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Exploring the Disease Duration of Urticaria and Associated Determinants in Primary Care. 在初级保健中探讨荨麻疹的病程和相关决定因素。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-30 DOI: 10.1111/cea.70170
R Soegiharto, B J Hengevelt, N Boekema-Bakker, I A M Groenewegen, A C Knulst, J M P A Van den Reek, H Röckmann
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引用次数: 0
Comparison Between a Rush and a Conventional Oral Immunotherapy Protocol to Treat Cow's Milk and Hen's Egg Allergy. CompITO Study Methodology. Rush与传统口服免疫治疗方案治疗牛奶和鸡蛋过敏的比较。编译研究方法。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-30 DOI: 10.1111/cea.70168
Itziar Eusebio-Cartagena, Rodrigo Jiménez-Saiz, Vanesa Esteban, Emilio Nuñez-Borque, Alessandra Ruiz-Sánchez, Carmelo Escudero, Silvia Sánchez-García, Juan Trujillo, Audrey Dunn-Galvin, María Dolores P Ibáñez-Sandin, Pablo Rodríguez Del Río
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引用次数: 0
Global Burden of Elderly Atopic Dermatitis (1990-2021) and Projections to 2030: A Socio-Demographic Index Analysis. 全球老年人特应性皮炎负担(1990-2021)和2030年预测:社会人口指数分析。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-29 DOI: 10.1111/cea.70169
Ruiqian Yao, Lin Du, Haixia Zhao, Xiaoyan Yang, Erwen Kou, Bo Wang, Yuanjie Zhu
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引用次数: 0
Early and Sustained Asthma Control and Remission in Real-World Patients With Severe Eosinophilic Asthma Treated With Benralizumab: XALOC-2. Benralizumab: XALOC-2治疗严重嗜酸性哮喘患者的早期和持续哮喘控制和缓解
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-29 DOI: 10.1111/cea.70162
Erika Penz, Thomas Rothe, Lieven Dupont, Trung N Tran, Andrew Menzies-Gow, Anat Shavit, David Cohen, Tanja Plate, Sheena Kayaniyil, An Herreman, Claudio Schuoler, Benjamin Emmanuel, Marek Lommatzsch

Background: Prospective real-world data concerning the early and sustained effects of benralizumab on asthma control in patients with severe eosinophilic asthma (SEA) is lacking.

Methods: XALOC-2 is a prospective, observational, multi-national, real-world study in adults with SEA treated with benralizumab. This integrated analysis assessed Asthma Control Questionnaire (ACQ) scores, achievement of 3-component clinical remission (which included well-controlled symptoms [ACQ score ≤ 0.75], no exacerbations, and no use of maintenance oral corticosteroids [mOCS]), and other clinical outcomes, over a 12-month baseline period and up to Week 56. Associations between remission status and key baseline characteristics were also assessed.

Results: 535 patients were included. Median (interquartile range) ACQ score at baseline was 3.0 (2.2-3.8). At Week 1, 58.0% (282/486) of patients had ACQ score reductions of ≥ 0.5 points (minimal clinically important difference [MCID]) and 35.0% (170/486) had reductions of ≥ 1 point (2× MCID). By Week 56, these increased to 78.6% (276/351) and 62.1% (218/351), respectively. Improved asthma control after benralizumab initiation was similar irrespective of previous biologic use status. By Week 56, clinical remission criteria were achieved in 26.7% (70/262) of patients versus 0% (0/374) at baseline. No mOCS use, lower body mass index, better asthma symptom control and higher peak blood eosinophil count at baseline were associated with meeting 3-component clinical remission criteria at Week 56.

Conclusions: Real-world patients receiving benralizumab showed early and sustained improvements in asthma symptoms, regardless of previous biologic use. More than a quarter of patients achieved clinical asthma remission after 1 year of benralizumab treatment.

背景:缺乏关于benralizumab对严重嗜酸性哮喘(SEA)患者哮喘控制的早期和持续影响的前瞻性现实数据。方法:XALOC-2是一项前瞻性、观察性、多国、真实世界的研究,在接受贝纳利珠单抗治疗的成人SEA患者中进行。该综合分析评估了哮喘控制问卷(ACQ)评分、三组分临床缓解(包括症状控制良好[ACQ评分≤0.75]、无恶化、不使用维持性口服皮质类固醇[mOCS])的实现情况,以及12个月基线期至第56周的其他临床结果。缓解状态和关键基线特征之间的关系也被评估。结果:共纳入535例患者。基线时ACQ评分中位数(四分位间距)为3.0(2.2-3.8)。在第1周,58.0%(283 /486)的患者ACQ评分降低≥0.5分(最小临床重要差异[MCID]), 35.0%(170/486)的患者ACQ评分降低≥1分(2× MCID)。到第56周,这两个数字分别上升到78.6%(276/351)和62.1%(218/351)。在贝纳利珠单抗开始使用后,哮喘控制的改善是相似的,与之前的生物使用状态无关。到第56周,26.7%(70/262)的患者达到了临床缓解标准,而基线时为0%(0/374)。未使用mOCS、较低的体重指数、较好的哮喘症状控制和较高的基线血嗜酸性粒细胞峰值计数与第56周满足3组分临床缓解标准相关。结论:现实世界中,接受贝纳利珠单抗治疗的患者哮喘症状出现了早期和持续的改善,无论之前是否使用过生物制剂。超过四分之一的患者在贝纳利珠单抗治疗1年后达到临床哮喘缓解。
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引用次数: 0
Validation of the PEN-FAST Penicillin Allergy Clinical Decision Rule in an Asian Cohort. PEN-FAST青霉素过敏临床决策规则在亚洲队列中的验证。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-25 DOI: 10.1111/cea.70164
Xin Rong Lim, Ryan Xuan Wei Teo, Justina Wei-Lyn Tan, Sze-Chin Tan, Khai-Pang Leong, Faith Li-Ann Chia, Samuel Shang-Ming Lee, Claire Min-Li Teo, Grace Yin-Lai Chan, Bernard Yu-Hor Thong

Introduction: A false penicillin allergy label often leads to the unnecessary avoidance of beta-lactam antibiotics, contributing to antimicrobial resistance and suboptimal clinical outcomes. The PEN-FAST clinical decision rule is a simple, point-of-care tool with a high negative predictive value (NPV) designed to identify low-risk patients who may not require extensive allergy testing. This study aims to validate the performance of the PEN-FAST clinical decision rule in an Asian population.

