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Total immunoglobulin E levels in induced sputum reflect asthma control status 诱导痰中总免疫球蛋白E水平反映哮喘控制状况。
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-01-05 DOI: 10.1002/clt2.70021
Wenhui Chen, Xiaofang Liu, Xiujuan Yao, Yanghe Hao, Zhuo Zhou, Chengshuo Wang, Ming Wang, Luo Zhang

Background

Most patients with severe asthma are sensitized to at least one allergen. Whether local immunoglobulin E (IgE) in induced sputum reflects asthma control status has not been investigated.

Methods

Patients with asthma were classified as well controlled, partly controlled, and uncontrolled asthma (UCA) according to Global Initiative for Asthma 2022 guidelines. Lung function and fractional exhaled nitric oxide (FeNO) were evaluated. Induced sputum was collected and total IgE and Phadiatop (IgE to common inhalant allergens) measurements were performed. General clinical characteristics and pulmonary inflammation indicators were analyzed between the three groups of asthmatic patients. Univariate and multifactor ordinal logistic regression were used to model the relationship between pulmonary inflammation indicators and asthma control status. The ability of sputum total IgE in identifying different levels of asthma control was assessed by receiver operating characteristic curve (ROC).

Results

Patients with UCA had worse lung function and airway inflammation as indicated by lower levels of forced expiratory volume in 1s (FEV1)%pred, FEV1/FVC, MEF75%pred, MEF50%pred and MEF25%pred, and higher levels of FeNO and sputum eosinophil% compared with the WCA group. In addition, higher levels of total sputum IgE and Phadiatop were found in patients with UCA than in patients with WCA and PCA. Univariate and multifactor ordinal logistic regression analysis indicated that sputum total IgE was the unique significant risk factor for poor asthma control (adjusted odds ratio = 6.25; 95% CI, 1.07–36.55; p < 0.05) among pulmonary inflammation indicators including different indices of pulmonary function test, sputum IgE and FeNO. Sputum total IgE levels showed a significant correlation with asthma control scores (r = 0.53, p < 0.001). Moreover, ROC analysis showed that the predictive value of sputum total IgE for patients with UCA was 0.82 (95% CI, 0.74–0.9).

Conclusion

Sputum total IgE reflects levels of asthma control, and can be used as an indicator of UCA.

背景:大多数严重哮喘患者至少对一种过敏原过敏。诱导痰中的局部免疫球蛋白 E(IgE)是否能反映哮喘控制状况,目前尚未进行研究:方法:根据《全球哮喘倡议 2022》指南,将哮喘患者分为控制良好、部分控制和未控制哮喘(UCA)。评估肺功能和呼出一氧化氮分数(FeNO)。收集诱导痰,并进行总 IgE 和 Phadiatop(对常见吸入性过敏原的 IgE)测定。分析了三组哮喘患者的一般临床特征和肺部炎症指标。采用单变量和多因素序数逻辑回归建立肺部炎症指标与哮喘控制状况之间的关系模型。通过接收器操作特征曲线(ROC)评估了痰总IgE识别不同哮喘控制水平的能力:结果:与WCA组相比,UCA患者的肺功能和气道炎症较差,表现为1秒内用力呼气容积(FEV1)%pred、FEV1/FVC、MEF75%pred、MEF50%pred和MEF25%pred水平较低,FeNO和痰嗜酸性粒细胞%水平较高。此外,与 WCA 和 PCA 患者相比,UCA 患者的总痰 IgE 和 Phadiatop 水平更高。单变量和多因素序数逻辑回归分析表明,痰总 IgE 是哮喘控制不佳的唯一重要风险因素(调整后的几率比=6.25;95% CI,1.07-36.55;P 结论:痰总 IgE 反映了哮喘控制不佳的风险因素:痰总 IgE 反映了哮喘控制水平,可用作 UCA 的指标。
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引用次数: 0
The present and future of digital health, digital medicine, and digital therapeutics for allergic diseases 数字健康、数字医学和过敏性疾病的数字治疗的现在和未来。
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-01-03 DOI: 10.1002/clt2.70020
He Zhang, Yang Cao, Haibo Jiang, Qilin Zhou, Qintai Yang, Lei Cheng

Background

Digital health, digital medicine, and digital therapeutics integrate advanced computer technologies into healthcare, aiming to improve efficiency and patient outcomes. These technologies offer innovative solutions for the management of allergic diseases, which affect a significant proportion of the global population and are increasing in prevalence.

Body

This review examines the current progress and future potential of digital health in allergic disease management. It highlights key advancements, including telehealth, mobile health (mHealth), artificial intelligence, clinical decision support systems (CDSS), and digital biomarkers, with a focus on their relevance to allergic disease management. The role of digital tools in improving treatment adherence, enabling remote care, and integrating environmental and patient data into personalized care models is discussed. Challenges such as data privacy, interoperability, and equitable access are addressed, alongside potential strategies to overcome these barriers.

