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Digital Innovation in Asthma Management in Italy: Results From the “Confronting Asthma Survey” 意大利哮喘管理的数字创新:来自“面对哮喘调查”的结果。
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-10-17 DOI: 10.1002/clt2.70109
Manuela Latorre, Pierluigi Paggiaro, Cristina Cardini, Giovanni Paoletti, Emanuele Nappi, Mario Di Gioacchino, Enrico Heffler, Francesco Blasi, Giorgio Walter Canonica, Francesca Puggioni, SANI Network

Background

The rapid digital transformation has significantly impacted healthcare, particularly through eHealth solutions that offer great potential for managing chronic respiratory conditions such as asthma. This study explores the impact, attitudes, and acceptance of digital technologies in asthma management in Italy.

Methods

A structured 34-item survey, developed in two versions for patients and physicians, was administered independently and anonymously to adult asthma patients and to specialists in pulmonology and allergology. The questionnaires collected data on demographics, professional background, digital habits (for work and leisure), use of digital tools such as apps and smart inhalers, doctor–patient digital communication, familiarity with online health resources, and perceived barriers to digital adoption. Data were collected anonymously via REDCap, with oversight from the Severe Asthma Network in Italy (SANI).

Results

A total of 134 patients and 180 doctors participated. Findings revealed a predominantly positive attitude toward digital tools, with 85% of physicians and 74.4% of patients embracing a “digital mindset.” Nevertheless, digital innovations remain underutilized in clinical practice. While 85.6% of patients reported regularly using digital tools in their daily lives, 91.5% stated that their doctors had never recommended apps or websites for asthma self-management. Digital solutions such as mobile apps, wearable spirometers, and telemedicine are recognized for their potential benefits—clinicians highlighted symptoms self-tracking (17.2%), improved adherence (22.7%), and enhanced clinical interventions (11.7%) as key advantages. However, adoption is hindered by concerns such as information technology (IT) compliance (62.5%), legal risks (11.5%), and skepticism about the reliability of remote data (40.6%). Furthermore, 59.9% of clinicians and 66.8% of patients recognized a knowledge gap regarding the potential benefits of smart inhalers and digital therapeutics in respiratory care.

Conclusion

The study highlights a positive attitude toward digital tools in asthma management but reveals limited adoption in clinical practice. Key barriers include IT compliance concerns and knowledge gaps. Addressing these challenges through education and regulatory support could enhance digital integration, improving asthma care.

背景:快速的数字化转型对医疗保健产生了重大影响,特别是通过电子健康解决方案,为管理哮喘等慢性呼吸系统疾病提供了巨大潜力。本研究探讨了意大利哮喘管理中数字技术的影响、态度和接受程度。方法:对成人哮喘患者、肺病学和过敏症学专家进行独立匿名的34项结构化调查,分为患者和医生两种版本。调查问卷收集的数据包括人口统计、专业背景、数字习惯(工作和休闲)、应用程序和智能吸入器等数字工具的使用、医患数字沟通、对在线卫生资源的熟悉程度以及对采用数字技术的感知障碍。在意大利严重哮喘网络(SANI)的监督下,通过REDCap匿名收集数据。结果:共有134名患者和180名医生参与。调查结果显示,人们对数字工具的态度主要是积极的,85%的医生和74.4%的患者拥有“数字心态”。然而,数字创新在临床实践中仍未得到充分利用。虽然85.6%的患者报告在日常生活中经常使用数字工具,但91.5%的患者表示他们的医生从未推荐过哮喘自我管理的应用程序或网站。数字解决方案(如移动应用程序、可穿戴肺活量计和远程医疗)因其潜在益处而得到认可——临床医生强调了症状自我跟踪(17.2%)、提高依从性(22.7%)和增强临床干预(11.7%)是主要优势。然而,对信息技术(IT)合规性(62.5%)、法律风险(11.5%)和对远程数据可靠性的怀疑(40.6%)等问题的担忧阻碍了采用。此外,59.9%的临床医生和66.8%的患者认识到关于智能吸入器和数字治疗在呼吸保健中的潜在益处的知识差距。结论:该研究强调了对哮喘管理中数字工具的积极态度,但在临床实践中采用有限。主要障碍包括IT遵从性问题和知识差距。通过教育和监管支持来应对这些挑战,可以加强数字化整合,改善哮喘治疗。
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引用次数: 0
ST2+ Erythroid Progenitors Suppress Allergic Asthma by Scavenging IL-33 in Young Mice ST2+红系祖细胞通过清除IL-33抑制幼鼠过敏性哮喘
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-10-17 DOI: 10.1002/clt2.70111
Chang Li, Jie Liu, Xiaoshi Li, Wenlong Chen, Ying Zhang, Heng Sun, Cunni Zheng, Quan Liu

Background

Although IL-33/ST2 signaling has been implicated in adult asthma, its contribution to early-onset allergic asthma remains poorly understood. Here, we examined the postnatal dynamics of IL-33 and its regulation by splenic ST2+ erythroid progenitors (EPs).

