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Risk factors for drug resistance in allergen immunotherapy for allergic rhinitis: a systematic review and meta-analysis. 变应性鼻炎过敏原免疫治疗耐药的危险因素:系统回顾和荟萃分析。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-23 eCollection Date: 2025-01-01 DOI: 10.3389/falgy.2025.1743260
Zhi-Qiang Zhang, Jing-Yang Li, Jinyu Geng, Xin-Hua Zhu

Background: Allergen Immunotherapy (AIT) is largely considered to be the only therapy that can provide relief from allergic rhinitis (AR).Although its effectiveness has been confirmed by the results of a large number of practical studies such as randomized controlled trials, it may in some cases have a poor or no response to treatment due to the development of resistance under the influence of certain risk factors. The purpose of this Meta-analysis was to examine the risk factors for AR resistance to AIT treatment.

Methods: A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception to August 2025. Study quality was assessed using the NOS scale, AHRQ criteria, and the GRADE framework. Statistical analyses, performed with R 4.5.0 and Stata 14, employed fixed-or random-effects models to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was explored via sensitivity analyses, and publication bias was evaluated using funnel plots with Begg and Egger tests.

Results: A total of 12 studies involving 2,552 patients were included in this Meta-analysis. The results suggest that the following factors may be associated with AR resistance to treatment with AIT. Gender: male (OR = 1.53, 95% CI: 1.08-2.18); Specific diagnostic antibody aspects: s-IgE/t-IgE ratio (OR = 1.09, 95% CI: 1.02-1.16), sIgE, sIgG4; For cytokines: IL-10, IL-35, TGF-beta, IFN-gamma; On blood parameters: Eosinophil; Immune Cell Aspects:TH2/CD4, TFH2/CD4, CD23 + BNSM, CD23 + BSM, TFR/CD4, TFR/TFH2; Clinical/personal characteristics: demographics, disease severity, allergen type, treatment details, treatment adherence, symptom control, lung function, airway inflammation, inflammatory markers, immunologic markers, imaging markers, environmental and behavioral factors. With respect to the heterogeneity analysis, the heterogeneity of the other analyses was relatively low, except for age and t-IgE levels, where there was significant heterogeneity.

Conclusion: The risk of developing resistance to AIT treatment for AR is closely associated with patient factors including gender, antibodies, cytokines, hematological parameters, clinical/personal characteristics, immune cells, and other indicators.

Systematic review registration: PROSPERO CRD420251154551.

背景:过敏原免疫疗法(AIT)在很大程度上被认为是唯一可以缓解过敏性鼻炎(AR)的治疗方法。虽然其有效性已被随机对照试验等大量实际研究结果所证实,但在某些情况下,由于在某些危险因素的影响下产生耐药性,治疗效果较差或无疗效。本荟萃分析的目的是检查对AIT治疗的AR耐药的危险因素。方法:综合检索PubMed、Embase、Web of Science、Cochrane Library自成立至2025年8月的文献。采用NOS量表、AHRQ标准和GRADE框架评估研究质量。采用r4.5.0和Stata 14进行统计分析,采用固定或随机效应模型计算95%置信区间(ci)的合并优势比(ORs)。通过敏感性分析探讨异质性,并使用Begg和Egger检验的漏斗图评估发表偏倚。结果:本meta分析共纳入12项研究,涉及2552例患者。结果提示,以下因素可能与AR对AIT治疗的耐药有关。性别:男性(OR = 1.53, 95% CI: 1.08-2.18);特异性诊断抗体方面:s-IgE/t-IgE比值(OR = 1.09, 95% CI: 1.02-1.16), sIgE, sIgG4;对于细胞因子:IL-10, IL-35, tgf - β, ifn - γ;血液参数:嗜酸性粒细胞;免疫细胞方面:TH2/CD4、TFH2/CD4、CD23 + BNSM、CD23 + BSM、TFR/CD4、TFR/TFH2;临床/个人特征:人口统计学、疾病严重程度、过敏原类型、治疗细节、治疗依从性、症状控制、肺功能、气道炎症、炎症标志物、免疫标志物、影像学标志物、环境和行为因素。异质性分析方面,除年龄和t-IgE水平存在显著异质性外,其他分析的异质性均较低。结论:AR患者对AIT治疗产生耐药风险与患者性别、抗体、细胞因子、血液学参数、临床/个人特征、免疫细胞等指标密切相关。系统评价注册:PROSPERO CRD420251154551。
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引用次数: 0
Specific IgE to tropomyosin increases the diagnostic accuracy of shrimp allergy. 原肌球蛋白特异性IgE可提高对虾过敏的诊断准确性。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-23 eCollection Date: 2026-01-01 DOI: 10.3389/falgy.2026.1737009
Prapasri Kulalert, Piyawut Kreetapirom, Surapon Piboonpocanun, Orathai Jirapongsananuruk, Nattakan Authong, Nantika Khodtecha, Orapan Poachanukoon, Sira Nanthapisal

Purpose: Skin prick test (SPT) and the level of serum-specific IgE (sIgE) antibodies to shrimp have low specificity in the diagnosis of shrimp allergy. Measurement of sIgE to tropomyosin is available as a test, but the accuracy remains controversial. This study aims to evaluate the diagnostic accuracy of sIgE measurement to tropomyosin in the diagnosis of shrimp allergy and compare the diagnostic performance to SPT and sIgE to shrimp.