Conclusion

Digital therapy will play an important role in allergic diseases, and the further development of digital therapies will effectively promote the development of clinical research, digital biomarkers, hypoallergenic environments and digital twins. More research is needed to support the progress of digital therapy for allergic diseases.

背景:数字健康、数字医学和数字治疗将先进的计算机技术集成到医疗保健中,旨在提高效率和患者的治疗效果。这些技术为过敏性疾病的管理提供了创新的解决方案,这些疾病影响着全球很大一部分人口,并且患病率正在上升。本文综述了数字健康在变态反应性疾病管理中的当前进展和未来潜力。它强调了关键的进展,包括远程医疗、移动医疗(mHealth)、人工智能、临床决策支持系统(CDSS)和数字生物标志物,重点是它们与过敏性疾病管理的相关性。讨论了数字工具在提高治疗依从性、实现远程护理以及将环境和患者数据集成到个性化护理模型中的作用。解决了数据隐私、互操作性和公平访问等挑战,以及克服这些障碍的潜在战略。结论:数字治疗将在过敏性疾病中发挥重要作用,数字治疗的进一步发展将有效促进临床研究、数字生物标志物、低过敏性环境和数字双胞胎的发展。需要更多的研究来支持过敏性疾病的数字治疗的进展。
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引用次数: 0
Disease control and quality of life in chronic spontaneous urticaria and recurrent angioedema are strongly linked, but not in all patients 慢性自发性荨麻疹和复发性血管性水肿的疾病控制和生活质量密切相关,但并非所有患者都如此。
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-01-03 DOI: 10.1002/clt2.70026
Sophia Neisinger, Pascale Salameh, Annika Gutsche, Felix Aulenbacher, Frank Siebenhaar, Marcus Maurer

Background

Patient-reported outcome measures (PROMs) help to assess disease control and quality of life (QoL) in chronic spontaneous urticaria (CSU) and recurrent angioedema (RA). This study aimed to assess the correlation between two different concepts: disease control and QoL, using disease-specific PROMs.

Methods

We analyzed data from 445 CSU and 330 RA patients who completed both a disease control and QoL PROM as part of the clinical routine. We included the UCT and CU-Q2oL for CSU and AECT and AE-QoL for RA.

Results

In CSU and RA, disease control scores positively correlated with QoL scores (Spearman's rho correlation coefficient (CR) −0.757, −0.735; p < 0.001) with better disease control corresponding to better quality of life. However, 5.9% of CSU patients and 28% of RA patients with complete disease control had impaired QoL. In CSU, QoL was impaired in 69.2% of patients based on the CU-Q2oL and in 62.7% of patients based on a single numeric question from the UCT, with a mismatch in 89/445 patients. In RA, QoL was impaired in 58.5% using the AE-QoL and in 52.7% using a single numeric question from the AECT30mo, with a mismatch in 69/330 patients. Different domains of the QoL PROMs showed different degrees of influence on disease control, with “Itching/Embarrassment” showing the strongest correlation with the UCT (CR −0.804; p < 0.001) and “Functioning” with the AECT3mo (CR −0.824; p < 0.001).

Conclusion

Although most patients with controlled disease have better quality of life, unexpectedly, quality of life remains impaired in up to one-fourth of patients with completely controlled CSU and RA. Reasons behind this should be investigated in further studies.

背景:患者报告的预后指标(PROMs)有助于评估慢性自发性荨麻疹(CSU)和复发性血管性水肿(RA)的疾病控制和生活质量(QoL)。本研究旨在利用疾病特异性PROMs评估两个不同概念:疾病控制和生活质量之间的相关性。方法:我们分析了445例CSU和330例RA患者的数据,这些患者完成了疾病控制和QoL PROM,作为临床常规的一部分。我们纳入了CSU的UCT和CU-Q2oL, RA的AECT和AE-QoL。结果:在CSU和RA中,疾病控制评分与生活质量评分呈正相关(Spearman’s rho相关系数(CR) -0.757, -0.735;结论:尽管大多数疾病得到控制的患者生活质量较好,但出人意料的是,高达四分之一的CSU和RA完全控制患者的生活质量仍然受损。这背后的原因应该在进一步的研究中调查。
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引用次数: 0
Cost-of-illness analysis of chronic urticaria clinical management in five countries of Latin America 拉丁美洲五个国家慢性荨麻疹临床管理的疾病成本分析。
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-01-01 DOI: 10.1002/clt2.70016
Jorge Sánchez, Leidy Álvarez, José Ignacio Larco, Luis Ensina, Guillermo Guidos-Fogelbach, Cesar A. Reyes-López, German D. Ramon, Karla Robles-Velasco, Ivan Cherrez-Ojeda

Introduction

Chronic spontaneous urticaria (CSU) is a disease with a high impact on the quality of life of patients. There are some evaluations of the economic cost of the disease in developed countries, but there is little information about the economic cost of the disease in developing countries. Our aim was to assess the economic diagnostic and therapeutic expenses of CSU in five Latin American (LA) countries.