Methods

Plasma IL-33 levels were measured in neonatal and young mice. Wild Type (WT) and Il33−/− mice were exposed to house dust mite (HDM) to assess airway inflammation and asthma. ST2+ EPs were analyzed for IL-33 responsiveness, transcriptomic/epigenomic profiles, and IL-33 scavenging capacity. EP depletion was performed to evaluate their role in HDM-induced inflammation.

Results

Plasma IL-33 levels fluctuated during the postnatal period, peaking at postnatal day 7 (PND7). WT mice exhibited more severe HDM-induced airway inflammation than Il33−/− mice. Splenic ST2+ EPs, abundant in early life but absent by PND28, displayed minimal IL-33–induced signaling or transcriptomic/epigenomic alterations, yet efficiently scavenged IL-33. Depletion of EPs exacerbated HDM-induced inflammation, accompanied by increased T follicular helper cells (Tfh) and IgE+ B cells.

Conclusion

ST2+ EPs function as transient IL-33 scavengers during early life, attenuating its pro-asthmatic effects and preserving immune homeostasis.

背景:尽管IL-33/ST2信号通路与成人哮喘有关,但其在早发性过敏性哮喘中的作用仍知之甚少。在这里,我们研究了IL-33的出生后动态及其通过脾ST2+红系祖细胞(EPs)的调节。方法:测定新生小鼠和幼鼠血浆IL-33水平。野生型(WT)和Il33-/-小鼠暴露于屋尘螨(HDM)以评估气道炎症和哮喘。分析ST2+ EPs的IL-33响应性、转录组/表观基因组谱和IL-33清除能力。通过EP耗竭来评估它们在hdm诱导炎症中的作用。结果:血浆IL-33水平在产后波动,在产后第7天达到峰值(PND7)。WT小鼠比Il33-/-小鼠表现出更严重的hdm诱导的气道炎症。脾脏ST2+ EPs在生命早期丰富,但PND28缺失,表现出最小的IL-33诱导的信号或转录组/表观基因组改变,但有效清除IL-33。EPs的消耗加重了hdm诱导的炎症,并伴有T滤泡辅助细胞(Tfh)和IgE+ B细胞的增加。结论:ST2+ EPs在生命早期具有短暂性IL-33清除剂的作用,可减弱其促哮喘作用,维持免疫稳态。
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引用次数: 0
A Novel Cell Culture System to Improve MRGPRX2 Research in Human Skin Mast Cells 一种新的细胞培养系统提高人皮肤肥大细胞MRGPRX2的研究。
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-10-16 DOI: 10.1002/clt2.70112
Zhuoran Li, Jean Schneikert, Anja Wegner, Torsten Zuberbier, Magda Babina

Background

MRGPRX2, a receptor central to mast cell (MC) activation and related skin diseases, is selectively expressed in skin MCs but downregulated during culture by stem cell factor (SCF) and interleukin-4 (IL-4).

Objective

To identify culture conditions that preserve MC viability while restoring MRGPRX2 expression and function.

Methods

Human skin MCs were cultured in standard or serum-free Accell medium (both with SCF). After 3 days, MRGPRX2 expression was assessed by flow cytometry, degranulation by mediator release assays, and signaling by Western blotting.

Results

Accell medium increased MRGPRX2 expression to ~1.7-fold and enhanced degranulation to Substance P and codeine. It also promoted stronger and more sustained ERK and AKT phosphorylation, while FcεRI-mediated responses were largely unaffected.

Conclusion

Short-term incubation in serum-free Accell medium restores MRGPRX2 expression and signaling in cultured skin MCs without impairing viability. This simple adjustment yields a practical and reliable model for MRGPRX2-focused studies.

