Pub Date : 2023-11-22eCollection Date: 2023-01-01DOI: 10.3389/falgy.2023.1228353
Peter L Weegels, Antoine H P America
Amylase trypsin inhibitors (ATIs) play an important role in wheat allergies and potentially in non-coeliac wheat sensitivity. Food processing could be important to mitigate the pathogenic properties of ATIs, e.g., by denaturation, glycation, enzymatic hydrolysis, cross-linking, and oxidation and reduction. These modifications also impact the solubility and extractability. The complex solubility behaviour of ATI isoforms (water and salt soluble, but also chloroform-methanol soluble, solubility depending on the redox state) becomes even more complex upon processing due to denaturation and (bio)chemical modifications. This significantly hinders the feasibility of quantitative extraction. Moreover, changes in biofunctionality may occur during the process of extraction, and the changes in ATI due to food processing will be more difficult to assess. Heat treatment decreases the extractability of ATIs with water, NaCl, and other buffer extracts, and binding of IgE from wheat-allergic persons to ATIs as observed with Western blotting is decreased or absent. IgE binding is reduced with the total extract in chaotropic and reducing agents. However, it can be increased when the proteins are hydrolyzed by proteases. Fermentation involving certain species of Fructolactobacilli (FLB), followed by baking, decreases the amount of ATIs and IgE binding to ATIs. In yeast-fermented bread, the amount of ATIs decreased in a similar manner, but IgE binding was more prominent, indicating that there was a modification of ATIs that affected the epitope recognition. When isolated ATIs are ingested with high ATI degrading FLB, the immune response in mice is less elevated in vivo, when compared with ATI without high ATI degrading FLB. The pathogenic effects on the skin of dogs and one wheat-allergic child are also decreased when soluble proteins or isolated ATIs are reduced with the thioredoxin/thioredoxin reductase NADPH system. Glycation on the other hand has been shown to potentiate the allergenic properties of ATIs as evidenced by the large increase in IgE binding. The impact of food processing on the pathogenic properties of ATIs is hardly studied in vivo in humans. There seem to be opportunities to mitigate the pathogenic properties in vitro, but potentiation of pathogenic properties is also frequently observed. This requires a deeper understanding on the impact of food processing on the pathogenicity of ATIs.
淀粉酶胰蛋白酶抑制剂(ATIs)在小麦过敏症和潜在的非乳糜泻小麦过敏症中发挥着重要作用。食品加工对减轻 ATIs 的致病特性非常重要,例如通过变性、糖化、酶水解、交联、氧化和还原。这些修饰也会影响溶解性和可提取性。由于变性和(生物)化学修饰,ATI 异构体复杂的溶解性能(水溶性和盐溶性,也可溶于氯仿-甲醇,溶解度取决于氧化还原状态)在加工过程中变得更加复杂。这极大地阻碍了定量提取的可行性。此外,在萃取过程中,生物功能可能会发生变化,食品加工导致的 ATI 变化将更难评估。热处理会降低 ATIs 与水、NaCl 和其他缓冲提取物的可提取性,用 Western 印迹法观察到的小麦过敏者的 IgE 与 ATIs 的结合会减少或消失。在混沌剂和还原剂中,总提取物与 IgE 的结合会减少。然而,当蛋白质被蛋白酶水解时,IgE结合率会增加。某些种类的果酸乳杆菌(FLB)发酵后再进行烘烤,会减少 ATIs 的数量和 IgE 与 ATIs 的结合。在酵母发酵的面包中,ATIs 的数量也以类似的方式减少,但 IgE 结合却更加明显,这表明 ATIs 发生了改变,影响了表位识别。与不含高ATI降解FLB的ATI相比,当小鼠摄入含有高ATI降解FLB的分离ATI时,体内免疫反应的升高程度较低。当使用硫氧还原酶/硫氧还原酶 NADPH 系统还原可溶性蛋白质或分离的 ATI 时,对狗和一名小麦过敏儿童皮肤的致病作用也会降低。另一方面,糖化被证明会增强 ATI 的致敏特性,IgE 结合力的大幅增加就是证明。关于食品加工对 ATIs 致病性的影响,几乎没有在人体中进行过研究。在体外似乎有机会减轻致病性,但也经常观察到致病性的增强。这就需要更深入地了解食品加工对 ATIs 致病性的影响。
{"title":"Impact of food processing on the allergenic properties of amylase trypsin inhibitors from wheat.","authors":"Peter L Weegels, Antoine H P America","doi":"10.3389/falgy.2023.1228353","DOIUrl":"https://doi.org/10.3389/falgy.2023.1228353","url":null,"abstract":"<p><p>Amylase trypsin inhibitors (ATIs) play an important role in wheat allergies and potentially in non-coeliac wheat sensitivity. Food processing could be important to mitigate the pathogenic properties of ATIs, e.g., by denaturation, glycation, enzymatic hydrolysis, cross-linking, and oxidation and reduction. These modifications also impact the solubility and extractability. The complex solubility behaviour of ATI isoforms (water and salt soluble, but also chloroform-methanol soluble, solubility depending on the redox state) becomes even more