Marius-Ionuţ Iuraşcu, Zsuzsanna Balla, Catarina Pereira, Noémi Andrási, Lilian Varga, Dorottya Csuka, Ágnes Szilágyi, Kornelia Tripolszki, Suliman Khan, Iuliana Susnea, Peter Bauer, Claudia Cozma, Henriette Farkas
Background
Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) is a rare disease caused by low level (type I) or dysfunction (type II) of the C1-inhibitor protein with subsequent reduction of certain complement protein levels.
Methods
To develop and test the reliability of a two-tier method based on C1-INH and C4 quantitation followed by genetic analysis from dried blood spot (DBS) for establishing the diagnosis of C1-INH-HAE. C1-INH and C4 proteins have been quantified in human plasma using a classical immuno-assay and in DBS using a newly developed proteolytic liquid chromatography–mass spectrometry method. Genetic analysis was carried out as reported previously (PMID: 35386643) and by a targeted next-generation sequencing panel, multiplex ligation-dependent probe amplification and in some cases whole genome sequencing.
Results
DBS quantification of C1-INH and C4 showed the same pattern as plasma, offering the possibility of screening patients with AE symptoms either locally or remotely. Genetic analysis from DBS verified each of the previously identified SERPING1 mutations of the tested C1-INH-HAE patients and revealed the presence of other rare variations in genes that may be involved in the pathogenesis of AE episodes.
Conclusions
C1-INH/C4 quantification in DBS can be used for screening of hereditary AE and DNA extracted from dried blood spots is suitable for identifying various types of mutations of the SERPING1 gene.
{"title":"Application of a dried blood spot based proteomic and genetic assay for diagnosing hereditary angioedema","authors":"Marius-Ionuţ Iuraşcu, Zsuzsanna Balla, Catarina Pereira, Noémi Andrási, Lilian Varga, Dorottya Csuka, Ágnes Szilágyi, Kornelia Tripolszki, Suliman Khan, Iuliana Susnea, Peter Bauer, Claudia Cozma, Henriette Farkas","doi":"10.1002/clt2.12317","DOIUrl":"https://doi.org/10.1002/clt2.12317","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) is a rare disease caused by low level (type I) or dysfunction (type II) of the C1-inhibitor protein with subsequent reduction of certain complement protein levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To develop and test the reliability of a two-tier method based on C1-INH and C4 quantitation followed by genetic analysis from dried blood spot (DBS) for establishing the diagnosis of C1-INH-HAE. C1-INH and C4 proteins have been quantified in human plasma using a classical immuno-assay and in DBS using a newly developed proteolytic liquid chromatography–mass spectrometry method. Genetic analysis was carried out as reported previously (PMID: 35386643) and by a targeted next-generation sequencing panel, multiplex ligation-dependent probe amplification and in some cases whole genome sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DBS quantification of C1-INH and C4 showed the same pattern as plasma, offering the possibility of screening patients with AE symptoms either locally or remotely. Genetic analysis from DBS verified each of the previously identified <i>SERPING1</i> mutations of the tested C1-INH-HAE patients and revealed the presence of other rare variations in genes that may be involved in the pathogenesis of AE episodes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>C1-INH/C4 quantification in DBS can be used for screening of hereditary AE and DNA extracted from dried blood spots is suitable for identifying various types of mutations of the <i>SERPING1</i> gene.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138432293","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}
Sarah Kidwai, Pietro Barbiero, Irma Meijerman, Alberto Tonda, Paula Perez-Pardo, Pietro Lio ́, Anke H. van der Maitland-Zee, Daniel L. Oberski, Aletta D. Kraneveld, Alejandro Lopez-Rincon
Background
Not being well controlled by therapy with inhaled corticosteroids and long-acting β2 agonist bronchodilators is a major concern for severe-asthma patients. The current treatment option for these patients is the use of biologicals such as anti-IgE treatment, omalizumab, as an add-on therapy. Despite the accepted use of omalizumab, patients do not always benefit from it. Therefore, there is a need to identify reliable biomarkers as predictors of omalizumab response.
Methods
Two novel computational algorithms, machine-learning based Recursive Ensemble Feature Selection (REFS) and rule-based algorithm Logic Explainable Networks (LEN), were used on open accessible mRNA expression data from moderate-to-severe asthma patients to identify genes as predictors of omalizumab response.
Results
With REFS, the number of features was reduced from 28,402 genes to 5 genes while obtaining a cross-validated accuracy of 0.975. The 5 responsiveness predictive genes encode the following proteins: Coiled-coil domain- containing protein 113 (CCDC113), Solute Carrier Family 26 Member 8 (SLC26A), Protein Phosphatase 1 Regulatory Subunit 3D (PPP1R3D), C-Type lectin Domain Family 4 member C (CLEC4C) and LOC100131780 (not annotated). The LEN algorithm found 4 identical genes with REFS: CCDC113, SLC26A8 PPP1R3D and LOC100131780. Literature research showed that the 4 identified responsiveness predicting genes are associated with mucosal immunity, cell metabolism, and airway remodeling.
Conclusion and clinical relevance
Both computational methods show 4 identical genes as predictors of omalizumab response in moderate-to-severe asthma patients. The obtained high accuracy indicates that our approach has potential in clinical settings. Future studies in relevant cohort data should validate our computational approach.