背景:MRGPRX2是肥大细胞(MC)活化和相关皮肤病的中枢受体,在皮肤MC中选择性表达,但在培养过程中被干细胞因子(SCF)和白细胞介素-4 (IL-4)下调。目的:寻找既能保持MC活力又能恢复MRGPRX2表达和功能的培养条件。方法:在标准或无血清Accell培养基(均含SCF)中培养人皮肤MCs。3天后,通过流式细胞术、介质释放法和Western blotting检测MRGPRX2的表达。结果:加速细胞培养基使MRGPRX2表达量增加约1.7倍,增强了对P物质和可待因的脱颗粒作用。它还促进了更强、更持久的ERK和AKT磷酸化,而fcε ri介导的反应在很大程度上不受影响。结论:在无血清Accell培养基中短期孵育可恢复培养的皮肤MCs中MRGPRX2的表达和信号传导,而不影响其生存能力。这种简单的调整为以mrgprx2为重点的研究提供了实用可靠的模型。
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引用次数: 0
Next Generation Sequencing of Genes With Epigenetic Alterations in Mastocytosis 肥大细胞增多症表观遗传改变基因的下一代测序。
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-10-01 DOI: 10.1002/clt2.70106
Aleksandra Górska, Thierry van De Wetering, Marta Sobalska-Kwapis, Bogusław Nedoszytko, Danuta Gutowska-Owsiak, Marek Niedoszytko

Aim

Mastocytosis is a neoplastic disease of the bone marrow associated with the risk of frequent and severe allergic reactions. However, the genetic predisposition is not fully understood, and the crucial element in pathogenesis is the presence of the oncogenic KIT p. D816 V gene mutation. The epigenetic mechanism has also been suggested as playing a role in mastocytosis.

Objective

Based on our previous epigenetic studies, we have selected 110 candidate genes which were sequenced by next generation sequencing (NGS) to identify somatic mutations.

Method

The study group consisted of 32 patients with mastocytosis (16 females and 16 males) plus 16 controls (8 females and 8 males). Whole peripheral blood was collected from all the subjects and genotyped by NGS on the Illumina platform (targeted sequencing).

Results

We analysed 4272 genetic variations in the pre-selected candidate genes and found five regions that showed a significant difference between the patient and control group. Two of them were found in the TET2 gene located on chromosome 4 and the other three alterations were found in the genes DNMT3A, SETD2 and BRD4 located on chromosomes 2, 3 and 19, respectively. Two out of the five genetic variants have not been previously reported, despite the fact that all four genes have been described to be associated with mastocytosis.

Conclusions

The results align with our previous findings, which determined TET2, DNMT3A, SETD2 and BRD4 genes as promising candidates for further analysis, warranting future study in a larger cohort of mastocytosis patients.

目的:肥大细胞增多症是一种与频繁和严重过敏反应风险相关的骨髓肿瘤疾病。然而,遗传易感性尚不完全清楚,发病机制的关键因素是致癌的KIT p. d816v基因突变的存在。表观遗传机制也被认为在肥大细胞增多症中起作用。目的:在前人表观遗传学研究的基础上,选择110个候选基因,通过下一代测序(NGS)进行体细胞突变鉴定。方法:研究组32例肥大细胞增多症患者(女16例,男16例)加16例对照组(女8例,男8例)。采集所有受试者全外周血,在Illumina平台上进行NGS基因分型(靶向测序)。结果:我们分析了预先选择的候选基因中的4272个遗传变异,发现患者和对照组之间有5个区域表现出显著差异。其中2处位于第4号染色体上的TET2基因,另外3处分别位于第2、3、19号染色体上的DNMT3A、SETD2和BRD4基因。这五种基因变异中有两种以前没有报道过,尽管事实上这四种基因都被描述为与肥大细胞增多症有关。结论:结果与我们之前的研究结果一致,确定TET2、DNMT3A、SETD2和BRD4基因是进一步分析的有希望的候选基因,保证未来在更大的肥大细胞增多症患者队列中进行研究。
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引用次数: 0
Digital Monitoring of Symptoms and Lung Function During Birch Pollen Season in Pediatric Patients 儿科桦树花粉季节症状和肺功能的数字监测。
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-09-29 DOI: 10.1002/clt2.70101
Tiina Helena Tanninen, Paula Hannele Reiterä, Annika Saarto, Janne Burman, Anna Susanna Pelkonen, Mika Juhani Mäkelä

Background

Mobile health (mHealth) applications for asthma and allergic rhinitis (AR) may guide patients in following medication use, symptoms, and lung function supporting self-management.

Objective

The primary study objective was to investigate the objective effect of birch pollen on asthma and AR symptoms and medicine use in pediatric patients with varying levels of birch-specific immunoglobulin E (IgE) during the 2022 birch pollen season using digital tools. The secondary objectives were to determine the effect of birch pollen on Asthma Control Test scores, and to record the subjective benefits in self-management while using the application.