Methods: A retrospective review of medical records from January 2006 to February 2023 was conducted at our institution's outpatient allergy clinic. Patients underwent skin prick and intradermal testing, followed by oral drug provocation testing (DPT) or direct oral DPT without prior skin testing (ST). Positive results were defined as positive skin test outcomes or immediate/delayed reactions following drug challenge. PEN-FAST scores were compared to allergy testing results.

Results: A total of 357 patients were included, with 85 (23.8%) undergoing direct DPT without prior ST. None had a history of severe cutaneous allergic reaction as their index reaction. The median age was 49 years (interquartile range [IQR]: 34-63), and 61.9% were female. Forty-seven patients (13.2%) had positive test results, including 26 positive reactions following DPT. PEN-FAST scores of 0-5 were distributed as follows: 25 (7.0%), 159 (44.5%), 31 (8.7%), 96 (26.9%), 4 (1.1%) and 42 (11.8%). Among those with PEN-FAST scores ≤ 2 (n = 215), 16 (7.4%) had a positive test. Of these, 7 developed urticaria, 8 developed mild delayed maculopapular exanthem and 1 had a positive skin test. A PEN-FAST score cutoff of ≤ 2 yielded sensitivity of 66.0% (95% CI: 50.7%-79.1%), specificity of 64.2% (95% CI: 58.6%-69.5%), a positive predictive value (PPV) of 21.8% (95% CI: 17.8%-26.5%) and a NPV of 92.6% (95% CI: 89.2%-94.9%). The area under the receiver operating characteristic curve was 0.66 (95% CI: 0.58-0.75).

Conclusion: The PEN-FAST clinical decision rule demonstrates a high NPV in an Asian population, supporting its potential utility in identifying individuals unlikely to have true penicillin allergy and enabling direct DPT in low-risk patients without prior ST. However, the modest area under the curve (AUC) of 0.66 reflects limited overall discriminatory ability.

错误的青霉素过敏标签常常导致不必要地避免使用β -内酰胺类抗生素,导致抗菌素耐药性和次优临床结果。PEN-FAST临床决策规则是一种简单的,具有高阴性预测值(NPV)的即时护理工具,旨在识别可能不需要广泛过敏测试的低风险患者。本研究旨在验证PEN-FAST临床决策规则在亚洲人群中的表现。方法:回顾性分析我院过敏门诊2006年1月至2023年2月的病历。患者首先进行皮肤刺破和皮内试验,然后进行口服药物激发试验(DPT)或不事先进行皮肤试验(ST)的直接口服DPT。阳性结果定义为皮肤试验结果阳性或药物刺激后立即/延迟反应。将PEN-FAST评分与过敏测试结果进行比较。结果:共纳入357例患者,其中85例(23.8%)接受直接DPT治疗,既往无ST.;年龄中位数为49岁(四分位数间距[IQR]: 34-63),女性占61.9%。结果阳性47例(13.2%),其中DPT术后阳性反应26例。0-5分的PEN-FAST得分分布为:25分(7.0%)、159分(44.5%)、31分(8.7%)、96分(26.9%)、4分(1.1%)、42分(11.8%)。在PEN-FAST评分≤2的患者(n = 215)中,16例(7.4%)呈阳性。其中7例发展为荨麻疹,8例发展为轻度迟发性黄斑丘疹,1例皮肤试验阳性。如果PEN-FAST评分临界值≤2,则敏感性为66.0% (95% CI: 50.7%-79.1%),特异性为64.2% (95% CI: 58.6%-69.5%),阳性预测值(PPV)为21.8% (95% CI: 17.8%-26.5%), NPV为92.6% (95% CI: 89.2%-94.9%)。受试者工作特征曲线下面积为0.66 (95% CI: 0.58 ~ 0.75)。结论:PEN-FAST临床决策规则在亚洲人群中显示出较高的NPV,支持其在识别不太可能发生真正青霉素过敏的个体和对无st病史的低风险患者进行直接DPT方面的潜在效用。然而,0.66的中等曲线下面积(AUC)反映了有限的总体区分能力。
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引用次数: 0
Management and Research Progress of Severe Asthma in China 中国重症哮喘的管理与研究进展。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-25 DOI: 10.1111/cea.70166
Xiaoying Chen, Rui Feng, Xiaolong Ji, Bizhou Li, Tao Liu, Jing Li, Ruchong Chen

Asthma is one of the most common chronic respiratory diseases, persisting across the life course and affecting approximately 300 million people worldwide. Severe asthma, defined as asthma remaining uncontrolled despite adherence to optimised high-dose inhaled corticosteroids/long-acting β2-agonist therapy and management of contributory factors, worsens upon dose reduction. In China, 3.4%–8.3% of patients with asthma have severe asthma, characterised by heterogeneity, frequent exacerbations, and considerable medical and economic burdens. Recent advances in the understanding of its pathogenesis, especially the development of biologics, have enabled new treatment strategies. This review incorporates recent progress from China regarding the epidemiology, pathogenesis, and biologic therapy for severe asthma.

