Louise J. Michaelis, Thomas Owen, Andrew D. Bright, Lucy Sherwin-Robson
<div> <section> <h3> Introduction</h3> <p>The recommended first-line treatment for anaphylaxis in the community is intramuscular injection of adrenaline. The treatment is a standardised dose of either a 150 μg or a 300 μg adrenaline auto-injector (AAI) device depending upon the patient's weight. Currently, no standardised mechanisms exist to transition patients onto the higher 300 μg dose when they reach 25–30 kg (depending upon the manufacturer).</p> </section> <section> <h3> Methods</h3> <p>We undertook analysis of NHS prescriptions data dispensed in the community in England to identify rates of non-standard AAI dose prescribing. Non-standard prescribing is defined as patients who are likely to have exceeded the 25–30 kg threshold but still received a 150 μg dose. Data were limited to the most recent AAI prescription for an individual patient that occurred in the last 2 years (December 2022–2024). Patient weight at the time of prescribing was approximated using an age-to-weight correlation model. AAI recommended switching weights, based on device metadata, were compared to the patients' approximated weight to identify non-standard prescribing. Statistical comparison between rates of non-standard prescribing and patient deprivation was computed using Kendall's Tau correlation coefficient. A complementary analysis to identify patients who received a 300 μg dose but were likely under the 25–30 kg threshold was also carried out.</p> </section> <section> <h3> Results</h3> <p>Overall, 46,999 patients were identified as having received a 150 μg strength injector in their most recent AAI prescription; of these, over 95% received two or more devices in line with national guidance. Estimates based on age for weight growth centiles show that between 9480 (20.2%) and at least 1747 (3.7%) of those prescribed a 150 μg autoinjector were likely to exceed the weight threshold for this dose. Using a Resuscitation Council UK guideline of age 6 years for switching to a 300 μg dose, the estimated proportion prescribed a non-standard AAI dose increases to 23,059 patients (49.1%). Estimated rates of non-standard AAI prescribing were found to be higher in areas of England with the most deprivation. Conservative estimates found only 67 children likely under 25 kg and 330 children likely under 30 kg who received a 300 μg dose.</p> </section> <section> <h3> Conclusions</h3> <p>This analysis of community AAI prescriptions in England suggests that underdosing of AAI prescriptions in children and adults is not uncommon. Healthcare professionals with patients at risk of anaphy
{"title":"Adrenaline Auto-Injector Prescribing in Primary Care in England: An Analysis of Non-Standard Dosing","authors":"Louise J. Michaelis, Thomas Owen, Andrew D. Bright, Lucy Sherwin-Robson","doi":"10.1111/cea.70163","DOIUrl":"10.1111/cea.70163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The recommended first-line treatment for anaphylaxis in the community is intramuscular injection of adrenaline. The treatment is a standardised dose of either a 150 μg or a 300 μg adrenaline auto-injector (AAI) device depending upon the patient's weight. Currently, no standardised mechanisms exist to transition patients onto the higher 300 μg dose when they reach 25–30 kg (depending upon the manufacturer).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We undertook analysis of NHS prescriptions data dispensed in the community in England to identify rates of non-standard AAI dose prescribing. Non-standard prescribing is defined as patients who are likely to have exceeded the 25–30 kg threshold but still received a 150 μg dose. Data were limited to the most recent AAI prescription for an individual patient that occurred in the last 2 years (December 2022–2024). Patient weight at the time of prescribing was approximated using an age-to-weight correlation model. AAI recommended switching weights, based on device metadata, were compared to the patients' approximated weight to identify non-standard prescribing. Statistical comparison between rates of non-standard prescribing and patient deprivation was computed using Kendall's Tau correlation coefficient. A complementary analysis to identify patients who received a 300 μg dose but were likely under the 25–30 kg threshold was also carried out.