Annika Gutsche, Martin Metz, Melba Munoz, Kit Wong, Ted Omachi, Rui Zhao, Marcus Maurer, Vasiliki Zampeli, Markus Magerl
<p>To the Editor,</p><p>Symptomatic dermographism (SD), a common subtype of chronic inducible urticaria (CIndU), involves transient, strip-shaped wheals that itch and burn when the skin is stroked or scratched.<span><sup>1</sup></span> SD affects ≥0.5% of the population,<span><sup>2</sup></span> yet despite its high frequency and marked impact on quality of life, diagnostic tools and treatment options are limited.<span><sup>1, 3</sup></span></p><p>Diagnosis is based on the patient's medical history and provocation testing.<span><sup>2</sup></span> Historically, provocation testing used a smooth, blunt object to stroke the skin, but variations in individuals' disease presentation highlighted the need for validated, reproducible tools.<span><sup>3</sup></span> The FricTest®4.0<span><sup>4</sup></span> is a hand-held, flat plastic comb-like tool with four smooth pins (3.0–4.5 mm long) firmly stroked along the skin. The resulting wheals determine the critical friction threshold (CFT), the shortest pin length/minimum pressure that elicits a positive wheal response.<span><sup>5</sup></span></p><p>This study aimed to assess the reliability (reproducibility and repeatability) of FricTest inter-rater agreement (results from two different raters on the same patient at the same visit) and intra-rater agreement (results from the same rater on the same patient 7–14 days apart). Reliable results are important for monitoring treatment effects, helping patients understand triggers, and improving management. We assume that each patient's left and right forearms are the same, that visits are the same, and that previous provocation did not affect the reaction of subsequent tests.</p><p>This single-center study was conducted at the Urticaria Center of Reference and Excellence<span><sup>6</sup></span> at the Charité Hospital, Berlin, Germany. Adults had SD for >6 weeks, had active SD at enrollment, and gave written informed consent. The study followed the Declaration of Helsinki principles, and the Berlin Charité Ethics Committee approved the protocol.</p><p>The primary endpoint, inter-rater agreement, was the intraclass correlation coefficient (ICC) between the CFT assessments of two raters within the same patient. The CFT scale is 0–4 (0 = no response, 4 = maximum response). ICCs plus upper and lower 95% confidence intervals (CI) were calculated using a mixed-effects linear model methodology.<span><sup>7</sup></span> Rater A and B agreement was quantified using weighted kappa across four categories: left forearm, right forearm, Visit 1, and Visit 2. An ICC<0.4 indicated poor reliability, and 0.6–0.8 indicated substantial reliability.</p><p>Two raters randomized to the order of assessments (Forearm 1 [right], Forearm 2 [left]) administered and recorded all FricTest results. At Visit 1, Rater A applied the FricTest to Forearm 1, covered the arm, and left the room. Rater B then applied the FricTest to Forearm 2, covered the arm, and left the room. Ten minutes af
致编辑：症状性皮炎（SD）是慢性诱发性荨麻疹（CIndU）的一种常见亚型，表现为一过性、条状的麦粒肿，当皮肤受到抚摸或抓挠时会出现瘙痒和烧灼感、3 诊断基于患者的病史和激惹试验。2 历史上，激惹试验使用光滑的钝器划动皮肤，但个体疾病表现的差异凸显了对有效、可重复工具的需求。3 FricTest®4.04 是一种手持式扁平塑料梳状工具，带有四个光滑的针脚（3.0-4.5 毫米长），可沿着皮肤用力划动。5 本研究旨在评估 FricTest 的评分者间一致性（由两名不同评分者在同一次就诊中对同一患者得出的结果）和评分者内部一致性（由同一评分者在相隔 7-14 天后对同一患者得出的结果）的可靠性（再现性和可重复性）。可靠的结果对于监测治疗效果、帮助患者了解诱发因素和改善管理非常重要。我们假定每位患者的左右前臂是一样的，就诊时间也是一样的，而且之前的诱发不会影响后续测试的反应。这项单中心研究在德国柏林夏里特医院的荨麻疹卓越参考中心6进行。研究对象为荨麻疹持续6周、入选时荨麻疹处于活动期、并出具知情同意书的成年人。该研究遵循《赫尔辛基宣言》的原则，并获得了柏林夏里特伦理委员会的批准。主要终点--评分者之间的一致性是指两名评分者对同一患者的CFT评估之间的类内相关系数（ICC）。CFT 量表为 0-4（0 = 无反应，4 = 最大反应）。采用混合效应线性模型方法计算 ICC 和上下 95% 置信区间 (CI)。7 采用加权卡帕法量化评分者 A 和 B 在左前臂、右前臂、第 1 次就诊和第 2 次就诊四个类别中的一致性。ICC<0.4 表示可靠性较差，0.6-0.8 表示可靠性较高。两名评分员随机分配评估顺序（前臂 1 [右]、前臂 2 [左]），实施并记录所有 FricTest 结果。在访问 1 中，评分员 A 对前臂 1 进行了 FricTest 测试，盖上手臂后离开房间。然后，测评员 B 对前臂 2 进行了 FricTest 测试，盖住手臂并离开房间。第一次施测十分钟后，测评员 A 返回，揭开前臂 1，记录下反应，然后重新盖上手臂。评分员 B 重复这一过程。在 16 名参与者（62.5% 为女性）中，我们观察到当评分者 A 和 B 在同一次就诊中对同一患者进行评估时，评分者之间的一致性非常高，左前臂的加权卡帕值为 0.86，右前臂的加权卡帕值为 0.77（表 1，图 1）。当两名评分员在不同的就诊时间对同一患者进行评估时，在就诊第 1 次时，一致性为中等（加权卡帕为 0.56），但在就诊第 2 次时，一致性提高到了相当高的水平（0.79；表 1）。评分员 A 和 B 报告的加权卡方值分别为 0.72 和 0.73，表明在第 1 次和第 2 次就诊时评分员之间的一致性很高。总体而言，ICC 测量结果的一致性很高，评分员之间的可靠性为 0.89（95% CI 0.71，0.94），评分员内部的可靠性为 0.81（95% CI 0.60，0.92）。在第 1 次和第 2 次检查中，评分员 A 和 B 之间的平均差分别为 0.06 和 0.13。我们的研究验证了 FricTest 的有效性，证明了它作为 SD 诊断和监测工具的可靠性。8 我们的研究结果表明，在诱导 SD 患者出现喘息时，评分者之间几乎完全一致，评分者内部也基本一致。准确确定患者的 CFT 可以提高 SD 诊断的准确性，并最终改善对患者病情的管理。尽管存在这些波动，但每位评分者发现疾病活动变化的一致性证实了我们的评估工具在识别 SD 改善和恶化方面的稳健性。
{"title":"Assessing the reliability of the FricTest® 4.0 for diagnosing symptomatic dermographism","authors":"Annika Gutsche, Martin Metz, Melba Munoz, Kit Wong, Ted Omachi, Rui Zhao, Marcus Maurer, Vasiliki Zampeli, Markus Magerl","doi":"10.1002/clt2.70005","DOIUrl":"10.1002/clt2.70005","url":null,"abstract":"<p>To the Editor,</p><p>Symptomatic dermographism (SD), a common subtype of chronic inducible urticaria (CIndU), involves transient, strip-shaped wheals that itch and burn when the skin is stroked or scratched.<span><sup>1</sup></span> SD affects ≥0.5% of the population,<span><sup>2</sup></span> yet despite its high frequency and marked impact on quality of life, diagnostic tools and treatment options are limited.<span><sup>1, 3</sup></span></p><p>Diagnosis is based on the patient's medical history and provocation testing.<span><sup>2</sup></span> Historically, provocation testing used a smooth, blunt object to stroke the skin, but variations in individuals' disease presentation highlighted the need for validated, reproducible tools.<span><sup>3</sup></span> The FricTest®4.0<span><sup>4</sup></span> is a hand-held, flat plastic comb-like tool with four smooth pins (3.0–4.5 mm long) firmly stroked along the skin. The resulting wheals determine the critical friction threshold (CFT), the shortest pin length/minimum pressure that elicits a positive wheal response.<span><sup>5</sup></span></p><p>This study aimed to assess the reliability (reproducibility and repeatability) of FricTest inter-rater agreement (results from two different raters on the same patient at the same visit) and intra-rater agreement (results from the same rater on the same patient 7–14 days apart). Reliable results are important for monitoring treatment effects, helping patients understand triggers, and improving management. We assume that each patient's left and right forearms are the same, that visits are the same, and that previous provocation did not affect the reaction of subsequent tests.