Methods

Altogether, 48 pediatric participants were categorized into three groups based on their birch-specific IgE levels. Participants continued their existing asthma control therapy. For allergic rhinitis and conjunctivitis, antihistamines, intranasal corticosteroids (INCS) or a combination of INCS and intranasal antihistamines, and cromoglicates or local antihistamines were prescribed. The study involved daily asthma and allergic rhinitis symptom and medication reporting via the mHealth application (KAMU Health, Finland) combined with microspirometry during the birch pollen season in Helsinki, Finland.

Results

The patients preferred oral AR treatment. However, the low birch pollen levels may have contributed to moderate adherence to AR treatment. A low birch pollen load does not significantly impair lung function in young patients receiving anti-asthmatic treatment regularly. The majority of patients perceived this digital approach as beneficial, irrespective of their level of birch-specific sensitization.

Conclusion

Digital tools support asthma and AR care by enabling disease monitoring, patient engagement, and provide real-world insights for clinicians.

背景:哮喘和过敏性鼻炎(AR)的移动健康(mHealth)应用程序可以指导患者跟踪药物使用、症状和肺功能,支持自我管理。目的:主要研究目的是利用数字化工具,探讨2022年桦树花粉季节桦树花粉对不同水平桦树特异性免疫球蛋白E (IgE)患儿哮喘和AR症状及用药的客观影响。次要目标是确定桦树花粉对哮喘控制测试分数的影响,并记录使用该应用程序时自我管理的主观益处。方法:48名儿童参与者根据桦树特异性IgE水平分为三组。参与者继续他们现有的哮喘控制治疗。对于变应性鼻炎和结膜炎,开抗组胺药、鼻内皮质类固醇(INCS)或INCS与鼻内抗组胺药的组合,以及克罗莫酸盐或局部抗组胺药。该研究涉及在芬兰赫尔辛基桦树花粉季节期间,通过移动健康应用程序(KAMU Health,芬兰)每日哮喘和过敏性鼻炎症状和药物报告,并结合微肺活量测定。结果:患者首选口服AR治疗。然而,较低的桦树花粉水平可能有助于对AR治疗的中等依从性。在定期接受抗哮喘治疗的年轻患者中,低桦树花粉负荷不会显著损害肺功能。大多数患者认为这种数字化方法是有益的,无论他们的桦树特异性致敏程度如何。结论:数字工具通过实现疾病监测、患者参与和为临床医生提供真实世界的见解来支持哮喘和AR护理。
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引用次数: 0
Improving Diagnostic Accuracy in Respiratory Allergy: Monocentric Reevaluation of the GA2LEN Panel in Germany 提高呼吸道过敏的诊断准确性:德国GA2LEN小组的单中心重新评估
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-09-24 DOI: 10.1002/clt2.70102
Caroline Beutner, Christian Meyer, Moritz Maximilian Hollstein, Katharina Klara Hahn, Michael Peter Schön, Timo Buhl

Background

European guidelines recommend using a standardized baseline series of skin prick test (SPT) allergens for the diagnosis of airway allergies. In addition, local adaptation and/or extension of test panels according to regional exposure and sensitization patterns are increasingly being discussed.

Methods

Regional sensitization rates according to SPTs based on the most recent GA2LEN baseline series in Central Germany were retrospectively analyzed for 960 consecutive patients with respiratory symptoms at our university outpatient clinic. Additional SPT allergens of interest were further analyzed.

Results

High sensitization rates to the baseline SPT series were observed in our highly selected study cohort. The positivity rates were particularly high for olive pollen (30.8%) and plantain pollen (33.4%). Positive olive and birch pollen SPTs were found in 98.5% of olive-ash-birch pollen tested patients. High SPT positivity rates (98.1%) for plane tree and olive tree pollen were found, whereas only six patients (1.9%) were diagnosed with exclusive cypress pollen sensitization. Subgroup analysis of SPTs for palm tree pollen revealed that 92% of patients with palm tree positivity showed polysensitization, and all but one patient had concomitant grass pollen sensitization.

Conclusion

Regular evaluations of SPT series may be necessary because of climate change, extract production, and increasing population mobility. Ash and cypress pollen extracts could currently be removed from the baseline SPT panel without significantly decreasing diagnostic accuracy. Positive SPTs to non-native palm tree pollen may indicate the presence of IgE to cross-reacting panallergens, which may help to differentiate primary sensitization from cross-reactivity directly. Limitations include the retrospective monocentric design and lack of molecular IgE confirmation.

