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Drug fever-an immune-mediated delayed type hypersensitivity reaction to Vinca alkaloids in pediatric oncology patients, possibly mediated by cysteinyl leukotrienes. 药物热--儿科肿瘤患者对长春花生物碱的免疫介导型迟发型超敏反应,可能由半胱氨酰白三烯介导。
IF 3.3 Q2 ALLERGY Pub Date : 2024-08-06 eCollection Date: 2024-01-01 DOI: 10.3389/falgy.2024.1361403
Mona I Kidon, Soad Haj Yahia, Gadi Abebe-Campino, Nancy Agmon-Levin, Michal Yelon

Background: Drug hypersensitivity reactions are common in pediatric hemato-oncology patients due to multiple factors including immune compromise and pharmacological complexities. Fever can signify severe delayed-type hypersensitivity reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The etiology of fever as an isolated hypersensitivity reaction to chemotherapeutic agents not fully understood. Here, we report three children with intracranial neoplasms experiencing recurrent febrile reactions following Vinca alkaloid-based chemotherapy, mitigated by cysteinyl leukotriene receptor antagonist therapy.

Methods: We present a series of pediatric patients with diverse intracranial neoplasms who developed recurrent fever episodes after multiple courses of Vinca alkaloid-based chemotherapy. Treatment involved prophylactic and post-chemotherapy administration of a cysteinyl leukotriene receptor antagonist to prevent fever episodes and enable completion of chemotherapy regimens without protocol modifications or desensitization.

Results: All three patients experienced fever consistent with delayed-type hypersensitivity reactions to Vinca alkaloids. Prophylactic use of the leukotriene antagonist Montelukast successfully prevented fever recurrence, allowing uninterrupted completion of chemotherapy courses.

Conclusion: Our findings suggest that Montelukast, a leukotriene antagonist, may be beneficial in managing fever as a delayed-type hypersensitivity reaction to Vinca alkaloids in pediatric patients. Further research is warranted to elucidate the underlying mechanisms and leukotriene pathways involved in drug-induced fever reactions.

背景:由于免疫受损和药理复杂性等多种因素,药物超敏反应在儿科血液肿瘤患者中很常见。发热可能意味着严重的迟发型超敏反应,如伴有嗜酸性粒细胞增多和全身症状的药物反应(DRESS)或药物诱发超敏反应综合征(DIHS)。化疗药物引起的发热是一种孤立的超敏反应,其病因尚未完全明了。在此,我们报告了三名颅内肿瘤患儿在接受长春花生物碱类药物化疗后出现的复发性发热反应,并通过半胱氨酰白三烯受体拮抗剂治疗得到缓解:我们介绍了一系列患有不同颅内肿瘤的儿童患者,他们在接受多个疗程的长春花生物碱类化疗后出现了复发性发热。治疗包括预防性和化疗后服用半胱氨酰白三烯受体拮抗剂,以防止发热发作,并在不修改方案或不脱敏的情况下完成化疗:所有三名患者都出现了发热症状,与长春花生物碱迟发型超敏反应一致。预防性使用白三烯拮抗剂孟鲁司特成功地防止了发热复发,使化疗疗程得以不间断地完成:我们的研究结果表明,白三烯拮抗剂孟鲁司特可能有利于控制儿童患者因长春花生物碱引起的迟发型超敏反应而出现的发热。还需要进一步研究,以阐明药物诱发发热反应的潜在机制和白三烯途径。
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引用次数: 0
Adjuvant-independent airway sensitization and infection mouse models leading to allergic asthma. 导致过敏性哮喘的不依赖佐剂的气道致敏和感染小鼠模型。
IF 3.3 Q2 ALLERGY Pub Date : 2024-08-02 eCollection Date: 2024-01-01 DOI: 10.3389/falgy.2024.1423938
Mariem Radhouani, Philipp Starkl

Asthma is a chronic respiratory disease of global importance. Mouse models of allergic asthma have been instrumental in advancing research and novel therapeutic strategies for patients. The application of relevant allergens and physiological routes of exposure in such models has led to valuable insights into the complexities of asthma onset and development as well as key disease mechanisms. Furthermore, environmental microbial exposures and infections have been shown to play a fundamental part in asthma pathogenesis and alter disease outcome. In this review, we delve into physiological mouse models of allergic asthma and explore literature reports on most significant interplays between microbial infections and asthma development with relevance to human disease.