哮喘是最常见的慢性呼吸系统疾病之一,在整个生命过程中持续存在,影响全世界约3亿人。重度哮喘,定义为尽管坚持优化的高剂量吸入皮质类固醇/长效β2激动剂治疗和致病因素管理,哮喘仍未得到控制,但剂量减少后病情恶化。在中国,3.4%-8.3%的哮喘患者患有严重哮喘,其特点是异质性、频繁发作,以及相当大的医疗和经济负担。最近对其发病机制的理解取得了进展,特别是生物制剂的发展,使新的治疗策略成为可能。本文综述了中国在重症哮喘的流行病学、发病机制和生物治疗方面的最新进展。
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引用次数: 0
Managing Drug Hypersensitivities: Clinicians' Perceptions on an Optimised Documentation Tool With De-Labelling Feature. 管理药物超敏反应:临床医生对具有去标签功能的优化文档工具的看法。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-25 DOI: 10.1111/cea.70167
Veronique Shiwa, Sven Van Laere, Martine Grosber, Pieter Cornu
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引用次数: 0
Type-2 Biomarkers, Asthma Diagnosis and Lung Function Impairment in the General Population 普通人群中的2型生物标志物、哮喘诊断和肺功能损害。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-23 DOI: 10.1111/cea.70165
Sebastian Riemann, Andrei Malinovschi, Guy G. Brusselle
<p>The diagnosis of asthma is typically centred around the presence of four key hallmark features: variable respiratory symptoms, chronic airway inflammation, airway hyperresponsiveness and variable expiratory airflow limitation [<span>1-3</span>]. However, bronchodilator reversibility (BDR) is present in < 20% of (mild-to-moderate) asthma cases in primary care, limiting its diagnostic value [<span>4</span>]. Recent guidelines have shifted towards type-2 (T2) biomarkers. The 2022 ERS guideline supports FeNO > 50 ppb to confirm asthma when spirometry is normal or BDR absent, while recommending blood eosinophil counts (BEC) only for phenotyping [<span>1</span>]. The 2020 NAEPP guideline similarly endorses FeNO as an adjunct test, but not BEC [<span>5</span>]. In contrast, the 2024 BTS/SIGN/NICE guideline proposes FeNO (> 50 ppb) or elevated BEC as first-line diagnostic tests, removing the requirement for spirometry [<span>2</span>]. The Global Initiative for Asthma (GINA) recommends the use of FeNO and BEC mainly for asthma phenotyping [<span>3</span>].</p><p>We evaluated this biomarker-first approach as a potential screening tool for asthma in the general population using U.S. NHANES 2007–2012 data from 18,319 participants (aged 6–80) with FeNO and BEC measurements and asthma status (self-reported physician-diagnosed current asthma). FeNO was measured with NIOX MINO (NIOX MINO, Aerocrine, Stockholm, Sweden). FeNO was defined as normal (< 20 ppb in children and adolescents aged 6–18/< 25 ppb in adults), intermediate (20–35/25–50 ppb) and high (≥ 35/≥ 50 ppb). Associations with asthma status were assessed using multivariable regression adjusted for demographic and clinical covariates. Associations between asthma status, high biomarkers and airflow obstruction were restricted to adults ≥ 18 years without emphysema (<i>N</i> = 12,575). Airflow obstruction was defined as prebronchodilator FEV<sub>1</sub>/FVC below the lower limit of normal using the GLI-2012 reference values.</p><p>The average age in the study group was 36 years. This study group included 1584 participants with current asthma (8.6%). Compared to controls, participants with current asthma were generally younger (32.7 years), had higher BMI (28.1 ± 8.7 kg/m<sup>2</sup>) and 56.2% were female. Reported use of oral and inhaled corticosteroids in asthmatics amounted to 3.6% and 21.8%, respectively (of which 12.8% reported use of ICS/LABA inhaler). Overall asthma prevalence increased from 5.9% in participants with normal FeNO and BEC < 150/μL to 31.7% in those with high FeNO and BEC > 500/μL (Figure 1A). In each of the three FeNO categories, asthma prevalence increased gradually according to increasing BEC levels (5.9% to 13% in the case of low FeNO, 8.8% to 23.6% in intermediate FeNO and 4.4% to 31.7% in participants with high FeNO).</p><p>Compared to individuals with low BEC and FeNO, moderate increases in BEC (150–300/μL) were associated with 1.3- to 3.2-fold higher o