Methods: Patients with a history of immediate reaction to shrimp allergy were recruited. All participants underwent SPT with commercial shrimp extract. Measurements of sIgE to shrimp and tropomyosin were carried out. An oral food challenge (OFC) with shrimp was performed to confirm the diagnosis.

Results: Fifty symptomatic patients (mean age 27.3 years) with suspected shrimp allergy were evaluated. OFC confirmed allergy in 13 (26%) patients. Diagnostic modalities offered distinct advantages and limitations. Tropomyosin sIgE (rPen a 1) yielded superior specificity (91.9%) at the cost of sensitivity (23.1%), while extract-based tests (SPT and shrimp sIgE) provided better sensitivity (46.2%-61.5%) but lacked specificity (43.2%-51.4%). Implementing a two-step algorithm-combining SPT with tropomyosin sIgE-successfully optimized specificity to 94.6%. Nevertheless, given the suboptimal predictive values across all methods (PPV 25%-50%; NPV 73%-77%), these tools alone cannot safely guide management, and OFC remains essential.

Conclusion: Measurements of sIgE to tropomyosin provided higher specificity and increased diagnostic efficiency than SPT and measurement of sIgE to shrimp for the diagnosis of shrimp allergy.

目的:皮肤点刺试验(SPT)及对虾血清特异性IgE (sIgE)抗体水平对对虾过敏的诊断特异性较低。sIgE对原肌球蛋白的测量是一种可用的测试,但其准确性仍然存在争议。本研究旨在评价sIgE测定对原肌球蛋白诊断对虾过敏的准确性,并比较其与SPT和sIgE对对虾过敏的诊断性能。方法:招募有对虾过敏直接反应史的患者。所有参与者都接受了商业虾提取物的SPT。测定了对虾的sIgE和原肌凝蛋白。用对虾进行口腔食物挑战(OFC)以确认诊断。结果:对50例疑似对虾过敏的有症状患者(平均年龄27.3岁)进行了评估。OFC证实13例(26%)患者过敏。诊断方式具有明显的优势和局限性。原肌球蛋白sIgE (rPen a 1)在敏感性(23.1%)的代价下获得了更好的特异性(91.9%),而基于提取物的试验(SPT和虾sIgE)提供了更好的敏感性(46.2%-61.5%),但缺乏特异性(43.2%-51.4%)。实施两步算法-将SPT与原肌球蛋白sige结合-成功地将特异性优化到94.6%。然而,考虑到所有方法的预测值都不理想(PPV为25%-50%,NPV为73%-77%),仅凭这些工具无法安全地指导管理,OFC仍然是必不可少的。结论:测定对原肌球蛋白的sIgE比SPT和测定对虾的sIgE诊断对虾过敏具有更高的特异性和更高的诊断效率。
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引用次数: 0
Clinical evaluation of pediatric olfactory disorders: a review from etiology to management. 儿童嗅觉障碍的临床评价:从病因到治疗的综述。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-21 eCollection Date: 2026-01-01 DOI: 10.3389/falgy.2026.1741382
Eleonora M C Trecca, Marella Reale, Luca Leone, Michele Cassano, Antonio Della Volpe, Ignazio La Mantia, Fabio Pagella, Elena Cantone

Olfactory perception plays a fundamental role in nutrition, emotional development, and social behavior, yet olfactory disorders (OD) in children remain largely underrecognized and understudied. This mini review summarizes current evidence and proposes a structured clinical approach for the evaluation and management of pediatric OD. Etiologies are diverse, encompassing congenital syndromes such as Kallmann and CHARGE, post-infectious and post-traumatic forms, inflammatory airway diseases, and structural or iatrogenic causes. Accurate diagnosis begins with a detailed medical history and comprehensive ENT examination, complemented by psychophysical olfactory testing adapted for pediatric populations. Although several validated tools exist-such as the Sniffin' Sticks, U-Sniff, Pediatric Smell Wheel, and pBOT-6-standardized age-specific protocols and normative data remain limited. Imaging techniques, particularly MRI, provide valuable insights into congenital and acquired abnormalities of the olfactory bulbs and tracts, while CT is reserved for sinonasal or bony pathology. Multidisciplinary collaboration among pediatricians, neurologists, endocrinologists, geneticists, and otolaryngologists is essential to achieve etiological precision. Management strategies depend on the underlying cause and include medical or surgical treatment for reversible conditions, intranasal corticosteroids for inflammatory diseases, and olfactory training for post-infectious or congenital forms. Regular follow-up with objective testing and family education supports recovery and long-term adaptation. Despite the scarcity of pediatric-specific evidence, this review highlights the need for awareness, early diagnosis, and individualized management of OD in children, proposing a practical diagnostic and therapeutic framework to guide clinical decision-making in everyday ENT practice. A structured search strategy was applied to summarize the currently available evidence and highlight practical implications for clinical care.