</p><p>This single-center study was conducted at the Urticaria Center of Reference and Excellence<span><sup>6</sup></span> at the Charité Hospital, Berlin, Germany. Adults had SD for >6 weeks, had active SD at enrollment, and gave written informed consent. The study followed the Declaration of Helsinki principles, and the Berlin Charité Ethics Committee approved the protocol.</p><p>The primary endpoint, inter-rater agreement, was the intraclass correlation coefficient (ICC) between the CFT assessments of two raters within the same patient. The CFT scale is 0–4 (0 = no response, 4 = maximum response). ICCs plus upper and lower 95% confidence intervals (CI) were calculated using a mixed-effects linear model methodology.<span><sup>7</sup></span> Rater A and B agreement was quantified using weighted kappa across four categories: left forearm, right forearm, Visit 1, and Visit 2. An ICC<0.4 indicated poor reliability, and 0.6–0.8 indicated substantial reliability.</p><p>Two raters randomized to the order of assessments (Forearm 1 [right], Forearm 2 [left]) administered and recorded all FricTest results. At Visit 1, Rater A applied the FricTest to Forearm 1, covered the arm, and left the room. Rater B then applied the FricTest to Forearm 2, covered the arm, and left the room. Ten minutes af","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616020","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}
<p>Dear Editor,</p><p>We would like to respond to the recent publication by Matsumoto et al. “Milk ladder versus early oral immunotherapy in infants with cow's milk protein (CMP) allergy” which we read with interest<span><sup>1</sup></span> In this single center retrospective observational study the authors compared the efficacy and safety of milk ladder (ML) with early-oral immunotherapy (E-OIT) in children under the age of 2 years.</p><p>For over 10 years, milk ladders have been used as the mainstay of treatment for both IgE and non-IgE mediated cow’s milk protein allergy (CMPA) in Ireland. As described in this publication, the ML involves the home-based graded reintroduction of CMP containing foods in a stepwise fashion from least to most allergenic forms. This practice has been deemed safe and successful in Irish settings.<span><sup>2</sup></span> As the use of Dietary advancement therapies (DATs) including MLs and OIT become more widespread in the global allergy community we strongly support the recollection of local data and thank the authors for publishing this paper which adds to the collective knowledge on the treatment of CMPA. This paper led us to consider our practice for patient selection and the differences between what is possible and practical in the clinical setting versus what is best practice.</p><p>In clinical practice the use of clinical history of parental reported immediate symptoms and proof of sensitisation is used to confirm milk allergy instead of the gold-standard Oral Food Challenge (OFC). Prior to the initiation of OIT international guidelines indicates the use of OFC to confirm the diagnosis.<span><sup>3</sup></span> In the protocol described by Matsumoto et al. they included patients with either parent reported immediate symptoms or proof of sensitisation (Milk specific IgE > 5 kUA/L). We agree with the authors that this is a limitation of the study. We feel that in the absence of a challenge proven allergy, it is likely that this cohort included children with parent reported symptoms alone (with no sensitisation or allergy) or asymptomatic sensitisation.</p><p>Previous studies comparing the use of OIT with total milk avoidance identified approximately half of children screened with parent reported symptoms AND evidence of sensitisation (IgE > 0.35) had a negative double-blind placebo-controlled food challenge to milk.<span><sup>4</sup></span></p><p>The same limitations were discussed in research from our Irish team, we compared the use of ML and milk avoidance in real-life diagnosed CMPA patients (positive clinical history and allergy tests without OFC) and decided to label the primary outcome as reintroduction of milk instead of tolerance.<span><sup>5</sup></span></p><p>DATs can be used in high-risk patients for the first introduction of CMP. This may be helpful when there is hesitation to introduce milk and can enable and empower families to introduce it at home in a graded way. For example, in high risk a
{"title":"Comment on: Matsumoto et al.","authors":"Molly Cremin, Sadhbh Hurley, Juan Trujillo","doi":"10.1002/clt2.70000","DOIUrl":"10.1002/clt2.70000","url":null,"abstract":"<p>Dear Editor,</p><p>We would like to respond to the recent publication by Matsumoto et al. “Milk ladder versus early oral immunotherapy in infants with cow's milk protein (CMP) allergy” which we read with interest<span><sup>1</sup></span> In this single center retrospective observational study the authors compared the efficacy and safety of milk ladder (ML) with early-oral immunotherapy (E-OIT) in children under the age of 2 years.</p><p>For over 10 years, milk ladders have been used as the mainstay of treatment for both IgE and non-IgE mediated cow’s milk protein allergy (CMPA) in Ireland. As described in this publication, the ML involves the home-based graded reintroduction of CMP containing foods in a stepwise fashion from least to most allergenic forms. This practice has been deemed safe and successful in Irish settings.<span><sup>2</sup></span> As the use of Dietary advancement therapies (DATs) including MLs and OIT become more widespread in the global allergy community we strongly support the recollection of local data and thank the authors for publishing this paper which adds to the collective knowledge on the treatment of CMPA. This paper led us to consider our practice for patient selection and the differences between what is possible and practical in the clinical setting versus what is best practice.