Antonella Marrocco, Jennifer A Mitchel, Margaret Parker, Maureen McGill, Robert P Chase, Scott T Weiss, Diane R Gold, Peter J Castaldi, Elliot Israel, Jin-Ah Park, Joanne E Sordillo
{"title":"Transcriptomic profiles of well-differentiated airway epithelial cells in response to environmental triggers of asthma exacerbation.","authors":"Antonella Marrocco, Jennifer A Mitchel, Margaret Parker, Maureen McGill, Robert P Chase, Scott T Weiss, Diane R Gold, Peter J Castaldi, Elliot Israel, Jin-Ah Park, Joanne E Sordillo","doi":"10.1111/all.16226","DOIUrl":"https://doi.org/10.1111/all.16226","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michaela Lucas, Hugo W F Mak, Jasmine T Y Lee, Rishabh Kulkarni, Sophia S C Chan, Philip H Li
Background: The consequences of drug allergy remain a global health concern. Drug allergy is often a neglected topic and many non-specialists lack sufficient knowledge or confidence in evaluating or managing this common condition. Evidence-based interventions to better equip non-specialists to tackle drug allergy are needed. The aim of the study is to evaluate the effectiveness of an intensive educational course on drug allergy knowledge and practice of non-specialists.
Methods: A randomized crossover trial (NCT06399601) was conducted among practicing physicians and nurses participating in an intensive drug allergy course-Advances in Drug Allergy & Penicillin Testing (ADAPT). Participants' baseline knowledge and self-reported practices were assessed with standardized questionnaires (scored from 0 to 100, with "satisfactory" defined as ≥60/100). Participants were randomized into two cohorts and attended ADAPT at different time points. Serial responses before and after the course were compared within and between cohorts.
Results: Seventy participants (25 physicians, 45 nurses) randomized into two groups completed the course. Baseline drug allergy knowledge (58.0 ± 19.9) and self-reported practice (36.9 ± 24.3) were unsatisfactory among non-specialists, with significantly lower scores from nurses than physicians in both domains (knowledge: 49.0 ± 17.4 vs. 74.0 ± 12.7; practice: 32.1 ± 21.3 vs. 53.3 ± 23.1; all p < 0.001). Following completion of ADAPT, participants demonstrated significant improvements in knowledge (58.0 ± 19.9 vs. 77.7 ± 15.9, p < 0.001) and self-reported practice (36.9 ± 24.3 vs. 71.0 ± 20.2, p < 0.001). All participants (100%) and 99% of participants agreed that the course improved their clinical knowledge and practice, respectively.
Conclusions: ADAPT, an intensive drug allergy educational course was effective in improving drug allergy knowledge and practice for non-specialists. Further longitudinal studies are required to evaluate long-term impact.
{"title":"Impact of a drug allergy education course for non-specialists: Findings from ADAPT-A randomized crossover trial.","authors":"Michaela Lucas, Hugo W F Mak, Jasmine T Y Lee, Rishabh Kulkarni, Sophia S C Chan, Philip H Li","doi":"10.1111/all.16270","DOIUrl":"https://doi.org/10.1111/all.16270","url":null,"abstract":"<p><strong>Background: </strong>The consequences of drug allergy remain a global health concern. Drug allergy is often a neglected topic and many non-specialists lack sufficient knowledge or confidence in evaluating or managing this common condition. Evidence-based interventions to better equip non-specialists to tackle drug allergy are needed. The aim of the study is to evaluate the effectiveness of an intensive educational course on drug allergy knowledge and practice of non-specialists.</p><p><strong>Methods: </strong>A randomized crossover trial (NCT06399601) was conducted among practicing physicians and nurses participating in an intensive drug allergy course-Advances in Drug Allergy & Penicillin Testing (ADAPT). Participants' baseline knowledge and self-reported practices were assessed with standardized questionnaires (scored from 0 to 100, with \"satisfactory\" defined as ≥60/100). Participants were randomized into two cohorts and attended ADAPT at different time points. Serial responses before and after the course were compared within and between cohorts.