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Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review. 对亚叶酸的超敏反应:涉及的机制基于两个病例报告和文献综述。
Matveï Apraxine, Marc Van den Eynde, Astrid De Cuyper, Françoise Pirson

Background: Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fluorouracil, are rare. Only seven publications report HSR to FA, mainly confirmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difficult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA.

Case presentation: Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The first patient described successive cycles with first back muscle pain, then chills and facial oedema and finally diffuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgE-mediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly.

Conclusions: These two cases of anaphylaxis to FA document the clinical manifestations associated with two different mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope to draw the practitioner's attention to FA as a potential agent of severe hypersensitivity, especially if symptoms remain after withdrawing the most suspected chemotherapeutic agents. We want also to stress the importance of allergy testing.

背景:抗肿瘤药物的超敏反应(HSR)是一个日益严重的问题,特别是当它们导致治疗中断时,有时没有任何等效的治疗选择。与奥沙利铂和5-氟尿嘧啶一起特别用于治疗消化道癌的亚叶酸(FA)的HSR是罕见的。只有7篇文献报道了FA引起的HSR,主要通过FA停止化疗后症状消失来证实。只有两篇论文描述了过敏测试。由于诊断困难,患者通常在停药前接受几个进一步的化疗周期,症状逐渐加重。病例介绍:在这里,我们记录了两个HSR到FA的病例,最初被错误地归因于奥沙利铂。第一位患者描述了连续的周期,首先是背部肌肉疼痛,然后是寒战和面部水肿,最后是弥漫性红斑伴唇水肿,尽管有预用药。过敏评估强调急性胰蛋白酶水平高,皮内FA试验呈阳性,指出免疫球蛋白E (IgE)介导的机制。第二例患者在服用FA期间,除了心动过速和去饱和外,还出现下背部肌肉疼痛和寒战。皮肤测试呈阴性胰蛋白酶水平正常停用FA后,症状未复发,因此患者可继续化疗。FA过敏的机制尚不清楚。症状的时间顺序提示ige介导的机制在过敏评估中未被记录。非ige介导的肥大细胞/嗜碱性粒细胞激活可能参与其中,特别是通过补体激活或通过mass相关G蛋白偶联受体X2 (MRGPRX2)。结论:这两例FA过敏反应的临床表现与两种不同机制的HSR有关。本文提供了一个机会来回顾有限的关于高铁到FA的文献。通过这些病例,我们希望引起从业者对FA作为一种潜在的严重过敏药物的关注,特别是如果在撤回最可疑的化疗药物后症状仍然存在。我们还想强调过敏测试的重要性。
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引用次数: 1
Identification of candidate aberrant differentially methylated/expressed genes in asthma. 哮喘候选异常差异甲基化/表达基因的鉴定。
Zongling Wang, Lizhi Wang, Lina Dai, Yanan Wang, Erhong Li, Shuyuan An, Fengliang Wang, Dan Liu, Wen Pan

Background: Asthma is an important non-communicable disease worldwide. DNA methylation is associated with the occurrence and development of asthma. We are aimed at assuring differential expressed genes (DEGs) modified by aberrantly methylated genes (DMGs) and pathways related to asthma by integrating bioinformatics analysis.

Methods: One mRNA dataset (GSE64913) and one gene methylation dataset (GSE137716) were selected from the Gene Expression Omnibus (GEO) database. Functional enrichment analysis was performed using GeneCodies 4.0 database. All gene expression matrices were analyzed by Gene set enrichment analysis (GSEA) software. STRING was applied to construct a protein-protein interaction (PPI) network to find the hub genes. Then, electronic validation was performed to verify the hub genes, followed by the evaluation of diagnostic value. Eventually, quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of hub genes.

Results: In total, 14 hypomethylated/high-expression genes and 10 hypermethylated/low-expression genes were obtained in asthma. Among them, 10 hub genes were identified in the PPI network. Functional analysis demonstrated that the differentially methylated/expressed genes were primarily associated with the lung development, cytosol and protein binding. Notably, HLA-DOA was enriched in asthma. FKBP5, WNT5A, TM4SF1, PDK4, EPAS1 and GMPR had potential diagnostic value for asthma.

Conclusion: The project explored the pathogenesis of asthma, which may provide a research basis for the prediction and the drug development of asthma.