Methods

A noninterventional multicenter cross-sectional study was conducted in five LA countries: Brazil, Colombia, Ecuador, Mexico, and Peru. To determine the frequency of medical interventions as well as clinical and sociodemographic characteristics of CSU patients, questionnaires were administered to patients, primary care physicians, allergists, and dermatologists. In each country, diagnostics and therapeutic expenses were calculated by reviewing medical records, health insurance, and interviews. The main outcome was the yearly economic burden from the healthcare insurance perspective in each country.

Results

According to the projected costs, Brazil had the highest urticaria cost per patient/year (7009.4 USD), followed by Mexico (3695.1 USD), Ecuador (3132.8 USD), Peru (2693.9 USD), and Colombia (2392.8 USD); the cost and the frequency of use of omalizumab and antihistamines explain the total cost differences between countries. Interventions such as medical visits and exams had similar costs between countries and represented less than 10% of total urticaria cost analysis in the five countries.

Conclusion

The cost of the CSU in LA varies widely based on the health insurance coverage, the cost of the therapies, and the frequency of therapies used. Strengthening national health systems, as well as following the recommendations of international guidelines, seems to reduce the cost of CSU and improve the quality of patients.

慢性自发性荨麻疹(CSU)是一种严重影响患者生活质量的疾病。发达国家对该病的经济成本进行了一些评估,但关于该病在发展中国家的经济成本的信息很少。我们的目的是评估五个拉丁美洲(LA)国家CSU的经济诊断和治疗费用。方法:在巴西、哥伦比亚、厄瓜多尔、墨西哥和秘鲁这五个洛杉矶国家进行了一项非介入性多中心横断面研究。为了确定医疗干预的频率以及CSU患者的临床和社会人口学特征,对患者、初级保健医生、过敏症专家和皮肤科医生进行了问卷调查。在每个国家,诊断和治疗费用是通过审查医疗记录、健康保险和访谈来计算的。从每个国家医疗保险的角度来看,主要的结果是每年的经济负担。结果:按预计成本计算,巴西每位患者/年的荨麻疹成本最高(7009.4美元),其次是墨西哥(3695.1美元)、厄瓜多尔(3132.8美元)、秘鲁(2693.9美元)和哥伦比亚(2392.8美元);omalizumab和抗组胺药的成本和使用频率解释了各国之间的总成本差异。医疗访问和检查等干预措施在各国之间的成本相似,在五个国家的荨麻疹总成本分析中所占比例不到10%。结论:洛杉矶CSU的费用因医疗保险覆盖范围、治疗费用和使用治疗频率的不同而有很大差异。加强国家卫生系统,以及遵循国际指南的建议,似乎可以降低CSU的成本并提高患者的质量。
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引用次数: 0
Towards a common approach for managing food allergy and serious allergic reactions (anaphylaxis) at school. GA2LEN and EFA consensus statement
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2024-12-29 DOI: 10.1002/clt2.70013
Antoine Deschildre, Montserrat Alvaro-Lozano, Antonella Muraro, Marcia Podesta, Debra de Silva, Mattia Giovannini, Simona Barni, Timothy E. Dribin, Mónica Sandoval-Ruballos, Aikaterini Anagnostou, Alessandro Fiocchi, Alice Toniolo, Andrew Bird, Angel Sánchez Sanz, Anna Asarnoj, Anna Nowak-Wegrzyn, Berber Vlieg-Boerstra, Brian P. Vickery, Carina Venter, Caroline Nilsson, Cecilia Parente, Céline Demoulin, David M. Fleischer, Diola Bijlhout, Edward F. Knol, Eleanor Garrow, Emma E. Cook, Fallon Schultz, Francesca Lazzarotto, Francesca Mori, Gary Wong, Gideon Lack, Graham Roberts, Gustavo Andres Marino, H. N. G. Oude Elberink, Helen A. Brough, Hugh A. Sampson, Jay Lieberman, Jennifer Gerdts, Jing Zhao, Josefine Gradman, Julia E. M. Upton, Julie Wang, Kati Palosuo, Kirsi M. Järvinen, Kirsten Beyer, Kunling Shen, Laura Polloni, Lianne Mandelbaum, Luciana Kase Tanno, Lucy A. Bilaver, Marcus S. Shaker, Margitta Worm, Maria Said, Mary Kelly, Mary Jane Marchisotto, Michael Makris, Mikaela Odemyr, Montserrat Fernandez-Rivas, Motohiro Ebisawa, Nandinee Patel, Pablo Rodríguez del Río, Pakit Vichyanond, Paul Turner, Pete Smith, Pilar Morón Gaspar, R. Sharon Chinthrajah, Rima Rachid, Roberta Bonaguro, Ruchi Gupta, Sabine Schnadt, Sakura Sato, Stefania Arasi, Stephanie Leonard, Sung Poblete, Susanne Halken, Thuy-My Le, Guillaume Pouessel, Tracey Dunn, Victoria Cardona, Torsten Zuberbier