背景:欧洲指南推荐使用标准化基线系列皮肤点刺试验(SPT)过敏原来诊断气道过敏。此外,正在越来越多地讨论根据区域暴露和敏化模式进行局部调整和/或扩展试验小组。方法回顾性分析德国中部地区以最新GA2LEN基线系列为基础的spt区域致敏率,对我院门诊960例连续出现呼吸道症状的患者进行分析。进一步分析其他感兴趣的SPT过敏原。结果在我们精心挑选的研究队列中观察到对基线SPT系列的高敏化率。橄榄花粉(30.8%)和车前草花粉(33.4%)的阳性率最高。98.5%的橄榄灰桦树花粉检测患者发现橄榄和桦树花粉SPTs阳性。梧桐树和橄榄树花粉的SPT阳性率高达98.1%,而柏树花粉仅为6例(1.9%)。棕榈树花粉的SPTs亚组分析显示,92%的棕榈树阳性患者表现为多敏化,除1例患者外,其余患者均伴有草花粉敏化。结论由于气候变化、提取物生产和人口流动的增加,定期评估SPT系列可能是必要的。目前可以从基线SPT面板中去除白蜡树和柏树花粉提取物,而不会显著降低诊断准确性。对非本地棕榈树花粉的阳性SPTs可能表明存在对交叉反应的泛过敏原的IgE,这可能有助于直接区分原发性致敏性和交叉反应性。局限性包括回顾性单中心设计和缺乏分子IgE确认。
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引用次数: 0
Identifying Genetic Variants in Patients With Cefaclor-Induced Anaphylaxis Using Human Leukocyte Antigen Typing and Whole-Exome Sequencing 使用人类白细胞抗原分型和全外显子组测序鉴定头孢氯诱导的过敏反应患者的遗传变异。
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-09-20 DOI: 10.1002/clt2.70103
Sung-Ryeol Kim, Da Eun Lee, Hyun Young Jung, In-Wha Kim, Hye-Ryun Kang, Kyung Hee Park, Jung-Won Park, Jung-Mi Oh, Jae-Hyun Lee

Background

Cefaclor is a commonly prescribed β-lactam antibiotic and a known major cause of immediate-type drug hypersensitivity in Korea. However, its genetic risk factors remain poorly understood. We aimed to identify genetic variants associated with cefaclor-induced anaphylaxis and evaluate their potential clinical implications.

Methods

Whole-exome sequencing and HLA genotyping were performed in 33 patients with cefaclor-induced anaphylaxis and 41 drug-tolerant controls. Associations were assessed using logistic regression. Selected variants were validated in an independent Korean population. Gene set enrichment analysis (GSEA) was performed using association statistics from all variants to investigate relevant biological pathways.

Results

A rare missense variant, rs765144578 in TPSAB1 was strongly associated with anaphylaxis and remained significant in the validation control group. It was found in 90.91% of patients with hypotension, suggesting a link to reaction severity. Rs192498095 in HLA-DRB5 showed a significant association in the discovery cohort. However, it was not detected in the replication set, likely due to its rarity and polymorphic nature. Co-occurrence of rs765144578 in TPSAB1 and rs192498095 in HLA-DRB5 markedly increased risk. GSEA revealed significant enrichment of the TNF-α signaling via NF-κB pathway, reflecting pathway-level immune activation.

Conclusion

Genetic variants in TPSAB1 and HLA-DRB5 may contribute to the risk of cefaclor-induced anaphylaxis, and TPSAB1 may also be associated with severity. These findings may support the development of future screening strategies or individualized risk prediction models in β-lactam allergy.

背景:头孢克洛是一种常用的β-内酰胺类抗生素,也是韩国已知的直接型药物过敏的主要原因。然而,其遗传风险因素仍然知之甚少。我们的目的是确定与头孢氯致过敏反应相关的遗传变异,并评估其潜在的临床意义。方法:对33例头孢氯致过敏反应患者和41例耐药对照进行全外显子组测序和HLA基因分型。使用逻辑回归评估相关性。选择的变异在独立的韩国人群中得到验证。利用所有变异的关联统计数据进行基因集富集分析(GSEA),以研究相关的生物学途径。结果:TPSAB1中罕见的错义变异rs765144578与过敏反应密切相关,并且在验证对照组中仍然显著。在90.91%的低血压患者中发现,这表明与反应严重程度有关。在发现队列中,HLA-DRB5中的Rs192498095显示出显著相关性。然而,在复制集中没有检测到它,可能是由于它的稀有性和多态性。TPSAB1基因中rs765144578和HLA-DRB5基因中rs192498095的共存显著增加了风险。GSEA显示NF-κB通路TNF-α信号显著富集,反映通路水平的免疫激活。结论:TPSAB1和HLA-DRB5基因变异可能增加头孢氯致过敏反应的风险,TPSAB1也可能与过敏反应的严重程度有关。这些发现可能支持未来β-内酰胺过敏筛查策略或个体化风险预测模型的发展。
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引用次数: 0
Reference Values and Determinants of Fractional Exhaled Nitric Oxide in a Representative Adult Population in Western Sweden 瑞典西部代表性成人呼出一氧化氮含量的参考值和决定因素
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-09-18 DOI: 10.1002/clt2.70107
Reshed Abohalaka, Selin Ercan, Lauri Lehtimäki, Saliha Selin Özuygur Ermis, Daniil Lisik, Muwada Bashir Awad Bashir, Radhika Jadhav, Linda Ekerljung, Göran Wennergren, Jan Lötvall, Teet Pullerits, Helena Backman, Madeleine Rådinger, Bright I. Nwaru, Hannu Kankaanranta