嗅觉感知在营养、情感发展和社会行为中起着重要作用,但儿童嗅觉障碍(OD)在很大程度上仍未得到充分认识和研究。这篇小型综述总结了目前的证据,并提出了一个结构化的临床方法来评估和管理儿科用药过量。病因多种多样,包括先天性综合征,如Kallmann和CHARGE,感染后和创伤后形式,炎症性气道疾病,以及结构或医源性原因。准确的诊断始于详细的病史和全面的耳鼻喉科检查,辅以适合儿科人群的心理物理嗅觉测试。虽然存在一些经过验证的工具,如Sniffin' Sticks, U-Sniff, Pediatric Smell Wheel和pbot -6,但标准化的年龄特定协议和规范性数据仍然有限。成像技术,特别是MRI,为先天性和获得性嗅球和嗅束异常提供了有价值的见解,而CT则用于鼻窦或骨病理。儿科医生、神经科医生、内分泌科医生、遗传学家和耳鼻喉科医生之间的多学科合作是实现病因精确的必要条件。管理策略取决于根本原因,包括对可逆性疾病的药物或手术治疗,对炎症性疾病的鼻内皮质类固醇治疗,以及对感染后或先天性疾病的嗅觉训练。定期随访,进行客观检测和家庭教育,有助于康复和长期适应。尽管缺乏儿科特异性证据,但本综述强调了对儿童OD的认识、早期诊断和个性化管理的必要性,提出了一个实用的诊断和治疗框架,以指导日常耳鼻喉科实践的临床决策。采用结构化搜索策略来总结当前可用的证据,并强调临床护理的实际意义。
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引用次数: 0
Editorial: Exploring the interconnection: obesity's role in asthma development and management. 社论:探索相互联系:肥胖在哮喘发展和管理中的作用。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/falgy.2025.1759789
Akira Yamasaki, Katsuyuki Tomita
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引用次数: 0
MRGPRX2-expressing mast cells are increased in the GI tract of individuals with active inflammatory bowel disease and hereditary α-tryptasemia. 表达mrgprx2的肥大细胞在活动性炎症性肠病和遗传性α-胰蛋白酶血症患者的胃肠道中增加。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/falgy.2025.1726096
Michelle Galeas-Pena, Jonathan J Lyons, Dhana Llivichuzhca-Loja, Steve Everman, Ghina Yaghi, Katelyn White, Sangita Sutradhar, Tanya O Robinson, Anna H Owings, Neha S Dhaliwal, Alexander Carlye, Liza Konnikova, Hydar Ali, Sarah C Glover

Introduction: Hereditary α-tryptasemia (HαT), defined by increased TPSAB1 copy number and elevated basal serum tryptase, is associated with mast cell (MC)-mediated symptoms. However, its role in gastrointestinal disease remains unclear. Because intestinal MCs express the non-IgE-dependent activation receptor MRGPRX2, we investigated whether MRGPRX2 expression and MC phenotypes are altered in individuals with HαT in the context of inflammatory bowel disease (IBD).

Methods: We genotyped 854 biobanked IBD samples to identify individuals with HαT. Spatial transcriptomic analysis was performed on descending colon tissue from individuals with HαT (n = 4) as well as tissue and severity matched non-HαT controls (n = 4). Small intestinal biopsies were additionally analyzed using mass cytometry (CyTOF) from HαT individuals (n = 5) and non-HαT controls (n = 9). Droplet digital PCR (ddPCR) was used to establish TPSAB1 copy number variant for HαT detection. Comparisons across groups were performed using Welch's t-test with effect sizes and 95% CI.

Results: Across complementary platforms, HαT was associated with increased gastrointestinal mast cell abundance and elevated expression of mast cell activation markers, including CD203c, LAMP-1, and SIGLEC8. Both spatial transcriptomics and ddPCR demonstrated significantly increased MRGPRX2 and SIGLEC8 transcript levels in IBD samples from individuals with HαT compared with matched non-HαT IBD controls.