哮喘的诊断通常以四个关键特征为中心:可变呼吸道症状、慢性气道炎症、气道高反应性和可变呼气气流限制[1-3]。然而,在初级保健中,支气管扩张剂可逆性(BDR)存在于20%的(轻度至中度)哮喘病例中,限制了其诊断价值。最近的指南已转向2型(T2)生物标志物。2022年ERS指南支持在肺活量测量正常或BDR缺失时,用50ppb的FeNO来确诊哮喘,而只推荐用血嗜酸性粒细胞计数(BEC)来诊断[1]表型。2020年NAEPP指南同样认可FeNO作为辅助测试,但不认可BEC[5]。相比之下,2024年BTS/SIGN/NICE指南建议将FeNO (50 ppb)或升高的BEC作为一线诊断检测,取消了肺量测定[2]的要求。全球哮喘倡议(GINA)建议使用FeNO和BEC主要用于哮喘表型[3]。我们使用美国NHANES 2007-2012数据,对这种生物标志物优先的方法作为普通人群哮喘的潜在筛查工具进行了评估,这些数据来自18319名参与者(6-80岁)的FeNO和BEC测量以及哮喘状态(自我报告的医生诊断的当前哮喘)。用NIOX MINO (NIOX MINO, Aerocrine, Stockholm, Sweden)测定FeNO。FeNO被定义为正常(6-18岁儿童和青少年20 ppb /成人25 ppb)、中等(20 - 35/25 - 50 ppb)和高(≥35/≥50 ppb)。使用多变量回归对人口统计学和临床协变量进行调整,评估与哮喘状态的关联。哮喘状态、高生物标志物和气流阻塞之间的关联仅限于≥18岁无肺气肿的成年人(N = 12575)。采用GLI-2012参考值将支气管扩张前FEV1/FVC低于正常下限定义为气流阻塞。研究小组的平均年龄为36岁。该研究组包括1584名哮喘患者(8.6%)。与对照组相比,目前患有哮喘的参与者通常更年轻(32.7岁),BMI更高(28.1±8.7 kg/m2), 56.2%为女性。报告使用口服和吸入皮质类固醇的哮喘患者分别占3.6%和21.8%(其中12.8%报告使用ICS/LABA吸入器)。总体哮喘患病率从FeNO和BEC 150/μL正常的5.9%增加到FeNO和BEC 500/μL高的31.7%(图1A)。在三种FeNO类别中,哮喘患病率随着BEC水平的增加而逐渐增加(低FeNO组为5.9%至13%,中等FeNO组为8.8%至23.6%,高FeNO组为4.4%至31.7%)。与低BEC和FeNO的个体相比,BEC中度升高(150-300 /μL)与当前哮喘的几率增加1.3- 3.2倍相关,这取决于FeNO水平。在BEC和FeNO最高的人群中,发现哮喘的几率高出3.7倍和7.1倍(在线补充)。使用FeNO 50 ppb和/或BEC 300 cells/μL的截断值,我们发现生物标志物阳性个体、哮喘诊断个体和气流阻塞个体之间存在异质性(图1B)。存在一个独特的亚组:没有正式哮喘诊断但生物标志物升高的个体,在某些情况下,并存气流阻塞。BEC≤300 ~ 500/μL、FeNO≤500/μL的非哮喘患者与FeNO≤300/μL的非哮喘患者相比,FEV1%的预测值明显低于FeNO≤300/μL的非哮喘患者。在这项基于人群的大型研究中,我们证明,在普通人群中,较高水平的FeNO和BEC始终与哮喘患病率增加有关。也许最引人注目的是,超过三分之二的FeNO高和BEC高于500/μL的人没有被诊断为哮喘,这可能表明(T2-)哮喘的诊断不足。为了支持这一假设,我们确定了一个没有哮喘诊断但T2生物标志物升高和气流阻塞的参与者亚组,发现没有哮喘和高T2生物标志物的参与者与没有哮喘但低T2生物标志物的参与者相比,FEV1显著降低。这些发现支持在普通人群中使用T2生物标志物FeNO和BEC筛查成人(T2高)哮喘。虽然T2生物标志物在初级保健中可能比用BDR进行肺活量测定更容易,但单独使用FeNO和/或BEC可能导致哮喘的过度诊断。在高测试前可能性人群中的诊断准确性研究先前表明,FeNO和BEC bbb的诊断准确性中等。因此,应建议临床医生将FeNO和BEC升高与客观肺功能检测(例如: (如BDR的肺活量测定或支气管挑战),并对可能不存在T2生物标志物升高的替代诊断或哮喘表型保持警惕[7,8]。NHANES研究的优势包括其大规模代表性设置,系统收集问卷,肺活量测定,FeNO测量和BEC。我们使用的NHANES数据是十多年前收集的,当时诊断哮喘算法尚未推荐FeNO或BEC测量,这为我们提供了在没有诊断偏差的情况下研究这些T2生物标志物的诊断效用的机会。本研究的局限性包括:医生诊断的哮喘的自我报告性质,这可能导致回忆性哮喘、错误分类和过度或不足诊断;缺乏过敏测试,以及临床相关结果(哮喘发作,因哮喘就诊)仅收集那些被诊断为哮喘的患者。总之,我们的分析强调了T2生物标志物FeNO和BEC作为普通人群中T2哮喘的首选筛查工具的潜力,可以更快地发现未确诊的哮喘患者。然而,在诊断途径中孤立地预先使用这些生物标志物可能导致哮喘的过度诊断,并且无法识别所有哮喘病例(例如,t2 -低哮喘)。研究概念与设计:g.g.b., A.M.;数据管理:s.r., A.M.;数据分析:S.R.;数据解释:s.r., a.m., G.G.B.;原稿:S.R.;审稿编辑:a.m., G.G.B.;srb声明:NHANES已获得NCHS研究伦理审查委员会(https://wwwn.cdc.gov/Nchs/Nhanes/)的批准,NCHS ERB协议号为2007-2008和2009-2010的NHANES编号为# 2005-06,NHANES 2011-2012的协议号为# 2011-17。所有参与者均获得了书面知情同意。报告阿斯利康、葛兰素史克和赛诺菲在提交的工作之外的会议支持;A.M.报告了Chiesi的顾问委员会费用、勃林格殷格翰的酬金以及NIOX和赛默飞世尔科学公司对研究者发起的研究的支持;G.G.B.报道了来自阿斯利康、勃林格殷格翰、奇耶西、葛兰素史克、默克夏普、诺华和赛诺菲再生龙的荣誉。除敏感数据类型外,NHANES数据可在https://wwwn.cdc.gov/Nchs/Nhanes/上公开获取。在Zenodo上可以在以下存储库中获得额外的在线补充:https://doi.org/10.5281/zenodo.17276627。
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引用次数: 0
Reassessing the Relationship Between Exhaled Nitric Oxide and Acute Bronchodilation in Asthma Patients 哮喘患者呼出一氧化氮与急性支气管扩张关系的再评估。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-21 DOI: 10.1111/cea.70156
Martin Färdig, Alain Michils, Renaud Louis, Mare Sabbe, Alain Van Muylem, Florence Schleich, Andrei Malinovschi