哮喘是一种全球性的慢性呼吸道疾病。过敏性哮喘小鼠模型在推动研究和为患者制定新型治疗策略方面发挥了重要作用。在这些模型中应用相关过敏原和生理接触途径,有助于深入了解哮喘发病和发展的复杂性以及关键疾病机制。此外,环境中的微生物暴露和感染已被证明在哮喘发病机制中起着根本性的作用,并改变着疾病的预后。在这篇综述中,我们将深入研究过敏性哮喘的生理小鼠模型,并探讨微生物感染与哮喘发病之间最重要的相互作用以及与人类疾病相关的文献报道。
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引用次数: 0
Eosinophil extracellular vesicles and DNA traps in allergic inflammation. 过敏性炎症中的嗜酸性粒细胞胞外囊泡和 DNA 陷阱。
IF 3.3 Q2 ALLERGY Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 10.3389/falgy.2024.1448007
Tobias Weihrauch, Rossana C N Melo, Natalie Gray, David Voehringer, Peter F Weller, Ulrike Raap

Eosinophil granulocytes, a specialized subset of white blood cells, have traditionally been associated with allergic responses and parasitic infections. However, recent research has unveiled their versatile roles in immune regulation beyond these classical functions. This review highlights the emerging field of eosinophil biology, with a particular focus on their release of extracellular vesicles (EVs) and extracellular DNA traps (EETs). It further explores potential implications of eosinophil-derived EVs and EETs for immune responses during inflammatory diseases. The release of EVs/EETs from eosinophils, which also affects the eosinophils themselves, may influence both local and systemic immune reactions, affecting the pathophysiology of conditions such as airway inflammation, chronic rhinosinusitis and atopic dermatitis.

嗜酸性粒细胞是白细胞的一个特殊亚群,传统上与过敏反应和寄生虫感染有关。然而,最近的研究揭示了嗜酸性粒细胞在这些经典功能之外的免疫调节中的多种作用。这篇综述重点介绍了嗜酸性粒细胞生物学这一新兴领域,尤其关注它们释放的胞外囊泡 (EV) 和胞外 DNA 陷阱 (EET)。它进一步探讨了嗜酸性粒细胞衍生的EVs和EETs对炎症性疾病期间免疫反应的潜在影响。嗜酸性粒细胞释放的 EVs/EETs 也会影响嗜酸性粒细胞本身,可能会影响局部和全身的免疫反应,从而影响气道炎症、慢性鼻炎和特应性皮炎等疾病的病理生理学。
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引用次数: 0
Efficacy of the PEN-FAST score in a French cohort of patients with reported allergy to penicillins. PEN-FAST 评分在法国一组报告对青霉素过敏的患者中的疗效。
IF 3.3 Q2 ALLERGY Pub Date : 2024-07-29 eCollection Date: 2024-01-01 DOI: 10.3389/falgy.2024.1439698
Anatole Hanniet, Marc Puyraveau, Florence Castelain, Fabien Pelletier, François Aubin

Introduction: Various clinical decision-making tools for penicillin allergy have been developed to guide delabeling strategies.

Objective: To evaluate the penicillin allergy PEN-FAST decision score in a retrospective cohort of patients, adults and children, with penicillin-reported allergy.

Methods: This monocentric retrospective cohort included patients with penicillin-reported allergy. All patients underwent penicillin allergy testing using skin tests and/or drug challenge. The PEN-FAST score sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and the area under the receiver operating characteristics curve (AUC) were calculated.

Results: Two hundred and fourteen patients were included (64 children and 150 adults). Allergy was confirmed in 52 cases (24%). A PEN-FAST score <3 points showed a poor discrimination capacity for the whole population (AUC = 0.66; 95% CI: 0.58-0.75), while it demonstrated a better discrimination capacity in the adults group (AUC = 0.71; 95% CI: 0.63-0.80). The sensitivity to identify penicillin allergy using this cutoff of less than 3 points was 0.67 (95% CI: 0.52-0.80); specificity, 0.58 (95% CI: 0.48-0.68); PPV, 0.43 (95% CI: 0.32-0.55); and NPV, 0.78 (95% CI: 0.68-0.87).