Discussion: These findings suggest that enhanced MRGPRX2 expression and mast cell activation may contribute to gastrointestinal symptoms in individuals with HαT, particularly in the setting of IBD. As interest in precision immunogenetics grows, defining mast cell phenotypes linked to α-tryptase copy number may help refine diagnostic evaluation and identify patients who could benefit from emerging mast cell-targeted therapeutic strategies in the context of IBD.

遗传α-胰蛋白酶血症(HαT),定义为TPSAB1拷贝数增加和基础血清胰蛋白酶升高,与肥大细胞(MC)介导的症状相关。然而,其在胃肠道疾病中的作用尚不清楚。由于肠道MCs表达非ige依赖性激活受体MRGPRX2,我们研究了炎症性肠病(IBD)中HαT患者MRGPRX2的表达和MC表型是否发生改变。方法:对854份IBD样本进行基因分型,以鉴定h - α t个体。对HαT患者(n = 4)和非HαT患者(n = 4)的降结肠组织进行空间转录组学分析。另外,对HαT个体(n = 5)和非HαT对照组(n = 9)的小肠活检进行细胞计数(CyTOF)分析。采用液滴数字PCR (ddPCR)建立TPSAB1拷贝数变异,用于h - α t检测。各组间比较采用Welch’st检验,具有效应量和95% CI。结果:在互补平台上,h - α t与胃肠道肥大细胞丰度增加和肥大细胞活化标志物(包括CD203c、LAMP-1和SIGLEC8)表达升高相关。空间转录组学和ddPCR均显示,与非HαT IBD对照相比,HαT个体IBD样本中MRGPRX2和SIGLEC8转录水平显著升高。讨论:这些发现表明,MRGPRX2表达增强和肥大细胞活化可能有助于h - α t患者的胃肠道症状,特别是在IBD患者中。随着人们对精确免疫遗传学的兴趣不断增长,确定与α-胰蛋白酶拷贝数相关的肥大细胞表型可能有助于改进诊断评估,并确定在IBD背景下可以从新兴肥大细胞靶向治疗策略中受益的患者。
{"title":"MRGPRX2-expressing mast cells are increased in the GI tract of individuals with active inflammatory bowel disease and hereditary α-tryptasemia.","authors":"Michelle Galeas-Pena, Jonathan J Lyons, Dhana Llivichuzhca-Loja, Steve Everman, Ghina Yaghi, Katelyn White, Sangita Sutradhar, Tanya O Robinson, Anna H Owings, Neha S Dhaliwal, Alexander Carlye, Liza Konnikova, Hydar Ali, Sarah C Glover","doi":"10.3389/falgy.2025.1726096","DOIUrl":"10.3389/falgy.2025.1726096","url":null,"abstract":"<p><strong>Introduction: </strong>Hereditary α-tryptasemia (HαT), defined by increased <i>TPSAB1</i> copy number and elevated basal serum tryptase, is associated with mast cell (MC)-mediated symptoms. However, its role in gastrointestinal disease remains unclear. Because intestinal MCs express the non-IgE-dependent activation receptor MRGPRX2, we investigated whether MRGPRX2 expression and MC phenotypes are altered in individuals with HαT in the context of inflammatory bowel disease (IBD).</p><p><strong>Methods: </strong>We genotyped 854 biobanked IBD samples to identify individuals with HαT. Spatial transcriptomic analysis was performed on descending colon tissue from individuals with HαT (<i>n</i> = 4) as well as tissue and severity matched non-HαT controls (<i>n</i> = 4). Small intestinal biopsies were additionally analyzed using mass cytometry (CyTOF) from HαT individuals (<i>n</i> = 5) and non-HαT controls (<i>n</i> = 9). Droplet digital PCR (ddPCR) was used to establish TPSAB1 copy number variant for HαT detection. Comparisons across groups were performed using Welch's <i>t</i>-test with effect sizes and 95% CI.</p><p><strong>Results: </strong>Across complementary platforms, HαT was associated with increased gastrointestinal mast cell abundance and elevated expression of mast cell activation markers, including CD203c, LAMP-1, and SIGLEC8. Both spatial transcriptomics and ddPCR demonstrated significantly increased <i>MRGPRX2</i> and <i>SIGLEC8</i> transcript levels in IBD samples from individuals with HαT compared with matched non-HαT IBD controls.</p><p><strong>Discussion: </strong>These findings suggest that enhanced MRGPRX2 expression and mast cell activation may contribute to gastrointestinal symptoms in individuals with HαT, particularly in the setting of IBD. As interest in precision immunogenetics grows, defining mast cell phenotypes linked to α-tryptase copy number may help refine diagnostic evaluation and identify patients who could benefit from emerging mast cell-targeted therapeutic strategies in the context of IBD.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1726096"},"PeriodicalIF":3.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12868144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127699","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}
引用次数: 0
A randomized, double-blind, placebo-controlled trial of soluble corn fiber supplementation for children with asthma. 一项补充可溶性玉米纤维治疗哮喘儿童的随机、双盲、安慰剂对照试验。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/falgy.2025.1707834
Matthew A Rank, Daisy L Barroso, Kathryn A Conn, Melissa Pecak, Matthew Scandura, Allyson H Hirsch, Haiwei Gu, Corrie M Whisner, Heather Shearer, Darcy Johnson, Natalia Argel, Cindy S Bauer, Sophia N Williams, Benjamin L Wright, James Woodward, Emily K Cope