<p>Fractional exhaled nitric oxide (Fe<sub>NO</sub>) is an established marker of type-2 airway inflammation valuable in asthma management [<span>1</span>]. However, non-inflammatory factors, such as changes in airway calibre, may also influence Fe<sub>NO</sub> levels. Airway narrowing reduces Fe<sub>NO</sub> levels, likely due to reduced epithelial surface area limiting the NO diffusion from the airway lining into the lumen [<span>2</span>]. This effect may even be more pronounced when peripheral airways are involved, as the majority of NO is produced in the conductive airways [<span>3</span>]. By studying the dynamics of Fe<sub>NO</sub> from pre-bronchodilator (BD) to post-BD, Michils et al. previously identified three distinct post-BD Fe<sub>NO</sub> profiles in asthma: a change ≤ ±10% (Fe<sub>NO</sub> =), an increase > +10% (Fe<sub>NO</sub>+) and a decrease exceeding > −10% (Fe<sub>NO</sub>–), suggesting that Fe<sub>NO</sub> may help locate the site of airway obstruction [<span>4</span>].</p><p>Therefore, in a larger population of unselected asthmatics with stricter BD-withhold, we studied whether the post-BD Fe<sub>NO</sub> =, Fe<sub>NO</sub>+ and Fe<sub>NO</sub>– profiles could be confirmed, and secondly, if they could be associated with clinical features.</p><p>This cross-sectional analysis included 236 asthmatics (63% females), aged 14–83 years, from the asthma clinic of Liège University Hospital (Belgium). Fe<sub>NO</sub> and dynamic spirometry were performed according to current international guidelines, measured sequentially, both before and 15 min after the inhalation of BD (400 μg of salbutamol), using the NIOX Vero equipment. Only patients scheduled for bronchial provocation tests were instructed to discontinue short-acting (SABA) and long-acting β2-agonists (LABA) for 8–24 h. Informed written consent was collected from all participants at enrolment.</p><p>Continuous and dichotomized variables were compared across the Fe<sub>NO</sub> profiles using the Kruskal–Wallis and the Chi<sup>2</sup> tests (Stata/IC 16.1). Statistical significance level was set at a <i>p</i>-value < 0.05.</p><p>The median (Q1, Q3) pre- and post-BD Fe<sub>NO</sub> levels (parts per billion) were 20.0 (13.0, 36.5) and 20.5 (12.0, 36.5) (<i>n</i> = 236), respectively (<i>p</i> = 0.079) (Online Repository 1). While only 107 (63.1%) withheld BD use prior to the test, pre- (19.0 [14.0, 34.0] vs. 22.0 [13.0, 40.0], <i>p</i> = 0.545) and post-BD Fe<sub>NO</sub> levels (19.0 [13.0, 34.0] vs. 21.0 [12.0, 41.0], <i>p</i> = 0.686) were similar across participants with and without prior BD use. In relation to pre- and post-BD Fe<sub>NO</sub> levels, 96 (40.7%) had a change ≤ −10% and ≤ +10% (Fe<sub>NO</sub> =) (22.0 [15.0, 42.0] vs. 21.0 [14.5, 41.5], <i>p</i> = 0.470), 73 (30.9%) an increase > +10% (Fe<sub>NO</sub>+) (19.0 [11.0, 43.0] vs. 28.0 [16.0, 50.0], <i>p</i> < 0.001) and 67 (28.4%) a decrease > −10% (Fe<sub>NO</sub>–) (18.0 [13.0, 27.0] vs. 14.0
呼气一氧化氮分数(FeNO)是2型气道炎症的一种确定的标志物,在哮喘管理中具有重要价值。然而,非炎症因素,如气道口径的改变,也可能影响FeNO水平。气道狭窄降低了一氧化氮水平,可能是由于上皮表面积的减少限制了一氧化氮从气道内壁扩散到管腔[2]。当周围气道受到影响时,这种影响甚至可能更加明显,因为大多数一氧化氮是在导电气道中产生的。Michils等通过研究支气管扩张剂(BD)前至BD后FeNO的动态变化,先前确定了哮喘患者在BD后FeNO的三种不同特征:变化≤±10% (FeNO =),增加+10% (FeNO+)和减少超过+ gt; - 10% (FeNO -),提示FeNO可能有助于定位气道阻塞部位[4]。因此,在更大的未选择的bd -保留更严格的哮喘人群中,我们研究了bd后FeNO =、FeNO+和FeNO -谱是否可以被证实,其次,它们是否与临床特征相关。横断面分析包括236例哮喘患者(63%为女性),年龄14-83岁,来自比利时li<e:1>大学医院哮喘门诊。采用NIOX Vero仪器,在吸入BD (400 μg沙丁胺醇)前和吸入15 min后,按照现行国际指南进行FeNO和动态肺活量测定。只有计划进行支气管激发试验的患者被指示停用短效(SABA)和长效β2激动剂(LABA) 8-24小时。在入组时收集所有参与者的知情书面同意。使用Kruskal-Wallis和Chi2检验(Stata/IC 16.1)比较连续变量和二分类变量在FeNO剖面上的差异。p值为&lt; 0.05。