GA2LEN and EFA propose minimum specifications for all industrialised countries/regions to work towards to support students with food allergies in educational settings. We reviewed research and legislation and gained feedback from over 100 patient and professional groups. We built shared expectations around: 1. training all school staff about what food allergy is, the symptoms of allergic reactions, what to do in an emergency, and when and how to use and store devices that laypeople can use to administer adrenaline (epinephrine). 2. preventing allergic reactions by using clear labelling on school menus and prepacked and non-prepacked foods and regular cleaning where students eat. 3. preparing for serious allergic reactions, with written emergency action plans for every student with food allergies, legislation allowing schools to store adrenaline for anyone who needs it in an emergency (not just those prescribed it), and training and legal safeguards for staff administering adrenaline. 4. including affected students by discussing food allergy in the curriculum, raising awareness among all students and caregivers and reviewing school processes regularly. It is time for national and international action at the policy level. Patient groups, education networks and professional societies all play a role in campaigning for shared next steps.

{"title":"Towards a common approach for managing food allergy and serious allergic reactions (anaphylaxis) at school. GA2LEN and EFA consensus statement","authors":"Antoine Deschildre,&nbsp;Montserrat Alvaro-Lozano,&nbsp;Antonella Muraro,&nbsp;Marcia Podesta,&nbsp;Debra de Silva,&nbsp;Mattia Giovannini,&nbsp;Simona Barni,&nbsp;Timothy E. Dribin,&nbsp;Mónica Sandoval-Ruballos,&nbsp;Aikaterini Anagnostou,&nbsp;Alessandro Fiocchi,&nbsp;Alice Toniolo,&nbsp;Andrew Bird,&nbsp;Angel Sánchez Sanz,&nbsp;Anna Asarnoj,&nbsp;Anna Nowak-Wegrzyn,&nbsp;Berber Vlieg-Boerstra,&nbsp;Brian P. Vickery,&nbsp;Carina Venter,&nbsp;Caroline Nilsson,&nbsp;Cecilia Parente,&nbsp;Céline Demoulin,&nbsp;David M. Fleischer,&nbsp;Diola Bijlhout,&nbsp;Edward F. Knol,&nbsp;Eleanor Garrow,&nbsp;Emma E. Cook,&nbsp;Fallon Schultz,&nbsp;Francesca Lazzarotto,&nbsp;Francesca Mori,&nbsp;Gary Wong,&nbsp;Gideon Lack,&nbsp;Graham Roberts,&nbsp;Gustavo Andres Marino,&nbsp;H. N. G. Oude Elberink,&nbsp;Helen A. Brough,&nbsp;Hugh A. Sampson,&nbsp;Jay Lieberman,&nbsp;Jennifer Gerdts,&nbsp;Jing Zhao,&nbsp;Josefine Gradman,&nbsp;Julia E. M. Upton,&nbsp;Julie Wang,&nbsp;Kati Palosuo,&nbsp;Kirsi M. Järvinen,&nbsp;Kirsten Beyer,&nbsp;Kunling Shen,&nbsp;Laura Polloni,&nbsp;Lianne Mandelbaum,&nbsp;Luciana Kase Tanno,&nbsp;Lucy A. Bilaver,&nbsp;Marcus S. Shaker,&nbsp;Margitta Worm,&nbsp;Maria Said,&nbsp;Mary Kelly,&nbsp;Mary Jane Marchisotto,&nbsp;Michael Makris,&nbsp;Mikaela Odemyr,&nbsp;Montserrat Fernandez-Rivas,&nbsp;Motohiro Ebisawa,&nbsp;Nandinee Patel,&nbsp;Pablo Rodríguez del Río,&nbsp;Pakit Vichyanond,&nbsp;Paul Turner,&nbsp;Pete Smith,&nbsp;Pilar Morón Gaspar,&nbsp;R. Sharon Chinthrajah,&nbsp;Rima Rachid,&nbsp;Roberta Bonaguro,&nbsp;Ruchi Gupta,&nbsp;Sabine Schnadt,&nbsp;Sakura Sato,&nbsp;Stefania Arasi,&nbsp;Stephanie Leonard,&nbsp;Sung Poblete,&nbsp;Susanne Halken,&nbsp;Thuy-My Le,&nbsp;Guillaume Pouessel,&nbsp;Tracey Dunn,&nbsp;Victoria Cardona,&nbsp;Torsten Zuberbier","doi":"10.1002/clt2.70013","DOIUrl":"https://doi.org/10.1002/clt2.70013","url":null,"abstract":"<p>GA<sup>2</sup>LEN and EFA propose minimum specifications for all industrialised countries/regions to work towards to support students with food allergies in educational settings. We reviewed research and legislation and gained feedback from over 100 patient and professional groups. We built shared expectations around: 1. training all school staff about what food allergy is, the symptoms of allergic reactions, what to do in an emergency, and when and how to use and store devices that laypeople can use to administer adrenaline (epinephrine). 2. preventing allergic reactions by using clear labelling on school menus and prepacked and non-prepacked foods and regular cleaning where students eat. 3. preparing for serious allergic reactions, with written emergency action plans for every student with food allergies, legislation allowing schools to store adrenaline for anyone who needs it in an emergency (not just those prescribed it), and training and legal safeguards for staff administering adrenaline. 4. including affected students by discussing food allergy in the curriculum, raising awareness among all students and caregivers and reviewing school processes regularly. It is time for national and international action at the policy level. Patient groups, education networks and professional societies all play a role in campaigning for shared next steps.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143120403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patients with detectable KIT p.D816V in peripheral blood are at high risk for adverse systemic events during venom immunotherapy and treatment failure
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2024-12-29 DOI: 10.1002/clt2.70019
Ajda Demšar Luzar, Jakob Otorepec, Mitja Košnik, Peter Kopač, Julij Šelb, Peter Korošec, Matija Rijavec