Introduction: Asthma is a multifactorial disease influenced by genetic and environmental factors, including diet. The gut microbiome contributes to airway inflammation via the gut-lung axis, partly through production of short chain fatty acids (SCFAs) from bacterial fermentation of dietary fiber. We hypothesized that dietary fiber supplementation could modulate the gut microbiome and increase SCFAs in children with asthma.

Methods: This is a double-blind, placebo-controlled trial of children who were randomized to consume 12 g of soluble corn fiber (SCF) as a supplement to their usual daily diet (50% the recommended daily fiber intake) or placebo for 4-6 weeks (clinicaltrials.gov NCT03673618). Dietary surveys, asthma symptom questionnaires, fecal, blood and nasal samples were collected before and after the intervention period to quantify fiber intake, asthma control, nasal and gut microbiome, and serum short chain fatty acids (SCFAs).

Results: Of the 20 children enrolled, 15 completed the intervention with an average adherence rate of 83%. SCFA concentrations and gut microbiome changes varied by individual and treatment group. No significant differences in gut or nasal alpha or beta diversity were observed between groups post-intervention. However, differential abundance analysis showed a trend toward increased Bifidobacterium in the SCF group compared to placebo (ANCOM-BC p = 0.0004, FDR q = 0.073).

Discussion: Supplementation of 50% of recommended daily fiber intake had minimal impact on asthma symptoms, the microbiome, or SCFA levels. Future studies should consider higher fiber doses, different fiber types, or targeting individuals with low baseline fiber intake to account for observed variability in microbiome and SCFA responses.

Clinical trial registration: https://clinicaltrials.gov/study/NCT03673618, identifier NCT03673618.

简介:哮喘是一种受遗传和环境因素影响的多因素疾病,包括饮食。肠道微生物群通过肠-肺轴促进气道炎症,部分是通过细菌发酵膳食纤维产生短链脂肪酸(SCFAs)。我们假设补充膳食纤维可以调节哮喘儿童的肠道微生物群并增加SCFAs。方法:这是一项双盲、安慰剂对照试验,儿童随机摄入12克可溶性玉米纤维(SCF)作为日常饮食的补充(推荐每日纤维摄入量的50%)或安慰剂,持续4-6周(clinicaltrials.gov NCT03673618)。在干预前后收集膳食调查、哮喘症状问卷、粪便、血液和鼻腔样本,量化纤维摄入量、哮喘控制、鼻腔和肠道微生物组以及血清短链脂肪酸(SCFAs)。结果:在入选的20名儿童中,15名完成了干预,平均依从率为83%。SCFA浓度和肠道微生物组的变化因个体和治疗组而异。干预后各组间肠道或鼻腔α或β多样性无显著差异。然而,差异丰度分析显示,与安慰剂相比,SCF组双歧杆菌数量有增加的趋势(ANCOM-BC p = 0.0004, FDR q = 0.073)。讨论:补充推荐的每日纤维摄入量的50%对哮喘症状、微生物组或SCFA水平的影响最小。未来的研究应考虑更高的纤维剂量,不同的纤维类型,或针对低基线纤维摄入量的个体,以解释观察到的微生物组和SCFA反应的变异性。临床试验注册:https://clinicaltrials.gov/study/NCT03673618,标识符NCT03673618。
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引用次数: 0
Case Report: Extending dosing intervals of biologics in adults severe asthma: a case series. 病例报告:延长成人严重哮喘生物制剂的给药间隔:一个病例系列。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/falgy.2025.1635540
Tomoya Harada, Miyu Nishigami, Hiroyuki Tanaka, Genki Inui, Hiroki Ishikawa, Hiroki Kohno, Yoshihiro Funaki, Tomohiro Sakamoto, Miki Takata, Ryota Okazaki, Masato Morita, Shin Kitatani, Akira Yamasaki

Background: Biological therapies have improved the control of severe asthma. However, biological therapies are expensive. Therefore, the cost-effective use of these medications after achieving improved disease control warrants consideration.