{"title":"A robust mRNA signature obtained via recursive ensemble feature selection predicts the responsiveness of omalizumab in moderate-to-severe asthma","authors":"Sarah Kidwai, Pietro Barbiero, Irma Meijerman, Alberto Tonda, Paula Perez-Pardo, Pietro Lio ́, Anke H. van der Maitland-Zee, Daniel L. Oberski, Aletta D. Kraneveld, Alejandro Lopez-Rincon","doi":"10.1002/clt2.12306","DOIUrl":"https://doi.org/10.1002/clt2.12306","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Not being well controlled by therapy with inhaled corticosteroids and long-acting β2 agonist bronchodilators is a major concern for severe-asthma patients. The current treatment option for these patients is the use of biologicals such as anti-IgE treatment, omalizumab, as an add-on therapy. Despite the accepted use of omalizumab, patients do not always benefit from it. Therefore, there is a need to identify reliable biomarkers as predictors of omalizumab response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two novel computational algorithms, machine-learning based Recursive Ensemble Feature Selection (REFS) and rule-based algorithm Logic Explainable Networks (LEN), were used on open accessible mRNA expression data from moderate-to-severe asthma patients to identify genes as predictors of omalizumab response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With REFS, the number of features was reduced from 28,402 genes to 5 genes while obtaining a cross-validated accuracy of 0.975. The 5 responsiveness predictive genes encode the following proteins: Coiled-coil domain- containing protein 113 (<i>CCDC113</i>), Solute Carrier Family 26 Member 8 (<i>SLC26A</i>), Protein Phosphatase 1 Regulatory Subunit 3D (<i>PPP1R3D</i>), C-Type lectin Domain Family 4 member C (<i>CLEC4C</i>) and <i>LOC100131780</i> (not annotated). The LEN algorithm found 4 identical genes with REFS: <i>CCDC113, SLC26A8 PPP1R3D</i> and <i>LOC100131780</i>. Literature research showed that the 4 identified responsiveness predicting genes are associated with mucosal immunity, cell metabolism, and airway remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and clinical relevance</h3>\u0000 \u0000 <p>Both computational methods show 4 identical genes as predictors of omalizumab response in moderate-to-severe asthma patients. The obtained high accuracy indicates that our approach has potential in clinical settings. Future studies in relevant cohort data should validate our computational approach.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137691337","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}
Bernard N. Jukema, Thomas C. Pelgrim, Sylvan L. J. E. Janssen, Thijs M. H. Eijsvogels, Alma Mingels, Wim Vroemen, Nienke Vrisekoop, Leo Koenderman
<p>To the Editor,</p><p>Type II inflammation is characterized by elevated blood eosinophils which makes these cells an important diagnostic and treatment target in, for instance, severe asthma. Therefore, blood eosinophil numbers are a main inclusion criterion for many clinical studies that have investigated the treatment of eosinophilic asthma with, for example, anti-IL5(Rα).<span><sup>1</sup></span> However, there is no consensus on cut-off values for blood eosinophils at inclusion as evidenced by a high variability between studies, ranging from 150 to 400 cells/μL. Moreover, the range of blood eosinophils in a healthy population, without confounding factors for increased blood eosinophils, is 30–330 cells/μL in males and 30–310 cells/μL in females.<span><sup>2</sup></span> This implies that the cut-off values used for clinical studies greatly overlap with blood eosinophil counts that are found in the healthy population. This inherently poses a problem as eosinophil blood counts seem to be inadequate to use for diagnosing eosinophilic diseases other than hypereosinophilia (>1500 cells/μL).</p><p>This overlap in eosinophil counts between patients and the healthy population limits the application of eosinophil numbers for discriminating between health and several inflammatory diseases. Eosinophil activation status ex vivo has already been investigated primarily with regard to asthma phenotypes,<span><sup>3</sup></span> but this study did not account for the effects of ex vivo activation caused by the manipulation of cells during sample work-up procedures. So, at least part of the activation phenotype might have been caused by enhanced sensitivity for ex vivo activation under these inflammatory conditions. Thus, a more promising approach in diagnosing eosinophilic disease would be to combine eosinophil numbers with their activation status under controlled conditions with minimal ex vivo manipulation.<span><sup>4</sup></span> This could improve eosinophil diagnostics, particularly in situations with (relative) eosinopenia. Unfortunately, there is surprisingly little evidence that blood eosinophil <i>counts</i> correlate with their activation status and/or responsiveness in vivo. Apart from activation ex vivo,<span><sup>5</sup></span> this lack of correlation can also be caused by homing of activated cells to the lung leaving behind non-activated cells in the blood.<span><sup>4, 6</sup></span></p><p>Most studies on eosinophil activation in vivo have been performed in the context of T-2 diseases. These studies imply that eosinophil activation in vivo is mainly driven by T-2 cytokines such as IL-5. Surprisingly little is known about eosinophil activation in vivo in donors without inflammatory diseases. Therefore, we designed this study on eosinophil activation in healthy individuals. Minimal ex vivo activation was achieved by analyzing blood eosinophils directly after venipuncture with a fast, automated, point-of-care, mobile flow cytometer (AQUIOS