</p><p><strong>Results: </strong>Seventy participants (25 physicians, 45 nurses) randomized into two groups completed the course. Baseline drug allergy knowledge (58.0 ± 19.9) and self-reported practice (36.9 ± 24.3) were unsatisfactory among non-specialists, with significantly lower scores from nurses than physicians in both domains (knowledge: 49.0 ± 17.4 vs. 74.0 ± 12.7; practice: 32.1 ± 21.3 vs. 53.3 ± 23.1; all p < 0.001). Following completion of ADAPT, participants demonstrated significant improvements in knowledge (58.0 ± 19.9 vs. 77.7 ± 15.9, p < 0.001) and self-reported practice (36.9 ± 24.3 vs. 71.0 ± 20.2, p < 0.001). All participants (100%) and 99% of participants agreed that the course improved their clinical knowledge and practice, respectively.</p><p><strong>Conclusions: </strong>ADAPT, an intensive drug allergy educational course was effective in improving drug allergy knowledge and practice for non-specialists. Further longitudinal studies are required to evaluate long-term impact.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisca Molina-Jiménez, Lola Ugalde-Triviño, Laura Arias-González, Elisa Armenteros, Carlos Relaño-Rupérez, Sergio Casabona, José Andrés Moreno-Monteagudo, María Teresa Pérez-Fernández, Verónica Martín-Domínguez, Jennifer Fernández-Pacheco, Emilio José Laserna-Mendieta, Patricia Muñoz-Hernández, Jorge García-Martínez, Javier Muñoz, Alfredo J Lucendo, Cecilio Santander, Pedro Majano
Background: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response.
Methods: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways.
Results: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment.
Conclusion: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.
背景:最近,我们在嗜酸性粒细胞食管炎(EoE)患者的食管上皮细胞中发现了一种失调蛋白质特征,包括与炎症和上皮屏障功能相关的蛋白质;然而,质子泵抑制剂(PPI)治疗对该特征的影响尚不清楚。在此,我们采用蛋白质组学方法研究:(1) PPI 治疗是否会改变 EoE 患者食管上皮蛋白质特征;(2) 基线蛋白质特征是否能预测 PPI 反应:我们使用一组成年食管上皮细胞增多症患者(25 人)和健康对照组(10 人)评估了食管活检的蛋白质特征。在食管水肿患者中,分别在 8 周 PPI 治疗前(前)和治疗后(后)进行食管活检,以确定组织学反应。PPI治疗后嗜酸性粒细胞计数用于对患者进行分类:≥15个嗜酸性粒细胞/hpf的患者为无应答者(非应答者),≥15个嗜酸性粒细胞/hpf的患者为应答者(应答者):对各组间不同累积蛋白的比较分析显示,有炎症的三组患者(应答者-PrePPI、非应答者-PrePPI 和非应答者-PostPPI)与无炎症的三组患者(对照组和应答者-PostPPI)之间存在共同特征。PPI疗法几乎逆转了应答者-PostPPI中EoE特异性食管蛋白特征,该特征富含与炎症和上皮屏障功能相关的通路。此外,我们还确定了一组候选蛋白,用于在治疗前区分应答者-PrePPI 和非应答者-PrePPI EoE 患者:这些发现提供了证据,证明 PPI 治疗可逆转食管炎性和上皮细胞蛋白的改变,从而为 PPI 临床反应的机制提供了新的见解。有趣的是,我们的研究结果还表明,PPI 反应可在 EoE 基线时预测。
{"title":"Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.","authors":"Francisca Molina-Jiménez, Lola Ugalde-Triviño, Laura Arias-González, Elisa Armenteros, Carlos Relaño-Rupérez, Sergio Casabona, José Andrés Moreno-Monteagudo, María Teresa Pérez-Fernández, Verónica Martín-Domínguez, Jennifer Fernández-Pacheco, Emilio José Laserna-Mendieta, Patricia Muñoz-Hernández, Jorge García-Martínez, Javier Muñoz, Alfredo J Lucendo, Cecilio Santander, Pedro Majano","doi":"10.1111/all.16261","DOIUrl":"https://doi.org/10.1111/all.16261","url":null,"abstract":"<p><strong>Background: </strong>Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response.</p><p><strong>Methods: </strong>We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways.</p><p><strong>Results: </strong>Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment.</p><p><strong>Conclusion: </strong>These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toshinori Nakamura, Taiji Nakano, Angela Simpson, Michihiro Kono, John A Curtin, Tomoko Kobayashi, Clare S Murray, Masashi Akiyama, Masahiro Imanishi, Masayuki Mikuriya, Adnan Custovic, Naoki Shimojo
Background: Hen's egg exposure through impaired skin barrier is considered a major mechanism of sensitization to eggs. However, the impact of filaggrin (FLG) gene loss-of-function mutations on the natural history of egg sensitization lacks consensus among studies.