Methods: This retrospective case series analyzed 69 adult patients with asthma who received biological therapies at our department between 2009 and 2023. Among them, 11 patients underwent dosing interval extension. We collected data on their clinical characteristics, asthma control status, and changes in clinical parameters after interval extension.

Results: At the time of dosing interval extension, the mean patient age was 62.1 years, with 5 female patients. Omalizumab was used in five cases, benralizumab in five, and dupilumab in one. The dosing intervals were extended by 1.5 to 2 times. The median duration from the initiation of biologics to interval extension was 7.0 months, with 6 patients undergoing extension within the first 7 months. One year after extension, asthma exacerbation occurred in only one patient receiving omalizumab. The frequency of exacerbations and the proportion of patients receiving oral corticosteroids (OCS) were decreased. The median ACT score remained at 25, while the median daily OCS dose decreased from 5.0 mg to 4.0 mg (prednisolone equivalent). The median % predicted FEV₁ changed from 84.9% to 78.3%.

Conclusions: For patients whose asthma control improves after initiating biological therapy, extending the dosing interval may be a feasible treatment option. Given the retrospective, single-center design and small sample size, these findings are exploratory and generate hypotheses that require validation in larger, prospective studies.

背景:生物疗法改善了重症哮喘的控制。然而,生物疗法是昂贵的。因此,在改善疾病控制后使用这些药物的成本效益值得考虑。方法:回顾性分析2009年至2023年在我科接受生物治疗的69例成人哮喘患者。其中延长给药间隔11例。我们收集了他们的临床特征、哮喘控制状况以及延长间隔后临床参数变化的数据。结果:延长给药间隔时,患者平均年龄为62.1岁,女性5例。5例使用Omalizumab, 5例使用benralizumab, 1例使用dupilumab。给药间隔延长1.5 ~ 2倍。从开始使用生物制剂到延长治疗间隔的中位持续时间为7.0个月,其中6例患者在前7个月内接受了延长治疗。延长治疗一年后,只有一名接受奥玛珠单抗治疗的患者出现哮喘加重。恶化的频率和接受口服皮质类固醇(OCS)的患者比例均有所下降。ACT中位评分保持在25分,而OCS中位每日剂量从5.0 mg降至4.0 mg(相当于泼尼松龙)。预测FEV 1的中位数百分比从84.9%变化到78.3%。结论:对于开始生物治疗后哮喘控制改善的患者,延长给药间隔可能是一种可行的治疗选择。考虑到回顾性、单中心设计和小样本量,这些发现是探索性的,并产生假设,需要在更大的前瞻性研究中验证。
{"title":"Case Report: Extending dosing intervals of biologics in adults severe asthma: a case series.","authors":"Tomoya Harada, Miyu Nishigami, Hiroyuki Tanaka, Genki Inui, Hiroki Ishikawa, Hiroki Kohno, Yoshihiro Funaki, Tomohiro Sakamoto, Miki Takata, Ryota Okazaki, Masato Morita, Shin Kitatani, Akira Yamasaki","doi":"10.3389/falgy.2025.1635540","DOIUrl":"10.3389/falgy.2025.1635540","url":null,"abstract":"<p><strong>Background: </strong>Biological therapies have improved the control of severe asthma. However, biological therapies are expensive. Therefore, the cost-effective use of these medications after achieving improved disease control warrants consideration.</p><p><strong>Methods: </strong>This retrospective case series analyzed 69 adult patients with asthma who received biological therapies at our department between 2009 and 2023. Among them, 11 patients underwent dosing interval extension. We collected data on their clinical characteristics, asthma control status, and changes in clinical parameters after interval extension.</p><p><strong>Results: </strong>At the time of dosing interval extension, the mean patient age was 62.1 years, with 5 female patients. Omalizumab was used in five cases, benralizumab in five, and dupilumab in one. The dosing intervals were extended by 1.5 to 2 times. The median duration from the initiation of biologics to interval extension was 7.0 months, with 6 patients undergoing extension within the first 7 months. One year after extension, asthma exacerbation occurred in only one patient receiving omalizumab. The frequency of exacerbations and the proportion of patients receiving oral corticosteroids (OCS) were decreased. The median ACT score remained at 25, while the median daily OCS dose decreased from 5.0 mg to 4.0 mg (prednisolone equivalent). The median % predicted FEV₁ changed from 84.9% to 78.3%.</p><p><strong>Conclusions: </strong>For patients whose asthma control improves after initiating biological therapy, extending the dosing interval may be a feasible treatment option. Given the retrospective, single-center design and small sample size, these findings are exploratory and generate hypotheses that require validation in larger, prospective studies.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1635540"},"PeriodicalIF":3.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12868160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127633","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}
引用次数: 0
Biologic therapies for severe pediatric asthma: efficacy, safety, and biomarker-guided selection. 重度儿童哮喘的生物疗法:疗效、安全性和生物标志物引导选择。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-20 eCollection Date: 2026-01-01 DOI: 10.3389/falgy.2026.1757445
Enrico Tondina, Alessia Claudia Codazzi, Riccardo Castorina, Rossana Di Micco, Cristina Dutto, Livia Leoncini Bartoli, Giovanni Lepore, Gian Luigi Marseglia, Ilaria Brambilla