这清楚地表明，血液嗜酸性粒细胞数量和它们的激活前状态之间存在完全的分离。我们的研究结果表明，嗜酸性粒细胞血室不能仅仅通过计数细胞数量(“数量”)来充分表征，因为标准化的数字并不一定反映它们(前)激活状态(“质量”)的标准化。这一发现不仅局限于测量嗜酸性粒细胞疾病的II型免疫状态，也适用于其他感染性/炎症性疾病和非病理性环境，如运动。我们的数据要求重新评估使用血液嗜酸性粒细胞计数作为嗜酸性细胞室状态的充分代表。直到最近，确定嗜酸性粒细胞室的激活状态被体外人工产物复杂化，这些人工产物已经开始于静脉穿刺的时刻。现在，随着快速、自动化、即时流式细胞术的出现，在广泛的健康和疾病环境中测量嗜酸性粒细胞的数量和质量是可行的。概念:Bernard N. Jukema, Sylvan L. J. E. Janssen, Alma Mingels, Wim Vroemen, Thijs M. H. Eijsvogels, Leo Koenderman。方法:Bernard N. Jukema, Sylvan L. J. E. Janssen, Thijs M. H. Eijsvogels, Leo Koenderman。数据分析:Bernard N. Jukema。可视化:Bernard N. Jukema。初稿编剧:伯纳德·n·朱科马，利奥·科恩德曼。最终论文的修改和审定:所有作者。aquos CL®负载放大器Go’流式细胞仪由美国佛罗里达州迈阿密的Beckman Coulter生命科学公司提供。该公司没有参与研究的设计，数据分析，文章的准备，或决定提交文章发表。作者声明，这项研究是在没有任何商业或财务关系的情况下进行的，这可能被解释为潜在的利益冲突。内梅亨大学医学中心;学术联盟基金。
{"title":"Exercise-induced eosinophil responses: Normal cell counts with a marked decrease in responsiveness","authors":"Bernard N. Jukema, Thomas C. Pelgrim, Sylvan L. J. E. Janssen, Thijs M. H. Eijsvogels, Alma Mingels, Wim Vroemen, Nienke Vrisekoop, Leo Koenderman","doi":"10.1002/clt2.12314","DOIUrl":"https://doi.org/10.1002/clt2.12314","url":null,"abstract":"<p>To the Editor,</p><p>Type II inflammation is characterized by elevated blood eosinophils which makes these cells an important diagnostic and treatment target in, for instance, severe asthma. Therefore, blood eosinophil numbers are a main inclusion criterion for many clinical studies that have investigated the treatment of eosinophilic asthma with, for example, anti-IL5(Rα).<span><sup>1</sup></span> However, there is no consensus on cut-off values for blood eosinophils at inclusion as evidenced by a high variability between studies, ranging from 150 to 400 cells/μL. Moreover, the range of blood eosinophils in a healthy population, without confounding factors for increased blood eosinophils, is 30–330 cells/μL in males and 30–310 cells/μL in females.<span><sup>2</sup></span> This implies that the cut-off values used for clinical studies greatly overlap with blood eosinophil counts that are found in the healthy population. This inherently poses a problem as eosinophil blood counts seem to be inadequate to use for diagnosing eosinophilic diseases other than hypereosinophilia (>1500 cells/μL).</p><p>This overlap in eosinophil counts between patients and the healthy population limits the application of eosinophil numbers for discriminating between health and several inflammatory diseases. Eosinophil activation status ex vivo has already been investigated primarily with regard to asthma phenotypes,<span><sup>3</sup></span> but this study did not account for the effects of ex vivo activation caused by the manipulation of cells during sample work-up procedures. So, at least part of the activation phenotype might have been caused by enhanced sensitivity for ex vivo activation under these inflammatory conditions. Thus, a more promising approach in diagnosing eosinophilic disease would be to combine eosinophil numbers with their activation status under controlled conditions with minimal ex vivo manipulation.<span><sup>4</sup></span> This could improve eosinophil diagnostics, particularly in situations with (relative) eosinopenia. Unfortunately, there is surprisingly little evidence that blood eosinophil <i>counts</i> correlate with their activation status and/or responsiveness in vivo. Apart from activation ex vivo,<span><sup>5</sup></span> this lack of correlation can also be caused by homing of activated cells to the lung leaving behind non-activated cells in the blood.<span><sup>4, 6</sup></span></p><p>Most studies on eosinophil activation in vivo have been performed in the context of T-2 diseases. These studies imply that eosinophil activation in vivo is mainly driven by T-2 cytokines such as IL-5. Surprisingly little is known about eosinophil activation in vivo in donors without inflammatory diseases. Therefore, we designed this study on eosinophil activation in healthy individuals. Minimal ex vivo activation was achieved by analyzing blood eosinophils directly after venipuncture with a fast, automated, point-of-care, mobile flow cytometer (AQUIOS","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134879447","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}
Oliver Pfaar, Angelika Sager, Ralph Mösges, Margitta Worm
Background
Subcutaneous allergen immunotherapy (SCIT) with depigmented, polymerized (DPP) birch pollen extract has been marketed at doses of up to 1000 DPP units/mL since 2001. We sought to determine the dose-dependent efficacy of a DPP birch pollen extract formulation in patients suffering from birch-pollen-induced allergic rhinitis or rhinoconjunctivitis with or without intermittent asthma.
Methods
A titrated conjunctival provocation test (CPT) was applied as a surrogate marker. This Phase II randomized, double-blind, parallel-group, dose-ranging clinical trial was performed at 39 centres in Germany, Lithuania and Poland. After randomization to four dose-level groups (100, 1000, 5000 and 10,000 DPP units/mL) and up-dosing, participants received maintenance SCIT with five monthly subcutaneous injections. The primary endpoint was the proportion of patients in whom a higher concentration of birch pollen (vs. baseline) was needed to elicit a positive CPT.
Results
Three hundred forty-three patients were included (mean (range) age: 42.6 (19–70)). The highest CPT responder rates were seen in the higher dose-level groups. In the intention-to-treat analysis, the difference between the 100 and 10,000 groups was statistically significant (p = 0.0118). Although the proportion of patients with ≥1 treatment-emergent adverse events increased with the dose, almost all these events were mild (65.6%) or moderate (18.5%).
Conclusion
Judging by the results of a CPT, the efficacy/safety ratio in SCIT appears to be favourable for a high-dose-level preparation of a DPP birch pollen extract.