</p><p>In clinical practice the use of clinical history of parental reported immediate symptoms and proof of sensitisation is used to confirm milk allergy instead of the gold-standard Oral Food Challenge (OFC). Prior to the initiation of OIT international guidelines indicates the use of OFC to confirm the diagnosis.<span><sup>3</sup></span> In the protocol described by Matsumoto et al. they included patients with either parent reported immediate symptoms or proof of sensitisation (Milk specific IgE > 5 kUA/L). We agree with the authors that this is a limitation of the study. We feel that in the absence of a challenge proven allergy, it is likely that this cohort included children with parent reported symptoms alone (with no sensitisation or allergy) or asymptomatic sensitisation.</p><p>Previous studies comparing the use of OIT with total milk avoidance identified approximately half of children screened with parent reported symptoms AND evidence of sensitisation (IgE > 0.35) had a negative double-blind placebo-controlled food challenge to milk.<span><sup>4</sup></span></p><p>The same limitations were discussed in research from our Irish team, we compared the use of ML and milk avoidance in real-life diagnosed CMPA patients (positive clinical history and allergy tests without OFC) and decided to label the primary outcome as reintroduction of milk instead of tolerance.<span><sup>5</sup></span></p><p>DATs can be used in high-risk patients for the first introduction of CMP. This may be helpful when there is hesitation to introduce milk and can enable and empower families to introduce it at home in a graded way. For example, in high risk a","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616021","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}
Torsten Zuberbier, Antonella Muraro, Ulugbek Nurmatov, Stefania Arasi, Katarina Stevanovic, Aikaterini Anagnostou, Roberta Bonaguro, Sharon Chinthrajah, Gideon Lack, Alessandro Fiocchi, Thuy-My Le, Paul Turner, Montserrat Alvaro Lozano, Elizabeth Angier, Simona Barni, Phillippe Bégin, Barbara Ballmer-Weber, Victoria Cardona, Carsten Bindslev-Jensen, Antonella Cianferoni, Nicolette de Jong, Debra de Silva, Antoine Deschildre, Audrey Dunn Galvin, Motohiro Ebisawa, David M. Fleischer, Jennifer Gerdts, Mattia Giovannini, Josefine Gradman, Susanne Halken, Syed Hasan Arshad, Ekaterina Khaleva, Susanne Lau, Richard Loh, Mika J. Mäkelä, Mary Jane Marchisotto, Laura Morandini, Charlotte G. Mortz, Caroline Nilsson, Anna Nowak-Wegrzyn, Marcia Podestà, Lars K. Poulsen, Graham Roberts, Pablo Rodríguez del Río, Hugh A. Sampson, Angel Sánchez, Sabine Schnadt, Peter K. Smith, Hania Szajewska, Natasa Teovska Mitrevska, Alice Toniolo, Carina Venter, Amena Warner, Gary W. K. Wong, Robert Wood, Margitta Worm
Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA2LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation.
{"title":"GA2LEN ANACARE consensus statement: Potential of omalizumab in food allergy management","authors":"Torsten Zuberbier, Antonella Muraro, Ulugbek Nurmatov, Stefania Arasi, Katarina Stevanovic, Aikaterini Anagnostou, Roberta Bonaguro, Sharon Chinthrajah, Gideon Lack, Alessandro Fiocchi, Thuy-My Le, Paul Turner, Montserrat Alvaro Lozano, Elizabeth Angier, Simona Barni, Phillippe Bégin, Barbara Ballmer-Weber, Victoria Cardona, Carsten Bindslev-Jensen, Antonella Cianferoni, Nicolette de Jong, Debra de Silva, Antoine Deschildre, Audrey Dunn Galvin, Motohiro Ebisawa, David M. Fleischer, Jennifer Gerdts, Mattia Giovannini, Josefine Gradman, Susanne Halken, Syed Hasan Arshad, Ekaterina Khaleva, Susanne Lau, Richard Loh, Mika J. Mäkelä, Mary Jane Marchisotto, Laura Morandini, Charlotte G. Mortz, Caroline Nilsson, Anna Nowak-Wegrzyn, Marcia Podestà, Lars K. Poulsen, Graham Roberts, Pablo Rodríguez del Río, Hugh A. Sampson, Angel Sánchez, Sabine Schnadt, Peter K. Smith, Hania Szajewska, Natasa Teovska Mitrevska, Alice Toniolo, Carina Venter, Amena Warner, Gary W. K. Wong, Robert Wood, Margitta Worm","doi":"10.1002/clt2.70002","DOIUrl":"10.1002/clt2.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA<sup>2</sup>LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590263","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}
<p>To the Editor,</p><p>Especially infants with eczema are at high risk for developing food allergies and it is the current understanding that sensitization occurs via the cutaneous route due to an impaired skin barrier function.<span><sup>1, 2</sup></span> Accordingly, a high peanut consumption in the household has been shown to be a possible risk factor for developing peanut allergy in infancy.<span><sup>3</sup></span> Therefore, German S3-guidelines on allergy prevention recommend that peanut allergy should first be ruled out in infants with moderate to severe atopic dermatitis, before introducing peanut into the infant's diet for preventive purposes.<span><sup>4</sup></span> During the last decades, vegan and plant-based diets have become a growing trend.<span><sup>5</sup></span> Tree nuts, such as cashews, hazelnuts and walnuts are a nutritional mainstay of plant-based diets and plant-based alternatives for milk and milk-products often contain tree nuts.<span><sup>5</sup></span> These changes in dietary habits may lead to a wider spread of tree nut allergens in households, increasing the risk for cutaneous exposure. There are hints, that individuals with peanut allergy have a higher likelihood of being allergic to tree nuts compared to the general population.<span><sup>6, 7</sup></span> Therefore, the aim of this study was to investigate how often peanut-sensitized infants and toddlers are sensitized to cashew, hazelnut and walnut as well as their seed storage proteins, which might be associated with a high risk for clinical reactivity.</p><p>The study cohort consists of infants and toddlers who were referred to the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité—Universitätsmedizin Berlin. Some of the patients underwent an oral food challenge (OFC) for routine diagnostics between 2007 and 2020. Blood as well as clinical data was collected from all patients in the frame of routine diagnostics. Inclusion criteria for the analysis of co-sensitization was age ≤2 years and specific IgE (sIgE) to peanut ≥0.1 kU/l.</p><p>The detection of sIgE to peanut, hazelnut, walnut and cashew and to their respective 2S albumins Ara h 2, Cor a 14, Jug r 1, Ana o 3 as well as to the 7S vicilin-like globulin Ara h 1, was performed by using the NOVEOS<sup>TM</sup> immunoanalyzer (Garden Grove, California, USA). Sensitization was defined as sIgE ≥0.1 kU/l.</p><p>In order to determine the probability for a positive hazelnut food challenge by Cor a 14-sIgE and for a positive cashew food challenge by Ana o 3-sIgE for each patient, probability curves by Beyer et al. and Lange et al. were utilized.<span><sup>8, 9</sup></span> Since there is no probability curve available for walnut, the individual risk for a positive OFC with walnut could not be estimated (see Supporting Information S1 for detailed methods).</p><p>Sera from 101 peanut-sensitized patients (peanut-sIgE ≥0.1 kU/l) were analyzed. The median age of the patients a