背景:哮喘是世界范围内重要的非传染性疾病。DNA甲基化与哮喘的发生和发展有关。我们的目标是通过整合生物信息学分析来确保由异常甲基化基因(dmg)修饰的差异表达基因(DEGs)和与哮喘相关的途径。方法:从gene Expression Omnibus (GEO)数据库中选择1个mRNA数据集(GSE64913)和1个基因甲基化数据集(GSE137716)。使用GeneCodies 4.0数据库进行功能富集分析。所有基因表达矩阵均采用基因集富集分析(GSEA)软件进行分析。利用STRING构建蛋白相互作用(protein-protein interaction, PPI)网络,寻找枢纽基因。然后,进行电子验证,验证中心基因,然后评估诊断价值。最后利用实时定量聚合酶链反应(qRT-PCR)检测枢纽基因的表达。结果:共获得哮喘低甲基化/高表达基因14个,高甲基化/低表达基因10个。其中,在PPI网络中鉴定出10个枢纽基因。功能分析表明,差异甲基化/表达基因主要与肺发育、细胞质和蛋白质结合相关。值得注意的是,HLA-DOA在哮喘中富集。FKBP5、WNT5A、TM4SF1、PDK4、EPAS1和GMPR对哮喘有潜在的诊断价值。结论:本项目探讨了哮喘的发病机制,可为哮喘的预测及药物开发提供研究依据。
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引用次数: 0
Underlying IPEX syndrome in a patient with idiopathic juvenile arthritis and vitiligo. 原发性幼年关节炎和白癜风患者的潜在IPEX综合征。
Leonardo Oliveira Mendonça, Adriana Pitchon Dos Reis Chuster, Mayra Barros Dorna, Samar Freschi Barros, Janaina Baptista Alves, Victor Lucas Gonçalves, Ariana Campos Yang, Jorge Kalil, Myrthes Anna Maragna Toledo-Barros, Cristina Maria Kokron

Background: IPEX syndrome is an X-linked inborn error of immunity clinically characterized by the triad of: enteropathy, polyendocrinopathy and eczema. However many other clinical presentations lacking the triad above described have been reported what underpin the need of careful clinical suspicion, immunological evaluation and genetic sequencing.

Case presentation: Here we report a case of a Brazilian boy with severe eczema as the first and only presentation requiring cyclosporin therapy. Progressive and cumulative symptoms of arthritis and enteropathy lead to the suspicion of an inborn error of immunity. Peripheral FOXP3 expression was normal (CD127-/CD4+/CD25+/FOXP3+-396 cells-63%) and a pathogenic mutation in FOXP3 gene (c.1150G>A; p.Ala384Thr), confirmed the diagnosis of IPEX syndrome.

Conclusions: IPEX syndrome should be suspected in patients presenting with severe eczema associated or not with other autoimmune/hyper inflammatory diseases in life. Our study also reinforces that FOXP3 expression by flowcytometry seems not to be a good screening method, and genetic sequencing is mandatory even in those with high suspicion and normal peripheral FOXP3 expression.

背景:IPEX综合征是一种以肠病、多内分泌病和湿疹为临床特征的x连锁先天性免疫错误。然而,据报道,许多其他临床表现缺乏上述三要素,因此需要仔细的临床怀疑、免疫学评估和基因测序。病例介绍:在这里我们报告一个巴西男孩与严重湿疹的第一个和唯一的表现需要环孢素治疗。关节炎和肠病的进行性和累积性症状导致怀疑是先天免疫错误。外周FOXP3表达正常(CD127-/CD4+/CD25+/FOXP3+-396细胞-63%),FOXP3基因发生致病性突变(c.1150G> a;p.Ala384Thr),证实了IPEX综合征的诊断。结论:生活中伴有或未伴有其他自身免疫性/高炎症性疾病的严重湿疹患者应怀疑IPEX综合征。我们的研究也强调FOXP3表达流式细胞术似乎不是一种很好的筛选方法,即使在高怀疑和正常外周FOXP3表达的患者中,基因测序也是强制性的。
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引用次数: 0
Diversity of malignancies in patients with different types of inborn errors of immunity. 不同类型先天性免疫缺陷患者恶性肿瘤的多样性。
Marzieh Tavakol, Samaneh Delavari, Fereshte Salami, Sarina Ansari, Seyed Erfan Rasouli, Zahra Chavoshzadeh, Roya Sherkat, Hamid Ahanchian, Soheila Aleyasin, Hossein Esmaeilzadeh, Nasrin Moazzen, Alireza Shafiei, Farhad Abolnezhadian, Sara Iranparast, Sareh Sadat Ebrahimi, Tannaz Moeini Shad, Salar Pashangzadeh, Farzad Nazari, Arezou Rezaei, Ali Saeedi-Boroujeni, Mohammad Nabavi, Saba Arshi, Morteza Fallahpour, Mohammad Hassan Bemanian, Samin Sharafian, Sima Shokri, Sarvin Eshaghi, Shiva Nazari, Bibi Shahin Shamsian, Mehrdad Dargahi Mal-Amir, Roya Khazaei, Pooya Ashkevari, Armin Khavandegar, Sabahat Haghi, Marzie Esmaeili, Hassan Abolhassani, Nima Rezaei

Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin's lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin's lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.

免疫细胞发育、成熟和/或功能中的遗传缺陷可导致先天性免疫错误(IEI),这可能使患者易患恶性肿瘤。患有IEI的儿童患癌症的总体风险在4%至25%之间,恶性肿瘤的类型高度依赖于导致IEI的特定突变基因。在这项回顾性队列研究中,我们调查了1999年至2020年间在伊朗国家登记处登记的3056例IEI患者。评估这些患者恶性肿瘤的频率及其与IEI类型的关系。本研究共纳入82例伴有恶性肿瘤的IEI患者。其中,最常见的恶性肿瘤类型是淋巴瘤(67.1%),其次是白血病(11%)和头颈部癌症(7.3%)。在确诊的淋巴瘤中,非霍奇金淋巴瘤是最常见的类型(43.9%),其次是不同亚型的霍奇金淋巴瘤(23.2%)。实体瘤(18.3%)在类型和定位上表现出很大的异质性。恶性肿瘤类型与生存状态的相关性以及恶性肿瘤类型与IEI实体之间的相关性均不显著。意识到IEI与癌症之间的关联,凸显了肿瘤学家和免疫学家在IEI患者恶性肿瘤早期诊断和个性化治疗策略方面协同努力的重要性。
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引用次数: 1
Impact of antigen avoidance test for fibrotic hypersensitivity pneumonitis in stable phase. 抗原避免试验对稳定期纤维化超敏性肺炎的影响。
Ryo Okuda, Tamiko Takemura, Tae Iwasawa, Shota Kaburaki, Tomohisa Baba, Eri Hagiwara, Takashi Ogura

Background: The antigen avoidance has been used in the diagnosis and treatment of hypersensitivity pneumonitis (HP); however, its usefulness in stable fibrotic HP is controversial.

Objective: To investigate the usefulness of the antigen avoidance test in patients with fibrotic HP in stable phase.

Methods: The antigen avoidance test was conducted during a 2-week hospitalization comparing clinical parameters at admission and before discharge. A retrospective review of patients who underwent surgical lung biopsy or transbronchial lung cryobiopsy, who were diagnosed with fibrotic HP by multi-disciplinary discussion, and whose disease progression was stable for more than two months before the antigen avoidance test was done.

Results: Between 2016 and 2021, 40 patients met the criteria, and 17 (43%) patients had a positive antigen avoidance test. The patients with positive in the antigen avoidance test had significantly greater annual forced vital capacity (FVC) decline than those with negative before the test (- 6.5% vs. - 0.3%, p = 0.045). The patients with positive antigen avoidance test had less annual FVC decline than those with negative in the year following the test (0.8% vs. - 5.0%, p = 0.048). The differences in annual improvement were found for serum Krebs von den Lungen-6 between the positive and negative patients in the year following the test (- 27% vs. - 5%, p = 0.049). In multivariate Cox hazard regression analysis, a negative result of the antigen avoidance test was a risk factor for death or acute exacerbation of fibrotic HP (HR = 0.26 [95% CI: 0.07-0.90], p = 0.034).

Conclusions: In fibrotic HP patients in stable phase, the antigen avoidance test under a 2-week hospitalization was valuable in predicting prognosis.