complex upon processing due to denaturation and (bio)chemical modifications. This significantly hinders the feasibility of quantitative extraction. Moreover, changes in biofunctionality may occur during the process of extraction, and the changes in ATI due to food processing will be more difficult to assess. Heat treatment decreases the extractability of ATIs with water, NaCl, and other buffer extracts, and binding of IgE from wheat-allergic persons to ATIs as observed with Western blotting is decreased or absent. IgE binding is reduced with the total extract in chaotropic and reducing agents. However, it can be increased when the proteins are hydrolyzed by proteases. Fermentation involving certain species of <i>Fructolactobacilli</i> (FLB), followed by baking, decreases the amount of ATIs and IgE binding to ATIs. In yeast-fermented bread, the amount of ATIs decreased in a similar manner, but IgE binding was more prominent, indicating that there was a modification of ATIs that affected the epitope recognition. When isolated ATIs are ingested with high ATI degrading FLB, the immune response in mice is less elevated <i>in vivo</i>, when compared with ATI without high ATI degrading FLB. The pathogenic effects on the skin of dogs and one wheat-allergic child are also decreased when soluble proteins or isolated ATIs are reduced with the thioredoxin/thioredoxin reductase NADPH system. Glycation on the other hand has been shown to potentiate the allergenic properties of ATIs as evidenced by the large increase in IgE binding. The impact of food processing on the pathogenic properties of ATIs is hardly studied <i>in vivo</i> in humans. There seem to be opportunities to mitigate the pathogenic properties <i>in vitro</i>, but potentiation of pathogenic properties is also frequently observed. This requires a deeper understanding on the impact of food processing on the pathogenicity of ATIs.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"4 ","pages":"1228353"},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10702574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-15eCollection Date: 2023-01-01DOI: 10.3389/falgy.2023.1298335
R Sáenz de Santa María, G Bogas, M Labella, A Ariza, M Salas, I Doña, M J Torres
A considerable number of pediatric patients treated with beta-lactam (BL) antibiotics develop delayed onset of skin rashes during the course of treatment. Although the most frequent cause of these symptoms is infectious, many cases are labeled as allergic reactions to these drugs. BL allergy labels could have a negative impact, as they imply avoidance of this group of drugs and the use of second-line antibiotics, leading to a potential increase in adverse effects and the utilization of less effective therapies. This constitutes a major public health concern and economic burden, as the use of broad-spectrum antibiotics can result in multidrug-resistant organisms and prolonged hospital stays. Therefore, it is crucial to delabel patients during childhood to avoid false labeling in adult life. Although the label of BL allergy is among the most frequent causes of allergy referral, its management remains controversial, and new diagnostic perspectives are changing the paradigm of managing BL allergies in children. Traditionally, drug provocation testing (DPT) was exclusively performed in patients who had previously obtained negative results from skin tests (STs). However, the sensitivity of STs is low, and the role of in vitro testing in the pediatric population is not well defined. Recent studies have demonstrated the safety of direct DPT without prior ST or serum tests for pediatric patients who report a low-risk reaction to BLs, which is cost-effective. However, there is still a debate on the optimal allergic workup to be performed in children with a benign immediate reaction and the management of children with severe cutaneous adverse drug reactions. In this review, we will discuss the impact of the label of BL allergy and the role of the different tools currently available to efficiently address BL allergy delabeling in children.