Conclusions: Although our data confirm a rather good discrimination value of a PEN-FAST score <3 points, its low negative predictive value (78%) did not advocate for its use as an accurate, simple and cost-effective clinical decision-making tool to effectively reduce the number of penicillin skin tests required before direct oral challenge. Further studies are required to improve the predictive capacity of the PEN-FAST score.

简介:针对青霉素过敏开发了各种临床决策工具,以指导脱标策略:在成人和儿童青霉素过敏患者的回顾性队列中评估青霉素过敏 PEN-FAST 决策评分:该单中心回顾性队列包括青霉素过敏的患者。所有患者都通过皮试和/或药物挑战进行了青霉素过敏测试。计算了 PEN-FAST 评分的敏感性、特异性、阴性预测值(NPV)和阳性预测值(PPV)以及接收者工作特征曲线下面积(AUC):共纳入 214 名患者(64 名儿童和 150 名成人)。其中 52 例(24%)确诊为过敏。PEN-FAST 评分 结论:尽管我们的数据证实了 PEN-FAST 评分具有相当好的区分价值
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引用次数: 0
Multidisciplinary management of type 2 inflammation diseases using a screening tool 利用筛查工具对 2 型炎症疾病进行多学科管理
IF 3.3 Q2 ALLERGY Pub Date : 2024-07-18 DOI: 10.3389/falgy.2024.1427279
Oscar Palomares, Carolina Cisneros, Francisco Javier Ortiz de Frutos, J. M. Villacampa, Ignacio Dávila
Dysregulation of type 2 (T2) immune response leads to an aberrant inflammatory reaction that constitutes the pathophysiological basis of diseases involving various organs. For this reason, several disorders can coexist in a single patient; however, as different specialists often treat these pathologies, T2 dysregulation, particularly when mild, is not always the first diagnostic suspicion. A breakdown in interdisciplinary communication or the lack of adequate tools to detect these entities can delay diagnosis, and this, together with a lack of coordination, can lead to suboptimal care. In this context, a multidisciplinary group of specialists in pneumology, immunology, allergology, dermatology and otorhinolaryngology compiled a list of the cardinal symptoms reported by patients presenting with T2 inflammation-related diseases: asthma, chronic rhinosinusitis, allergic rhinitis, allergic conjunctivitis, IgE-mediated food allergy, atopic dermatitis, eosinophilic oesophagitis, and NSAID-exacerbated respiratory disease (NERD). Using this information, we propose a simple, patient-friendly questionnaire that can be administered at any level of care to initially screen patients for suspected coexisting T2 diseases and referral to the appropriate specialist.
2型(T2)免疫反应失调会导致异常的炎症反应,这是涉及各种器官的疾病的病理生理基础。因此,一名患者可能同时患有多种疾病;然而,由于这些病症通常由不同的专科医生治疗,T2 反应失调(尤其是轻度失调)并不总是首先被怀疑。跨学科交流的中断或缺乏检测这些实体的适当工具会延误诊断,再加上缺乏协调,会导致护理效果不佳。在这种情况下,一个由肺病学、免疫学、过敏学、皮肤病学和耳鼻喉科专家组成的多学科小组编制了一份清单,列出了 T2 炎症相关疾病患者的主要症状:哮喘、慢性鼻炎、过敏性鼻炎、过敏性结膜炎、IgE 介导的食物过敏、特应性皮炎、嗜酸性粒细胞性食道炎和非甾体抗炎药加重的呼吸道疾病(NERD)。利用这些信息,我们提出了一种简单、方便患者填写的问卷,可在任何一级医疗机构使用,用于初步筛查疑似并存 T2 疾病的患者,并将其转诊至相应的专科医生。
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引用次数: 0
Editorial: What have we learned over the last 25 years assessing novel food and protein allergenicity 社论:过去 25 年中,我们在评估新型食物和蛋白质过敏原方面学到了什么?
IF 3.3 Q2 ALLERGY Pub Date : 2024-07-18 DOI: 10.3389/falgy.2024.1440478
Scott McClain, Gregory Ladics
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引用次数: 0