Background

Recent studies have highlighted the importance of routine screening for the somatic missense KIT p.D816V variant in peripheral blood leukocytes (PBL), and its association with severe sting anaphylaxis. Our study aimed to evaluate the clinical relevance of KIT p.D816V detected in PBL on systemic adverse events (SAEs) and the efficacy of venom immunotherapy (VIT).

Methods

This retrospective study included 839 patients receiving VIT. The KIT p.D816V variant was assayed with a highly sensitive, allele-specific, quantitative PCR.

Results

KIT p.D816V was detected in the PBL of 125 (15%) of 839 VIT patients. The majority (70%, 88/125) of these individuals had normal BST levels. Notably, half of the KIT-positive patients receiving honeybee venom immunotherapy had SAEs during treatment (48%, 18/37; p = 0.0136), and the KIT p.D816V allele burden was higher than 0.01% in the majority of those patients (61%, 11/18). Furthermore, a significant difference was observed between KIT-positive and KIT-negative patients treated with VIT in the past and who experienced a recurrent reaction to a sting after treatment termination (VIT failure). KIT-positive patients with VIT failure had a higher allele burden than those with successful VIT (80% vs. 40% with a KIT p.D816V higher than 0.01%; p = 0.0019). KIT p.D816V was a predictor of SAEs during honeybee VIT (univariate; OR = 2.43, p = 0.012/multivariate; OR = 2.26, p = 0.033) and a strong predictor of VIT failure in patients treated with wasp venom (univariate; OR = 4.1, p = 0.002/multivariate; OR = 3.54, p = 0.008).

Conclusion

Our study revealed the high clinical relevance of KIT p.D816V detected in PBL. KIT p.D816V was a significant predictor of SAEs during honeybee VIT and a significant predictor of VIT failure after completing wasp VIT.

{"title":"Patients with detectable KIT p.D816V in peripheral blood are at high risk for adverse systemic events during venom immunotherapy and treatment failure","authors":"Ajda Demšar Luzar,&nbsp;Jakob Otorepec,&nbsp;Mitja Košnik,&nbsp;Peter Kopač,&nbsp;Julij Šelb,&nbsp;Peter Korošec,&nbsp;Matija Rijavec","doi":"10.1002/clt2.70019","DOIUrl":"https://doi.org/10.1002/clt2.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Recent studies have highlighted the importance of routine screening for the somatic missense <i>KIT</i> p.D816V variant in peripheral blood leukocytes (PBL), and its association with severe sting anaphylaxis. Our study aimed to evaluate the clinical relevance of <i>KIT</i> p.D816V detected in PBL on systemic adverse events (SAEs) and the efficacy of venom immunotherapy (VIT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 839 patients receiving VIT. The <i>KIT</i> p.D816V variant was assayed with a highly sensitive, allele-specific, quantitative PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>KIT</i> p.D816V was detected in the PBL of 125 (15%) of 839 VIT patients. The majority (70%, 88/125) of these individuals had normal BST levels. Notably, half of the <i>KIT</i>-positive patients receiving honeybee venom immunotherapy had SAEs during treatment (48%, 18/37; <i>p</i> = 0.0136), and the <i>KIT</i> p.D816V allele burden was higher than 0.01% in the majority of those patients (61%, 11/18). Furthermore, a significant difference was observed between <i>KIT</i>-positive and <i>KIT</i>-negative patients treated with VIT in the past and who experienced a recurrent reaction to a sting after treatment termination (VIT failure). <i>KIT</i>-positive patients with VIT failure had a higher allele burden than those with successful VIT (80% vs. 40% with a <i>KIT</i> p.D816V higher than 0.01%; <i>p</i> = 0.0019). <i>KIT</i> p.D816V was a predictor of SAEs during honeybee VIT (univariate; OR = 2.43, <i>p</i> = 0.012/multivariate; OR = 2.26, <i>p</i> = 0.033) and a strong predictor of VIT failure in patients treated with wasp venom (univariate; OR = 4.1, <i>p</i> = 0.002/multivariate; OR = 3.54, <i>p</i> = 0.008).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study revealed the high clinical relevance of <i>KIT</i> p.D816V detected in PBL. <i>KIT</i> p.D816V was a significant predictor of SAEs during honeybee VIT and a significant predictor of VIT failure after completing wasp VIT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143120401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unique effect of aspirin on local 15-oxo-eicosatetraenoic acid synthesis in asthma patients with aspirin hypersensitivity 阿司匹林对阿司匹林过敏哮喘患者局部15-氧-二十碳四烯酸合成的独特影响。
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2024-12-25 DOI: 10.1002/clt2.70004
Piotr Szatkowski, Anna Gielicz, Adam Stępień, Patryk Hartwich, Radosław Kacorzyk, Hanna Plutecka, Adam Ćmiel, Gabriela Trąd-Wójcik, Marek Sanak, Lucyna Mastalerz