bd前后FeNO水平(十亿分之一)的中位数(Q1, Q3)分别为20.0(13.0,36.5)和20.5 (12.0,36.5)(n = 236) (p = 0.079) (Online Repository 1)。虽然只有107人(63.1%)在测试前拒绝使用BD,但在有和没有使用BD的参与者中,术前(19.0 [14.0,34.0]vs. 22.0 [13.0, 40.0], p = 0.545)和术后FeNO水平(19.0 [13.0,34.0]vs. 21.0 [12.0, 41.0], p = 0.686)相似。与bd前后的FeNO水平相比,96例(40.7%)FeNO变化≤- 10%和≤+10% (FeNO =) (22.0 [15.0, 42.0] vs. 21.0 [14.5, 41.5], p = 0.470), 73例(30.9%)FeNO增加&gt; +10% (FeNO+) (19.0 [11.0, 43.0] vs. 28.0 [16.0, 50.0], p &lt; 0.001), 67例(28.4%)FeNO - (18.0 [13.0, 27.0] vs. 14.0 [9.00, 22.0], p &lt; 0.001) (Online Repository 2)。当比较FeNO =、FeNO+和FeNO -谱时,既往使用BD的患者比例相似。在肺活量方面,三组间第一秒用力呼气量(FEV1)和FEV1/用力肺活量(FVC)均无差异。相应地,背景特征、疾病控制、生物标志物水平和药物使用相似。然而,与FeNO=和FeNO+型相比,FeNO -型的SABA处理程度较低。同样,LABA和吸入性皮质类固醇(ICS)在相同的FeNO患者中也不常见;但无统计学意义(表1)。同样,在既往使用BD的参与者(n = 129)中,BD前FEV1预测值为80% (n = 126), BD后FEV1阳性变化为5% (n = 115),目前不吸烟者(n = 200), SABA, LABA和/或长效毒碱激动剂(LAMA)治疗在FeNO - profile中较少见(Online Repository 3-9)。我们的第一个发现是证实了双相障碍后哮喘患者的FeNO =、FeNO+和FeNO -谱,并且这些模式与先前是否使用双相障碍无关。其次,FeNO -型患者较少接受哮喘药物治疗。我们的研究结果与先前的研究一致,即BD前后的FeNO没有显著差异,BD对FeNO的影响较小或没有影响[4-6]。然而,发现了三种不同的bd后FeNO谱,与Michils等人(n = 67)和Demey等人(n = 30)的论文一致。然而,我们的研究人群更大,总体上表现出更好的疾病控制,保留了肺功能,阻塞较少,对BD的反应较小,从而贡献了新的知识。基于通气分布试验和理论模型,Michils等人认为这些特征可能可以通过阻塞缓解部位来解释:分别是中央(FeNO =)、腺泡前(FeNO+)和腺泡内(FeNO -)气道。由于没有这样的测量,我们只能在这方面进行推测。尽管FeNO患者的临床特征总体上是相似的,但在FeNO -患者中,SABA的使用并不常见。在同一档案中,LABA和ICS的使用往往不太常见,但没有统计学意义。 这可能表明该组症状较少,因此用药较少,或者较低的治疗程度可能与更多的腺泡内气道阻塞有关。依赖于bd后正常受试者的可变性,用于定义FeNO谱的潜在任意阈值(±10%)可能是一个限制。然而,在一次重新测试中,Michils等人报告了可接受的可重复性,一个独立的研究小组最近证实了这些截断值与成人哮喘(n = 92)小气道功能障碍的关系。没有进行通风分布试验,这是主要的限制。然而,本研究的主要目的不是验证不同的FeNO行为的意义,因为我们已经在其他三个研究中这样做了;COPD和哮喘患者[4,7,9]。在一个相对较小的、均匀的、单中心的、控制良好的哮喘患者样本中,只有63.1%的人在测试前拒绝使用双相激素,我们的研究结果的普遍性仅限于相似的人群,总体上影响了我们研究结果的可靠性。基于一个更大且完全独立的哮喘患者队列,本研究证实了先前描述的三种不同的双相障碍后FeNO特征。这些特征似乎与先前的BD使用无关,可能反映气道阻塞的程度和/或阻塞缓解的部位。虽然这些模式的临床特征没有明显差异,但我们首先描述了FeNO -谱与支气管扩张剂使用频率低有关,表明哮喘表型较轻或治疗不足。因此,评估双相障碍前后的FeNO可能有助于了解哮喘疾病负担,并在理论上有助于确定气道阻塞的位置。因此,FeNO可能在哮喘控制和/或治疗评估的临床评估中被证明是有用的。然而,目前的研究还很有限,需要进一步的研究来确定其临床意义和临床应用潜力。马丁Färdig对研究的概念和设计、数据管理、数据分析和解释、手稿写作和编辑做出了贡献。Alain Michils, Renaud Louis, Mare Sabbe, Alain Van Muylem和Florence Schleich对研究的构思和设计,数据收集,数据解释和批判性地修改手稿做出了贡献。Andrei Malinovschi对研究的构思和设计、数据管理、数据解释做出了贡献,并对手稿进行了严格的修改。所有列出的作者在提交前都批准了手稿的最终版本,并同意对工作的各个方面负责。该研究是根据《赫尔辛基宣言》的指导方针进行的,并于2018年12月12日获得了Erasme大学医院伦理委员会(P2018/481)的多中心批准,并于2018年12月4日获得了lifranchge大学医院伦理委员
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引用次数: 0
Unsupervised Machine Learning Identifies Asthma Phenotypes in the Population-Based West Sweden Asthma Study 在基于人群的西瑞典哮喘研究中,无监督机器学习识别哮喘表型。
IF 5.2 2区 医学 Q1 ALLERGY Pub Date : 2025-10-15 DOI: 10.1111/cea.70161
Muwada Bashir Awad Bashir, Daniil Lisik, Saliha Selin Ozuygur Ermis, Rani Basna, Reshed Abohalaka, Selin Ercan, Helena Backman, Teet Pullerits, Roxana Mincheva, Göran Wennergren, Madeleine Rådinger, Jan Lötvall, Linda Ekerljung, Hannu Kankaanranta, Bright I. Nwaru
<p>Asthma is a heterogeneous disease, and a clear-cut characterisation of its phenotypes has historically been daunting for both clinical practice and research purposes [<span>1</span>]. Asthma phenotypes have been defined primarily based on clinical experience [<span>2</span>]. Computational science is helping to elucidate biological processes, with ongoing applications in asthma phenotyping [<span>3</span>]. In this context, clustering algorithms can learn from unlabeled data to produce distinct subgroups. This data-driven approach is believed to be less subjective and, with relevant input data, can produce clinically meaningful phenotypes [<span>4</span>]. Characterising asthma at a more granular level aligns with efforts towards precision medicine, potentially enabling improved and tailored management. By including a broad range of clinical, biological, and epidemiological parameters, we employed a machine learning approach to identify and describe asthma phenotypes in adults.