Editorial: A contemporary look at allergic rhinitis treatments: where are we heading? 社论:过敏性鼻炎治疗的现代视角:我们将何去何从?
IF 3.3 Q2 ALLERGY Pub Date : 2024-07-18 DOI: 10.3389/falgy.2024.1459032
Davor Plavec, C. Andaloro, Giorgio Ciprandi, I. La Mantia, Cesare Miani, A. Varricchio
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引用次数: 0
Development of systemic and mucosal immune responses against gut microbiota in early life and implications for the onset of allergies 生命早期针对肠道微生物群的全身和粘膜免疫反应的发展及其对过敏症发病的影响
IF 3.3 Q2 ALLERGY Pub Date : 2024-07-17 DOI: 10.3389/falgy.2024.1439303
Anna-Lena Pirker, Thomas Vogl
The early microbial colonization of human mucosal surfaces is essential for the development of the host immune system. Already during pregnancy, the unborn child is prepared for the postnatal influx of commensals and pathogens via maternal antibodies, and after birth this protection is continued with antibodies in breast milk. During this critical window of time, which extends from pregnancy to the first year of life, each encounter with a microorganism can influence children's immune response and can have a lifelong impact on their life. For example, there are numerous links between the development of allergies and an altered gut microbiome. However, the exact mechanisms behind microbial influences, also extending to how viruses influence host-microbe interactions, are incompletely understood. In this review, we address the impact of infants’ first microbial encounters, how the immune system develops to interact with gut microbiota, and summarize how an altered immune response could be implied in allergies.
人体粘膜表面的早期微生物定植对宿主免疫系统的发育至关重要。早在怀孕期间,胎儿就已通过母体抗体为出生后共生体和病原体的涌入做好了准备,出生后,母乳中的抗体将继续提供这种保护。在从怀孕到出生后第一年的这一关键时间窗口中,每一次与微生物的接触都会影响儿童的免疫反应,并对其一生产生影响。例如,过敏症的发生与肠道微生物群的改变之间就有许多联系。然而,人们对微生物影响背后的确切机制,以及病毒如何影响宿主与微生物之间的相互作用还不甚了解。在这篇综述中,我们将探讨婴儿首次接触微生物的影响、免疫系统如何发展以与肠道微生物群相互作用,并总结免疫反应的改变如何隐含在过敏症中。
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引用次数: 0
A human monoclonal antibody based immunoenzymetric assay to measure Fel d 1 concentrations in cat hair and pelt allergenic extracts 基于人类单克隆抗体的免疫酶测定法,用于测量猫毛和毛皮过敏原提取物中 Fel d 1 的浓度
IF 3.3 Q2 ALLERGY Pub Date : 2024-07-15 DOI: 10.3389/falgy.2024.1417879
Ronald L. Rabin, Derek Croote, Aaron Chen, E. Dobrovolskaia, Joyce Jia Wen Wong, Jessica Grossman, Robert G. Hamilton
In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.
在美国,有 19 种不同特异性的过敏原提取物被标准化,这意味着它们的效价是根据与美国参考标准的比较来确定的。对于猫过敏原提取物,其效价是通过测量 Fel d 1 含量(以 Fel d 1 单位表示)和与皮试反应相关的单位(生物等效过敏单位或 BAU)来确定的。目前,Fel d 1 含量是通过径向免疫扩散(RID)测定法来测量的,该方法使用多克隆羊抗血清,通过在琼脂凝胶中产生白色沉淀线来检测过敏原蛋白。然而,放射免疫扩散法操作繁琐,而且不同动物的多克隆血清可能存在定性差异,并可能识别与人类过敏性疾病无关的表位。在本报告中,我们介绍了一种针对 Fel d 1 的定量双位点免疫酶测定法(IEMA),它使用固定捕获和可溶性生物素标记的 Fel d 1 特异性人类 IgE 单克隆抗体(mAb)进行检测,这些抗体已被分级为 IgG4。它们共同夹住了提取物中的 Fel d 1 分子。使用纯化的天然 Fel d 1 作为校准物,在这种基于 mAb 的 IEMA 中直接测得每 Fel d 1 单位的 Fel d 1 含量为 3.12 ± 0.24 微克,即历史上报道的 Fel d 1 含量为 4 微克/Fel d 1 单位。在测量美国市场上销售的商品猫毛和猫皮提取物的生物效力时,这种 IEMA 似乎等同于 RID。
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引用次数: 0