Background

Nonsteroidal anti-inflammatory drugs–exacerbated respiratory disease (NSAIDs-ERD) is characterized by altered arachidonic acid (AA) metabolism. Aspirin hypersensitivity is diagnosed using aspirin challenge, while induced sputum is collected to perform cell counts and to identify local biomarkers in induced sputum supernatant (ISS). This study aimed to assess the levels of a newly identified eicosanoid, 15-oxo-eicosatetraenoic acid (15-oxo-ETE), in ISS at baseline and during aspirin-induced bronchospasm in patients with NSAIDs-ERD.

Methods

Oral aspirin challenge was performed in 27 patients with NSAIDs-ERD and in 17 patients with aspirin-tolerant asthma (ATA) serving as controls. Sputum was collected before and after aspirin challenge to determine eosinophil, neutrophil, macrophage, and lymphocyte counts as well as the concentration of AA metabolites via 15-lipoxygenase-1 (15-LOX-1) and 5-LOX pathways in ISS. Chromatography–tandem mass spectrometry was used to measure ISS levels of 15-oxo-ETE, 15-hydroxyeicosatetranoic acid (15-HETE), and leukotriene E4 (LTE4).

Results

At baseline, ISS levels of 15-oxo-ETE were higher in NSAIDs-ERD than in ATA (p = 0.04). In contrast, baseline 15-HETE levels in ISS were lower in patients with NSAIDs-ERD (p = 0.03). After aspirin challenge, 15-oxo-ETE levels decreased only in patients with NSAIDs-ERD (p = 0.001) who developed bronchospasm. In both study groups, there was a reduction in sputum macrophage count after aspirin challenge (p = 0.03 and p = 0.02, respectively) irrespective of bronchospasm.

Conclusions

Patients with NSAIDs-ERD are characterized by higher baseline 15-oxo-ETE levels in ISS than patients with ATA. Aspirin-induced bronchospasm inhibited the local generation of 15-oxo-ETE.

背景:非甾体抗炎药加重呼吸系统疾病(NSAIDs-ERD)以花生四烯酸(AA)代谢改变为特征。阿司匹林超敏反应是通过阿司匹林刺激来诊断的,同时收集诱导痰进行细胞计数,并在诱导痰上清(ISS)中识别局部生物标志物。本研究旨在评估一种新发现的类二十碳酸15-氧-二十碳四烯酸(15-氧- ete)在非甾体抗炎药- erd患者的ISS基线和阿司匹林诱导支气管痉挛期间的水平。方法:对27例非甾体抗炎药- erd患者和17例阿司匹林耐受性哮喘(ATA)患者进行口服阿司匹林治疗。通过15-脂氧合酶-1 (15-LOX-1)和5-LOX途径测定ISS患者服用阿司匹林前后的痰液中嗜酸性粒细胞、中性粒细胞、巨噬细胞和淋巴细胞的计数以及AA代谢物的浓度。采用色谱-串联质谱法测定15-氧- ete、15-羟基二碳四烷酸(15-HETE)和白三烯E4 (LTE4)的ISS水平。结果:基线时,NSAIDs-ERD患者15-oxo-ETE的ISS水平高于ATA患者(p = 0.04)。相比之下,NSAIDs-ERD患者ISS的基线15-HETE水平较低(p = 0.03)。服用阿司匹林后,只有发生支气管痉挛的非甾体抗炎药- erd患者15-oxo-ETE水平下降(p = 0.001)。在两个研究组中,与支气管痉挛无关,阿司匹林刺激后痰中巨噬细胞计数减少(分别为p = 0.03和p = 0.02)。结论:ISS患者nsaid - erd的基线15-oxo-ETE水平高于ATA患者。阿司匹林引起的支气管痉挛抑制15-oxo-ETE的局部生成。
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引用次数: 0
Role of eosinophil counts in mediating the association between asthma and colon cancer 嗜酸性粒细胞计数在哮喘和结肠癌之间的关联中的作用。
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2024-12-10 DOI: 10.1002/clt2.70012
Zhi-Qing Zhan, Ze-Min Huang, Zhi-Xin Xie, Hao-Bin Zhou, Yu-Hua Luo, Pei-Zhen Chen, Tian-Ye Luo, Baoqing Sun, Zhangkai J. Cheng