致编者，尤其是患有湿疹的婴儿是食物过敏的高危人群，目前的认识是，由于皮肤屏障功能受损，过敏是通过皮肤途径发生的。3 因此，德国关于过敏预防的 S3 指南建议，在将花生引入婴儿饮食以达到预防目的之前，应首先排除患有中度至重度特应性皮炎的婴儿对花生过敏的可能性。5 这些饮食习惯的改变可能会导致树坚果过敏原在家庭中更广泛地传播，增加皮肤接触的风险。有迹象表明，与普通人群相比，花生过敏患者对树坚果过敏的可能性更高、7 因此，本研究旨在调查对花生过敏的婴幼儿对腰果、榛子和核桃及其种子贮藏蛋白过敏的频率，这可能与临床反应性的高风险相关。其中一些患者在 2007 年至 2020 年期间接受了口服食物挑战 (OFC) 的常规诊断。所有患者的血液和临床数据都是在常规诊断框架内收集的。共敏性分析的纳入标准是年龄≤2 岁，花生特异性 IgE（sIgE）≥0.1 kU/l。使用 NOVEOSTM 免疫分析仪（Garden Grove, California, USA）检测对花生、榛子、核桃和腰果及其各自的 2S 白蛋白 Ara h 2、Cor a 14、Jug r 1、Ana o 3 以及 7S 类沧蛋白球蛋白 Ara h 1 的特异性 IgE。为了确定每位患者通过 Cor a 14-sIgE 进行榛子食物挑战和通过 Ana o 3-sIgE 进行腰果食物挑战的阳性概率，采用了 Beyer 等人和 Lange 等人的概率曲线、9 由于没有核桃的概率曲线，因此无法估计核桃 OFC 阳性的个体风险（详细方法见辅助信息 S1）。抽血时患者的中位年龄为 16 个月（范围：5-24 个月）。几乎所有患者（98%）都患有湿疹。96.0%的患者（n = 97）对至少一种树坚果的特异性 IgE ≥0.1 kU/l。大多数儿童对榛子（95 人；94.1%）过敏，其次是核桃（88 人；87.1%）和腰果（85 人；84.2%）。超过一半的患者（59/101；58.4%）对至少一种 2S 白蛋白过敏。42 名患者（41.6%）对 Cor a 14 和 Jug r 1 敏感，40 名患者（39.6%）对 Ana o 3 敏感（sIgE 水平见表 1）。我们检测到 80.2% 的患者（n = 81）对所有三种树坚果的 sIgE ≥0.1 kU/l。此外，26.7% 的儿童（n = 27）对所有相应的 2S 蛋白都显示出了 sIgE。对所有三种 2S 白蛋白都过敏的儿童对提取物的 sIgE 水平往往高于对任何一种或一种 2S 白蛋白都不过敏的儿童（数据未显示）。在年龄小于 12 个月的参与者中（n = 26；25.7%），88.5%（n = 23）对至少一种树坚果过敏，46.2%（n = 12）对至少一种 2S 白蛋白过敏，34.6%（n = 9）对所有三种 2S 白蛋白过敏（数据未显示）。在 101 个对花生过敏的婴幼儿中，5 个（5.0%）对榛子过敏的可能性为 90%，14 个（13.9%）对腰果过敏。在所有对花生过敏的儿童中，共有 15.8%（n = 16）的儿童对榛子和/或腰果过敏的预测概率至少达到 90%（图 1）。关于对花生过敏的儿童同时对树坚果过敏的问题，一些观察性研究表明，花生过敏是导致树坚果过敏的一个危险因素。在我们的分析中，几乎所有儿童（98%）都患有湿疹，而众所周知，湿疹是导致过敏和食物过敏的一个主要风险因素。
{"title":"Infants and toddlers with sensitization to peanut are often co-sensitized to tree nuts","authors":"Lara Meixner, Stephanie Heller, Friederike Bluhme, Valérie Trendelenburg, Kirsten Beyer, Birgit Kalb","doi":"10.1002/clt2.70008","DOIUrl":"10.1002/clt2.70008","url":null,"abstract":"<p>To the Editor,</p><p>Especially infants with eczema are at high risk for developing food allergies and it is the current understanding that sensitization occurs via the cutaneous route due to an impaired skin barrier function.<span><sup>1, 2</sup></span> Accordingly, a high peanut consumption in the household has been shown to be a possible risk factor for developing peanut allergy in infancy.<span><sup>3</sup></span> Therefore, German S3-guidelines on allergy prevention recommend that peanut allergy should first be ruled out in infants with moderate to severe atopic dermatitis, before introducing peanut into the infant's diet for preventive purposes.<span><sup>4</sup></span> During the last decades, vegan and plant-based diets have become a growing trend.<span><sup>5</sup></span> Tree nuts, such as cashews, hazelnuts and walnuts are a nutritional mainstay of plant-based diets and plant-based alternatives for milk and milk-products often contain tree nuts.<span><sup>5</sup></span> These changes in dietary habits may lead to a wider spread of tree nut allergens in households, increasing the risk for cutaneous exposure. There are hints, that individuals with peanut allergy have a higher likelihood of being allergic to tree nuts compared to the general population.<span><sup>6, 7</sup></span> Therefore, the aim of this study was to investigate how often peanut-sensitized infants and toddlers are sensitized to cashew, hazelnut and walnut as well as their seed storage proteins, which might be associated with a high risk for clinical reactivity.</p><p>The study cohort consists of infants and toddlers who were referred to the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité—Universitätsmedizin Berlin. Some of the patients underwent an oral food challenge (OFC) for routine diagnostics between 2007 and 2020. Blood as well as clinical data was collected from all patients in the frame of routine diagnostics. Inclusion criteria for the analysis of co-sensitization was age ≤2 years and specific IgE (sIgE) to peanut ≥0.1 kU/l.</p><p>The detection of sIgE to peanut, hazelnut, walnut and cashew and to their respective 2S albumins Ara h 2, Cor a 14, Jug r 1, Ana o 3 as well as to the 7S vicilin-like globulin Ara h 1, was performed by using the NOVEOS<sup>TM</sup> immunoanalyzer (Garden Grove, California, USA). Sensitization was defined as sIgE ≥0.1 kU/l.</p><p>In order to determine the probability for a positive hazelnut food challenge by Cor a 14-sIgE and for a positive cashew food challenge by Ana o 3-sIgE for each patient, probability curves by Beyer et al. and Lange et al. were utilized.<span><sup>8, 9</sup></span> Since there is no probability curve available for walnut, the individual risk for a positive OFC with walnut could not be estimated (see Supporting Information S1 for detailed methods).</p><p>Sera from 101 peanut-sensitized patients (peanut-sIgE ≥0.1 kU/l) were analyzed. The median age of the patients a","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582264","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}
Ruperto González-Pérez, Paloma Poza-Guedes, María Gabriela Martín-Voso, Inmaculada Sánchez-Machín