{"title":"A high-dose, depigmented polymerized birch pollen extract for subcutaneous allergen immunotherapy has a favourable efficacy/safety ratio","authors":"Oliver Pfaar, Angelika Sager, Ralph Mösges, Margitta Worm","doi":"10.1002/clt2.12315","DOIUrl":"https://doi.org/10.1002/clt2.12315","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Subcutaneous allergen immunotherapy (SCIT) with depigmented, polymerized (DPP) birch pollen extract has been marketed at doses of up to 1000 DPP units/mL since 2001. We sought to determine the dose-dependent efficacy of a DPP birch pollen extract formulation in patients suffering from birch-pollen-induced allergic rhinitis or rhinoconjunctivitis with or without intermittent asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A titrated conjunctival provocation test (CPT) was applied as a surrogate marker. This Phase II randomized, double-blind, parallel-group, dose-ranging clinical trial was performed at 39 centres in Germany, Lithuania and Poland. After randomization to four dose-level groups (100, 1000, 5000 and 10,000 DPP units/mL) and up-dosing, participants received maintenance SCIT with five monthly subcutaneous injections. The primary endpoint was the proportion of patients in whom a higher concentration of birch pollen (vs. baseline) was needed to elicit a positive CPT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three hundred forty-three patients were included (mean (range) age: 42.6 (19–70)). The highest CPT responder rates were seen in the higher dose-level groups. In the intention-to-treat analysis, the difference between the 100 and 10,000 groups was statistically significant (<i>p</i> = 0.0118). Although the proportion of patients with ≥1 treatment-emergent adverse events increased with the dose, almost all these events were mild (65.6%) or moderate (18.5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Judging by the results of a CPT, the efficacy/safety ratio in SCIT appears to be favourable for a high-dose-level preparation of a DPP birch pollen extract.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"109169667","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}
Freerk Prenzel, Susanne Abraham, Christoph Hirche, Gerrit Müller, Stephan Kaiser, Leonarda Serdani-Neuhaus, Rebecca Zingel, Inmaculada Martinez-Saguer
Background
Hereditary angioedema (HAE) is a potentially life-threatening inherited disease that causes recurrent, serious, and debilitating episodes of swelling. While evidence has improved in adult patients, data on the epidemiology and treatment of pediatric patients with HAE remain very limited. The aim of this study was to determine the incidence and prevalence of pediatric patients with HAE aged <12 years, as well as treatment patterns, co-medication, and specialties involved.
Methods
In this retrospective study (2016–2021), the German IQVIATM pharmacy claims (LRx) database was used to analyze prescriptions of HAE-specific treatments and co-medications.
Results
We found an HAE prevalence in pediatric patients aged <12 years of 2.51:100,000 and a 12-month prevalence of up to 1.02:100,000 between 2016 and 2021. Most HAE treatments were prescribed by outpatient clinics and pediatricians, with an increasing proportion of icatibant as an on-demand treatment and low rates of long-term prophylaxis (LTP). The prescription rate of analgesics as the most common co-medication decreased notably after HAE diagnosis.
Conclusion
Our findings provide insights into the epidemiology and current pediatric HAE treatment landscape in Germany. The obtained HAE prevalence in pediatric patients aged <12 years was even higher than the previously reported average of overall cohorts, whereas the LTP rate was low, which might indicate an unmet need for newer LTP treatment options in pediatric patients.
{"title":"Epidemiology and treatment of children with hereditary angioedema in Germany: A retrospective database study","authors":"Freerk Prenzel, Susanne Abraham, Christoph Hirche, Gerrit Müller, Stephan Kaiser, Leonarda Serdani-Neuhaus, Rebecca Zingel, Inmaculada Martinez-Saguer","doi":"10.1002/clt2.12313","DOIUrl":"https://doi.org/10.1002/clt2.12313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE) is a potentially life-threatening inherited disease that causes recurrent, serious, and debilitating episodes of swelling. While evidence has improved in adult patients, data on the epidemiology and treatment of pediatric patients with HAE remain very limited. The aim of this study was to determine the incidence and prevalence of pediatric patients with HAE aged <12 years, as well as treatment patterns, co-medication, and specialties involved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective study (2016–2021), the German IQVIA<sup>TM</sup> pharmacy claims (LRx) database was used to analyze prescriptions of HAE-specific treatments and co-medications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found an HAE prevalence in pediatric patients aged <12 years of 2.51:100,000 and a 12-month prevalence of up to 1.02:100,000 between 2016 and 2021. Most HAE treatments were prescribed by outpatient clinics and pediatricians, with an increasing proportion of icatibant as an on-demand treatment and low rates of long-term prophylaxis (LTP). The prescription rate of analgesics as the most common co-medication decreased notably after HAE diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings provide insights into the epidemiology and current pediatric HAE treatment landscape in Germany. The obtained HAE prevalence in pediatric patients aged <12 years was even higher than the previously reported average of overall cohorts, whereas the LTP rate was low, which might indicate an unmet need for newer LTP treatment options in pediatric patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"109168475","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}
Pekka Hurme, Reetta Sahla, Beate Rückert, Tero Vahlberg, Riitta Turunen, Tytti Vuorinen, Mübeccel Akdis, Maria Söderlund-Venermo, Cezmi Akdis, Tuomas Jartti
Background
Rhinovirus (RV)-induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV-induced immune responses in young children. We investigated cytokine profiles of sole RV- and dual RV-HBoV1-induced first wheezing episodes, and their association with severity and prognosis.
Methods
Fifty-two children infected with only RV and nine children infected with dual RV-HBoV1, aged 3–23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti-CD3/anti-CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years.