背景:抗原避免已被用于超敏性肺炎(HP)的诊断和治疗;然而,其在稳定性纤维化HP中的应用仍有争议。目的:探讨抗原避免试验在稳定期纤维化HP患者中的应用价值。方法:在住院2周期间进行抗原避免试验,比较入院和出院前的临床参数。回顾性分析行外科肺活检或经支气管肺低温活检,经多学科讨论诊断为纤维化性HP,且在抗原避免试验前病情进展稳定2个月以上的患者。结果:2016年至2021年,40例患者符合标准,17例(43%)患者抗原避免试验阳性。抗原回避试验阳性患者的年用力肺活量(FVC)下降幅度明显大于试验前阴性患者(- 6.5% vs - 0.3%, p = 0.045)。抗原回避试验阳性患者术后一年FVC下降率低于阴性患者(0.8% vs. - 5.0%, p = 0.048)。检测后一年,阳性和阴性患者血清克雷布斯-冯-登-伦根-6的年改善程度存在差异(- 27% vs - 5%, p = 0.049)。在多变量Cox风险回归分析中,抗原避免试验阴性结果是纤维化HP死亡或急性加重的危险因素(HR = 0.26 [95% CI: 0.07-0.90], p = 0.034)。结论:在稳定期纤维化HP患者中,住院2周抗原避免试验对预测预后有价值。
{"title":"Impact of antigen avoidance test for fibrotic hypersensitivity pneumonitis in stable phase.","authors":"Ryo Okuda,&nbsp;Tamiko Takemura,&nbsp;Tae Iwasawa,&nbsp;Shota Kaburaki,&nbsp;Tomohisa Baba,&nbsp;Eri Hagiwara,&nbsp;Takashi Ogura","doi":"10.1186/s13223-022-00748-1","DOIUrl":"https://doi.org/10.1186/s13223-022-00748-1","url":null,"abstract":"<p><strong>Background: </strong>The antigen avoidance has been used in the diagnosis and treatment of hypersensitivity pneumonitis (HP); however, its usefulness in stable fibrotic HP is controversial.</p><p><strong>Objective: </strong>To investigate the usefulness of the antigen avoidance test in patients with fibrotic HP in stable phase.</p><p><strong>Methods: </strong>The antigen avoidance test was conducted during a 2-week hospitalization comparing clinical parameters at admission and before discharge. A retrospective review of patients who underwent surgical lung biopsy or transbronchial lung cryobiopsy, who were diagnosed with fibrotic HP by multi-disciplinary discussion, and whose disease progression was stable for more than two months before the antigen avoidance test was done.</p><p><strong>Results: </strong>Between 2016 and 2021, 40 patients met the criteria, and 17 (43%) patients had a positive antigen avoidance test. The patients with positive in the antigen avoidance test had significantly greater annual forced vital capacity (FVC) decline than those with negative before the test (- 6.5% vs. - 0.3%, p = 0.045). The patients with positive antigen avoidance test had less annual FVC decline than those with negative in the year following the test (0.8% vs. - 5.0%, p = 0.048). The differences in annual improvement were found for serum Krebs von den Lungen-6 between the positive and negative patients in the year following the test (- 27% vs. - 5%, p = 0.049). In multivariate Cox hazard regression analysis, a negative result of the antigen avoidance test was a risk factor for death or acute exacerbation of fibrotic HP (HR = 0.26 [95% CI: 0.07-0.90], p = 0.034).</p><p><strong>Conclusions: </strong>In fibrotic HP patients in stable phase, the antigen avoidance test under a 2-week hospitalization was valuable in predicting prognosis.</p>","PeriodicalId":7702,"journal":{"name":"Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology","volume":"18 1","pages":"104"},"PeriodicalIF":0.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9733398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10329730","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: 1
Associations between food allergy, country of residence, and healthcare access. 食物过敏、居住国和医疗保健获取之间的关系。
Kaitlyn A Merrill, Elissa M Abrams, Sara V Good, Ruchi S Gupta, Carina Venter, Tara Lynn M Frykas, Michael A Golding, Jennifer L P Protudjer

Background: To date, little consideration has been given to access to allergy-related care, despite the fact that food allergy affects a considerable proportion of children. As such, the current study aimed to describe access to food allergy-related services in Canada and the United States (US).

Methods: Participants were recruited via social media from March-July 2021 and were asked to complete an online survey focused on food allergy-related medical care. Participants were Canadian and US residents who live with a child < 18 years old, with ≥ 1 food allergy. A series of logistic regressions were used to assess the associations between country of residence and type of allergy testing utilized during diagnosis.