{"title":"Approach for delabeling beta-lactam allergy in children.","authors":"R Sáenz de Santa María, G Bogas, M Labella, A Ariza, M Salas, I Doña, M J Torres","doi":"10.3389/falgy.2023.1298335","DOIUrl":"10.3389/falgy.2023.1298335","url":null,"abstract":"<p><p>A considerable number of pediatric patients treated with beta-lactam (BL) antibiotics develop delayed onset of skin rashes during the course of treatment. Although the most frequent cause of these symptoms is infectious, many cases are labeled as allergic reactions to these drugs. BL allergy labels could have a negative impact, as they imply avoidance of this group of drugs and the use of second-line antibiotics, leading to a potential increase in adverse effects and the utilization of less effective therapies. This constitutes a major public health concern and economic burden, as the use of broad-spectrum antibiotics can result in multidrug-resistant organisms and prolonged hospital stays. Therefore, it is crucial to delabel patients during childhood to avoid false labeling in adult life. Although the label of BL allergy is among the most frequent causes of allergy referral, its management remains controversial, and new diagnostic perspectives are changing the paradigm of managing BL allergies in children. Traditionally, drug provocation testing (DPT) was exclusively performed in patients who had previously obtained negative results from skin tests (STs). However, the sensitivity of STs is low, and the role of <i>in vitro</i> testing in the pediatric population is not well defined. Recent studies have demonstrated the safety of direct DPT without prior ST or serum tests for pediatric patients who report a low-risk reaction to BLs, which is cost-effective. However, there is still a debate on the optimal allergic workup to be performed in children with a benign immediate reaction and the management of children with severe cutaneous adverse drug reactions. In this review, we will discuss the impact of the label of BL allergy and the role of the different tools currently available to efficiently address BL allergy delabeling in children.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"4 ","pages":"1298335"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-14eCollection Date: 2023-01-01DOI: 10.3389/falgy.2023.1297425
Brandon Bautista-Becerril, Kurtis F Budden, Ramcés Falfán-Valencia
{"title":"Editorial: Microbiota and asthma.","authors":"Brandon Bautista-Becerril, Kurtis F Budden, Ramcés Falfán-Valencia","doi":"10.3389/falgy.2023.1297425","DOIUrl":"10.3389/falgy.2023.1297425","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"4 ","pages":"1297425"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-13DOI: 10.3389/falgy.2023.1302567
Julie Castagna, François Chasset, Jean-Eric Autegarden, Claire Le Thai, Emmanuelle Amsler, Annick Barbaud, Angèle Soria
Introduction Approximately 10% of individuals report a suspected allergy to penicillin, but according to allergy work-ups, only 10%–15% of them are truly allergic. A clinical decision score, the PEN-FAST, was developed and validated to identify adults with low-risk penicillin allergy. Objectives The objective of this study was to improve the performance of the PEN-FAST score, particularly for those with delayed hypersensitivity (HS), by improving the negative predictive value. Methods STEP 1: Retrospective evaluation of the PEN-FAST score in patients with proven immediate and delayed penicillin allergy. STEP 2: Identification of additional criteria among Step 1 patients misclassified by PEN-FAST score. Development of the PEN-FAST+ score using multivariable logistic regression in a prospective cohort of patients with a suspicion of HS to penicillin. STEP 3: Comparison of diagnostic performances of PEN-FAST and PEN-FAST+ scores. Results The PEN-FAST score showed limitations in predicting the relapse of immediate skin HS or delayed maculopapular exanthema, with 28.6% and 38.4% of patients misclassified, respectively. We identified two potential additional criteria: skin rash lasting more than 7 days and immediate reaction occurring in less than 1 h (generalized or localized on palmoplantar area or scalp itching/heat feeling). A total of 32/252 (12.7%) patients were confirmed to be allergic to penicillin. With PEN-FAST, 37% of patients ( n = 10) with delayed allergic penicillin HS were misclassified. With PEN-FAST+, 3 patients with delayed HS confirmed by a ST (11.1%) were misclassified. The AUC was significantly higher for PEN-FAST+ than PEN-FAST (85% vs. 72%, p = 0.03).
大约10%的人报告怀疑对青霉素过敏,但根据过敏检查,只有10% - 15%的人真正过敏。开发并验证了临床决策评分PEN-FAST,以识别低风险青霉素过敏的成人。本研究的目的是通过提高阴性预测值来提高PEN-FAST评分的性能,特别是对于延迟性超敏反应(HS)患者。方法:步骤1:回顾性评估立即和延迟青霉素过敏患者的PEN-FAST评分。步骤2:在被PEN-FAST评分错误分类的第1步患者中确定额外的标准。在怀疑对青霉素有HS的前瞻性队列患者中使用多变量logistic回归建立PEN-FAST+评分。步骤3:PEN-FAST与PEN-FAST+评分诊断性能比较。结果penfast评分在预测即刻性皮肤HS或延迟性黄斑丘疹复发方面存在局限性,分别有28.6%和38.4%的患者分错。我们确定了两个潜在的附加标准:持续7天以上的皮疹和在不到1小时内发生的立即反应(全身或局限于掌足底区或头皮瘙痒/发热感)。共有32/252例(12.7%)患者被确诊为青霉素过敏。在PEN-FAST中,37% (n = 10)迟发性过敏性青霉素HS患者被错误分类。在PEN-FAST+中,3例经ST确诊的迟发性HS患者(11.1%)被误诊。PEN-FAST+的AUC显著高于PEN-FAST (85% vs. 72%, p = 0.03)。
{"title":"Assessing delayed penicillin hypersensitivity using the PENFAST+ score","authors":"Julie Castagna, François Chasset, Jean-Eric Autegarden, Claire Le Thai, Emmanuelle Amsler, Annick Barbaud, Angèle Soria","doi":"10.3389/falgy.2023.1302567","DOIUrl":"https://doi.org/10.3389/falgy.2023.1302567","url":null,"abstract":"Introduction Approximately 10% of individuals report a suspected allergy to penicillin, but according to allergy work-ups, only 10%–15% of them are truly allergic. A clinical decision score, the PEN-FAST, was developed and validated to identify adults with low-risk penicillin allergy. Objectives The objective of this study was to improve the performance of the PEN-FAST score, particularly for those with delayed hypersensitivity (HS), by improving the negative predictive value. Methods STEP 1: Retrospective evaluation of the PEN-FAST score in patients with proven immediate and delayed penicillin allergy. STEP 2: Identification of additional criteria among Step 1 patients misclassified by PEN-FAST score. Development of the PEN-FAST+ score using multivariable logistic regression in a prospective cohort of patients with a suspicion of HS to penicillin. STEP 3: Comparison of diagnostic performances of PEN-FAST and PEN-FAST+ scores. Results The PEN-FAST score showed limitations in predicting the relapse of immediate skin HS or delayed maculopapular exanthema, with 28.6% and 38.4% of patients misclassified, respectively. We identified two potential additional criteria: skin rash lasting more than 7 days and immediate reaction occurring in less than 1 h (generalized or localized on palmoplantar area or scalp itching/heat feeling). A total of 32/252 (12.7%) patients were confirmed to be allergic to penicillin. With PEN-FAST, 37% of patients ( n = 10) with delayed allergic penicillin HS were misclassified. With PEN-FAST+, 3 patients with delayed HS confirmed by a ST (11.1%) were misclassified. The AUC was significantly higher for PEN-FAST+ than PEN-FAST (85% vs. 72%, p = 0.03).","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"129 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136351845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-13DOI: 10.3389/falgy.2023.1277244
Pavel Kudrin, Ana Rebane
RNA modifications have emerged as a fundamental mechanism of post-transcriptional gene regulation, playing vital roles in cellular physiology and the development of various diseases. While the investigation of RNA modifications has seen significant advancements, the exploration of their implication in allergic diseases has been comparatively overlooked. Allergic reactions, including hay fever, asthma, eczema and food allergies, result from hypersensitive immune responses, affecting a considerable population worldwide. Despite the high prevalence, the molecular mechanisms underlying these responses remain partially understood. The potential role of RNA modifications in modulating the hypersensitive immune responses has yet to be fully elucidated. This mini-review seeks to shed light on potential connections between RNA modifications and allergy, highlighting recent findings and potential future research directions. By expanding our understanding of the complex interplay between RNA modifications and allergic responses, we hope to unlock new avenues for allergy diagnosis, prognosis, and therapeutic intervention.
{"title":"Do RNA modifications contribute to modulation of immune responses in allergic diseases?","authors":"Pavel Kudrin, Ana Rebane","doi":"10.3389/falgy.2023.1277244","DOIUrl":"https://doi.org/10.3389/falgy.2023.1277244","url":null,"abstract":"RNA modifications have emerged as a fundamental mechanism of post-transcriptional gene regulation, playing vital roles in cellular physiology and the development of various diseases. While the investigation of RNA modifications has seen significant advancements, the exploration of their implication in allergic diseases has been comparatively overlooked. Allergic reactions, including hay fever, asthma, eczema and food allergies, result from hypersensitive immune responses, affecting a considerable population worldwide. Despite the high prevalence, the molecular mechanisms underlying these responses remain partially understood. The potential role of RNA modifications in modulating the hypersensitive immune responses has yet to be fully elucidated. This mini-review seeks to shed light on potential connections between RNA modifications and allergy, highlighting recent findings and potential future research directions. By expanding our understanding of the complex interplay between RNA modifications and allergic responses, we hope to unlock new avenues for allergy diagnosis, prognosis, and therapeutic intervention.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"33 16","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-10DOI: 10.3389/falgy.2023.1145809
Masami Taniguchi, Atsuhiko Sato, Haruhisa Mita
Although there are many case reports of asthma exacerbations with intravenous corticosteroids, especially hydrocortisone succinate, in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), the frequency and mechanism remain unclear. We hypothesized that N-ERD patients are potentially hypersensitive to succinates, especially succinate corticosteroids, based on the results of previous provocation studies and considered specific mechanisms. The objective of this study was to determine the frequency and mechanism of succinate corticosteroids hypersensitivity in patients with N-ERD. Eleven patients with stable, moderate to severe N-ERD were tested with hydrocortisone sodium succinate (HCs), hydrocortisone sodium phosphate (HCp), methylprednisolone sodium succinate (MPSLs), prednisolone sodium succinate (PSLs), and chloramphenicol sodium succinate (CPs, without a steroidal chemical structure) at doses below the normal dose through intravenous administration using a single-blind test. As a comparison, seven patients with aspirin-tolerant asthma (ATA) also underwent an intravenous provocation test of HCs. The positive intravenous provocation test rates of HCs 100–500 mg, HCp 500 mg, MPSLs 80 mg, PSLs 20 mg, and CPs 500 mg in N-ERD patients were 82% (9/11), 9% (1/11), 50% (5/10), 33% (1/3), and 86% (6/7), respectively. Most positive reactions began with a severe cough within 5 min of intravenous injection. The course of these hypersensitivity symptoms differed from those seen with the usual aspirin challenge test. The HCs 100–500 mg intravenous test was negative in all seven patients with ATA. In conclusion, patients with N-ERD have high rates of potential hypersensitivity to the succinate ester structure, which is not linked to the corticosteroid structure, but to the succinate ester structure. We hypothesized that the mechanism of hypersensitivity observed during rapid intravenous administration of succinate corticosteroids is mast cell activation via succinate receptor stimulation, rather than due to the corticosteroid itself.