Results
The mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL-1b, MIP-1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF-a, TARC, and ENA-78 in the RV-HBoV1 group compared with the RV group. In the convalescence phase, the RV-HBoV1 group was characterized by decreased expression of Fractalkine, MCP-3, and IL-8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p < 0.05), signifying that increased levels of epidermal growth factor and MIP-1b were related with a shorter duration of hospitalization in the RV-HBoV1 coinfection group but not in the RV group.
Conclusions
Different cytokine response profiles were detected between the RV and the RV-HBoV1 groups. Our results show the idea that RV-induced immune responses may be suppressed by HBoV1.
{"title":"Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus-induced first wheezing episode in children","authors":"Pekka Hurme, Reetta Sahla, Beate Rückert, Tero Vahlberg, Riitta Turunen, Tytti Vuorinen, Mübeccel Akdis, Maria Söderlund-Venermo, Cezmi Akdis, Tuomas Jartti","doi":"10.1002/clt2.12311","DOIUrl":"https://doi.org/10.1002/clt2.12311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rhinovirus (RV)-induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV-induced immune responses in young children. We investigated cytokine profiles of sole RV- and dual RV-HBoV1-induced first wheezing episodes, and their association with severity and prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifty-two children infected with only RV and nine children infected with dual RV-HBoV1, aged 3–23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti-CD3/anti-CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL-1b, MIP-1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF-a, TARC, and ENA-78 in the RV-HBoV1 group compared with the RV group. In the convalescence phase, the RV-HBoV1 group was characterized by decreased expression of Fractalkine, MCP-3, and IL-8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction <i>p</i> < 0.05), signifying that increased levels of epidermal growth factor and MIP-1b were related with a shorter duration of hospitalization in the RV-HBoV1 coinfection group but not in the RV group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Different cytokine response profiles were detected between the RV and the RV-HBoV1 groups. Our results show the idea that RV-induced immune responses may be suppressed by HBoV1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"109168510","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}
Fleur A. C. Jansen, Klaske van Norren, Joseph L. Baumert, Annegeet van den Bos, Joannes F. M. Jacobs, Stef J. Koppelman
<p>Peanut allergen Ara h 6 is known to maintain IgE-binding capacity upon exposure to digestive enzymes<span><sup>1</sup></span> and its presence in circulation after consumption of peanut has been demonstrated.<span><sup>2, 3</sup></span> Therefore, it has been speculated that food-derived allergens could be transferred via blood transfusion products, causing an allergic reaction in food-allergic recipients.<span><sup>4, 5</sup></span> However, in published case reports, presence of food allergen in donated material could not be confirmed due to lack of remaining transfusion material and/or lack of sensitive analytical methods. Using a newly developed sensitive immune-assay for detecting Ara h 6 in human serum, we now report to what extent consumed peanut allergens can be present in blood transfusion materials and estimate the associated risk for peanut-allergic recipients.</p><p>When five donors consumed peanut prior to blood donation (all donors gave informed consent to use their blood samples for clinical research, intervals ranging from 4 to 16 h; see methods in Supplementary Information), serum Ara h 6 levels were elevated up to 14 h after consumption (Figure 1). The highest serum Ara h 6 level was 4.20 ng/mL (±1.43 SEM), measured in serum collected 5 h after consumption.</p><p>We use an immunoassay (sandwich ELISA) to detect Ara h 6, and while this demonstrates that Ara h 6 in circulation possesses IgG epitopes, this does not necessarily mean that Ara h 6 in circulation still has allergenic activity. Such can be shown by basophil activation tests, however, within the current setting at our laboratories there was no access to those tests. Others have shown that levels of Ara h 6 detected in circulation after peanut consumption correlate with basophil activation potency<span><sup>3</sup></span> showing that Ara h 6 in circulation is still allergenic, but for our current study we do not have this proof, which is a limitation of our study.</p><p>Adhering to clinical guidelines for routine blood donation, 320 mL units of plasma were also obtained from these donors, at the same intervals after peanut consumption, and a similar pattern of Ara h 6 appearance was observed (Supporting Figures S1 and S2).</p><p>These data were obtained from donors that consumed at one eating occasion a relatively large amount of peanut. To get more insight into the clinical relevance of this observation, plasma samples from 20 adult subjects and a plasma omni pool product obtained from 600 donors (which is a routine transfusion product for clinical use) were analyzed for Ara h 6 content. As per blood donation guidelines, donors had no dietary restrictions and did not receive instruction to consume or avoid peanut. In 17 of the 20 individual plasma samples, Ara h 6 was detected (Figure 2). In eight of these samples, values above LLOQ were measured and two of these samples showed fairly high Ara h 6 levels: 1.09 ng/mL (±0.043 SEM) and 0.66 ng/mL (±0.066 SEM). Differenc
