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Early-life risk factors for recurrent wheezing in preschool children: A meta-analysis of 15 cohort studies. 学龄前儿童复发性喘息的早期生活危险因素:15项队列研究的荟萃分析。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-05-01 DOI: 10.2500/aap.2025.46.250020
Kaiwen Zheng, Xiang Wang

Background: Recurrent wheezing (RW) is particularly prevalent in preschool-age children and is strongly associated with the future development of asthma. Objective: Because no meta-analysis of risk factors for RW comprehensively assess is needful. Methods: The research was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of English-language studies was performed across four medical literature data bases. Subgroup analyses, sensitivity analyses, and evaluations of publication bias were carried out. Multiple cohort studies were included. Stata software and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) were used for data analysis; risk factors associated with positive results were discussed qualitatively. Results: A total of 15 cohort studies that covered 128,065 children were included. Some risk factors, including allergic rhinitis (odds ratio [OR] 4.16 [95% confidence interval {CI}, 1.06-16.33]), family history of asthma (OR 2.14 [95% CI, 1.24-3.69]), food allergy (OR 2.25 [95% CI, 1.73-2.93]), preterm (OR 1.87 [95% CI, 1.36-2.58]), male (OR 1.47 [95% CI, 1.17-1.84]), cesarean section (OR 1.36 [95% CI, 1.08-1.71]), environmental tobacco smoke (OR 2.15 [95% CI, 1.55-2.99]), got positive results. Conclusion: Risk factors for RW in preschool children were sought. This meta-analysis provides a new perspective theoretical basis for preventing childhood asthma.

背景:复发性喘息(RW)在学龄前儿童中尤为普遍,并与未来哮喘的发展密切相关。目的:由于不需要对RW的危险因素进行综合评价。方法:本研究按照系统评价和荟萃分析的首选报告项目(PRISMA)指南进行。在四个医学文献数据库中进行了英语研究的全面搜索。进行亚组分析、敏感性分析和发表偏倚评价。纳入了多个队列研究。使用Stata软件和GRADE of Recommendations, Assessment, Development and Evaluation (GRADE)进行数据分析;定性地讨论了与阳性结果相关的危险因素。结果:共纳入15项队列研究,涵盖128065名儿童。一些危险因素,包括过敏性鼻炎(比值比[OR] 4.16[95%可信区间{CI}, 1.06-16.33])、哮喘家族史(比值比[OR] 2.14 [95% CI, 1.24-3.69])、食物过敏(比值比[OR] 2.25 [95% CI, 1.73-2.93])、早产(比值比[OR] 1.87 [95% CI, 1.36-2.58])、男性(比值比[OR] 1.47 [95% CI, 1.17-1.84])、剖宫产(比值比[OR] 1.36 [95% CI, 1.08-1.71])、环境吸烟(比值比[OR] 2.15 [95% CI, 1.55-2.99])均获得阳性结果。结论:探讨学龄前儿童RW的危险因素。本荟萃分析为预防儿童哮喘提供了新的视角理论依据。
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引用次数: 0
Evaluation of the frequency of allergic diseases in pediatric patients with juvenile idiopathic arthritis. 儿童特发性关节炎患者变应性疾病发生频率的评价。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-05-01 DOI: 10.2500/aap.2025.46.250022
Ozge Yilmaz Topal, Nilufer Tekgoz, Melike Mehves Kaplan, Metin Yigit, Azize Pinar Metbulut, Elif Celikel, Ilknur Kulhas Celik, Banu Celikel Acar, Emine Dibek Misirlioglu

Objective: Allergic diseases are characterized by a T-helper type 2 (Th2) dominant immune response, whereas juvenile idiopathic arthritis (JIA) is an autoimmune condition attributed to the Th1 pathway of CD4+ T cells. Reciprocal inhibition between the Th1 and Th2 responses is proposed to result in mutual exclusion of their polarized immune responses and associated diseases. This study aimed to ascertain the frequency of allergic diseases among children with JIA. Methods: The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to assess symptoms of allergic diseases in children with JIA and a control group of children with no known autoimmune diseases. The presence of current wheezing, allergic rhinitis and/or rhinoconjunctivitis symptoms, eczema symptoms, and food allergy symptoms were assessed based on affirmative answers. Results: The ISAAC questionnaire was administered to 101 children with JIA and 99 healthy controls. The median (interquartile range [IQR]) age was 12.64 years (8.83-15.83 years) in the JIA group and 11.99 years (6.65-14.90 years) in the control group. Children with JIA had lower rates of current wheezing (p = 0.003), current allergic rhinitis (p < 0.001), current rhinoconjunctivitis (p = 0.006), current atopic dermatitis (p < 0.001), and current food allergy (p = 0.005) symptoms. In addition, ever having had allergic rhinitis, wheezing, and atopic dermatitis were less common in the JIA group. In the multivariate logistic regression model, the absence of autoimmune disease in the patient and the presence of any allergic disease in the mother emerged as independent risk factors for current wheezing symptoms and current rhinoconjunctivitis and/or rhinitis. Conclusion: The results of this study demonstrated that the frequency of allergic diseases was lower in the presence of JIA, an autoimmune disease. This offers further evidence of mutual opposition between diseases that involve the Th1 and Th2 pathways, but there remains no consensus on this matter. More comprehensive studies that delve into the molecular foundations of these diseases are still needed to reach more definitive conclusions.