Background

Fractional exhaled nitric oxide (FENO) is used to differentiate asthma inflammatory phenotypes and guide its management. However, data on FENO reference values in a representative adult population is limited. We aim to derive reference values and determinants of FENO in a representative adult population.

Methods

The West Sweden Asthma Study is a clinical-epidemiological population-representative study of randomly selected adults in Western Sweden. From this cohort, 943 subjects participated in comprehensive clinical investigations, including skin prick testing (SPT), specific immunoglobulin E (sIgE) analysis, and FENO measurement. Clinical allergy was defined as co-occurrence of atopy (positivity to SPT or sIgE) and self-reported allergic symptoms to the same allergen family. FENO levels were analysed in relation to the presence or absence of clinical allergy, asthma, and other factors.

Results

The 95th percentile of FENO ranged from 34 parts per billion (ppb) in those between 30 and 40 years old to 52 ppb in those ≤ 30 years old in the entire sample (N = 943), and from 26 to 37 ppb in those without clinical allergy, asthma, or chronic obstructive pulmonary disease (COPD) (n = 587), depending on age. Sex, smoking, clinical allergy, atopy, asthma, and hypertension influenced FENO levels, meanwhile, age, asthma, clinical allergy, and reversibility-related variables were significant determinants of FENO levels.

Conclusion

The 95th percentile (upper normal limit) for FENO ranges from 34 to 52 ppb overall, and from 26 to 37 ppb in those without clinical allergy, asthma, or COPD, depending on age. These findings provide a guide for interpreting FENO in the general population.