Results: Fifty-nine participants were included in the analysis (Canadian: 32/59; 54.2%; US residents: 27/59; 45.8%). Relative to Canadian participants, US respondents were less likely to be diagnosed using an oral food challenge (OFC; OR 0.16; 95% CI 0.04; 0.75: p < 0.05). Compared to children diagnosed by age 2 years, those diagnosed at age 3 years and older were less likely to have been diagnosed using an OFC (OR 0.12; 95% CI 0.01; 1.01; p = 0.05).

Conclusions: Access to food allergy-related services, varies between Canada and the US. We speculate that this variation may reflect differences in clinical practice and types of insurance coverage. Findings also underscore the need for more research centered on food allergy-related health care, specifically diagnostic testing, among larger and more diverse samples.

背景:迄今为止,很少考虑到获得过敏相关的护理,尽管事实上食物过敏影响了相当大比例的儿童。因此,目前的研究旨在描述加拿大和美国(US)获得食物过敏相关服务的情况。方法:参与者于2021年3月至7月通过社交媒体招募,并被要求完成一项关于食物过敏相关医疗保健的在线调查。结果:59名参与者被纳入分析(加拿大:32/59;54.2%;美国居民:27/59;45.8%)。与加拿大参与者相比,美国受访者不太可能被诊断为使用口腔食物挑战(OFC;或0.16;95% ci 0.04;0.75: p结论:加拿大和美国获得食物过敏相关服务的情况有所不同。我们推测这种差异可能反映了临床实践和保险范围类型的差异。研究结果还强调,需要在更大、更多样化的样本中开展更多以食物过敏相关医疗保健为中心的研究,特别是诊断测试。
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引用次数: 0
International recommendations on epinephrine auto-injector doses often differ from standard weight-based guidance: a review and clinical proposals. 关于肾上腺素自动注射器剂量的国际建议往往不同于基于体重的标准指南:回顾与临床建议。
Sten Dreborg, Graham Walter, Harold Kim

Background: In anaphylaxis, the dosing of injectable epinephrine in medical settings has been arbitrarily recommended to be 0.01 mg/kg of body weight. For ethical reasons, there have been no dose-response studies or double-blind studies performed on patients with active anaphylaxis. Intramuscular delivery of epinephrine has been the standard. Auto-injectors for use in the treatment of anaphylaxis are available in four strengths (0.1, 0.15, 0.3, and 0.5 mg). However, in many countries, only the 0.15 and 0.3 mg strengths are available. Consequently, many adult, heavy patients are prescribed the 0.3 mg dose, which may result in only one-fifth to one-third of the recommended weight-based dose being administered in heavy patients experiencing anaphylaxis. Underdosing may have therefore contributed to mortality in anaphylaxis.

Objective: To review the doses of epinephrine recommended for the treatment of anaphylaxis in the community, and assess whether recommendations should be made to increase dosing for heavy adult patients in hopes of avoiding future deaths from anaphylaxis.

Methods: We reviewed multiple national and international recommendations for the dosing of epinephrine. We also reviewed the literature on adverse drug reactions from epinephrine, lethal doses of epinephrine, and epinephrine dose-finding studies.

Results: The majority of national and regional professional societies and authorities recommend epinephrine delivered by auto-injectors at doses far lower than the generally accepted therapeutic dose of 0.01 mg/kg body weight. Furthermore, we found that the recommendations vary even within regions themselves.

Conclusions: We suggest prescribing more appropriate doses of epinephrine auto-injectors based on weight-based recommendations. There may be some exceptions, such as for patients with heart disease. We hypothesize that these recommendations will lead to improved outcomes of anaphylaxis.