目的:过敏性疾病以T辅助型2 (Th2)为主的免疫应答为特征,而幼年特发性关节炎(JIA)是一种与CD4+ T细胞Th1通路相关的自身免疫性疾病。Th1和Th2反应之间的相互抑制被认为会导致它们的极化免疫反应和相关疾病的相互排斥。本研究旨在了解JIA患儿变应性疾病的发生率。方法:采用国际儿童哮喘与过敏研究(ISAAC)问卷对JIA患儿和无自身免疫性疾病患儿的变应性疾病症状进行评估。根据肯定答案评估当前喘息、过敏性鼻炎和/或鼻结膜炎症状、湿疹症状和食物过敏症状的存在。结果:对101例JIA患儿和99例健康对照者进行ISAAC问卷调查。JIA组年龄中位数(四分位间距[IQR])为12.64岁(8.83 ~ 15.83岁),对照组为11.99岁(6.65 ~ 14.90岁)。JIA患儿当前哮喘发生率较低(p = 0.003),当前变应性鼻炎发生率较低(p = 0.003)。结论:本研究结果表明,JIA患儿存在自身免疫性疾病时,变应性疾病的发生率较低。这进一步证明了涉及Th1和Th2通路的疾病之间的相互对立,但在这一问题上仍未达成共识。为了得出更明确的结论,仍需要进行更全面的研究,深入研究这些疾病的分子基础。
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引用次数: 0
Can depression and anxiety be predicted in hereditary angioedema? A comprehensive assessment. 遗传性血管性水肿可以预测抑郁和焦虑吗?全面评估。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-05-01 DOI: 10.2500/aap.2025.46.250017
Hatice Serpil Akten, Emel Dilek, Mehmet Orman, Emine Nihal Mete Gokmen

Background: Hereditary angioedema (HAE) is a rare genetic disorder marked by unpredictable episodes of recurrent swelling. This unpredictability, combined with the risk of death and its impact on daily life, leads to significant psychological distress, which profoundly affects patients' quality of life. Objective: This study assessed the levels of depression, general anxiety, and death anxiety in patients with HAE, along with the factors that influence them. Methods: This single-center cohort study included patients ages ≥18 years and with HAE type 1 or 2, who were followed up at the Allergy and Clinical Immunology Department, Medical Faculty, Ege University, between December 2023 and September 2024. Participants completed questionnaires with regard to their demographics, general health, and disease characteristics. In addition, their psychological conditions were assessed by using the Hospital Anxiety and Depression Scale (HADS) and Templer Death Anxiety Scale, a tool that has not been previously applied to this group. Results: One hundred patients participated in the study, with a mean ± standard deviation age of 40.5 ± 14.5 years; 66% (n = 66) were women. Among the participants, 30% (n = 30) had a family history of death related to HAE, and 74% (n = 74) reported experiencing oropharyngeal/laryngeal edema. Anxiety was observed in 54% of the patients (n = 54), whereas 36% (n = 36) experienced depression. Women had higher levels of anxiety than men (p = 0.048), and younger patients (ages <65 years) exhibited greater anxiety levels (p = 0.022). Mild-to-moderate depression was more prevalent among patients who had experienced a recent laryngeal attack (p = 0.031). Seventy-seven percent of the patients (n = 77) reported experiencing death anxiety, which was notably higher in those who had recent laryngeal attacks (p = 0.004) and moderate-to-severe attacks (p = 0.003). Conclusion: Patients with HAE, especially those who experienced frequent severe attacks or recent laryngeal episodes, face a higher risk of psychological distress.

背景:遗传性血管性水肿(HAE)是一种罕见的遗传性疾病,其特征是不可预测的复发性肿胀发作。这种不可预测性,加上死亡风险及其对日常生活的影响,导致严重的心理困扰,从而深刻影响患者的生活质量。目的:本研究评估HAE患者的抑郁、一般焦虑和死亡焦虑水平及其影响因素。方法:这项单中心队列研究纳入了年龄≥18岁且患有1型或2型HAE的患者,这些患者于2023年12月至2024年9月在Ege大学医学院过敏和临床免疫学部门进行了随访。参与者完成了关于他们的人口统计、一般健康和疾病特征的问卷调查。此外,他们的心理状况通过医院焦虑和抑郁量表(HADS)和Templer死亡焦虑量表进行评估,这是一种以前未应用于该组的工具。结果:100例患者参与研究,平均±标准差年龄40.5±14.5岁;66% (n = 66)为女性。在参与者中,30% (n = 30)有与HAE相关的死亡家族史,74% (n = 74)报告出现口咽/喉水肿。54%的患者(n = 54)出现焦虑,36%的患者(n = 36)出现抑郁。女性的焦虑水平高于男性(p = 0.048),年轻患者的焦虑水平也高于男性(p = 0.048)。结论:HAE患者,尤其是那些经常经历严重发作或最近喉部发作的患者,面临着更高的心理困扰风险。
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引用次数: 0
Selective immunoglobulin E deficiency and its association with autoimmune and autoinflammatory diseases. 选择性免疫球蛋白E缺乏及其与自身免疫性和自身炎性疾病的关系。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-05-01 DOI: 10.2500/aap.2025.46.250016
Mehmet Emin Gerek, Fatih Colkesen, Tugba Onalan, Fatma Arzu Akkus, Mehmet Kilinc, Recep Evcen, Selim Kahraman, Sevket Arslan