Background

Epidemiological findings regarding the association between asthma and the risk of colon cancer (CC) are inconsistent. The causality and potential molecular mechanisms underlying asthma, eosinophil count, and CC remain unknown.

Methods

We performed Mendelian randomization (MR) analysis to investigate the causality between asthma and CC and attempted to demonstrate that asthma indirectly affects CC mediated by eosinophil count through mediation analysis. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Multiple bioinformatics tools were applied to further investigate the underlying mechanisms related to eosinophils that contribute to the pathogenesis of both asthma and CC.

Results

MR with mediation analyses suggested that eosinophil count may play a role in the mechanism through which asthma reduces the risk of CC. Our bioinformatic analyses identified PPP1R14A as a potential therapeutic target and an eosinophil-associated biomarker for CC patients. Higher expression of PPP1R14A may be associated with a poorer prognosis in CC patients. Additionally, the lysosome pathway emerges as a shared eosinophil-related pathway in both asthma and CC.

Conclusions

Eosinophils may contribute to a lower risk of CC in patients with asthma. PPP1R14A is a potential therapeutic target and biomarker for CC.

背景:关于哮喘与结肠癌(CC)风险之间关系的流行病学发现是不一致的。哮喘、嗜酸性粒细胞计数和CC的因果关系和潜在的分子机制尚不清楚。方法:采用孟德尔随机化(Mendelian randomization, MR)分析探讨哮喘与CC之间的因果关系,并试图通过中介分析证明哮喘间接影响嗜酸性粒细胞计数介导的CC。进行敏感性分析和多变量MR来检验我们研究结果的稳健性。结果:磁共振与中介分析表明,嗜酸性粒细胞计数可能在哮喘降低CC风险的机制中发挥作用。我们的生物信息学分析发现PPP1R14A是CC患者潜在的治疗靶点和嗜酸性粒细胞相关的生物标志物。PPP1R14A的高表达可能与CC患者预后较差有关。此外,溶酶体途径在哮喘和CC中都是一个共享的嗜酸性粒细胞相关途径。结论:嗜酸性粒细胞可能有助于降低哮喘患者患CC的风险。PPP1R14A是CC潜在的治疗靶点和生物标志物。
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引用次数: 0
Lifetime asthma incidence is related to age at onset and allergies in western Sweden 在瑞典西部,终生哮喘发病率与发病年龄和过敏有关。
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2024-12-10 DOI: 10.1002/clt2.70015
Reshed Abohalaka, Selin Ercan, Lauri Lehtimäki, Linda Ekerljung, Helena Backman, Fatma Zehra Uslu, Saliha Selin Ozuygur Ermis, Madeleine Rådinger, Bright I. Nwaru, Hannu Kankaanranta

Although asthma is more frequently diagnosed in childhood, a substantial proportion of cases manifests in adulthood. Nonetheless, few studies have comprehensively examined asthma incidence across different ages, genders, and asthma phenotypes. We conducted a retrospective evaluation of asthma incidence from birth to late adulthood, stratified by age, gender, and the presence or absence of allergies. Our analysis indicates that a significant number of asthma cases emerged in adulthood, particularly among middle-aged women, with adult-onset asthma surpassing childhood-onset asthma after the age of 35 years. Additionally, allergic asthma was more common in younger than older individuals but decreases with age, ultimately leading to a higher proportion of non-allergic asthma in older than younger individuals. These findings underscore the predominance of adult-onset asthma among females and confirm the majority of allergic asthma in children, which declines with age. Additionally, increasing age is associated with increased incidence of non-allergic asthma. Asthma heterogeneity should be considered in both clinical management and research.