{"title":"Hypersensitivity to intravenous succinate corticosteroids in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease","authors":"Masami Taniguchi, Atsuhiko Sato, Haruhisa Mita","doi":"10.3389/falgy.2023.1145809","DOIUrl":"https://doi.org/10.3389/falgy.2023.1145809","url":null,"abstract":"Although there are many case reports of asthma exacerbations with intravenous corticosteroids, especially hydrocortisone succinate, in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), the frequency and mechanism remain unclear. We hypothesized that N-ERD patients are potentially hypersensitive to succinates, especially succinate corticosteroids, based on the results of previous provocation studies and considered specific mechanisms. The objective of this study was to determine the frequency and mechanism of succinate corticosteroids hypersensitivity in patients with N-ERD. Eleven patients with stable, moderate to severe N-ERD were tested with hydrocortisone sodium succinate (HCs), hydrocortisone sodium phosphate (HCp), methylprednisolone sodium succinate (MPSLs), prednisolone sodium succinate (PSLs), and chloramphenicol sodium succinate (CPs, without a steroidal chemical structure) at doses below the normal dose through intravenous administration using a single-blind test. As a comparison, seven patients with aspirin-tolerant asthma (ATA) also underwent an intravenous provocation test of HCs. The positive intravenous provocation test rates of HCs 100–500 mg, HCp 500 mg, MPSLs 80 mg, PSLs 20 mg, and CPs 500 mg in N-ERD patients were 82% (9/11), 9% (1/11), 50% (5/10), 33% (1/3), and 86% (6/7), respectively. Most positive reactions began with a severe cough within 5 min of intravenous injection. The course of these hypersensitivity symptoms differed from those seen with the usual aspirin challenge test. The HCs 100–500 mg intravenous test was negative in all seven patients with ATA. In conclusion, patients with N-ERD have high rates of potential hypersensitivity to the succinate ester structure, which is not linked to the corticosteroid structure, but to the succinate ester structure. We hypothesized that the mechanism of hypersensitivity observed during rapid intravenous administration of succinate corticosteroids is mast cell activation via succinate receptor stimulation, rather than due to the corticosteroid itself.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":" 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135190893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-09DOI: 10.3389/falgy.2023.1296894
Enrique Gómez de la Fuente, Isam Alobid, Iñigo Ojanguren, Victoria Rodríguez-Vázquez, Beatriz Pais, Víctor Reyes, Miriam Espinosa, África Luca de Tena, Irantzu Muerza, Eduard Vidal-Barraquer
Background Patients with asthma (AS), atopic dermatitis (AD), allergic rhinitis (AR), eosinophilic esophagitis (EoE), chronic rhinosinusitis with nasal polyps (CRSwNP), chronic urticaria (CU), non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD), and certain phenotypes of chronic obstructive pulmonary disease (COPD), among others, have a common underlying pathogenesis known as Type 2 inflammation (T2i). These diseases often coexist with other T2i conditions and have a substantial impact on the quality of life (QoL) of patients. However, limited data on patients’ experiences, perspectives, and current management of T2i diseases have been published thus far. Aims This survey, promoted by the patient-driven T2i Network Project, aimed at identifying the common drivers and challenges related to the QoL of patients with T2i diseases by putting the patient's perspective at the force and including it in the design of new care strategies. Methodology An anonymous online survey was carried out through convenience sampling between May and June 2023. The survey was codesigned by members of different patient associations, healthcare professionals and healthcare quality experts, and implemented using EUSurvey and distributed through eight patient associations from Spain. The survey consisted of 29 questions related to the participant's sociodemographic features, a series of self-reported multiple choice or rating scale questions, including diagnosis, QoL measures, disease severity, healthcare resource utilization, and quality of care. Results The survey included 404 participants, members from eight patient associations, the majority of whom had moderate-to-severe self-reported disease severity (93%) and one or more coexisting pathologies related to T2i (59%). Patients with more than one pathology had a significantly greater impact on QoL than those with only one pathology ( p < .001). Participants with self-reported severe symptoms reported significantly worse QoL than those with mild-to-moderate severity ( p < .001). More than half of the patients (56%) felt constantly bothered by the unpredictability of their illness caused by potential exposure to known or unknown disease triggers. The lack of coordination between specialists and primary care was also expressed as an area of dissatisfaction by participants, with 52% indicating a complete lack of coordination and 21% indicating an average coordination. Conclusion This article reports the initial findings of a patient-led initiative, which highlights the common QoL challenges faced by individuals with type 2 inflammation-related diseases and emphasizes the importance of further clinical research to improve the management of this patient group. Considering the significant impact on QoL, a multidisciplinary approach integrated into new healthcare protocols has the potential to improve patient management and QoL, shorten the time to diagnosis and reduce healthcare resource