Background: Selective immunoglobulin E deficiency (sIgED) is a rare condition characterized by low serum IgE levels with normal levels of other immunoglobulin classes. The prevalence of sIgED varies considerably across populations, with a higher prevalence observed in clinical settings. Studies report sIgED prevalence that ranges up to 9.7% in patients attending rheumatology clinics, 8.1% in allergy/immunology clinics, and 2.6% in healthy blood donors. Its role in immune regulation and association with autoimmune and autoinflammatory disorders remains poorly understood. Objective: This study aimed to investigate the relationship between sIgED and immune-mediated diseases by hypothesizing that sIgED may predispose individuals to an increased prevalence of these conditions. Methods: This retrospective cohort study analyzed data from 3692 patients at a tertiary care center between November 2018 and December 2023. Patients with IgE levels ≤2.5 IU/mL and normal levels of other immunoglobulin classes were classified as having sIgED, whereas those with IgE levels >2.5 IU/mL served as controls. Autoimmune and autoinflammatory diseases were identified by using medical records and International Classification of Diseases codes. Statistical analyses were performed to compare the prevalence of these conditions between the groups. Results: The prevalence of autoimmune and autoinflammatory diseases was significantly higher in the sIgED group versus controls (25.2% versus 15.6%; p < 0.001). Conditions such as Hashimoto thyroiditis, vitiligo, familial Mediterranean fever, and Behçet disease were disproportionately observed in patients with sIgED. Demographic characteristics, including age and gender, were not significantly different between the groups (p = 0.171 and p = 0.257, respectively). Conclusion: The sIgED is associated with a higher prevalence of autoimmune and autoinflammatory diseases, which underscores its potential role in immune dysregulation. This finding highlights the need for further prospective, multicenter studies to validate these associations, elucidate underlying mechanisms, and explore potential clinical implications of IgE deficiency in immune-mediated pathologies.

背景:选择性免疫球蛋白E缺乏(sIgED)是一种罕见的疾病,其特征是血清IgE水平低,而其他免疫球蛋白类水平正常。sIgED的患病率在人群中差异很大,在临床环境中观察到更高的患病率。研究报告sIgED患病率在风湿病诊所高达9.7%,过敏/免疫学诊所为8.1%,健康献血者为2.6%。它在免疫调节中的作用以及与自身免疫和自身炎症疾病的关联仍然知之甚少。目的:本研究旨在探讨sIgED与免疫介导性疾病之间的关系,假设sIgED可能使个体易患这些疾病。方法:本回顾性队列研究分析了2018年11月至2023年12月在某三级医疗中心就诊的3692例患者的数据。IgE水平≤2.5 IU/mL且其他免疫球蛋白类别水平正常的患者被归类为sIgED,而IgE水平≤2.5 IU/mL的患者作为对照组。利用医疗记录和国际疾病分类代码对自身免疫性和自身炎症性疾病进行鉴定。进行统计分析,比较各组之间这些疾病的患病率。结果:sIgED组自身免疫性和自身炎症性疾病的患病率明显高于对照组(25.2% vs 15.6%;结论:sIgED与自身免疫性和自身炎症性疾病的较高患病率相关,这强调了其在免疫失调中的潜在作用。这一发现强调了进一步的前瞻性、多中心研究的必要性,以验证这些关联,阐明潜在的机制,并探索IgE缺乏在免疫介导病理中的潜在临床意义。
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引用次数: 0
Risk factors predisposing children to transient hypogammaglobulinemia of infancy. 儿童易患婴儿期短暂性低γ球蛋白血症的危险因素。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-05-01 DOI: 10.2500/aap.2025.46.250019
Mehmet Halil Celiksoy, Ilke Yildirim, Kubra Yirgin, Zeynep Haziroglu Okmen

Introduction: Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder characterized by reduced serum immunoglobulin G (IgG) levels in early infancy. Objective: This study aimed to identify potential risk factors associated with THI. Methods: Children with THI and normoglobulinemic healthy children were compared by using a questionnaire that addressed possible risk factors. Results: In total, 108 participants were enrolled, 54 patients with THI and 54 healthy controls. The median age at diagnosis of the patients with THI was 17 months (range, 4-38 months), and 40 (74.1%) were boys. In the control group, the median age was 22 months (range, 16-61 months), and 27 (50.0%) were boys. Male sex (p = 0.004), cesarean section birth (p = 0.003), low maternal education (p = 0.001), low paternal education (p = 0.004), analgesic use during pregnancy (p = 0.001), antibiotic use during pregnancy (p = 0.001), multivitamin use during pregnancy (p = 0.001), gestational diabetes or preeclampsia (p = 0.039), smoking exposure (p = 0.001), atopic disease (p = 0.001), and familial atopy (p = 0.001) were associated with THI, whereas low socioeconomic level (p = 0.001) and breast-feeding for > 6 months (p = 0.032) were less likely in the THI group. Conclusion: There are several features of pregnancy history and family demographics that are associated with THI.