背景:呼气一氧化氮分数(FENO)用于区分哮喘炎症表型并指导其治疗。然而,关于具有代表性的成年人群的FENO参考值的数据是有限的。我们的目标是在一个有代表性的成年人群中得出参考值和FENO的决定因素。方法:西瑞典哮喘研究是一项临床流行病学人群代表性研究,随机选择瑞典西部的成年人。从该队列中,943名受试者参加了全面的临床调查,包括皮肤点刺试验(SPT)、特异性免疫球蛋白E (sIgE)分析和FENO测量。临床变态反应被定义为特应性(SPT或sIgE阳性)和自我报告的对同一过敏原家族的过敏症状的共同发生。分析了FENO水平与是否存在临床过敏、哮喘和其他因素的关系。结果:在整个样本中,年龄在30至40岁之间的FENO的第95百分位范围从十亿分之34 (ppb)到≤30岁的52 ppb (N = 943),而在没有临床过敏、哮喘或慢性阻塞性肺疾病(COPD)的人群中(N = 587),根据年龄的不同,FENO的第95百分位范围从26到37 ppb。性别、吸烟、临床变态反应、特应性、哮喘和高血压影响FENO水平,年龄、哮喘、临床变态反应和可逆性相关变量是FENO水平的重要决定因素。结论:FENO的第95百分位(正常上限)总体范围为34至52 ppb,无临床过敏、哮喘或COPD的患者范围为26至37 ppb,具体取决于年龄。这些发现为解释一般人群的FENO提供了指导。
{"title":"Reference Values and Determinants of Fractional Exhaled Nitric Oxide in a Representative Adult Population in Western Sweden","authors":"Reshed Abohalaka,&nbsp;Selin Ercan,&nbsp;Lauri Lehtimäki,&nbsp;Saliha Selin Özuygur Ermis,&nbsp;Daniil Lisik,&nbsp;Muwada Bashir Awad Bashir,&nbsp;Radhika Jadhav,&nbsp;Linda Ekerljung,&nbsp;Göran Wennergren,&nbsp;Jan Lötvall,&nbsp;Teet Pullerits,&nbsp;Helena Backman,&nbsp;Madeleine Rådinger,&nbsp;Bright I. Nwaru,&nbsp;Hannu Kankaanranta","doi":"10.1002/clt2.70107","DOIUrl":"10.1002/clt2.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fractional exhaled nitric oxide (FE<sub>NO</sub>) is used to differentiate asthma inflammatory phenotypes and guide its management. However, data on FE<sub>NO</sub> reference values in a representative adult population is limited. We aim to derive reference values and determinants of FE<sub>NO</sub> in a representative adult population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The West Sweden Asthma Study is a clinical-epidemiological population-representative study of randomly selected adults in Western Sweden. From this cohort, 943 subjects participated in comprehensive clinical investigations, including skin prick testing (SPT), specific immunoglobulin E (sIgE) analysis, and FE<sub>NO</sub> measurement. Clinical allergy was defined as co-occurrence of atopy (positivity to SPT or sIgE) and self-reported allergic symptoms to the same allergen family. FE<sub>NO</sub> levels were analysed in relation to the presence or absence of clinical allergy, asthma, and other factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 95<sup>th</sup> percentile of FE<sub>NO</sub> ranged from 34 parts per billion (ppb) in those between 30 and 40 years old to 52 ppb in those ≤ 30 years old in the entire sample (<i>N</i> = 943), and from 26 to 37 ppb in those without clinical allergy, asthma, or chronic obstructive pulmonary disease (COPD) (<i>n</i> = 587), depending on age. Sex, smoking, clinical allergy, atopy, asthma, and hypertension influenced FE<sub>NO</sub> levels, meanwhile, age, asthma, clinical allergy, and reversibility-related variables were significant determinants of FE<sub>NO</sub> levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The 95<sup>th</sup> percentile (upper normal limit) for FE<sub>NO</sub> ranges from 34 to 52 ppb overall, and from 26 to 37 ppb in those without clinical allergy, asthma, or COPD, depending on age. These findings provide a guide for interpreting FE<sub>NO</sub> in the general population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085100","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
Distinct Phenotypes of Peripheral Innate Lymphoid Cells and T Cells in Type 2 and Non-Type 2 Asthma 2型和非2型哮喘患者外周血固有淋巴样细胞和T细胞的不同表型
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-09-18 DOI: 10.1002/clt2.70108
Maura M. Kere, Sophia Björkander, Simon Kebede Merid, Natalia Hernandez-Pacheco, Paul Maier, Anne-Sophie Merritt, Anna Bergström, Inger Kull, Carsten O. Daub, Jenny Mjösberg, Christopher Andrew Tibbitt, Erik Melén

Background

Investigation of T cell and innate lymphoid cell (ILC) subsets in type 2 (T2) and non-type 2 (non-T2) asthma are needed to elucidate disease mechanisms. In this study, we aimed to identify ILC, CD4+, and CD8+ T cell populations in blood that differentiate between T2 and non-T2 features in subjects with and without asthma.

Methods

The study population included 86 young adults selected from the Swedish population-based BAMSE cohort. Asthma and non-asthma subjects with sensitization to inhalant allergens and/or blood eosinophil count ≥ 0.3 × 109/L were classified into T2 groups. Non-T2 groups were defined by the absence of sensitization to inhalant allergens and blood eosinophil count < 0.3 × 109/L. PBMC samples underwent 18-parameter flow cytometry to identify ILC and CD4+ and CD8+ T cell populations. Logistic regression models were employed on normalized flow cytometry data after hierarchical clustering.

Results

A higher frequency of CD4+ CRTH2+ T memory cells was associated with T2 features independent of asthma status. The frequency of CD62L+ ILC2s was higher and CD4+ KLRG1+ central memory T cells was lower specifically in T2 asthma. Non-T2 asthma was associated with increased frequencies of CD45RO+ ILC2s and CD8+ memory T cells.

Conclusion

Our results suggest that T2 asthma and non-T2 asthma are characterized by distinct features related to ILC and T cell populations. Further investigation of particularly ILC and CD8+ T cell subsets in non-T2 asthma could offer a deeper understanding of underlying disease mechanisms for this endotype.