虽然哮喘在儿童期更常被诊断出来,但相当大比例的病例在成年期出现。然而,很少有研究全面调查了不同年龄、性别和哮喘表型的哮喘发病率。我们对从出生到成年晚期的哮喘发病率进行了回顾性评估,并按年龄、性别和是否过敏进行了分层。我们的分析表明,大量哮喘病例出现在成年期,特别是在中年妇女中,35岁以后成人发作的哮喘超过儿童期发作的哮喘。此外,过敏性哮喘在年轻人中比老年人更常见,但随着年龄的增长而减少,最终导致老年人非过敏性哮喘的比例高于年轻人。这些发现强调了成人哮喘在女性中的优势,并证实了过敏性哮喘在儿童中的大多数,随着年龄的增长而下降。此外,年龄的增长与非过敏性哮喘发病率的增加有关。在临床管理和研究中均应考虑哮喘的异质性。
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引用次数: 0
M2 macrophage derived HMOX1 defines chronic rhinosinusitis with nasal polyps M2巨噬细胞衍生的HMOX1定义慢性鼻窦炎伴鼻息肉。
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2024-12-07 DOI: 10.1002/clt2.70014
Enhao Wang, Yanghe Hao, Jing Song, Jing Yuan, Yu Hong, Ying Li, Yang Wang, Chengshuo Wang, Ming Wang, Luo Zhang

Background

Molecular signatures of chronic rhinosinusitis with nasal polyps (CRSwNP) related to macrophages remain unclear. This study aimed to develop a macrophage-associated diagnostic signature for CRSwNP.

Methods

Transcriptome data from 54 patients with CRSwNP and 37 healthy controls across GSE136825, GSE36830, and GSE72713 were used to identify differentially expressed genes (DEGs) between two groups. Gene Set Enrichment Analysis and Weighted Gene Co-Expression Network Analysis pinpointed crucial pathways and gene clusters. A diagnostic model was created from these analyses and receiver operating characteristic curve (ROC), and further validated in our transcriptome data from 29 samples. Immune cell infiltration analysis was performed and linked those diagnostic genes to macrophages and verified by single-cell RNA sequencing data. Immunofluorescence co-staining of CD163 and HMOX1 was performed in nasal tissues. Mouse bone marrow-derived macrophage (BMDMs) cultures were used in functional experiments. Correlations between the expression of HMOX1 and eotaxin genes were investigated.

Results

DEGs of CRSwNP versus control group were enriched in the INTERLEUKIN_4_AND_13_SIGNALING pathways. A four-gene diagnostic model (HMOX1, ALOX5, F13A1 and ITGB2) was developed and demonstrated high diagnostic precision with an area under ROC curve of 0.980 for training dataset and 0.895 for test dataset. M2 macrophage presence and HMOX1 expression significantly correlated with CRSwNP (p < 0.001). Single-cell RNA sequencing data underscored the altered cellular composition in CRSwNP, with HMOX1 notably expressed in M2 macrophages. Immunofluorescence staining highlighted the increased infiltration of CD163+ M2 macrophages in nasal mucosa samples of eosinophilic CRSwNP, which correlated with HMOX1 protein levels (p < 0.05). The HMOX1 inhibitor zinc protoporphyrin reduced the ratio of CD163 + HMOX1 + M2 macrophages in mouse BMDM cultures (p < 0.05). HMOX1 expression showed a strong positive correlation with the expression of eotaxin genes (CCL11, CCL24, and CCL26; p < 0.05 respectively).

Conclusion

M2 macrophage-derived HMOX1 can be used as an innovative diagnostic signature for CRSwNP, which might be a potential regulator of eosinophilic inflammation.

背景:慢性鼻窦炎伴鼻息肉(CRSwNP)与巨噬细胞相关的分子特征尚不清楚。本研究旨在开发巨噬细胞相关的CRSwNP诊断特征。方法:使用来自54例CRSwNP患者和37名健康对照者的转录组数据,通过GSE136825、GSE36830和GSE72713鉴定两组之间的差异表达基因(DEGs)。基因集富集分析和加权基因共表达网络分析确定了关键途径和基因簇。根据这些分析和受试者工作特征曲线(ROC)建立诊断模型,并在29个样本的转录组数据中进一步验证。进行免疫细胞浸润分析,将这些诊断基因与巨噬细胞联系起来,并通过单细胞RNA测序数据进行验证。对鼻组织进行CD163和HMOX1的免疫荧光共染色。小鼠骨髓源性巨噬细胞(bmdm)培养物用于功能实验。研究了HMOX1与eotaxin基因表达的相关性。结果:与对照组相比,CRSwNP的deg在白细胞介素_4_和_13_信号通路中富集。建立了四基因诊断模型(HMOX1、ALOX5、F13A1和ITGB2),训练集的ROC曲线下面积为0.980,测试集的ROC曲线下面积为0.895,诊断精度较高。结论:M2巨噬细胞衍生的HMOX1可作为CRSwNP的创新诊断标志,可能是嗜酸性炎症的潜在调节因子。
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引用次数: 0
期刊
Clinical and Translational Allergy
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