental Asthma in Mice","authors":"Marlena Tynecka, Agnieszka Tarasik, Bartosz Hanczaruk, Adrian Janucik, Krystian Czolpinski, Alicja Walewska, Arkadiusz Zbikowski, Anna Zeller, Agnieszka Kulczynska-Przybik, Magdalena Niemira, Joanna Reszec-Gielazyn, Barbara Mroczko, Adam Kretowski, Cezmi A. Akdis, Milena Sokolowska, Marcin Moniuszko, Cagatay Karaaslan, Andrzej Eljaszewicz","doi":"10.1111/all.70126","DOIUrl":"10.1111/all.70126","url":null,"abstract":"<p>Asthma is a complex airway disorder driven by diverse immunological pathways. While type 2 (T2)-mediated inflammation is well characterized, the mechanisms underlying T2-low (also referred to as mixed inflammatory phenotype) or non-T2-mediated asthma, often associated with Th1/Th17-driven immune responses and high pulmonary neutrophilic inflammation, remain poorly understood. This study investigates airway remodeling in acute and chronic experimental asthma models induced by house dust mite extract to elucidate inflammatory and structural changes. Two acute T2-low models demonstrated pronounced airway inflammation characterized by goblet cell hyperplasia, collagen deposition, and significant upregulation of extracellular matrix remodeling and fibroblast activation. In contrast, the chronic Th17-mediated model exhibited reduced ECM deposition, increased matrix metalloproteinase (MMP) activity, and a distinct molecular signature dominated by IL-17A-driven pathways, indicative of ECM degradation and structural instability. Furthermore, the acute models showed immune cell apoptosis as the predominant cell death mechanism. In contrast, the chronic inflammation model was marked by necroptosis localized to structural lung cells, contributing to persistent inflammation and remodeling. Our findings provide new insights into the distinct immunopathological mechanisms underlying airway remodeling and fibrosis in T2-low and Th17-mediated asthma phenotypes. The study emphasizes the need for advanced preclinical models and targeted therapeutic strategies to address ECM dysregulation and chronic inflammation to progress in airway remodeling treatment in asthma.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 1","pages":"170-184"},"PeriodicalIF":12.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDIgG4-related chronic rhinosinusitis (IgG4-CRS) is a new clinical entity characterized by nasal lesions; however, its pathogenesis remains unclear. This study aimed to reveal single-cell transcriptomic changes in patients with IgG4-CRS via single-cell RNA sequencing (scRNA-seq) and illustrate its pathogenesis at the single-cell level.METHODSNasal mucosal tissues from five patients with IgG4-CRS were used for unbiased scRNA-seq. Bioinformatic analysis was performed using these five samples and three published control samples. Immunohistochemical and multicolor immunofluorescence analyses were performed to validate the sequencing results.RESULTSA total of 49,063 cells and 11 sub-clusters were identified. CXCL12 secretion increased in endothelial cells and fibroblasts, and CXCR4 was upregulated in the immune cells of IgG4-CRS. Enhanced chemotaxis mediated by the CXCL12-CXCR4 axis recruits excess immune cells and overactivation. Compared with those in the control group, the immunocompetence of CD4+ T cells and cytotoxicity of CD8+ T cells were enhanced in the IgG4-CRS group, and B cells were more differentiated to secrete IgG-type plasma cells.CONCLUSIONSChemotaxis of the CXCL12-CXCR4 axis plays a role in the pathogenesis of IgG4-CRS by influencing both the immune and nonimmune cells of IgG4-CRS.