婴儿期短暂性低γ球蛋白血症(THI)是一种异质性疾病,其特征是婴儿期早期血清免疫球蛋白G (IgG)水平降低。目的:本研究旨在确定与THI相关的潜在危险因素。方法:采用问卷调查的方法对THI患儿和正常球蛋白血症患儿进行比较,以确定可能的危险因素。结果:共纳入108名受试者,54名THI患者和54名健康对照。THI患者诊断时的中位年龄为17个月(范围4-38个月),其中40例(74.1%)为男孩。对照组中位年龄为22个月(范围16-61个月),男童27例(50.0%)。男性(p = 0.004)、剖宫产(p = 0.003)、母亲受教育程度低(p = 0.001)、父亲受教育程度低(p = 0.004)、怀孕期间使用止痛药(p = 0.001)、怀孕期间使用多种维生素(p = 0.001)、妊娠糖尿病或子痫前期(p = 0.039)、吸烟(p = 0.001)、特应性疾病(p = 0.001)和家族性特应性(p = 0.001)与THI相关。而低社会经济水平(p = 0.001)和母乳喂养1 - 6个月(p = 0.032)的THI组更不可能。结论:妊娠史和家庭人口统计学特征与THI有关。
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引用次数: 0
Single-bag rapid drug desensitization for chemotherapeutic hypersensitivity reactions: A single-center experience. 化疗超敏反应的单袋快速药物脱敏:单中心经验。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-05-01 DOI: 10.2500/aap.2025.46.250014
Ozcan Gul, Makbule Seda Bayrak Durmaz, Reyhan Yıldız, Fuat Aytekin, Nazan Beyhan, Orhun Efe, Sevim Bavbek

Background: Rapid drug desensitization (RDD) is a procedure that provides temporary tolerance to chemotherapeutics for appropriate patients who experience hypersensitivity reactions (HSR), which allow them to continue their treatments. Due to the labor-intensive and time-consuming nature of the commonly used multiple-bag RDD procedure, there is a need to develop an alternative protocol. We aimed to share our experiences with single-bag RDD in patients experiencing HSRs with chemotherapeutics. Methods: The study was conducted by retrospectively reviewing the files of patients who experienced immediate-type HSRs to chemotherapeutics and underwent single-bag RDD. The severity of HSRs was classified according to the Brown grading system. Prick and/or intradermal skin tests were performed with the relevant agents. The protocols were applied as a single-bag, 12-step process. Results: The study comprised 46 patients (women/men, 35/11; mean ± standard deviation age, 55.9 ± 11.9 years; 27 HSRs to platinums; 16 HSRs to taxanes; and 3 HSRs to biologic agents). Nine patients (19.6%) had an initial HSR of grade 1, 26 patients (56.5%) had an initial HSR of grade 2, and 11 patients (23.9%) had an initial HSR of grade 3. The skin testing result with the responsible drug was positive in 15 of 42 (35.7%), and the rate of positive responses in patients with grade 1, 2, and 3 initial HSRs was 37.5%, 33.3%, and 40%, respectively. A total of 163 single-bag RDDs procedures were performed, and 17 breakthrough reactions (BTR) occurred during the procedure (five of these reactions [29.5%] were grade 1; nine [53.9%] were grade 2; three [17.6%] were grade 3). Of these BTRs, 16 occurred with platinums and one with rituximab; no BTRs were observed with taxanes. In conclusion, 99.3% of the total 163 single-bag RDD procedures were successfully completed. Conclusion: Our experience indicates that single-bag RDD can be a safe and effective alternative that saves time and labor in appropriate patients.

背景:快速药物脱敏(RDD)是一种为出现超敏反应(HSR)的适当患者提供暂时化疗耐受性的方法,使他们能够继续治疗。由于常用的多袋RDD过程的劳动密集型和耗时性,需要开发一种替代协议。我们的目的是分享我们在化疗后发生hsr的患者中进行单袋RDD的经验。方法:回顾性分析对化疗药物发生立即型hsr并行单袋RDD的患者资料。根据布朗分级系统对hsr的严重程度进行分类。用相关药剂进行点刺和/或皮内皮肤试验。该方案采用单袋12步流程。结果:共纳入46例患者(男女35/11;平均±标准差年龄55.9±11.9岁;27个高铁到铂金;16对紫杉烷的高铁;对生物制剂的hsr为3)。9名患者(19.6%)的初始HSR为1级,26名患者(56.5%)的初始HSR为2级,11名患者(23.9%)的初始HSR为3级。42例患者中有15例(35.7%)的皮肤试验结果为阳性,1级、2级和3级初始HSRs患者的阳性反应率分别为37.5%、33.3%和40%。共进行163例单袋rdd手术,手术过程中发生17例突破性反应(BTR),其中5例(29.5%)为1级反应;2级9例(53.9%);3例(17.6%)为3级。在这些btr中,16例发生在铂类药物组,1例发生在利妥昔单抗组;紫杉烷未观察到btr。总而言之,163个单袋RDD程序中99.3%成功完成。结论:我们的经验表明,在合适的患者中,单袋RDD是一种安全有效的替代方法,节省了时间和劳动力。
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引用次数: 0
Allergic comorbidities in fibromyalgia. 纤维肌痛的过敏性合并症。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-03-01 DOI: 10.2500/aap.2025.46.240080
Eli Magen, Eugene Merzon, Ilan Green, Israel Magen, Avivit Golan-Cohen, Shlomo Vinker, Ariel Israel