Background: Severe pediatric asthma is a heterogeneous, high-burden disease marked by variable corticosteroid responsiveness, frequent exacerbations, and substantial impairment in quality of life. Advances in airway immunobiology, particularly the delineation of type-2 (T2) pathways (IgE, IL-5, IL-4/IL-13) and epithelial alarmins, have enabled the development of targeted biologic therapies for biomarker-defined patient subgroups.

Objective: To synthesize current evidence on the efficacy and safety of biologic therapies for severe pediatric asthma and to translate biomarker-driven selection into practical clinical guidance, while outlining emerging therapeutic directions.

Summary of findings: Targeted biologics, anti-IgE (omalizumab), anti-IL-5/IL-5Rα (mepolizumab, benralizumab; pediatric data for reslizumab remain limited), anti-IL-4Rα (dupilumab), and anti-TSLP (tezepelumab) improve disease control, reduce severe exacerbations, and enable steroid-sparing in appropriately selected children. Benefits are greatest in T2-high profiles, particularly with elevated blood eosinophils and/or fractional exhaled nitric oxide (FeNO), while tezepelumab shows efficacy across biomarker strata. Lung-function gains are modest to moderate but clinically meaningful. Persisting gaps include optimal treatment duration, stopping rules, long-term safety, cost, and equitable access.

Conclusions: Biologic therapies have reshaped the care of severe pediatric asthma, operationalizing precision medicine through immunologic endotyping and biomarker-guided selection. Priorities now include standardized definitions of response and remission, robust long-term safety data, and strategies to ensure equitable access across diverse pediatric populations.

背景:重度儿童哮喘是一种异质性、高负担的疾病,其特征是可变的皮质类固醇反应性、频繁恶化和生活质量的严重损害。气道免疫生物学的进展,特别是2型(T2)通路(IgE、IL-5、IL-4/IL-13)和上皮报警信号的描述,使得针对生物标志物定义的患者亚群的靶向生物治疗得以发展。目的:综合目前关于重症儿童哮喘生物疗法的有效性和安全性的证据,将生物标志物驱动的选择转化为实际的临床指导,同时概述新兴的治疗方向。研究结果总结:靶向生物制剂,抗ige (omalizumab),抗il -5/IL-5Rα (mepolizumab, benralizumab; reslizumab的儿科数据仍然有限),抗il - 4r α (dupilumab)和抗tslp (tezepelumab)在适当选择的儿童中改善疾病控制,减少严重恶化,并使类固醇节省。在t2高的情况下获益最大,特别是血液嗜酸性粒细胞升高和/或部分呼出一氧化氮(FeNO),而tezepelumab在所有生物标志物层面都显示出疗效。肺功能的改善是中度到中度,但具有临床意义。持续存在的差距包括最佳治疗时间、停药规则、长期安全性、成本和公平获取。结论:通过免疫内分型和生物标志物引导选择,生物疗法重塑了重症儿童哮喘的护理,实现了精准医疗。现在的优先事项包括反应和缓解的标准化定义,可靠的长期安全性数据,以及确保在不同儿科人群中公平获得治疗的战略。
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引用次数: 0
Case Series: Combination of dupilumab and omalizumab as a way to reduce dupilumab-associated adverse events in severe atopic dermatitis. 病例系列:dupilumab和omalizumab联合用于减少严重特应性皮炎患者dupilumab相关不良事件。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-16 eCollection Date: 2025-01-01 DOI: 10.3389/falgy.2025.1696897
Daria S Fomina, Olga A Mukhina, Elizaveta L Sedova, Marina S Lebedkina, Elena N Bobrikova, Alexander V Karaulov, Mariana A Lysenko, Harald Renz

Dupilumab is a fully human monoclonal antibody directed against the interleukin-4 receptor subunit α, the common chain of the IL-4 and IL-13 receptors. Dupilumab has been demonstrated to be highly effective in the treatment of severe atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps. Despite the favorable tolerability of dupilumab, several publications and reviews have reported various adverse events, including conjunctivitis, keratitis, and face and neck treatment-resistant dermatitis, which reduce patients' quality of life and may necessitate the cancellation of therapy. The current standard of care for severe chronic diseases involves a collaborative approach between the patient and their physician. The majority of patients who respond well to this type of systemic atopic dermatitis (AtD) therapy are reluctant to interrupt dupilumab treatment due to the previously mentioned adverse events. The combination of dupilumab and anti-IgE therapy (omalizumab) may be beneficial for individuals who undergo dupilumab treatment for AtD and experience severe adverse events.