背景:在过敏性休克的医疗环境中,注射用肾上腺素的剂量被武断地推荐为 0.01 毫克/千克体重。出于伦理原因,目前尚未对活动性过敏性休克患者进行剂量反应研究或双盲研究。肌肉注射肾上腺素一直是标准用药。用于治疗过敏性休克的自动注射器有四种强度(0.1、0.15、0.3 和 0.5 毫克)。然而,在许多国家,只有 0.15 和 0.3 毫克两种强度的自动注射器。因此,许多体重较重的成年患者会被处方 0.3 毫克的剂量,这可能导致发生过敏性休克的体重较重患者的用药量仅为推荐剂量的五分之一到三分之一。因此,剂量不足可能会导致过敏性休克患者死亡:目的:回顾建议用于治疗社区过敏性休克的肾上腺素剂量,并评估是否应建议增加体重较重的成年患者的剂量,以避免今后因过敏性休克而死亡:我们回顾了多个国家和国际上关于肾上腺素剂量的建议。我们还查阅了有关肾上腺素药物不良反应、肾上腺素致死剂量和肾上腺素剂量测定研究的文献:结果:大多数国家和地区的专业协会和权威机构都建议使用自动注射器注射肾上腺素,其剂量远远低于公认的治疗剂量(0.01 毫克/千克体重)。此外,我们还发现,即使在同一地区,推荐的剂量也不尽相同:结论:我们建议根据基于体重的建议,处方更适当剂量的肾上腺素自动注射器。可能会有一些例外情况,如心脏病患者。我们假设这些建议将改善过敏性休克的治疗效果。
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引用次数: 0
LncRNAs ENST00000499459 and TCONS_00004989 enhance asthma progression in children with house dust mite-induced allergic asthma. LncRNAs ENST00000499459和tcon_00004989促进屋尘螨诱发的过敏性哮喘儿童哮喘进展。
Zhang Xude, Feng Shaojie, Guo Beibei, Liu Jingjing, Xu Donghua, Liu Fengxia

Background: Long non-coding RNAs (lncRNAs) have been extensively reported to play critical roles in the pathogenesis of various disease, especially in cancer. However, little is known about the role of lncRNAs in the pathogenesis of pediatric allergic asthma.

Methods: High-throughput sequencing analysis was performed to identify differentially expressed mRNAs and lncRNAs in peripheral blood mononuclear cells (PBMCs) from 3 children with allergic asthma and 3 matched healthy controls. Bioinformatics analysis was used to select candidate lncRNAs and mRNAs that may be involved in the pathogenesis of asthma. Candidate lncRNAs were validated in a larger size of asthma patients and healthy controls. Finally, lncRNAs and molecular pathways associated with the pathogenesis of allergic asthma were identified by competing endogenous RNA (ceRNA) analysis.

Results: Five differentially expressed lncRNAs were identified after high-throughput sequencing and verified by real-time PCR. LncRNAs ENST0000631797, TCONS_00004989 and ENST00000499459 were verified to be differentially expressed in allergic asthma. Besides, ENST00000499459/DIXDC1 axis was identified to play a crucial role in allergic asthma after comprehensive ceRNA network analysis.

Conclusion: ENST00000499459 and TCONS_00004989 are potential biomarkers for house dust mite-induced allergic asthma.

背景:长链非编码rna (lncRNAs)已被广泛报道在多种疾病,特别是癌症的发病机制中发挥关键作用。然而,lncrna在儿童过敏性哮喘发病机制中的作用尚不清楚。方法:采用高通量测序方法,对3例过敏性哮喘患儿和3例健康对照者外周血单个核细胞(PBMCs)中差异表达的mrna和lncRNAs进行鉴定。利用生物信息学分析筛选可能参与哮喘发病机制的候选lncrna和mrna。候选lncrna在更大规模的哮喘患者和健康对照中得到验证。最后,通过竞争内源性RNA (ceRNA)分析确定了与过敏性哮喘发病机制相关的lncRNAs和分子通路。结果:高通量测序鉴定出5个差异表达lncrna,并进行实时PCR验证。LncRNAs ENST0000631797、tcon_00004989和ENST00000499459在过敏性哮喘中被证实存在差异表达。此外,综合ceRNA网络分析发现ENST00000499459/DIXDC1轴在过敏性哮喘中发挥关键作用。结论:ENST00000499459和tcon_00004989是屋尘螨诱发过敏性哮喘的潜在生物标志物。
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引用次数: 0
Are peanut oral food challenges still useful? An evaluation of children with suspected peanut allergy, sensitization to Ara h 2 and controlled asthma. 花生口服食物挑战仍然有用吗?疑似花生过敏、Ara h 2致敏和哮喘控制儿童的评价。
Iida Ojaniemi, Susanna Salmivesi, Antti Tikkakoski, Jussi Karjalainen, Lauri Lehtimäki, Rüdiger Schultz

Background: Sensitization to Ara h 2 has been proposed as a promising biological marker for the severity of peanut allergy and may reduce the need for oral food challenges. This study aimed to evaluate whether peanut oral food challenge is still a useful diagnostic tool for children with suspected peanut allergy and an elevated level of Ara h 2-specific IgE. Additionally, we assessed whether well-controlled asthma is an additional risk for severe reactions.