<p>To the Editor,</p><p>The unified airway hypothesis suggests that the upper and lower airways constitute a single, interconnected organ, sharing significant physiological traits such as immunology, pathophysiology, epidemiology, and clinical features.<span><sup>1</sup></span> Allergic rhinitis (AR), various forms of chronic rhinosinusitis (CRS), including those with nasal polyposis (NP), and severe asthma (SA) share a common underlying pathogenesis known as type-2 inflammation (T2).<span><sup>2</sup></span> These coexisting conditions represent a substantial clinical burden and significantly impact patients' quality of life (QoL) through a variety of disruptive symptoms The SNOT-22 is a validated questionary designed to assess the symptom burden of CRS and has proven effective utility in evaluating both QoL and symptom control in AR.<span><sup>3, 4</sup></span></p><p>Mepolizumab, a monthly subcutaneous IL-5 antagonist monoclonal antibody, has been approved for treating various type 2 inflammatory conditions, including both eosinophilic SA and CRSwNP.<span><sup>5, 6</sup></span> The performance of mepolizumab on SNOT-22 scores has not been completely assessed in patients afflicted with Unified Airway Disease (UAD).</p><p>This Phase IV, single-center observational cohort investigation, conducted at Hospital Universitario de Canarias in Tenerife, Spain, aimed to evaluate the real-world performance of mepolizumab 100 mg every 4 weeks (100 mg-q4w) over 52-weeks on SNOT-22 scores in patients aged over 18 years with UAD, including uncontrolled SA and persistent mite (<i>Dermatophagoides spp</i>. and/or <i>Blomia tropicalis</i>) AR, with or without comorbid CRSwNP. Key inclusion criteria were a clinician-confirmed diagnosis of SA and AR with a T2 signature according to specific guidelines<span><sup>7, 8</sup></span> and a CRSwNP diagnosis based on EPOS criteria.<span><sup>9</sup></span> Pregnant and breast-feeding women were excluded. The study was approved by the local Ethical Committee of our Institution and informed consent was signed by all participants.</p><p>Data from clinical records collected between January 2021 and July 2024 were retrospectively analyzed, with a total of 102 patients screened. Among them, 71 patients—40 females and 31 males, median age 48 years (IQR 21)—were confirmed as eligible for the study (Table S1). Outcome data from all participants were gathered and compared at two time points: before (T0) and 52-weeks post-commencement (T1) of monthly mepolizumab. Quantitative variables were presented as median and interquartile range (IQR), whereas qualitative variables were expressed as number of observations and percentage. Individual SNOT-22 item scores were summed, and a median domain score was derived. Pulmonary function test, including pre- and post-bronchodilator spirometry (Datospir 600<sup>®</sup>, Sibel S.A.U., Barcelona, Spain) and a validated asthma control test (ACT) were conducted in accordance with daily practice guid
{"title":"Evaluation of real-world efficacy of mepolizumab on SNOT-22 outcomes in patients with unified airway disease","authors":"Ruperto González-Pérez, Paloma Poza-Guedes, María Gabriela Martín-Voso, Inmaculada Sánchez-Machín","doi":"10.1002/clt2.70006","DOIUrl":"10.1002/clt2.70006","url":null,"abstract":"<p>To the Editor,</p><p>The unified airway hypothesis suggests that the upper and lower airways constitute a single, interconnected organ, sharing significant physiological traits such as immunology, pathophysiology, epidemiology, and clinical features.<span><sup>1</sup></span> Allergic rhinitis (AR), various forms of chronic rhinosinusitis (CRS), including those with nasal polyposis (NP), and severe asthma (SA) share a common underlying pathogenesis known as type-2 inflammation (T2).<span><sup>2</sup></span> These coexisting conditions represent a substantial clinical burden and significantly impact patients' quality of life (QoL) through a variety of disruptive symptoms The SNOT-22 is a validated questionary designed to assess the symptom burden of CRS and has proven effective utility in evaluating both QoL and symptom control in AR.<span><sup>3, 4</sup></span></p><p>Mepolizumab, a monthly subcutaneous IL-5 antagonist monoclonal antibody, has been approved for treating various type 2 inflammatory conditions, including both eosinophilic SA and CRSwNP.<span><sup>5, 6</sup></span> The performance of mepolizumab on SNOT-22 scores has not been completely assessed in patients afflicted with Unified Airway Disease (UAD).</p><p>This Phase IV, single-center observational cohort investigation, conducted at Hospital Universitario de Canarias in Tenerife, Spain, aimed to evaluate the real-world performance of mepolizumab 100 mg every 4 weeks (100 mg-q4w) over 52-weeks on SNOT-22 scores in patients aged over 18 years with UAD, including uncontrolled SA and persistent mite (<i>Dermatophagoides spp</i>. and/or <i>Blomia tropicalis</i>) AR, with or without comorbid CRSwNP. Key inclusion criteria were a clinician-confirmed diagnosis of SA and AR with a T2 signature according to specific guidelines<span><sup>7, 8</sup></span> and a CRSwNP diagnosis based on EPOS criteria.<span><sup>9</sup></span> Pregnant and breast-feeding women were excluded. The study was approved by the local Ethical Committee of our Institution and informed consent was signed by all participants.</p><p>Data from clinical records collected between January 2021 and July 2024 were retrospectively analyzed, with a total of 102 patients screened. Among them, 71 patients—40 females and 31 males, median age 48 years (IQR 21)—were confirmed as eligible for the study (Table S1). Outcome data from all participants were gathered and compared at two time points: before (T0) and 52-weeks post-commencement (T1) of monthly mepolizumab. Quantitative variables were presented as median and interquartile range (IQR), whereas qualitative variables were expressed as number of observations and percentage. Individual SNOT-22 item scores were summed, and a median domain score was derived. Pulmonary function test, including pre- and post-bronchodilator spirometry (Datospir 600<sup>®</sup>, Sibel S.A.U., Barcelona, Spain) and a validated asthma control test (ACT) were conducted in accordance with daily practice guid","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557306","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}
To understand the connection between Muc5AC expression and the likelihood of rhinosinusitis, with the goal of providing insights into its prospective use as a biomarker.
Methods
We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases for studies up to November 2023 to conduct a literature review. After screening and quality assessment, eligible studies meeting the criteria were included. Muc5AC expression and rhinosinusitis association was analyzed by STATA 14.0.