{"title":"Addressing the unmet needs in patients with type 2 inflammatory diseases: when quality of life can make a difference","authors":"Enrique Gómez de la Fuente, Isam Alobid, Iñigo Ojanguren, Victoria Rodríguez-Vázquez, Beatriz Pais, Víctor Reyes, Miriam Espinosa, África Luca de Tena, Irantzu Muerza, Eduard Vidal-Barraquer","doi":"10.3389/falgy.2023.1296894","DOIUrl":"https://doi.org/10.3389/falgy.2023.1296894","url":null,"abstract":"Background Patients with asthma (AS), atopic dermatitis (AD), allergic rhinitis (AR), eosinophilic esophagitis (EoE), chronic rhinosinusitis with nasal polyps (CRSwNP), chronic urticaria (CU), non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD), and certain phenotypes of chronic obstructive pulmonary disease (COPD), among others, have a common underlying pathogenesis known as Type 2 inflammation (T2i). These diseases often coexist with other T2i conditions and have a substantial impact on the quality of life (QoL) of patients. However, limited data on patients’ experiences, perspectives, and current management of T2i diseases have been published thus far. Aims This survey, promoted by the patient-driven T2i Network Project, aimed at identifying the common drivers and challenges related to the QoL of patients with T2i diseases by putting the patient's perspective at the force and including it in the design of new care strategies. Methodology An anonymous online survey was carried out through convenience sampling between May and June 2023. The survey was codesigned by members of different patient associations, healthcare professionals and healthcare quality experts, and implemented using EUSurvey and distributed through eight patient associations from Spain. The survey consisted of 29 questions related to the participant's sociodemographic features, a series of self-reported multiple choice or rating scale questions, including diagnosis, QoL measures, disease severity, healthcare resource utilization, and quality of care. Results The survey included 404 participants, members from eight patient associations, the majority of whom had moderate-to-severe self-reported disease severity (93%) and one or more coexisting pathologies related to T2i (59%). Patients with more than one pathology had a significantly greater impact on QoL than those with only one pathology ( p &lt; .001). Participants with self-reported severe symptoms reported significantly worse QoL than those with mild-to-moderate severity ( p &lt; .001). More than half of the patients (56%) felt constantly bothered by the unpredictability of their illness caused by potential exposure to known or unknown disease triggers. The lack of coordination between specialists and primary care was also expressed as an area of dissatisfaction by participants, with 52% indicating a complete lack of coordination and 21% indicating an average coordination. Conclusion This article reports the initial findings of a patient-led initiative, which highlights the common QoL challenges faced by individuals with type 2 inflammation-related diseases and emphasizes the importance of further clinical research to improve the management of this patient group. Considering the significant impact on QoL, a multidisciplinary approach integrated into new healthcare protocols has the potential to improve patient management and QoL, shorten the time to diagnosis and reduce healthcare resource ","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":" 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135292676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-06DOI: 10.3389/falgy.2023.1004170
Sandra D. Anderson, Pascale Kippelen
Exercise induced bronchoconstriction (EIB) describes the transient narrowing of the airways that follows vigorous exercise. It commonly occurs in children and adults who have asthma and in elite athletes. The primary stimulus is proposed to be loss of water, by evaporation, from the airway surface due to conditioning inspired air. The mechanism, whereby this evaporative loss of water provokes contraction of the bronchial smooth muscle, is thought to be an increase in osmolarity of the airway surface liquid. The increase in osmolarity causes mast cells to release histamines, prostaglandins, and leukotrienes. It is these mediators that contract smooth muscle causing the airways to narrow.