Methods: A retrospective analysis of 107 children with sensitization to Ara h 2-specific IgE (> 0.35 kU/l) undergoing open peanut challenges during 2012-2018 in the Tampere University Hospital Allergy Centre, Finland.

Results: Of the 107 challenges, 82 (77%) were positive. Serum levels of Ara h 2 -sIgE were higher in subjects with a positive challenge than in those who remained negative (median 32.9 (IQR 6.7-99.8) vs. 2.1 (IQR 1.0-4.9) kU/l), p < 0.001) but were not significantly different between subjects with and without anaphylaxis. No correlation was observed between the serum level of Ara h 2-sIgE and reaction severity grading. Well-controlled asthma did not affect the challenge outcome.

Conclusions: Elevated levels of Ara h 2-specific IgE are associated with a positive outcome in peanut challenges but not a reliable predictor of reaction severity. Additionally, well-controlled asthma is not a risk factor for severe reactions in peanut challenges in children with sensitization to Ara h 2.

背景:对Ara h2的致敏性已被认为是花生过敏严重程度的一种有前景的生物标志物,并可能减少口服食物的需求。本研究旨在评估花生口服食物挑战是否仍然是一个有用的诊断工具,儿童疑似花生过敏和Ara h2特异性IgE水平升高。此外,我们评估了控制良好的哮喘是否会增加严重反应的风险。方法:回顾性分析2012-2018年芬兰坦佩雷大学医院过敏中心107例对Ara h2特异性IgE (> 0.35 kU/l)过敏的儿童。结果:107例挑战中,82例(77%)为阳性。血清Ara h2 -sIgE水平在花生攻毒阳性受试者中高于阴性受试者(中位数32.9 (IQR 6.7-99.8) vs. 2.1 (IQR 1.0-4.9) kU/l), p结论:Ara h2特异性IgE水平升高与花生攻毒阳性结果相关,但不是反应严重程度的可靠预测因子。此外,控制良好的哮喘并不是对花生过敏的儿童发生严重反应的危险因素。
{"title":"Are peanut oral food challenges still useful? An evaluation of children with suspected peanut allergy, sensitization to Ara h 2 and controlled asthma.","authors":"Iida Ojaniemi,&nbsp;Susanna Salmivesi,&nbsp;Antti Tikkakoski,&nbsp;Jussi Karjalainen,&nbsp;Lauri Lehtimäki,&nbsp;Rüdiger Schultz","doi":"10.1186/s13223-022-00743-6","DOIUrl":"https://doi.org/10.1186/s13223-022-00743-6","url":null,"abstract":"<p><strong>Background: </strong>Sensitization to Ara h 2 has been proposed as a promising biological marker for the severity of peanut allergy and may reduce the need for oral food challenges. This study aimed to evaluate whether peanut oral food challenge is still a useful diagnostic tool for children with suspected peanut allergy and an elevated level of Ara h 2-specific IgE. Additionally, we assessed whether well-controlled asthma is an additional risk for severe reactions.</p><p><strong>Methods: </strong>A retrospective analysis of 107 children with sensitization to Ara h 2-specific IgE (> 0.35 kU/l) undergoing open peanut challenges during 2012-2018 in the Tampere University Hospital Allergy Centre, Finland.</p><p><strong>Results: </strong>Of the 107 challenges, 82 (77%) were positive. Serum levels of Ara h 2 -sIgE were higher in subjects with a positive challenge than in those who remained negative (median 32.9 (IQR 6.7-99.8) vs. 2.1 (IQR 1.0-4.9) kU/l), p < 0.001) but were not significantly different between subjects with and without anaphylaxis. No correlation was observed between the serum level of Ara h 2-sIgE and reaction severity grading. Well-controlled asthma did not affect the challenge outcome.</p><p><strong>Conclusions: </strong>Elevated levels of Ara h 2-specific IgE are associated with a positive outcome in peanut challenges but not a reliable predictor of reaction severity. Additionally, well-controlled asthma is not a risk factor for severe reactions in peanut challenges in children with sensitization to Ara h 2.</p>","PeriodicalId":7702,"journal":{"name":"Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology","volume":" ","pages":"100"},"PeriodicalIF":0.0,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40492227","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: 1
Economic impact of self-administered subcutaneous versus clinic-administered intravenous immunoglobulin G therapy in Alberta, Canada: a population-based cohort study. 在加拿大阿尔伯塔省,自体皮下注射与临床静脉注射免疫球蛋白G治疗的经济影响:一项基于人群的队列研究。
Bruce Ritchie, Karen J B Martins, Dat T Tran, Heather Blain, Lawrence Richer, Scott W Klarenbach