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 46,999 patients were identified as having received a 150 μg strength injector in their most recent AAI prescription; of these, over 95% received two or more devices in line with national guidance. Estimates based on age for weight growth centiles show that between 9480 (20.2%) and at least 1747 (3.7%) of those prescribed a 150 μg autoinjector were likely to exceed the weight threshold for this dose. Using a Resuscitation Council UK guideline of age 6 years for switching to a 300 μg dose, the estimated proportion prescribed a non-standard AAI dose increases to 23,059 patients (49.1%). Estimated rates of non-standard AAI prescribing were found to be higher in areas of England with the most deprivation. Conservative estimates found only 67 children likely under 25 kg and 330 children likely under 30 kg who received a 300 μg dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This analysis of community AAI prescriptions in England suggests that underdosing of AAI prescriptions in children and adults is not uncommon. Healthcare professionals with patients at risk of anaphy","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"56 1","pages":"30-40"},"PeriodicalIF":5.2,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430496","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}
R Soegiharto, B J Hengevelt, N Boekema-Bakker, I A M Groenewegen, A C Knulst, J M P A Van den Reek, H Röckmann
{"title":"Exploring the Disease Duration of Urticaria and Associated Determinants in Primary Care.","authors":"R Soegiharto, B J Hengevelt, N Boekema-Bakker, I A M Groenewegen, A C Knulst, J M P A Van den Reek, H Röckmann","doi":"10.1111/cea.70170","DOIUrl":"https://doi.org/10.1111/cea.70170","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"Comparison Between a Rush and a Conventional Oral Immunotherapy Protocol to Treat Cow's Milk and Hen's Egg Allergy. CompITO Study Methodology.","authors":"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","doi":"10.1111/cea.70168","DOIUrl":"10.1111/cea.70168","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruiqian Yao, Lin Du, Haixia Zhao, Xiaoyan Yang, Erwen Kou, Bo Wang, Yuanjie Zhu
{"title":"Global Burden of Elderly Atopic Dermatitis (1990-2021) and Projections to 2030: A Socio-Demographic Index Analysis.","authors":"Ruiqian Yao, Lin Du, Haixia Zhao, Xiaoyan Yang, Erwen Kou, Bo Wang, Yuanjie Zhu","doi":"10.1111/cea.70169","DOIUrl":"https://doi.org/10.1111/cea.70169","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Early and Sustained Asthma Control and Remission in Real-World Patients With Severe Eosinophilic Asthma Treated With Benralizumab: XALOC-2.","authors":"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","doi":"10.1111/cea.70162","DOIUrl":"https://doi.org/10.1111/cea.70162","url":null,"abstract":"<p><strong>Background: </strong>Prospective real-world data concerning the early and sustained effects of benralizumab on asthma control in patients with severe eosinophilic asthma (SEA) is lacking.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Validation of the PEN-FAST Penicillin Allergy Clinical Decision Rule in an Asian Cohort.","authors":"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","doi":"10.1111/cea.70164","DOIUrl":"https://doi.org/10.1111/cea.70164","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Management and Research Progress of Severe Asthma in China","authors":"Xiaoying Chen, Rui Feng, Xiaolong Ji, Bizhou Li, Tao Liu, Jing Li, Ruchong Chen","doi":"10.1111/cea.70166","DOIUrl":"10.1111/cea.70166","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"56 2","pages":"147-166"},"PeriodicalIF":5.2,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veronique Shiwa, Sven Van Laere, Martine Grosber, Pieter Cornu
{"title":"Managing Drug Hypersensitivities: Clinicians' Perceptions on an Optimised Documentation Tool With De-Labelling Feature.","authors":"Veronique Shiwa, Sven Van Laere, Martine Grosber, Pieter Cornu","doi":"10.1111/cea.70167","DOIUrl":"https://doi.org/10.1111/cea.70167","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"Type-2 Biomarkers, Asthma Diagnosis and Lung Function Impairment in the General Population","authors":"Sebastian Riemann, Andrei Malinovschi, Guy G. Brusselle","doi":"10.1111/cea.70165","DOIUrl":"10.1111/cea.70165","url":null,"abstract":"<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","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"56 2","pages":"173-175"},"PeriodicalIF":5.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12879270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354109","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}
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
{"title":"Reassessing the Relationship Between Exhaled Nitric Oxide and Acute Bronchodilation in Asthma Patients","authors":"Martin Färdig, Alain Michils, Renaud Louis, Mare Sabbe, Alain Van Muylem, Florence Schleich, Andrei Malinovschi","doi":"10.1111/cea.70156","DOIUrl":"10.1111/cea.70156","url":null,"abstract":"<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","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 12","pages":"1268-1271"},"PeriodicalIF":5.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12740540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343956","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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