{"title":"The CXCL12-CXCR4 Axis Mediates Lymphocyte Immune Overactivation in IgG4-Related Chronic Rhinosinusitis.","authors":"Jing Ding,Li Cui,Chengshuo Wang,Ming Wei,Yuan Zhang,Luo Zhang,Yingshi Piao","doi":"10.1111/all.70124","DOIUrl":"https://doi.org/10.1111/all.70124","url":null,"abstract":"BACKGROUNDIgG4-related chronic rhinosinusitis (IgG4-CRS) is a new clinical entity characterized by nasal lesions; however, its pathogenesis remains unclear. This study aimed to reveal single-cell transcriptomic changes in patients with IgG4-CRS via single-cell RNA sequencing (scRNA-seq) and illustrate its pathogenesis at the single-cell level.METHODSNasal mucosal tissues from five patients with IgG4-CRS were used for unbiased scRNA-seq. Bioinformatic analysis was performed using these five samples and three published control samples. Immunohistochemical and multicolor immunofluorescence analyses were performed to validate the sequencing results.RESULTSA total of 49,063 cells and 11 sub-clusters were identified. CXCL12 secretion increased in endothelial cells and fibroblasts, and CXCR4 was upregulated in the immune cells of IgG4-CRS. Enhanced chemotaxis mediated by the CXCL12-CXCR4 axis recruits excess immune cells and overactivation. Compared with those in the control group, the immunocompetence of CD4+ T cells and cytotoxicity of CD8+ T cells were enhanced in the IgG4-CRS group, and B cells were more differentiated to secrete IgG-type plasma cells.CONCLUSIONSChemotaxis of the CXCL12-CXCR4 axis plays a role in the pathogenesis of IgG4-CRS by influencing both the immune and nonimmune cells of IgG4-CRS.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"2 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDSeborrheic dermatitis (SD) is a common skin disease characterized by epithelial barrier breakdown. The epithelial barrier theory (EBT) implicates epithelial barrier disruption in the development of epithelial barrier diseases (EBDs). We hypothesized that SD is associated with an increased risk of EBDs and investigated the bidirectional association between SD and EBDs.METHODSRetrospective cohort study of 5,083,689 patients using a large US administrative claims database from January 1, 2016, to June 30, 2022. The mean (standard deviation) follow-up was 3.25 (1.75) years with a total follow-up of over 16 million person-years. The outcomes were a diagnosis of (i) SD after an EBD and (ii) EBD after SD, analyzed using a multivariable Cox proportional hazards model (hazard ratio [95% confidence interval]).RESULTSThe risk of SD was increased after EBD diagnosis for multiple diseases, including atopic dermatitis [2.46 (2.40, 2.53)], alopecia areata [3.47 (3.24, 3.71)], contact dermatitis [1.92 (1.88, 1.96)], psoriasis [2.62 (2.54, 2.69)], rosacea [2.84 (2.78, 2.90)], hidradenitis suppurativa [1.79 (1.63, 1.97)], rhinosinusitis [1.34 (1.32, 1.35)], food allergy [1.47 (1.42, 1.54)], celiac disease [1.55 (1.43, 1.68)], ocular allergy [1.55 (1.49, 1.61)], and dry eye [1.54 (1.52, 1.56)]. The risk of EBD after SD diagnosis followed similar trends, with the largest effect estimates being psoriasis [3.52 (3.42, 3.61)], rosacea [2.85 (2.79, 2.92)], and alopecia areata [2.81 (2.61, 3.03)].CONCLUSIONSOur results support the EBT as a shared driver of EBD pathogenesis at not only local (e.g., skin) barriers but also at non-local sites, including the respiratory, gastrointestinal, and ocular epithelial barriers.
{"title":"Bidirectional Associations Between Seborrheic Dermatitis and Epithelial Barrier Diseases: A Retrospective Cohort Study.","authors":"Sabrina Meng,Ronald Berna,Junko Takeshita,Ole Hoffstad,Daniel Shin,Nandita Mitra,David J Margolis","doi":"10.1111/all.70112","DOIUrl":"https://doi.org/10.1111/all.70112","url":null,"abstract":"BACKGROUNDSeborrheic dermatitis (SD) is a common skin disease characterized by epithelial barrier breakdown. The epithelial barrier theory (EBT) implicates epithelial barrier disruption in the development of epithelial barrier diseases (EBDs). We hypothesized that SD is associated with an increased risk of EBDs and investigated the bidirectional association between SD and EBDs.METHODSRetrospective cohort study of 5,083,689 patients using a large US administrative claims database from January 1, 2016, to June 30, 2022. The mean (standard deviation) follow-up was 3.25 (1.75) years with a total follow-up of over 16 million person-years. The outcomes were a diagnosis of (i) SD after an EBD and (ii) EBD after SD, analyzed using a multivariable Cox proportional hazards model (hazard ratio [95% confidence interval]).RESULTSThe risk of SD was increased after EBD diagnosis for multiple diseases, including atopic dermatitis [2.46 (2.40, 2.53)], alopecia areata [3.47 (3.24, 3.71)], contact dermatitis [1.92 (1.88, 1.96)], psoriasis [2.62 (2.54, 2.69)], rosacea [2.84 (2.78, 2.90)], hidradenitis suppurativa [1.79 (1.63, 1.97)], rhinosinusitis [1.34 (1.32, 1.35)], food allergy [1.47 (1.42, 1.54)], celiac disease [1.55 (1.43, 1.68)], ocular allergy [1.55 (1.49, 1.61)], and dry eye [1.54 (1.52, 1.56)]. The risk of EBD after SD diagnosis followed similar trends, with the largest effect estimates being psoriasis [3.52 (3.42, 3.61)], rosacea [2.85 (2.79, 2.92)], and alopecia areata [2.81 (2.61, 3.03)].CONCLUSIONSOur results support the EBT as a shared driver of EBD pathogenesis at not only local (e.g., skin) barriers but also at non-local sites, including the respiratory, gastrointestinal, and ocular epithelial barriers.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"20 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Inflammasome in IgE-Mediated Anaphylaxis.","authors":"S Fernandez-Bravo,R Fernandez-Santamaria","doi":"10.1111/all.70123","DOIUrl":"https://doi.org/10.1111/all.70123","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"110 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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