Background: The relationship between fibromyalgia (FM) and allergic diseases remains poorly understood, despite emerging evidence that suggests a possible association. Objective: This study aimed to evaluate the prevalence of allergic comorbidities in patients with FM compared with a matched control group. Methods: We conducted a retrospective, population-based case-control study within Leumit Health Services, which caters to ∼750,000 members. Patients meeting the evolving criteria of the American College of Rheumatology from January 2002 to December 2023 were included. Control subjects were selected from the same population base but did not have a diagnosis of FM, were matched 5:1 on sex, age, and year of first membership. All diagnoses were identified by using International Classification of Diseases, Ninth Revision (ICD-9) codes up to March 2024. Results: The analysis included 15,869 patients diagnosed with FM and 79,345 matched controls. There was a predominant female representation (82.1%) in both groups. The prevalence of bronchial asthma was higher in patients with FM compared with the controls, with an odds ratio (OR) of 1.91. The patients with FM also exhibited higher rates of both nonseasonal and seasonal allergic rhinitis, with ORs of 1.60 and 1.30, respectively, and chronic rhinosinusitis without nasal polyps demonstrated an OR of 2.46. Acute allergic conjunctivitis had an OR of 2.05. Skin-related allergies such as contact dermatitis and atopic dermatitis showed ORs of 1.48 and 1.41, respectively. Furthermore, the patients with FM displayed elevated rates of various forms of urticaria and chronic pruritus, alongside higher incidences of food allergies and specific drug allergies. Anaphylactic reactions to food were notably more common in patients with FM, who presented an OR of 2.50. Conclusion: FM is associated with a higher prevalence of allergic diseases compared with the controls. Analysis of these findings suggests the need for allergological assessments in FM management.

背景:纤维肌痛(FM)和过敏性疾病之间的关系仍然知之甚少,尽管新出现的证据表明可能存在关联。目的:本研究旨在评估FM患者过敏性合并症的患病率,并与匹配的对照组进行比较。方法:我们在Leumit健康服务中心进行了一项回顾性的、基于人群的病例对照研究,该研究覆盖了约75万名成员。从2002年1月到2023年12月,符合美国风湿病学会不断发展的标准的患者被纳入。对照受试者从相同的人群基础中选择,但没有诊断为FM,在性别,年龄和首次加入的年份上按5:1匹配。所有诊断均采用截至2024年3月的《国际疾病分类第九次修订版》(ICD-9)代码进行鉴定。结果:分析包括15869名确诊为FM的患者和79345名匹配的对照组。两组均以女性占主导地位(82.1%)。与对照组相比,FM患者的支气管哮喘患病率更高,优势比(OR)为1.91。FM患者的非季节性变应性鼻炎和季节性变应性鼻炎的发生率也更高,OR分别为1.60和1.30,无鼻息肉的慢性鼻窦炎的OR为2.46。急性变应性结膜炎OR为2.05。皮肤相关过敏如接触性皮炎和特应性皮炎的or分别为1.48和1.41。此外,FM患者表现出各种形式的荨麻疹和慢性瘙痒的发生率升高,同时食物过敏和特定药物过敏的发生率也较高。食物过敏反应在FM患者中更为常见,其OR为2.50。结论:与对照组相比,FM与较高的过敏性疾病患病率相关。对这些发现的分析表明,在FM管理中需要进行过敏学评估。
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引用次数: 0
Dose-response studies of methylated and nonmethylated CpG ODNs from Bifidobacterium longum subsp. infantis for optimizing Treg cell stimulation. 长双歧杆菌甲基化和非甲基化CpG ODNs的剂量反应研究。优化婴儿Treg细胞刺激。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-03-01 DOI: 10.2500/aap.2025.46.250001
Dongmei Li, Idalia Cruz, Sharareh Sorkhabi, Patricia L Foley, Julie Wagner, Joseph A Bellanti