已知花生过敏原Ara h6在暴露于消化酶后仍能维持ige结合能力，并且在食用花生后其存在于循环中已得到证实。2,3因此，有人推测食物来源的过敏原可以通过输血制品转移，引起食物过敏接受者的过敏反应。然而，在已发表的病例报告中，由于缺乏剩余的输血材料和/或缺乏敏感的分析方法，无法确认捐赠材料中存在食物过敏原。使用新开发的灵敏免疫测定法检测人血清中的Ara h6，我们现在报告食用花生过敏原可以存在于输血材料中的程度，并估计花生过敏接受者的相关风险。当5名献血者在献血前食用花生(所有献血者知情同意将其血液样本用于临床研究，时间间隔为4至16小时;(见补充信息中的方法)，食用后14小时血清Ara h 6水平升高(图1)。食用后5小时采集的血清中Ara h 6水平最高为4.20 ng/mL(±1.43 SEM)。我们使用免疫测定法(夹心ELISA)检测Ara h6，虽然这表明循环中的Ara h6具有IgG表位，但这并不一定意味着循环中的Ara h6仍然具有致敏活性。这可以通过嗜碱性粒细胞激活试验来证明，然而，在我们实验室目前的环境下，没有机会进行这些试验。其他研究表明，食用花生后循环中检测到的Ara h6水平与嗜碱性粒细胞激活能力相关，表明循环中的Ara h6仍然具有致敏性，但就我们目前的研究而言，我们没有这一证据，这是我们研究的局限性。根据临床常规献血指南，在食用花生后，以相同的时间间隔从这些献血者处获得320毫升血浆，观察到类似的Ara h 6外观模式(支持图S1和S2)。这些数据是从一次食用相对大量花生的供体中获得的。为了更深入地了解这一观察结果的临床相关性，对来自20名成人受试者的血浆样本和来自600名献血者的血浆全池产品(这是临床使用的常规输血产品)进行了Ara h 6含量分析。根据献血指南，献血者没有饮食限制，也没有收到食用或避免花生的指示。在20个个体血浆样本中，有17个检测到Ara h 6(图2)。在其中8个样本中，测量到高于LLOQ的值，其中两个样本显示相当高的Ara h 6水平:1.09 ng/mL(±0.043 SEM)和0.66 ng/mL(±0.066 SEM)。这些献血者Ara h 6水平的差异可能是由于摄入花生的量或摄入花生与献血之间的时间(或两种因素的结合)。血浆全能池产品中Ara h6含量为0.56 ng/mL(±0.15 SEM)。目前尚不清楚花生过敏原在血液循环中的浓度是多少才能引发体内的全身反应，也不知道输血是否能达到这样的水平，但可以根据文献中报道的嗜碱性粒细胞激活阈值进行估计。例如，Hemmings等人的体外研究6表明，0.1-0.18 ng/mL Ara h 6可触发嗜碱性粒细胞脱粒;Mose等人的体外研究3表明，食用花生后获得的人血清样品中含有0.025-0.05 ng/mL Ara h 6，可使被动致敏的嗜碱性粒细胞脱粒。然而，报告的阈值不同，可能是由于方法的差异，也可能是由于肥大细胞和嗜碱性粒细胞对Ara h 6的敏感性在患者之间的差异。本研究中研究的血浆全能池产品将在临床实践中以每公斤体重12-15毫升的剂量使用(根据其产品数据表)，导致受体稀释约3.5 - 4.5倍。这将导致受体循环中的Ara h 6浓度为0.12-0.16 ng/mL。这些模拟的Ara h6浓度与嗜碱性粒细胞激活的阈值相同，或略高于阈值，这表明使用混合血浆产品输血可以引发花生过敏受体的过敏反应。在这个阶段，没有临床数据证明Ara h6在输血产品中的反应性。例如，供体和受体IgG的作用可能会阻止Ara h6与效应细胞结合，这需要进一步探索。后续研究可能包括(Ara h 6阳性)输血材料的嗜碱性粒细胞激活试验，或类似的花生致敏动物体内实验。 其他抗消化花生过敏原(如Ara h2)的重要性也应加以探讨，因为这些过敏原可以进一步增强输血产品的致敏负荷。目前，只有Ara h6被考虑，因为没有方法可以检测和量化血液样本中的其他花生过敏原。Fleur a.c. Jansen:数据管理(主管);调查(领导);验证(平等);可视化(平等);写作-原稿(同等)。Klaske van Norren:方法论(平等);监督(平等);写作—评审与编辑(同等)。约瑟夫·l·鲍默特:概念化(平等);写作—评审与编辑(同等)。安妮吉特·范登·博斯:资源(相等);写作—评审与编辑(同等)。乔安娜·f·m·雅各布斯:资源(平等);写作—评审与编辑(同等)。Stef J. Koppelman:概念化(平等);方法(平等);监督(平等);验证(平等);写作——原稿(引子)。Fleur A. C. Jansen, Klaske van Norren, Joseph L. Baumert, Annegeet van den Bos和Joannes F. M. Jacobs报告没有利益冲突。Stef J. Koppelman是DBV Technologies的顾问，超出了本文的范围。
{"title":"Peanut allergen Ara h 6 is detectable in blood transfusion products","authors":"Fleur A. C. Jansen, Klaske van Norren, Joseph L. Baumert, Annegeet van den Bos, Joannes F. M. Jacobs, Stef J. Koppelman","doi":"10.1002/clt2.12307","DOIUrl":"10.1002/clt2.12307","url":null,"abstract":"<p>Peanut allergen Ara h 6 is known to maintain IgE-binding capacity upon exposure to digestive enzymes<span><sup>1</sup></span> and its presence in circulation after consumption of peanut has been demonstrated.<span><sup>2, 3</sup></span> Therefore, it has been speculated that food-derived allergens could be transferred via blood transfusion products, causing an allergic reaction in food-allergic recipients.<span><sup>4, 5</sup></span> However, in published case reports, presence of food allergen in donated material could not be confirmed due to lack of remaining transfusion material and/or lack of sensitive analytical methods. Using a newly developed sensitive immune-assay for detecting Ara h 6 in human serum, we now report to what extent consumed peanut allergens can be present in blood transfusion materials and estimate the associated risk for peanut-allergic recipients.</p><p>When five donors consumed peanut prior to blood donation (all donors gave informed consent to use their blood samples for clinical research, intervals ranging from 4 to 16 h; see methods in Supplementary Information), serum Ara h 6 levels were elevated up to 14 h after consumption (Figure 1). The highest serum Ara h 6 level was 4.20 ng/mL (±1.43 SEM), measured in serum collected 5 h after consumption.</p><p>We use an immunoassay (sandwich ELISA) to detect Ara h 6, and while this demonstrates that Ara h 6 in circulation possesses IgG epitopes, this does not necessarily mean that Ara h 6 in circulation still has allergenic activity. Such can be shown by basophil activation tests, however, within the current setting at our laboratories there was no access to those tests. Others have shown that levels of Ara h 6 detected in circulation after peanut consumption correlate with basophil activation potency<span><sup>3</sup></span> showing that Ara h 6 in circulation is still allergenic, but for our current study we do not have this proof, which is a limitation of our study.</p><p>Adhering to clinical guidelines for routine blood donation, 320 mL units of plasma were also obtained from these donors, at the same intervals after peanut consumption, and a similar pattern of Ara h 6 appearance was observed (Supporting Figures S1 and S2).</p><p>These data were obtained from donors that consumed at one eating occasion a relatively large amount of peanut. To get more insight into the clinical relevance of this observation, plasma samples from 20 adult subjects and a plasma omni pool product obtained from 600 donors (which is a routine transfusion product for clinical use) were analyzed for Ara h 6 content. As per blood donation guidelines, donors had no dietary restrictions and did not receive instruction to consume or avoid peanut. In 17 of the 20 individual plasma samples, Ara h 6 was detected (Figure 2). In eight of these samples, values above LLOQ were measured and two of these samples showed fairly high Ara h 6 levels: 1.09 ng/mL (±0.043 SEM) and 0.66 ng/mL (±0.066 SEM). Differenc","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135410143","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}