Results
Including weighted mean difference and 95% confidence interval, were reported. The meta-analysis included 16 studies with 1448 rhinosinusitis patients. MUC5AC expression was significantly up-regulated in both chronic rhinosinusitis with nasal polyps (CRSwNP; WMD: 0.52; 95% CI: 0.41–0.63) and chronic rhinosinusitis without nasal polyps (CRSsNP; WMD: 0.42; 95% CI: 0.28–0.56) patients compared to controls. IHC positive area analysis corroborated these findings, with elevated MUC5AC levels in CRSwNP (WMD: 25.61; 95% CI: 22.41–28.81) and CRSsNP (WMD: 39.74; 95% CI: 25.6–53.88) patients. Subgroup analysis based on tissue type (nasal tissue fluid and sinus mucosa) consistently supported the overall results.
Conclusion
Our meta-analysis robustly demonstrates a significant association between elevated MUC5AC expression and rhinosinusitis risk. This finding underscores the potential of MUC5AC as a molecular marker, providing valuable insights for future research and potential therapeutic interventions in rhinosinusitis management.
{"title":"The expression of MUC5AC in patients with rhinosinusitis: A systematic review and meta-analysis","authors":"Yitao Li","doi":"10.1002/clt2.70003","DOIUrl":"10.1002/clt2.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To understand the connection between Muc5AC expression and the likelihood of rhinosinusitis, with the goal of providing insights into its prospective use as a biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases for studies up to November 2023 to conduct a literature review. After screening and quality assessment, eligible studies meeting the criteria were included. Muc5AC expression and rhinosinusitis association was analyzed by STATA 14.0.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Including weighted mean difference and 95% confidence interval, were reported. The meta-analysis included 16 studies with 1448 rhinosinusitis patients. MUC5AC expression was significantly up-regulated in both chronic rhinosinusitis with nasal polyps (CRSwNP; WMD: 0.52; 95% CI: 0.41–0.63) and chronic rhinosinusitis without nasal polyps (CRSsNP; WMD: 0.42; 95% CI: 0.28–0.56) patients compared to controls. IHC positive area analysis corroborated these findings, with elevated MUC5AC levels in CRSwNP (WMD: 25.61; 95% CI: 22.41–28.81) and CRSsNP (WMD: 39.74; 95% CI: 25.6–53.88) patients. Subgroup analysis based on tissue type (nasal tissue fluid and sinus mucosa) consistently supported the overall results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our meta-analysis robustly demonstrates a significant association between elevated MUC5AC expression and rhinosinusitis risk. This finding underscores the potential of MUC5AC as a molecular marker, providing valuable insights for future research and potential therapeutic interventions in rhinosinusitis management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Systematic review registration</h3>\u0000 \u0000 <p>CRD42024518932.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557307","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}
Claudia Arasa, Niamh Hyland, Caroline Nilsson, Eva Sverremark-Ekström
<p>To the Editor,</p><p><i>Staphylococcus (S</i>.<i>) aureus</i> is an intermittent or permanent skin colonizer in 90% of patients with airway diseases, and staphylococcal enterotoxin-IgE serum levels have been linked to both allergy and severe asthma.<span><sup>1, 2</sup></span> During pregnancy, immune adaptation is required to ensure fetal growth,<span><sup>3</sup></span> and type 2 responses are enhanced. These changes potentially worsen allergic conditions and increase the susceptibility to certain infections.<span><sup>4</sup></span></p><p>Here we investigate the immune response to Staphylococcal enterotoxin A (SEA), a strong inducer of type 1 responses, in individuals with Th2-skewing,<span><sup>5</sup></span> using peripheral blood mononuclear cells (PBMC) from allergic and non-allergic, pregnant and non-pregnant women<span><sup>6</sup></span> (Figure 1A). Staphylococcal enterotoxins cause polyclonal T cell activation crosslinking the MHC-II on antigen-presenting cells (APCs) to the T-cell receptor (TCR) on T-cells (Figure 1B), leading to a strong proinflammatory response, potentially increasing IgE-production or disrupting the maternal-fetal tolerance.</p><p>Allergic individuals exhibited reduced Tbet expression (Figure 1C), associated with Th1 response, and lower type 1 cytokine production (IFN-γ and TNF; Figure 1D). These differences were not observed during pregnancy (Figure S1A). GATA3 expression, linked to Th2 responses, was lower in allergic individuals regardless of their pregnancy status (Figure 1E), but there was no difference in type 2 cytokine secretion (IL-5 and IL-13; Figure S1B and Figure 1F). Type 3- and regulatory T cell markers (RORγt or FoxP3 expression and IL-17 and IL-10 secretion, respectively) did not differ in any of the groups (Figure S1C,D). Analyzing IFN-γ and TNF production in conventional T cells outside of pregnancy showed comparable IFN-γ levels between allergic and non-allergic individuals (Figure 1G). During pregnancy, IFN-γ production was significantly reduced in non-allergic individuals (Figure 1H) but not in allergic (Figure 1I). TNF production was lower in allergic individuals, but it increased during pregnancy (Figure S2A).</p><p>We have previously shown that the response to SEA by unconventional lymphocytes is delayed, and that their activation strongly contributes to the elicited cytokine storm<span><sup>7</sup></span> (Figure 2A). Therefore, we wanted to elucidate whether the allergy-related differences seen in conventional T cell activation correlated with variations in the unconventional lymphocyte compartment. All the analyzed cell types showed a consistent pattern, characterized by a significantly lower expression of IFN-γ (Figure 2B) and TNF (Figure S2B) in allergic women. Furthermore, analyzing the longitudinal response of unconventional lymphocytes to SEA in pregnant allergic women, we identified significantly higher production of both IFN-γ (Figure 2C) and TNF (Figure S2C) across all the st
{"title":"Pregnancy impacts allergy-related differences in the response to a type-1 stimulus, staphylococcal enterotoxin A","authors":"Claudia Arasa, Niamh Hyland, Caroline Nilsson, Eva Sverremark-Ekström","doi":"10.1002/clt2.70007","DOIUrl":"10.1002/clt2.70007","url":null,"abstract":"<p>To the Editor,</p><p><i>Staphylococcus (S</i>.<i>) aureus</i> is an intermittent or permanent skin colonizer in 90% of patients with airway diseases, and staphylococcal enterotoxin-IgE serum levels have been linked to both allergy and severe asthma.<span><sup>1, 2</sup></span> During pregnancy, immune adaptation is required to ensure fetal growth,<span><sup>3</sup></span> and type 2 responses are enhanced. These changes potentially worsen allergic conditions and increase the susceptibility to certain infections.<span><sup>4</sup></span></p><p>Here we investigate the immune response to Staphylococcal enterotoxin A (SEA), a strong inducer of type 1 responses, in individuals with Th2-skewing,<span><sup>5</sup></span> using peripheral blood mononuclear cells (PBMC) from allergic and non-allergic, pregnant and non-pregnant women<span><sup>6</sup></span> (Figure 1A). Staphylococcal enterotoxins cause polyclonal T cell activation crosslinking the MHC-II on antigen-presenting cells (APCs) to the T-cell receptor (TCR) on T-cells (Figure 1B), leading to a strong proinflammatory response, potentially increasing IgE-production or disrupting the maternal-fetal tolerance.