</p><p>The study sample was derived from the West Sweden Asthma Study (WSAS), a longitudinal cohort study investigating different aspects of airway diseases among a representative sample of adults, which started in 2008 [<span>5</span>]. A total of 3101 individuals underwent clinical investigations, of which 1895 subjects who had ever had asthma were included in the current study. Asthma was defined as self-reported ever asthma. Age at onset was determined through the follow-up question “at what age did your asthma start?”. In total, 44 variables were selected, based on clinical experience and previous studies (see details at https://osf.io/ucrnt).</p><p>Missing data were imputed using multiple imputation with random forest. The phenotypes were derived using Deep Embedded Clustering, a novel approach that combines deep learning with clustering to discover patterns in complex data [<span>6</span>]. The R packages NbClust, Monte Carlo reference-based consensus clustering (M3C), and Adjusted Rand Index (ARI) were used to decide the optimal number of clusters based on consensus of 30 internal validation indices. The proposed numbers were evaluated in conjunction with clinical experience to determine the final optimal number of clusters (details at https://osf.io/ucrnt/). Continuous data were expressed as means and standard deviations (SD). Group comparisons were performed by one-way analysis of variance with the Tukey post hoc test or Kruskal–Wallis test, as appropriate, for continuous variables and the Chi-square for categorical variables (details at https://osf.io/ucrnt/).</p><p>Cluster 1 had the oldest average age at asthma onset (35 years), while cluster 4 had the youngest average age (13 years) (Figure 1). Cluster 1 also had the oldest average chronological age (65 years), highest average BMI (28.5 kg/m<sup>2</sup>), highest proportion of smokers and average pack-year history, most respiratory symptoms, but the lowest proportion of allergic sensitization and family hist
另一方面,早发轻度特应性哮喘表型(第4簇)可能代表了传统的儿童期哮喘,其特点是过敏致敏性高,哮喘控制较好,症状负担低。我们的数据表明,这种表型也可能具有最高的缓解率,因为根据最近的症状和药物使用定义,这种表型在患有当前哮喘的患者中所占比例最低,这表明尽管这种表型在儿童时期发展,但可能是短暂的。总之,在一个有代表性的哮喘成人样本中发现了四种临床相关的哮喘表型,通过哮喘发病年龄、严重程度、肺功能、症状模式和炎症来区分。这些表型为催化重要的哮喘研究提供了一个新的环境,包括免疫途径的详细分析,假设的危险因素建模,合并症/多病概况的特征,以及评估未来的临床结果。构思了这个研究的想法。M.B.A.B.在B.I.N. l.e.、g.w.、h.k.和R.B.的指导下处理数据、进行分析、起草手稿并设计图表。M.B.A.B.参与了数据处理和分析的实施。BN为研究和数据收集的设计和实施做出了贡献。所有作者都讨论了结果,并为最终稿件做出了贡献。本研究由B.I.N.和h.k.监督,并由瑞典哥德堡地区伦理审查委员会批准。伦理批准号034-08 906-16 593-08和052-16。所有参与者在参与研究前均给予书面同意。报告了来自阿斯利康、勃林格殷格翰、基耶西、科维斯制药、葛兰素史克、Medscape、默沙明、诺华、Orion制药和赛诺菲的讲座和咨询的个人费用。所有其他作者声明与当前工作没有利益冲突。由于与研究参与者的协议和治理限制,研究数据不能公开共享。
{"title":"Unsupervised Machine Learning Identifies Asthma Phenotypes in the Population-Based West Sweden Asthma Study","authors":"Muwada Bashir Awad Bashir,&nbsp;Daniil Lisik,&nbsp;Saliha Selin Ozuygur Ermis,&nbsp;Rani Basna,&nbsp;Reshed Abohalaka,&nbsp;Selin Ercan,&nbsp;Helena Backman,&nbsp;Teet Pullerits,&nbsp;Roxana Mincheva,&nbsp;Göran Wennergren,&nbsp;Madeleine Rådinger,&nbsp;Jan Lötvall,&nbsp;Linda Ekerljung,&nbsp;Hannu Kankaanranta,&nbsp;Bright I. Nwaru","doi":"10.1111/cea.70161","DOIUrl":"10.1111/cea.70161","url":null,"abstract":"&lt;p&gt;Asthma