Background: Allergen immunotherapy (AIT) is the most effective treatment for atopic allergic diseases, aiming to induce regulatory T cells (Treg) that modify the immune response to specific allergens, which leads to long-term tolerance and reduced symptoms. Enhancing Treg activity is crucial for improving immunotherapy outcomes. In a previous murine model study, we examined the effects of a synthetic methylated DNA oligodeoxynucleotide (ODN) from the Bl-T2 m5C motif of Bifidobacterium longum subsp. infantis. The ODN that contains the methylated BI-T2 m5C motif (methylated ODNA) sequence conjugated with ovalbumin induced Treg production, whereas ODN that contains the unmethylated BI-T2 m5C motif (unmethylated ODNB) induced proinflammatory responses, which demonstrated the potential of methylated ODNs for AIT. Objective: In building on these results, this study explored the effects of methylated and nonmethylated DNA motifs from B. longum subsp. infantis on inflammation and Treg induction, while investigating the dose-response relationships of methylated Cytosine-phosphate-Guanine (CpG) ODNs for optimal Treg stimulation in clinical applications. Methods: Serum levels of IL-17A, IL-4, IL-10, and transforming growth factor beta (TGF-β) were measured by enzyme linked immunosorbent assay (ELISA), and flow cytometry assessed splenic Treg populations in BALB/c mice receiving graded doses of methylated or unmethylated ODNs. Mice were immunized intraperitoneally with a single 100-μg dose (plan A) or multiple 25 μg (plan B) or 100 μg (plan C) doses. Calf thymic DNA served as a positive control, with phosphate-buffered saline solution and alum as negative controls. Results: Methylated ODNs significantly increased CD25+FOXP3+ Tregs compared with unmethylated ODNs and controls. Plan A (100 μg) elevated serum IL-10, which indicated effective Treg induction, whereas plan B (four 25 μg doses) did not activate Tregs. Plan C (multiple 100 μg doses) reduced Treg responses, which highlighted a critical dosing threshold for optimal Treg induction. Conclusion: This study demonstrated the potential of methylated DNA motifs as therapeutic agents in AIT. The dose-response relationships of methylated CpG ODNs from B. longum pave the way for clinical applications that target Treg activity in allergic diseases.

背景:过敏原免疫疗法(Allergen immunotherapy, AIT)是治疗特应性变态反应性疾病最有效的方法,旨在诱导调节性T细胞(regulatory T cells, Treg)改变对特定过敏原的免疫反应,从而导致长期耐受性和减轻症状。增强Treg活性对改善免疫治疗效果至关重要。在之前的一项小鼠模型研究中,我们检测了长双歧杆菌Bl-T2 m5C基序合成的甲基化DNA寡脱氧核苷酸(ODN)的影响。对象的。含有甲基化的BI-T2 m5C基序(甲基化的ODNA)序列与卵清蛋白结合的ODN诱导Treg产生,而含有未甲基化的BI-T2 m5C基序(未甲基化的ODNB)的ODN诱导促炎反应,这表明甲基化的ODN在AIT中的潜力。目的:在这些结果的基础上,本研究探讨了长芽孢杆菌亚种甲基化和非甲基化DNA基序的影响。同时研究甲基化胞嘧啶-磷酸-鸟嘌呤(CpG) ODNs的剂量-反应关系,以在临床应用中获得最佳的Treg刺激。方法:采用酶联免疫吸附法(ELISA)检测BALB/c小鼠血清IL-17A、IL-4、IL-10和转化生长因子β (TGF-β)水平,并用流式细胞术评估接受分级剂量甲基化或未甲基化odn的小鼠脾Treg群。小鼠腹腔注射单次100 μg剂量(a方案)或多次25 μg (B方案)或100 μg (C方案)免疫。小牛胸腺DNA作为阳性对照,磷酸盐缓冲盐水溶液和明矾作为阴性对照。结果:与未甲基化的ODNs和对照组相比,甲基化的ODNs显著增加CD25+FOXP3+ Tregs。方案A (100 μg)升高血清IL-10,表明Treg诱导有效,而方案B(4次25 μg剂量)未激活Treg。方案C(多次100 μg剂量)降低了Treg反应,这突出了最佳Treg诱导的临界剂量阈值。结论:本研究证明了甲基化DNA基序作为AIT治疗药物的潜力。长芽胞杆菌甲基化CpG ODNs的剂量-反应关系为靶向Treg活性在过敏性疾病中的临床应用铺平了道路。
{"title":"Dose-response studies of methylated and nonmethylated CpG ODNs from <i>Bifidobacterium</i> longum subsp. <i>infantis</i> for optimizing Treg cell stimulation.","authors":"Dongmei Li, Idalia Cruz, Sharareh Sorkhabi, Patricia L Foley, Julie Wagner, Joseph A Bellanti","doi":"10.2500/aap.2025.46.250001","DOIUrl":"10.2500/aap.2025.46.250001","url":null,"abstract":"<p><p><b>Background:</b> Allergen immunotherapy (AIT) is the most effective treatment for atopic allergic diseases, aiming to induce regulatory T cells (Treg) that modify the immune response to specific allergens, which leads to long-term tolerance and reduced symptoms. Enhancing Treg activity is crucial for improving immunotherapy outcomes. In a previous murine model study, we examined the effects of a synthetic methylated DNA oligodeoxynucleotide (ODN) from the Bl-T2 m5C motif of <i>Bifidobacterium longum</i> subsp. <i>infantis</i>. The ODN that contains the methylated BI-T2 m5C motif (methylated ODNA) sequence conjugated with ovalbumin induced Treg production, whereas ODN that contains the unmethylated BI-T2 m5C motif (unmethylated ODNB) induced proinflammatory responses, which demonstrated the potential of methylated ODNs for AIT. <b>Objective:</b> In building on these results, this study explored the effects of methylated and nonmethylated DNA motifs from <i>B. longum</i> subsp. <i>infantis</i> on inflammation and Treg induction, while investigating the dose-response relationships of methylated Cytosine-phosphate-Guanine (CpG) ODNs for optimal Treg stimulation in clinical applications. <b>Methods:</b> Serum levels of IL-17A, IL-4, IL-10, and transforming growth factor beta (TGF-β) were measured by enzyme linked immunosorbent assay (ELISA), and flow cytometry assessed splenic Treg populations in BALB/c mice receiving graded doses of methylated or unmethylated ODNs. Mice were immunized intraperitoneally with a single 100-μg dose (plan A) or multiple 25 μg (plan B) or 100 μg (plan C) doses. Calf thymic DNA served as a positive control, with phosphate-buffered saline solution and alum as negative controls. <b>Results:</b> Methylated ODNs significantly increased CD25<sup>+</sup>FOXP3<sup>+</sup> Tregs compared with unmethylated ODNs and controls. Plan A (100 μg) elevated serum IL-10, which indicated effective Treg induction, whereas plan B (four 25 μg doses) did not activate Tregs. Plan C (multiple 100 μg doses) reduced Treg responses, which highlighted a critical dosing threshold for optimal Treg induction. <b>Conclusion:</b> This study demonstrated the potential of methylated DNA motifs as therapeutic agents in AIT. The dose-response relationships of methylated CpG ODNs from <i>B. longum</i> pave the way for clinical applications that target Treg activity in allergic diseases.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 2","pages":"98-104"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rapid drug desensitization in seven patients with delayed hypersensitivity reactions to biologics and targeted therapies: Reason, successes, and failures. 7例对生物制剂和靶向治疗迟发性超敏反应患者的快速药物脱敏:原因、成功和失败。
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-03-01 DOI: 10.2500/aap.2025.46.240101
Tugba Onalan, Fatih Colkesen, Mehmet Emin Gerek, Fatma Arzu Akkus, Recep Evcen, Sevket Arslan