背景:需要研究2型(T2)和非2型(非T2)哮喘中的T细胞和先天淋巴样细胞(ILC)亚群来阐明疾病机制。在这项研究中,我们的目的是鉴定血液中ILC、CD4+和CD8+ T细胞群,这些细胞群在有和没有哮喘的受试者中区分T2和非T2特征。方法:研究人群包括从瑞典人群为基础的BAMSE队列中选择的86名年轻人。对吸入性过敏原致敏和/或血嗜酸性粒细胞计数≥0.3 × 109/L的哮喘和非哮喘患者分为T2组。非t2组通过对吸入性过敏原无致敏和血嗜酸性粒细胞计数9/L来定义。PBMC样品采用18参数流式细胞术检测ILC、CD4+和CD8+ T细胞群。分层聚类后的归一化流式细胞仪数据采用Logistic回归模型。结果:CD4+ CRTH2+ T记忆细胞的较高频率与T2特征相关,与哮喘状态无关。CD62L+ ILC2s频率增高,CD4+ KLRG1+中枢记忆T细胞频率降低。非t2哮喘与CD45RO+ ILC2s和CD8+记忆T细胞的频率增加有关。结论:我们的研究结果表明,T2哮喘和非T2哮喘具有与ILC和T细胞群相关的不同特征。进一步研究ILC和CD8+ T细胞亚群在非t2哮喘中的作用,可以更深入地了解这种内型的潜在疾病机制。
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引用次数: 0
Food Sensitization Is Associated With Atopic Dermatitis Severity, Gut-Derived Metabolites and Leaky Gut in Adults 食物致敏与成人特应性皮炎严重程度、肠道衍生代谢物和肠漏有关
IF 4 2区 医学 Q2 ALLERGY Pub Date : 2025-09-18 DOI: 10.1002/clt2.70094
Leszek Blicharz, Emilia Samborowska, Radosław Zagożdżon, Joanna Czuwara, Michał Zych, Aleksander Roszczyk, Michał Zaremba, Michał Dadlez, Zbigniew Samochocki, Małgorzata Olszewska, Lidia Rudnicka

Background

Gut microbiome dysbiosis may cause metabolic dysregulation and intestinal barrier impairment. The latter are hypothesized to provoke food allergy and aggravate cutaneous inflammation. Our objective was to determine the prevalence of food sensitization in adult patients with atopic dermatitis and relate it to the disease severity and the biomarkers of the gut-skin axis.

Methods

50 adult patients with atopic dermatitis and 25 controls were enrolled in this cross-sectional study. Disease severity was determined by using SCORAD and EASI scores. Liquid chromatography-mass spectrometry, Luminex, and Polycheck immunoassays were performed to detect serum concentrations of total IgE, food-specific IgEs, gut-derived metabolites, and leaky gut-related biomarkers.

Results

Food sensitization was significantly more prevalent in patients with atopic dermatitis than in the controls. The severity of atopic dermatitis (EASI, SCORAD) was higher in patients with food sensitization and correlated with the number of positive food-specific IgEs. Higher concentrations of total IgE and higher numbers of positive food-specific IgEs were associated with lower concentrations of short-chain fatty acids and higher concentrations of indoxyl and leaky gut-related biomarkers (LBP, syndecan-4, IL-10, IL-22).

Conclusion

The results suggest a relationship between food sensitization and the severity of atopic dermatitis. This could be partly associated with gut-derived metabolites and intestinal barrier impairment. Fiber-rich diet and restriction of protein could hold potential for upregulating short-chain fatty acids and downregulating indoxyl, which may translate to decreasing the likelihood of food sensitization in atopic dermatitis. Notably, the cross-sectional nature of this exploratory study limits the ability to draw causal inferences, which should be further examined in future prospective research.

背景:肠道微生物群失调可引起代谢失调和肠道屏障损伤。后者被认为会引起食物过敏并加重皮肤炎症。我们的目的是确定成人特应性皮炎患者食物致敏的患病率,并将其与疾病严重程度和肠道-皮肤轴的生物标志物联系起来。方法:50例成人特应性皮炎患者和25例对照者进行横断面研究。采用SCORAD和EASI评分确定疾病严重程度。采用液相色谱-质谱法、Luminex和Polycheck免疫分析法检测血清总IgE、食物特异性IgE、肠道衍生代谢物和漏肠相关生物标志物的浓度。结果:食物致敏在特应性皮炎患者中比在对照组中更为普遍。食物致敏患者的特应性皮炎(EASI, SCORAD)严重程度较高,且与食物特异性IgEs阳性数量相关。较高浓度的总IgE和较高数量的阳性食物特异性IgE与较低浓度的短链脂肪酸和较高浓度的吲哚酚和漏肠相关生物标志物(LBP, syndecan-4, IL-10, IL-22)相关。结论:食物致敏与特应性皮炎的严重程度有关。这可能与肠源性代谢物和肠屏障损伤部分相关。富含纤维的饮食和限制蛋白质可能具有上调短链脂肪酸和下调吲哚酚的潜力,这可能转化为降低特应性皮炎患者食物致敏的可能性。值得注意的是,这项探索性研究的横断面性质限制了得出因果推论的能力,这应该在未来的前瞻性研究中进一步研究。
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引用次数: 0
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Clinical and Translational Allergy
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