{"title":"A proposal to account for the stimulus, the mechanism, and the mediators released in exercise-induced bronchoconstriction","authors":"Sandra D. Anderson, Pascale Kippelen","doi":"10.3389/falgy.2023.1004170","DOIUrl":"https://doi.org/10.3389/falgy.2023.1004170","url":null,"abstract":"Exercise induced bronchoconstriction (EIB) describes the transient narrowing of the airways that follows vigorous exercise. It commonly occurs in children and adults who have asthma and in elite athletes. The primary stimulus is proposed to be loss of water, by evaporation, from the airway surface due to conditioning inspired air. The mechanism, whereby this evaporative loss of water provokes contraction of the bronchial smooth muscle, is thought to be an increase in osmolarity of the airway surface liquid. The increase in osmolarity causes mast cells to release histamines, prostaglandins, and leukotrienes. It is these mediators that contract smooth muscle causing the airways to narrow.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"13 17","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135590243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-06DOI: 10.3389/falgy.2023.1272851
Alexandra F. Santos, Margitta Worm, Shoko Kurita, Tania Wong, Davide Contato, Elia Pirillo, A. Esther Esteban, Paolo Tassinari, Flavia Perna, R. Sharon Chinthrajah
Background Few studies have addressed how food allergy may impact differently on the daily lives of adults with food allergies and caregivers for food-allergic dependents. Objective To explore similarities and differences in life experiences and unmet needs between individuals caring for a child with food allergy and adults with food allergy world-wide. Methods Two multinational, virtual, interactive, moderated discussions of specific questions between respectively people with food allergies and caregivers for people with food allergies, with experienced clinicians participating. Results Sixteen individuals living with food allergies and nine caregivers took part in the two roundtables. Food avoidance and antihistamines were the most common treatments for food-allergic reactions in both groups. Caregivers reported greater burden of disease on affected individuals and families than did adult patients. Adult panelists considered autoinjectors easy to use but caregivers reported additional emotional stress thinking about autoinjector use. Caregivers described an ever-present fear of inattention and of overlooking a risk factor for a severe reaction, whereas adult panelists showed a determination not to let their food allergies interfere with living their lives. Both groups had safety-conscious attitudes to treatments, but adult patients emphasized convenience while caregivers prioritized reduced severity of reactions and eliminated fear. Both groups confirmed the need for improved, trusted sources of information, and for resources and training programs for any new therapies. Conclusion The interactive exchange provided insights into differences between adult patients and caregivers, notably in fear and confidence in daily life, severity of disease impact, and unmet needs for treatments.
{"title":"Living with food allergies: the experiences of adult patients and caregivers","authors":"Alexandra F. Santos, Margitta Worm, Shoko Kurita, Tania Wong, Davide Contato, Elia Pirillo, A. Esther Esteban, Paolo Tassinari, Flavia Perna, R. Sharon Chinthrajah","doi":"10.3389/falgy.2023.1272851","DOIUrl":"https://doi.org/10.3389/falgy.2023.1272851","url":null,"abstract":"Background Few studies have addressed how food allergy may impact differently on the daily lives of adults with food allergies and caregivers for food-allergic dependents. Objective To explore similarities and differences in life experiences and unmet needs between individuals caring for a child with food allergy and adults with food allergy world-wide. Methods Two multinational, virtual, interactive, moderated discussions of specific questions between respectively people with food allergies and caregivers for people with food allergies, with experienced clinicians participating. Results Sixteen individuals living with food allergies and nine caregivers took part in the two roundtables. Food avoidance and antihistamines were the most common treatments for food-allergic reactions in both groups. Caregivers reported greater burden of disease on affected individuals and families than did adult patients. Adult panelists considered autoinjectors easy to use but caregivers reported additional emotional stress thinking about autoinjector use. Caregivers described an ever-present fear of inattention and of overlooking a risk factor for a severe reaction, whereas adult panelists showed a determination not to let their food allergies interfere with living their lives. Both groups had safety-conscious attitudes to treatments, but adult patients emphasized convenience while caregivers prioritized reduced severity of reactions and eliminated fear. Both groups confirmed the need for improved, trusted sources of information, and for resources and training programs for any new therapies. Conclusion The interactive exchange provided insights into differences between adult patients and caregivers, notably in fear and confidence in daily life, severity of disease impact, and unmet needs for treatments.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"36 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135680005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-06DOI: 10.3389/falgy.2023.1248432
Jason L. N. Girkin, Leon A. Sokulsky, Malcolm R. Starkey, Philip M. Hansbro, Paul S. Foster, Adam M. Collison, Joerg Mattes
Introduction Eosinophilic esophagitis (EoE) is associated with allergen-driven inflammation of the esophagus and an upregulated Th2 cytokine signature. Recombinant interleukin (IL)-13 (rIL-13) administration to mice induces some of the hallmark features of EoE, including increased eotaxin expression and eosinophil recruitment. Inflammation in EoE has previously been shown to depend on the expression of TRAIL and MID-1, which reduced protein phosphatase 2A (PP2A) activity. The relationship between IL-13 and TRAIL signalling in esophageal eosinophilia is currently unknown. Objective To investigate the interaction between IL-13-driven eosinophil infiltration and TRAIL or MID-1 in the esophagus. Method We administered rIL-13 to wild type (WT), TRAIL-deficient ( Tnsf10 −/− ) or STAT6-deficient (STAT6 −/− ) mice and targeted MID-1 with small interfering RNA. Results rIL-13 administration to mice increased TRAIL and MID-1 expression in the esophagus while reducing PP2A activity. TRAIL deficient, but not STAT6 deficient mice demonstrated increased MID-1 expression and PP2A reduction upon IL-13 challenge which correlated with eosinophil infiltration into the esophagus. Silencing MID-1 expression with siRNA completely ablated IL-13 induced eosinophil infiltration of the esophagus, restored PP2A activity, and reduced eotaxin-1 expression. Conclusion IL-13-driven eosinophil infiltration of the esophagus induced eosinophilia and eotaxin-1 expression in a STAT6-dependent and MID-1-dependent manner. This study highlights a novel mechanism employed by IL-13 to perpetuate eosinophil infiltration.