Backround: Rapid drug desensitization (RDD) is commonly used for immediate drug hypersensitivity reactions (DHR) across various drugs. In delayed DHRs, the conventional approach is slow desensitization; however, limitations may arise due to drug-specific or disease-related factors. With the increasing role of targeted molecular drugs in delayed DHRs, data on the efficacy of RDD in these contexts remain scarce. Objective: This case series aims to explore the rationale and outcomes of RDD in managing delayed DHRs associated with targeted therapies. Methods: We analyzed data from patients referred to a tertiary university hospital's drug allergy outpatient clinic between January 2021 and April 2024. The subjects experienced delayed DHRs during treatment with targeted drugs and, subsequently, underwent RDD. Results: The drugs administered via RDD included bevacizumab, rituximab, daratumumab, lenalidomide, bortezomib, and carfilzomib. The index reactions included maculopapular eruptions (MPE), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Delayed breakthrough reactions were observed in four of seven patients. RDD with bortezomib was unsuccessful in all three patients, and delayed reactions were observed in all patients with severe cutaneous adverse reactions (AGEP and DRESS). Conclusion: Suggesting significant success of RDD for delayed DHRs induced by targeted therapies may be overly optimistic. Nevertheless, four of seven patients, including one with AGEP, were able to continue their treatment. Managing patients with advanced diseases and delayed DHR poses notable challenges. The risk to patient survival from withholding life-saving medication must be weighed against the risks of desensitization. The low sensitivity of skin tests and the critical waiting period complicate decision-making. Given the unique contribution of targeted agents in the treatment of severe, life-threatening diseases, further research on desensitization is warranted.

背景:快速药物脱敏(RDD)通常用于多种药物的即时药物超敏反应(DHR)。在延迟dhr中,常规方法是缓慢脱敏;然而,由于药物特异性或疾病相关因素,可能会出现限制。随着靶向分子药物在迟发性dhr中的作用越来越大,关于RDD在这些情况下疗效的数据仍然很少。目的:本病例系列旨在探讨RDD治疗与靶向治疗相关的延迟性dhr的基本原理和结果。方法:我们分析了2021年1月至2024年4月在某三级大学医院药物过敏门诊就诊的患者的数据。受试者在靶向药物治疗期间出现延迟dhr,随后发生RDD。结果:通过RDD给药的药物包括贝伐单抗、利妥昔单抗、达拉单抗、来那度胺、硼替佐米和卡非佐米。指标反应包括黄斑丘疹(MPE)、嗜酸性粒细胞增多及全身症状的药物反应(DRESS)和急性全身性脓疱病(AGEP)。7例患者中有4例出现延迟突破反应。在所有3例患者中,硼替佐米的RDD治疗均不成功,所有出现严重皮肤不良反应(AGEP和DRESS)的患者均出现延迟反应。结论:认为RDD治疗由靶向治疗引起的迟发性DHRs取得显著成功可能过于乐观。然而,7名患者中有4名,包括1名AGEP患者,能够继续接受治疗。管理晚期疾病患者和延迟DHR带来了显著的挑战。停止使用救命药物对患者生存的风险必须与脱敏的风险进行权衡。皮肤试验的低灵敏度和关键的等待期使决策复杂化。鉴于靶向药物在治疗严重、危及生命的疾病方面的独特贡献,对脱敏的进一步研究是有必要的。
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引用次数: 0
Association between allergic diseases and hypertension: Co-occurrence pattern analysis. 过敏性疾病与高血压的关系:共现模式分析
IF 2.6 3区 医学 Q2 ALLERGY Pub Date : 2025-03-01 DOI: 10.2500/aap.2025.46.240110
Xueshan Cao, Guanqi Zhao, Huiyuan Peng, Yuanqi Mi, Mengge Zhou, Yang Guo