Background: Self-administered subcutaneous immunoglobulin G (SCIg) reduces nursing time and eliminates the need for treatment at ambulatory care clinics, as compared with clinic-based intravenously administered IgG (IVIg), and are therapeutically equivalent. Estimating the economic impact of self-administered SCIg versus clinic-administered IVIg therapy may guide treatment recommendations.

Methods: A retrospective population-based cohort study using administrative data from Alberta was performed; those treated with IgG between April 1, 2012 and March 31, 2019 were included. Costs for medical laboratory staff and nursing time, as well as ambulatory care visits were considered. Univariate generalized linear model regression with gamma distribution and log link was used to compare cost ($CDN 2020) between SCIg and IVIg administration. Stratified analysis by age (≥ 18-years; < 18-years) was performed.

Results: Among 7,890 (6,148 adults; 1,742 children) individuals who received IgG, the average administration cost per patient-year of self-administered SCIg was $5,386 (95% confidence interval [CI] $5,039, $5,734) lower than clinic-administered IVIg; per patient-year cost of self-administered SCIg was $817 (95% CI $723, $912) versus $6,204 (95% CI $6,100, $6,308) for clinic-administered IVIg. The per patient-year cost of self-administered SCIg was $5,931 (95% CI $5,543, $6,319) lower among adults and $3,177 (95% CI $2,473, $3,882) lower among children compared with clinic-administered IVIg. An estimated $31.0 million (95% CI $29.0, $33.0) in cost savings to the health system would be realised if 80% of individuals switched from clinic-administered IVIg to self-administered SCIg.

Conclusions: Self-administered SCIg is substantially less costly from a health care payer perspective in Canada. Within this type of health system, switching to self-administered SCIg has the potential to reduce overall health care costs, lessen nursing burden, and may increase clinic-based capacity for others.

背景:与以临床为基础的静脉注射IgG (IVIg)相比,自我皮下注射免疫球蛋白G (SCIg)减少了护理时间,消除了在门诊治疗的需要,并且治疗等效。评估自我给药SCIg与临床给药IVIg治疗的经济影响可以指导治疗建议。方法:采用艾伯塔省的行政数据进行回顾性人群队列研究;纳入2012年4月1日至2019年3月31日期间接受IgG治疗的患者。考虑了医疗实验室人员和护理时间以及门诊就诊的费用。采用伽马分布和对数链接的单变量广义线性模型回归比较SCIg和IVIg给药的成本($CDN 2020)。按年龄(≥18岁)分层分析结果:7890例(6148例成人;在接受IgG治疗的1,742名儿童中,自我给药SCIg的每患者年平均给药成本为5,386美元(95%可信区间[CI] 5,039美元,5,734美元),低于临床给药IVIg;自我给药SCIg的每位患者年成本为817美元(95% CI为723美元,912美元),而临床给药IVIg的每位患者年成本为6204美元(95% CI为6100美元,6308美元)。与临床给药IVIg相比,成人自我给药SCIg的每位患者年成本低5,931美元(95% CI $5,543, 6,319美元),儿童患者年成本低3,177美元(95% CI $2,473, 3,882美元)。如果80%的个人从临床给药IVIg转向自我给药SCIg,估计可为卫生系统节省3100万美元(95% CI $ 290, $33.0)的成本。结论:从加拿大卫生保健支付者的角度来看,自我施用SCIg的成本大大降低。在这种类型的卫生系统中,转向自我管理的SCIg有可能降低总体卫生保健成本,减轻护理负担,并可能增加诊所为他人提供的能力。
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引用次数: 5
期刊
Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology
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