嗜酸性食管炎(EoE)与过敏原驱动的食管炎症和Th2细胞因子信号上调有关。重组白细胞介素(IL)-13 (IL -13)给药小鼠可诱导EoE的一些标志性特征,包括eotaxin表达增加和嗜酸性粒细胞募集。先前已经证明EoE中的炎症依赖于TRAIL和MID-1的表达,从而降低蛋白磷酸酶2A (PP2A)的活性。食道嗜酸性粒细胞增多症中IL-13和TRAIL信号之间的关系目前尚不清楚。目的探讨il -13驱动的食管嗜酸性粒细胞浸润与TRAIL或MID-1的相互作用。方法我们给野生型(WT)、trail缺陷(Tnsf10−/−)或STAT6缺陷(STAT6−/−)小鼠注射rIL-13,并用小干扰RNA靶向MID-1。结果rIL-13使小鼠食管TRAIL和MID-1表达增加,PP2A活性降低。TRAIL缺陷而非STAT6缺陷小鼠在IL-13攻击后表现出MID-1表达增加和PP2A减少,这与嗜酸性粒细胞浸润到食道有关。用siRNA沉默MID-1表达完全消除IL-13诱导的食管嗜酸性粒细胞浸润,恢复PP2A活性,降低eotaxin-1表达。结论il -13驱动的食管嗜酸性粒细胞浸润诱导嗜酸性粒细胞增多和eotaxin-1的表达以stat6依赖和mid -1依赖的方式表达。本研究强调了IL-13维持嗜酸性粒细胞浸润的新机制。
{"title":"A unique role for IL-13 in inducing esophageal eosinophilia through MID-1 and STAT6","authors":"Jason L. N. Girkin, Leon A. Sokulsky, Malcolm R. Starkey, Philip M. Hansbro, Paul S. Foster, Adam M. Collison, Joerg Mattes","doi":"10.3389/falgy.2023.1248432","DOIUrl":"https://doi.org/10.3389/falgy.2023.1248432","url":null,"abstract":"Introduction Eosinophilic esophagitis (EoE) is associated with allergen-driven inflammation of the esophagus and an upregulated Th2 cytokine signature. Recombinant interleukin (IL)-13 (rIL-13) administration to mice induces some of the hallmark features of EoE, including increased eotaxin expression and eosinophil recruitment. Inflammation in EoE has previously been shown to depend on the expression of TRAIL and MID-1, which reduced protein phosphatase 2A (PP2A) activity. The relationship between IL-13 and TRAIL signalling in esophageal eosinophilia is currently unknown. Objective To investigate the interaction between IL-13-driven eosinophil infiltration and TRAIL or MID-1 in the esophagus. Method We administered rIL-13 to wild type (WT), TRAIL-deficient ( Tnsf10 −/− ) or STAT6-deficient (STAT6 −/− ) mice and targeted MID-1 with small interfering RNA. Results rIL-13 administration to mice increased TRAIL and MID-1 expression in the esophagus while reducing PP2A activity. TRAIL deficient, but not STAT6 deficient mice demonstrated increased MID-1 expression and PP2A reduction upon IL-13 challenge which correlated with eosinophil infiltration into the esophagus. Silencing MID-1 expression with siRNA completely ablated IL-13 induced eosinophil infiltration of the esophagus, restored PP2A activity, and reduced eotaxin-1 expression. Conclusion IL-13-driven eosinophil infiltration of the esophagus induced eosinophilia and eotaxin-1 expression in a STAT6-dependent and MID-1-dependent manner. This study highlights a novel mechanism employed by IL-13 to perpetuate eosinophil infiltration.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"9 8","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135589668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}