</p><p>Allergic individuals exhibited reduced Tbet expression (Figure 1C), associated with Th1 response, and lower type 1 cytokine production (IFN-γ and TNF; Figure 1D). These differences were not observed during pregnancy (Figure S1A). GATA3 expression, linked to Th2 responses, was lower in allergic individuals regardless of their pregnancy status (Figure 1E), but there was no difference in type 2 cytokine secretion (IL-5 and IL-13; Figure S1B and Figure 1F). Type 3- and regulatory T cell markers (RORγt or FoxP3 expression and IL-17 and IL-10 secretion, respectively) did not differ in any of the groups (Figure S1C,D). Analyzing IFN-γ and TNF production in conventional T cells outside of pregnancy showed comparable IFN-γ levels between allergic and non-allergic individuals (Figure 1G). During pregnancy, IFN-γ production was significantly reduced in non-allergic individuals (Figure 1H) but not in allergic (Figure 1I). TNF production was lower in allergic individuals, but it increased during pregnancy (Figure S2A).</p><p>We have previously shown that the response to SEA by unconventional lymphocytes is delayed, and that their activation strongly contributes to the elicited cytokine storm<span><sup>7</sup></span> (Figure 2A). Therefore, we wanted to elucidate whether the allergy-related differences seen in conventional T cell activation correlated with variations in the unconventional lymphocyte compartment. All the analyzed cell types showed a consistent pattern, characterized by a significantly lower expression of IFN-γ (Figure 2B) and TNF (Figure S2B) in allergic women. Furthermore, analyzing the longitudinal response of unconventional lymphocytes to SEA in pregnant allergic women, we identified significantly higher production of both IFN-γ (Figure 2C) and TNF (Figure S2C) across all the st","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496243","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}
We would like to thank the authors for their thoughtful and constructive comments on our publication, “Milk ladder versus early oral immunotherapy in infants with cow's milk protein allergy.” We appreciate their interest and engagement in this clinical discussion on the management of cow milk protein allergy (CMPA).
The use of dietary advancement therapies (DATs) such as milk and egg ladders is becoming widespread in the global allergy community. It is important to collect and share local data on these practices to expand our collective knowledge of the treatment of food allergies.
As the authors rightly pointed out, our study was conducted in a real-world clinical setting where, due to various practical constraints, we used parent-reported clinical histories and sensitization markers instead of the gold-standard Oral Food Challenge (OFC) for most patients. Data on patients who only had previous immediate allergic reactions due to the ingestion of cow milk protein is shown Table S1. The remaining patients had high levels of cow milk-specific IgE (>5 kUA/L), which exceeded 95% of the predicted value for diagnosing CMPA. We acknowledge that this is a limitation and agree that the absence of a challenge-proven allergy could have led to the inclusion of some children with asymptomatic sensitization or those with parent-reported symptoms without OFC. Nonetheless, we aimed to reflect the reality of clinical practice in which OFC is not always feasible or conducted in every case.
We also concur with the authors' insightful differentiation between the primary, secondary, and tertiary allergy prevention and the need to carefully classify patients undergoing milk introduction based on their clinical history and sensitization status. The suggestion that some patients in our study may have undergone the primary or secondary prevention is an important consideration. This underscores the complexity of managing food allergies in clinical settings where treatment protocols often overlap.
In agreement with the authors, we recognize that tolerance and reintroduction outcomes must be carefully labeled, particularly in the absence of prior confirmation of allergy through the OFC. We believe that further studies employing more rigorous diagnostic criteria will be crucial to refine treatment protocols and ensure that true allergic responses are addressed in our interventions.
Once again, we appreciate the authors' valuable feedback and our opportunity to further clarify and discuss the important aspects of CMPA management. We hope that our study contributes meaningfully to the ongoing advancement of DATs, such as Milk Ladder and Early Oral Immunotherapy, and we welcome further comments and discussions in this field.
Chisato Inuo: Writing—original draft. Yurika Matsumoto: Writing—review and editing.
{"title":"Response to comments on ‘Milk ladder versus early oral immunotherapy in infants with cow's milk protein allergy’","authors":"Chisato Inuo, Yurika Matsumoto","doi":"10.1002/clt2.70001","DOIUrl":"10.1002/clt2.70001","url":null,"abstract":"<p>Dear Editor,</p><p>We would like to thank the authors for their thoughtful and constructive comments on our publication, “Milk ladder versus early oral immunotherapy in infants with cow's milk protein allergy.” We appreciate their interest and engagement in this clinical discussion on the management of cow milk protein allergy (CMPA).</p><p>The use of dietary advancement therapies (DATs) such as milk and egg ladders is becoming widespread in the global allergy community. It is important to collect and share local data on these practices to expand our collective knowledge of the treatment of food allergies.</p><p>As the authors rightly pointed out, our study was conducted in a real-world clinical setting where, due to various practical constraints, we used parent-reported clinical histories and sensitization markers instead of the gold-standard Oral Food Challenge (OFC) for most patients. Data on patients who only had previous immediate allergic reactions due to the ingestion of cow milk protein is shown Table S1. The remaining patients had high levels of cow milk-specific IgE (>5 kU<sub>A</sub>/L), which exceeded 95% of the predicted value for diagnosing CMPA. We acknowledge that this is a limitation and agree that the absence of a challenge-proven allergy could have led to the inclusion of some children with asymptomatic sensitization or those with parent-reported symptoms without OFC. Nonetheless, we aimed to reflect the reality of clinical practice in which OFC is not always feasible or conducted in every case.</p><p>We also concur with the authors' insightful differentiation between the primary, secondary, and tertiary allergy prevention and the need to carefully classify patients undergoing milk introduction based on their clinical history and sensitization status. The suggestion that some patients in our study may have undergone the primary or secondary prevention is an important consideration. This underscores the complexity of managing food allergies in clinical settings where treatment protocols often overlap.</p><p>In agreement with the authors, we recognize that tolerance and reintroduction outcomes must be carefully labeled, particularly in the absence of prior confirmation of allergy through the OFC. We believe that further studies employing more rigorous diagnostic criteria will be crucial to refine treatment protocols and ensure that true allergic responses are addressed in our interventions.</p><p>Once again, we appreciate the authors' valuable feedback and our opportunity to further clarify and discuss the important aspects of CMPA management. We hope that our study contributes meaningfully to the ongoing advancement of DATs, such as Milk Ladder and Early Oral Immunotherapy, and we welcome further comments and discussions in this field.</p><p><b>Chisato Inuo</b>: Writing—original draft. <b>Yurika Matsumoto</b>: Writing—review and editing.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496244","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}
Following the increased use of biological agents, a subset of patients experiences hypersensitivity reaction (HSR). We reported our experience with rapid drug desensitization (RDD) to nine biologics (rituximab, infliximab, cetuximab, trastuzumab, pertuzumab, nivolumab, brentuximab, tocilizumab and filgrastim) and identified risk factors for breakthrough reactions (BTRs).