Diagnosing new-onset asthma in a paediatric clinical trial setting in school-age children 在儿科临床试验环境中诊断学龄儿童新发哮喘
IF 3.3 Q2 ALLERGY Pub Date : 2024-07-15 DOI: 10.3389/falgy.2024.1418922
Graham Roberts, E. Valovirta, S. Halken, Peter A. Eng, Mika J. Mäkelä, K. L. Lødrup Carlsen, Roland Knecht, L. P. Malmberg
Asthma is a common chronic disease in children. It is a dynamic condition—symptoms change over time, and the outcome of diagnostic tests can vary. Consequently, evaluating the onset of asthma at a single point in time, perhaps when patients are asymptomatic with limited impairment of the lung function, may result in false diagnostic conclusions. The absence of consistent gold-standard diagnostic criteria in children challenges the ability of any study to ascertain an effect of treatment on asthma prevention. A comprehensive review of the diagnostic criteria used for new-onset asthma in school-age children was conducted based on existing recommendations from published clinical guidance, alongside evidence from paediatric asthma prevention trials. Findings from the review were used to propose suggestions for diagnosing new-onset asthma in future asthma prevention trials. Despite an overall lack of consensus in the published clinical guidance, there are similarities between the various recommendations for diagnosing asthma in children, which typically involve assessing the variable symptoms and supplementing the medical history with objective measures of lung function. For future paediatric asthma prevention trials, we suggest that paediatric clinical trials should use a new-onset asthma definition that incorporates the concepts of “possible”, “probable” and “confirmed” asthma. “Possible” asthma would capture self-reported features of chronic symptoms and symptom relief with β2-agonist bronchodilator (suggesting reversibility). “Probable” asthma would include symptom chronicity, self-reported symptom relief with β2-agonist bronchodilator, and objective features of asthma (reversibility or bronchial hyper-responsiveness). A “confirmed” diagnosis would be made only if there is a positive response to controller therapy. These suggestions aim to improve the diagnosis of new-onset childhood asthma in clinical trials, which will be useful in the design and conduct of future paediatric asthma prevention trials.
哮喘是儿童常见的慢性疾病。它是一种动态的疾病--症状会随着时间的推移而变化,诊断测试的结果也会不同。因此,在单个时间点评估哮喘的发病情况,也许是在患者无症状、肺功能受损有限的情况下,可能会得出错误的诊断结论。由于缺乏一致的儿童金标准诊断标准,因此任何研究都难以确定治疗对哮喘预防的效果。根据已发布的临床指南中的现有建议,并结合儿科哮喘预防试验的证据,我们对学龄儿童新发哮喘的诊断标准进行了全面审查。审查结果用于提出在未来哮喘预防试验中诊断新发哮喘的建议。尽管已出版的临床指南总体上缺乏共识,但诊断儿童哮喘的各种建议之间存在相似之处,通常涉及评估各种症状,并通过肺功能的客观测量来补充病史。对于未来的儿科哮喘预防试验,我们建议儿科临床试验应使用新发哮喘的定义,其中包含 "可能"、"可能 "和 "确诊 "哮喘的概念。"可能 "哮喘将包括自我报告的慢性症状特征以及使用 β2-激动剂支气管扩张剂后症状缓解的情况(表明可逆性)。"疑似 "哮喘包括症状慢性化、使用 β2-激动剂支气管扩张剂后症状缓解的自我报告,以及哮喘的客观特征(可逆性或支气管高反应性)。只有在对控制疗法有积极反应时,才能做出 "确诊"。这些建议旨在改进临床试验中对新发儿童哮喘的诊断,这将有助于设计和开展未来的儿童哮喘预防试验。
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引用次数: 0
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Frontiers in allergy
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