is a heterogeneous disease, and a clear-cut characterisation of its phenotypes has historically been daunting for both clinical practice and research purposes [&lt;span&gt;1&lt;/span&gt;]. Asthma phenotypes have been defined primarily based on clinical experience [&lt;span&gt;2&lt;/span&gt;]. Computational science is helping to elucidate biological processes, with ongoing applications in asthma phenotyping [&lt;span&gt;3&lt;/span&gt;]. In this context, clustering algorithms can learn from unlabeled data to produce distinct subgroups. This data-driven approach is believed to be less subjective and, with relevant input data, can produce clinically meaningful phenotypes [&lt;span&gt;4&lt;/span&gt;]. Characterising asthma at a more granular level aligns with efforts towards precision medicine, potentially enabling improved and tailored management. By including a broad range of clinical, biological, and epidemiological parameters, we employed a machine learning approach to identify and describe asthma phenotypes in adults.&lt;/p&gt;&lt;p&gt;The study sample was derived from the West Sweden Asthma Study (WSAS), a longitudinal cohort study investigating different aspects of airway diseases among a representative sample of adults, which started in 2008 [&lt;span&gt;5&lt;/span&gt;]. A total of 3101 individuals underwent clinical investigations, of which 1895 subjects who had ever had asthma were included in the current study. Asthma was defined as self-reported ever asthma. Age at onset was determined through the follow-up question “at what age did your asthma start?”. In total, 44 variables were selected, based on clinical experience and previous studies (see details at https://osf.io/ucrnt).&lt;/p&gt;&lt;p&gt;Missing data were imputed using multiple imputation with random forest. The phenotypes were derived using Deep Embedded Clustering, a novel approach that combines deep learning with clustering to discover patterns in complex data [&lt;span&gt;6&lt;/span&gt;]. The R packages NbClust, Monte Carlo reference-based consensus clustering (M3C), and Adjusted Rand Index (ARI) were used to decide the optimal number of clusters based on consensus of 30 internal validation indices. The proposed numbers were evaluated in conjunction with clinical experience to determine the final optimal number of clusters (details at https://osf.io/ucrnt/). Continuous data were expressed as means and standard deviations (SD). Group comparisons were performed by one-way analysis of variance with the Tukey post hoc test or Kruskal–Wallis test, as appropriate, for continuous variables and the Chi-square for categorical variables (details at https://osf.io/ucrnt/).&lt;/p&gt;&lt;p&gt;Cluster 1 had the oldest average age at asthma onset (35 years), while cluster 4 had the youngest average age (13 years) (Figure 1). Cluster 1 also had the oldest average chronological age (65 years), highest average BMI (28.5 kg/m&lt;sup&gt;2&lt;/sup&gt;), highest proportion of smokers and average pack-year history, most respiratory symptoms, but the lowest proportion of allergic sensitization and family hist","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"56 2","pages":"170-172"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12879267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291368","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}
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Clinical and Experimental Allergy
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