Method
This was a retrospective review (2013–2022) of patients with immediate HSRs to biological agents. Initial HSRs were classified as grade 1, 2, or 3 in their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed using implicated agents. The phenotypes of HSRs were defined as Type I, cytokine-release syndrome (CRS), mixed reactions (cytokine-release + type I) based on history, clinical presentations and skin tests with implicated biologicals. A 12-step RDD protocol was used.
Results
The study comprised 45 patients (F/M: 31/14, median age: 55 (range: 20–69)). Majority of the patients reacted at the first infusion (n: 29/45, 64.4%). The majority of initial HSRs were grade 3 (n: 24/45, 53.3%) and grade 2 (n: 21/45, 46.6%); none were grade 1. Initial reactions were presented as type I (n: 20/45, 44.4%), CRS (n: 12/45, 26.6%) and mixed (n: 13/45, 28.8%). A total of 258 RDDs were performed and 98.4% of them were completed successfully. BTRs occurred in 36/258 (13.9%) infusions of RDDs. There was no significant association between the BTRs and age, drug cycle, SPT and IDT positivity, gender, comorbidities, or atopy.
Conclusion
In our experience, 98.4% of 258 RDDs to biologics were successfully completed; RDD was safe and effective for our population.
{"title":"Retrospective analysis of rapid drug desensitization with biologic agents: A single center experience","authors":"Döne Gülçin Unutmaz Erkaya, Makbule Seda Bayrak Durmaz, Begüm Görgülü Akın, Sevim Bavbek","doi":"10.1002/clt2.12397","DOIUrl":"10.1002/clt2.12397","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Following the increased use of biological agents, a subset of patients experiences hypersensitivity reaction (HSR). We reported our experience with rapid drug desensitization (RDD) to nine biologics (rituximab, infliximab, cetuximab, trastuzumab, pertuzumab, nivolumab, brentuximab, tocilizumab and filgrastim) and identified risk factors for breakthrough reactions (BTRs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This was a retrospective review (2013–2022) of patients with immediate HSRs to biological agents. Initial HSRs were classified as grade 1, 2, or 3 in their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed using implicated agents. The phenotypes of HSRs were defined as Type I, cytokine-release syndrome (CRS), mixed reactions (cytokine-release + type I) based on history, clinical presentations and skin tests with implicated biologicals. A 12-step RDD protocol was used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study comprised 45 patients (F/M: 31/14, median age: 55 (range: 20–69)). Majority of the patients reacted at the first infusion (<i>n</i>: 29/45, 64.4%). The majority of initial HSRs were grade 3 (<i>n</i>: 24/45, 53.3%) and grade 2 (<i>n</i>: 21/45, 46.6%); none were grade 1. Initial reactions were presented as type I (<i>n</i>: 20/45, 44.4%), CRS (<i>n</i>: 12/45, 26.6%) and mixed (<i>n</i>: 13/45, 28.8%). A total of 258 RDDs were performed and 98.4% of them were completed successfully. BTRs occurred in 36/258 (13.9%) infusions of RDDs. There was no significant association between the BTRs and age, drug cycle, SPT and IDT positivity, gender, comorbidities, or atopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In our experience, 98.4% of 258 RDDs to biologics were successfully completed; RDD was safe and effective for our population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459511","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}
Neera Chakrapani, Kyra Swiontek, Judith M. Hübschen, Jörg Fischer, Maria Ruiz-Castell, Francoise Codreanu-Morel, Farah Hannachi, Martine Morisset, Markus Ollert, Annette Kuehn, Claude P. Muller, Christiane Hilger
Background
The α-Gal syndrome (AGS) is characterized by the presence of specific IgE-antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal). Sensitization to α-Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α-Gal in a high-risk cohort of forestry employees (FE) in Luxembourg.
Methods
Questionnaires and serum samples of FE from Luxembourg (n = 219) were retrospectively analyzed. α-Gal specific IgE was quantified by ImmunoCAP, α-Gal specific IgG and subclasses IgG1–4 were determined by ELISA. Additionally, sera from population-based controls (n = 150) and two groups of food-allergic patients, patients with AGS (n = 45) and fish-allergic patients (n = 22) were assessed for IgG antibody responses to α-Gal and cod extract.
Results
Twenty-one percent of FE was sensitized to α-Gal (sIgE ≥ 0.1 kUA/L). Both sensitized and non-sensitized FE exhibited high levels of α-Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish-allergic patients was similar to the profile of the controls for which anti-α-Gal responses were dominated by IgG2 antibodies. α-Gal sIgG4 levels were either very low or undetectable in all groups.
Conclusion
Our study provides evidence for a continuous stimulation of α-Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α-Gal.
{"title":"Recurrent tick bites induce high IgG1 antibody responses to α-Gal in sensitized and non-sensitized forestry employees in Luxembourg","authors":"Neera Chakrapani, Kyra Swiontek, Judith M. Hübschen, Jörg Fischer, Maria Ruiz-Castell, Francoise Codreanu-Morel, Farah Hannachi, Martine Morisset, Markus Ollert, Annette Kuehn, Claude P. Muller, Christiane Hilger","doi":"10.1002/clt2.12396","DOIUrl":"https://doi.org/10.1002/clt2.12396","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The α-Gal syndrome (AGS) is characterized by the presence of specific IgE-antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal). Sensitization to α-Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α-Gal in a high-risk cohort of forestry employees (FE) in Luxembourg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Questionnaires and serum samples of FE from Luxembourg (<i>n</i> = 219) were retrospectively analyzed. α-Gal specific IgE was quantified by ImmunoCAP, α-Gal specific IgG and subclasses IgG<sub>1–4</sub> were determined by ELISA. Additionally, sera from population-based controls (<i>n</i> = 150) and two groups of food-allergic patients, patients with AGS (<i>n</i> = 45) and fish-allergic patients (<i>n</i> = 22) were assessed for IgG antibody responses to α-Gal and cod extract.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-one percent of FE was sensitized to α-Gal (sIgE ≥ 0.1 kU<sub>A</sub>/L). Both sensitized and non-sensitized FE exhibited high levels of α-Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish-allergic patients was similar to the profile of the controls for which anti-α-Gal responses were dominated by IgG2 antibodies. α-Gal sIgG4 levels were either very low or undetectable in all groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides evidence for a continuous stimulation of α-Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α-Gal.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435630","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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