Dupilumab是一种针对白细胞介素-4受体亚基α (IL-4和IL-13受体的共同链)的全人源单克隆抗体。Dupilumab已被证明在治疗严重特应性皮炎、哮喘和慢性鼻窦炎伴鼻息肉方面非常有效。尽管dupilumab具有良好的耐受性,但一些出版物和综述报道了各种不良事件,包括结膜炎、角膜炎、面部和颈部治疗难治性皮炎,这些不良事件降低了患者的生活质量,可能需要取消治疗。目前严重慢性疾病的护理标准涉及病人和医生之间的合作方法。大多数对这种类型的系统性特应性皮炎(AtD)治疗反应良好的患者由于前面提到的不良事件而不愿中断杜匹单抗治疗。dupilumab联合抗ige治疗(omalizumab)可能对接受dupilumab治疗AtD并经历严重不良事件的个体有益。
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引用次数: 0
Feasibility in a homeopathy for seasonal allergic rhinitis RCT: importance of therapeutic relationship and organizational capacity. 顺势疗法治疗季节性变应性鼻炎的可行性:治疗关系和组织能力的重要性。
IF 3.1 Q2 ALLERGY Pub Date : 2026-01-15 eCollection Date: 2025-01-01 DOI: 10.3389/falgy.2025.1694531
J Siewert, L Joschko, R Schleicher, B Stöckigt, M Teut, S N Willich, B Brinkhaus, E Jansen

Introduction: Seasonal allergic rhinitis (SAR) patients often use homeopathy for symptom relief. The HOMEOSAR trial, a randomized, placebo-controlled, triple-blind multicenter study, included a qualitative sub-study to assess feasibility. This sub-study specifically examined the feasibility of the study, focusing in particular on two mechanism-rich domains-the therapeutic relationship and study organization-with special attention to study procedures, physician-patient relationships, organizational aspects, and interactions with the study team.

Methods: Semi-structured interviews with trial participants were conducted 6-8 weeks after baseline, corresponding to 2-4 weeks after study intervention ended. Data were coded, categorized, and analyzed using qualitative content analysis, both inductively from the material and deductively based on study aims. MAXQDA® software was used to support analysis.

Results: Fifteen patients (mean age 43 years; range 20-67; 11 male) participated in the qualitative study (n = 8 standardized homeopathy, n = 2 individualized homeopathy, n = 5 placebo). They were recruited from nine study centers in Berlin. Results of the qualitative sub-study indicate the overall feasibility of the HOMEOSAR trial. Patients highlighted the empathetic and professional relationships with physicians and the supportive contact with the study team. While the documentation was seen as well-structured and clear, it was also described as time-consuming.

Conclusion: Findings of this qualitative study provide design-level recommendations (e.g., upfront communication of consultation length, digital diaries with free-text, tracked medication shipping, single contact point) for RCT studies. Beyond the specific homeopathy study context, these findings offer important methodological insights for designing patient-centered RCTs in complex intervention settings not only in the field of Complementary and Integrative Medicine.

简介:季节性变应性鼻炎(SAR)患者常采用顺势疗法缓解症状。HOMEOSAR试验是一项随机、安慰剂对照、三盲多中心研究,包括一项定性子研究来评估可行性。这个子研究特别考察了研究的可行性,特别关注两个机制丰富的领域——治疗关系和研究组织——特别关注研究程序、医患关系、组织方面以及与研究团队的互动。方法:在基线后6-8周,即研究干预结束后2-4周,对试验参与者进行半结构化访谈。对数据进行编码、分类和定性内容分析,包括根据材料进行归纳和根据研究目的进行演绎。使用MAXQDA®软件支持分析。结果:15例患者(平均年龄43岁,范围20-67岁,男性11例)参与了定性研究(标准化顺势疗法8例,个体化顺势疗法2例,安慰剂5例)。他们是从柏林的九个研究中心招募的。定性子研究的结果表明HOMEOSAR试验的总体可行性。患者强调了与医生的共情和专业关系,以及与研究团队的支持联系。虽然文件被认为结构良好和清晰,但也被描述为耗时。结论:本定性研究的结果为RCT研究提供了设计层面的建议(例如,咨询时间的预先沟通,自由文本的数字日记,跟踪药物运输,单一接触点)。除了特定的顺势疗法研究背景之外,这些发现为在复杂干预环境中设计以患者为中心的随机对照试验提供了重要的方法学见解,而不仅仅是在补充医学和中西医结合领域。
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引用次数: 0
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Frontiers in allergy
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