Background: The hypertension risk in the co-occurrence of allergic diseases remains largely unknown. Objective: We aimed to investigate the association between allergic diseases co-occurrence pattern and hypertension morbidity and mortality, and to evaluate additive interaction effects between allergic diseases. Methods: A nationally representative population from the U.S. National Health Interview Survey 2012 was enrolled. Hypertension and five specific allergic diseases, including asthma, allergic rhinitis (AR), food allergy (FA), eczema, and other allergy (OA), were determined. Hypertension mortality was identified until December 31, 2019. We evaluated additive interaction effects between two allergic diseases on hypertension risk: relative excess risk due to interaction (RERI) and attributable proportion of joint effect due to interaction (AP) (shown as percentages) were calculated. For modifiable lifestyle factors with significant heterogeneity in the subgroups, we examined the effect modification. Results: Totally, 34,392 participants were enrolled. Four co-occurrence patterns of two allergic diseases were associated with an increased risk of hypertension, including AR + FA (odds ratio [OR] 2.25 [95% confidence interval {CI}, 1.52-3.35]), eczema + OA (OR 1.94 [95% CI, 1.14-3.30]), AR + eczema (OR 1.76 [95% CI, 1.18-2.64]), asthma + AR (OR 1.67 [95% CI, 1.33-2.08]). Five co-occurrence patterns of three allergic diseases were associated with increased risk of hypertension. Additive interactions were seen in AR + FA (RERI, 0.65; AP, 29%), eczema + OA (RERI, 0.43; AP, 22%), AR + eczema (RERI, 0.21; AP, 12%), and asthma + AR (RERI, 0.05; AP, 3%). The significant association between asthma + FA and hypertension was only seen among participants with a body mass index (BMI) ≥ 30 kg/m² (p = 0.021). With a median follow-up of 7.5 years, one co-occurrence pattern of asthma + FA showed a significant increased risk of hypertension mortality (hazard ratio 4.32, 95% CI: 1.52-12.23), with an additive interaction was observed (RERI, 2.33; AP, 52%). Conclusion: We identified several allergic diseases co-occurrence patterns with a significantly increased risk of hypertension morbidity and mortality. Potential biologic additive effect among allergic diseases and effect modification of BMI was found. Precision primary prevention of hypertension is necessary for patients with co-occurring allergic diseases.

背景:过敏性疾病合并高血压的风险在很大程度上仍然未知。目的:探讨变态反应性疾病共发病模式与高血压发病率和死亡率的关系,并评价变态反应性疾病之间的加性相互作用。方法:纳入2012年美国全国健康访谈调查中具有全国代表性的人群。测定高血压和5种特定变态反应性疾病,包括哮喘、变应性鼻炎(AR)、食物过敏(FA)、湿疹和其他变态反应(OA)。截至2019年12月31日,高血压死亡率已确定。我们评估了两种过敏性疾病对高血压风险的加性相互作用效应:计算了相互作用的相对过量风险(rei)和相互作用联合效应的可归因比例(AP)(以百分比表示)。对于亚组中具有显著异质性的可改变的生活方式因素,我们检查了影响的改变。结果:共纳入34,392名受试者。两种过敏性疾病的四种共发生模式与高血压风险增加相关,包括AR + FA(比值比[OR] 2.25[95%可信区间{CI}, 1.52-3.35])、湿疹+ OA(比值比[OR] 1.94 [95% CI, 1.14-3.30])、AR +湿疹(比值比[OR] 1.76 [95% CI, 1.18-2.64])、哮喘+ AR(比值比[OR] 1.67 [95% CI, 1.33-2.08])。三种过敏性疾病的五种共现模式与高血压风险增加有关。AR + FA存在加性相互作用(RERI, 0.65;AP, 29%),湿疹+ OA (rei, 0.43;AP, 22%), AR +湿疹(rei, 0.21;AP, 12%),哮喘+ AR (RERI, 0.05;美联社,3%)。哮喘+ FA和高血压之间的显著关联仅在体重指数(BMI)≥30 kg/m²的参与者中发现(p = 0.021)。中位随访时间为7.5年,哮喘+ FA共发生的一种模式显示高血压死亡风险显著增加(危险比4.32,95% CI: 1.52-12.23),并观察到加性相互作用(RERI, 2.33;美联社,52%)。结论:我们确定了几种过敏性疾病与高血压发病率和死亡率显著增加的共同发生模式。发现变应性疾病中潜在的生物加性效应及BMI的效应改变。对并发过敏性疾病的患者进行高血压的精准一级预防是必要的。
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