Idun Holmdahl, Sandip Chakraborty, Angela Hoyer, Anastasia Filiou, Anna Asarnoj, Anders Sjölander, Magnus P. Borres, Marianne van Hage, Gunilla Hedlin, Jon R. Konradsen, Cilla Söderhäll
Background
Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood.
Objective
Our aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3 months. Additionally, to investigate the relationship between protein expression and clinical parameters.
Method
We measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3 months (PW-R, n = 113/145) and 101 healthy controls (HC) aged 6–48 months in the GEWAC cohort using the antibody-mediated proximity extension-based assay (Olink Proteomics, Uppsala).
Results
Of the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL-10, IL-6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF-β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24 h preceding blood sampling (OSM, CASP8, IL-10, TNF-β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3 months, differential protein expressions were still seen between PW-R and HC for three (IL-10, SIRT2 and FGF21) of the 10 proteins.
Conclusion
Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.
{"title":"Inflammatory related plasma proteins involved in acute preschool wheeze","authors":"Idun Holmdahl, Sandip Chakraborty, Angela Hoyer, Anastasia Filiou, Anna Asarnoj, Anders Sjölander, Magnus P. Borres, Marianne van Hage, Gunilla Hedlin, Jon R. Konradsen, Cilla Söderhäll","doi":"10.1002/clt2.12308","DOIUrl":"https://doi.org/10.1002/clt2.12308","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Our aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3 months. Additionally, to investigate the relationship between protein expression and clinical parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3 months (PW-R, <i>n</i> = 113/145) and 101 healthy controls (HC) aged 6–48 months in the GEWAC cohort using the antibody-mediated proximity extension-based assay (Olink Proteomics, Uppsala).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL-10, IL-6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF-β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24 h preceding blood sampling (OSM, CASP8, IL-10, TNF-β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3 months, differential protein expressions were still seen between PW-R and HC for three (IL-10, SIRT2 and FGF21) of the 10 proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71932379","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}
Nanike Esterhuizen, Dilys M. Berman, Frank H. Neumann, Linus Ajikah, Lynne J. Quick, Erin Hilmer, Andri Van Aardt, Juanette John, Rebecca Garland, Trevor Hill, Jemma Finch, Werner Hoek, Marion Bamford, Riaz Y. Seedat, Ahmed I. Manjra, Jonny Peter
Background
Pollen monitoring has been discontinuously undertaken in South Africa, a country with high biodiversity, a seasonal rainfall gradient, and nine biomes from arid to subtropical. The South African Pollen Monitoring Network was set up in 2019 to conduct the first long-term national aerospora monitoring across multiple biomes, providing weekly reports to allergy sufferers and healthcare providers.
Methods
Daily airborne pollen concentrations were measured from August 2019 to August 2021 in seven cities across South Africa. Updated pollen calendars were created for the major pollen types (>3%), the average Annual Pollen Index over 12 months was calculated, and the results were compared to available historical data.
Results
The main pollen types were from exotic vegetation. The most abundant taxa were Poaceae, Cupressaceae, Moraceae and Buddleja. The pollen season start, peak and end varied widely according to the biome and suite of pollen taxa. The main tree season started in the last week of August, peaked in September and ended in early December. Grass seasons followed rainfall patterns: September–January and January–April for summer and winter rainfall areas, respectively. Major urban centres, for example, Johannesburg and Pretoria in the same biome with similar rainfall, showed substantive differences in pollen taxa and abundance. Some major differences in pollen spectra were detected compared with historical data. However, we are cognisant that we are describing only 2 years of data that may be skewed by short-term weather patterns.
Conclusions
Differences in pollen spectra and concentrations were noted across biomes and between geographically close urban centres. Comparison with historical data suggests pollen spectra and seasons may be changing due to anthropogenic climate change and landscaping. These data stress the importance of regional and continuous pollen monitoring for informed care of pollinosis.
{"title":"The South African Pollen Monitoring Network: Insights from 2 years of national aerospora sampling (2019–2021)","authors":"Nanike Esterhuizen, Dilys M. Berman, Frank H. Neumann, Linus Ajikah, Lynne J. Quick, Erin Hilmer, Andri Van Aardt, Juanette John, Rebecca Garland, Trevor Hill, Jemma Finch, Werner Hoek, Marion Bamford, Riaz Y. Seedat, Ahmed I. Manjra, Jonny Peter","doi":"10.1002/clt2.12304","DOIUrl":"10.1002/clt2.12304","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pollen monitoring has been discontinuously undertaken in South Africa, a country with high biodiversity, a seasonal rainfall gradient, and nine biomes from arid to subtropical. The South African Pollen Monitoring Network was set up in 2019 to conduct the first long-term national aerospora monitoring across multiple biomes, providing weekly reports to allergy sufferers and healthcare providers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Daily airborne pollen concentrations were measured from August 2019 to August 2021 in seven cities across South Africa. Updated pollen calendars were created for the major pollen types (>3%), the average Annual Pollen Index over 12 months was calculated, and the results were compared to available historical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The main pollen types were from exotic vegetation. The most abundant taxa were Poaceae, Cupressaceae, Moraceae and <i>Buddleja</i>. The pollen season start, peak and end varied widely according to the biome and suite of pollen taxa. The main tree season started in the last week of August, peaked in September and ended in early December. Grass seasons followed rainfall patterns: September–January and January–April for summer and winter rainfall areas, respectively. Major urban centres, for example, Johannesburg and Pretoria in the same biome with similar rainfall, showed substantive differences in pollen taxa and abundance. Some major differences in pollen spectra were detected compared with historical data. However, we are cognisant that we are describing only 2 years of data that may be skewed by short-term weather patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Differences in pollen spectra and concentrations were noted across biomes and between geographically close urban centres. Comparison with historical data suggests pollen spectra and seasons may be changing due to anthropogenic climate change and landscaping. These data stress the importance of regional and continuous pollen monitoring for informed care of pollinosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135371678","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}
Karoline Krause, Hanna Bonnekoh, Jannis Jelden-Thurm, Riccardo Asero, Ana Maria Gimenez-Arnau, José C. Cardoso, Clive Grattan, Emek Kocatürk, Undine Lippert, Marcus Maurer, Martin Metz, Petra Staubach, Margarida Goncalo, Pavel Kolkhir
Background
Urticarial vasculitis (UV) should be differentiated from chronic spontaneous urticaria (CSU) in patients initially presenting with recurrent wheals, although criteria for differential diagnosis remain ill-defined.
Objectives
To set the goals, define criteria and unmet needs in UV diagnosis and differential diagnosis with CSU, and explore the possibility of coexistence of both diseases.
Methods
Thirteen experts experienced in UV research participated in a Delphi survey of European Academy of Allergy and Clinical Immunology taskforce. This Delphi survey involved three rounds of anonymous responses to n = 32 questions with the aim to aggregate the experts' opinions and to achieve consensus. Urticaria specialists (n = 130, most from Urticaria Centers of Reference and Excellence) evaluated the consensus statements and recommendations in the fourth and final round.
Results
The panel agreed that essential criteria to guide a skin biopsy in patients with recurrent wheals should include at least one of the following features: wheal duration >24 h, bruising/postinflammatory hyperpigmentation, and systemic symptoms. Leukocytoclasia and fibrin deposits were identified as a minimum set of UV histological criteria. As agreed by the panel members, CSU and normocomplementemic UV (NUV) may coexist in some patients.
Conclusions
The use of established criteria for the diagnosis and differential diagnosis of UV in patients with recurrent wheals can help guide the diagnostic approach and prompt earlier treatment. Further studies should investigate whether CSU and NUV are different entities or part of a disease spectrum.
{"title":"Differential diagnosis between urticarial vasculitis and chronic spontaneous urticaria: An international Delphi survey","authors":"Karoline Krause, Hanna Bonnekoh, Jannis Jelden-Thurm, Riccardo Asero, Ana Maria Gimenez-Arnau, José C. Cardoso, Clive Grattan, Emek Kocatürk, Undine Lippert, Marcus Maurer, Martin Metz, Petra Staubach, Margarida Goncalo, Pavel Kolkhir","doi":"10.1002/clt2.12305","DOIUrl":"https://doi.org/10.1002/clt2.12305","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Urticarial vasculitis (UV) should be differentiated from chronic spontaneous urticaria (CSU) in patients initially presenting with recurrent wheals, although criteria for differential diagnosis remain ill-defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To set the goals, define criteria and unmet needs in UV diagnosis and differential diagnosis with CSU, and explore the possibility of coexistence of both diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirteen experts experienced in UV research participated in a Delphi survey of European Academy of Allergy and Clinical Immunology taskforce. This Delphi survey involved three rounds of anonymous responses to <i>n</i> = 32 questions with the aim to aggregate the experts' opinions and to achieve consensus. Urticaria specialists (<i>n</i> = 130, most from Urticaria Centers of Reference and Excellence) evaluated the consensus statements and recommendations in the fourth and final round.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The panel agreed that essential criteria to guide a skin biopsy in patients with recurrent wheals should include at least one of the following features: wheal duration >24 h, bruising/postinflammatory hyperpigmentation, and systemic symptoms. Leukocytoclasia and fibrin deposits were identified as a minimum set of UV histological criteria. As agreed by the panel members, CSU and normocomplementemic UV (NUV) may coexist in some patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The use of established criteria for the diagnosis and differential diagnosis of UV in patients with recurrent wheals can help guide the diagnostic approach and prompt earlier treatment. Further studies should investigate whether CSU and NUV are different entities or part of a disease spectrum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50137934","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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