Objective: To evaluate the association between the natural course of egg sensitization and FLG mutations.
Methods: We used Japanese and the UK birth cohorts (CHIBA and MAAS) to identify the longitudinal patterns of egg sensitization until mid-school age and examined the relationship between the identified patterns and FLG mutations. Sensitization was assessed using egg white-specific IgE levels or skin prick tests (SPTs). Egg allergy was confirmed by parental reports and sensitization. Latent class growth analysis identified longitudinal patterns.
Results: Three similar patterns of egg sensitization (persistent, early-onset remitting, and no/low grade classes) were identified in both cohorts, with differing prevalence estimates. The proportion of children with egg allergy in the persistent class at 7 or 8 years of age was 23% (CHIBA) and 20% (MAAS). Consistently in both cohorts, FLG mutations were significantly associated only with the persistent class. Children with FLG mutations had an approximately four-fold increased risk of being in the persistent sensitization class (RRRs: 4.3, 95%C.I. (1.2-16.0), p = .03 in CHIBA; 4.3 (1.3-14.7), p = .02 in MAAS).
Conclusion: FLG loss-of-function mutations are associated with persistent egg sensitization in both Japanese and European ethnicities, and the mutations might be a potential biomarker for identifying the risk of persistent egg sensitization/allergy in early infancy. Future studies should incorporate oral food challenges to confirm this relationship.
{"title":"Trajectories of egg sensitization in childhood: Two birth cohorts in Asia and Europe.","authors":"Toshinori Nakamura, Taiji Nakano, Angela Simpson, Michihiro Kono, John A Curtin, Tomoko Kobayashi, Clare S Murray, Masashi Akiyama, Masahiro Imanishi, Masayuki Mikuriya, Adnan Custovic, Naoki Shimojo","doi":"10.1111/all.16264","DOIUrl":"https://doi.org/10.1111/all.16264","url":null,"abstract":"<p><strong>Background: </strong>Hen's egg exposure through impaired skin barrier is considered a major mechanism of sensitization to eggs. However, the impact of filaggrin (FLG) gene loss-of-function mutations on the natural history of egg sensitization lacks consensus among studies.</p><p><strong>Objective: </strong>To evaluate the association between the natural course of egg sensitization and FLG mutations.</p><p><strong>Methods: </strong>We used Japanese and the UK birth cohorts (CHIBA and MAAS) to identify the longitudinal patterns of egg sensitization until mid-school age and examined the relationship between the identified patterns and FLG mutations. Sensitization was assessed using egg white-specific IgE levels or skin prick tests (SPTs). Egg allergy was confirmed by parental reports and sensitization. Latent class growth analysis identified longitudinal patterns.</p><p><strong>Results: </strong>Three similar patterns of egg sensitization (persistent, early-onset remitting, and no/low grade classes) were identified in both cohorts, with differing prevalence estimates. The proportion of children with egg allergy in the persistent class at 7 or 8 years of age was 23% (CHIBA) and 20% (MAAS). Consistently in both cohorts, FLG mutations were significantly associated only with the persistent class. Children with FLG mutations had an approximately four-fold increased risk of being in the persistent sensitization class (RRRs: 4.3, 95%C.I. (1.2-16.0), p = .03 in CHIBA; 4.3 (1.3-14.7), p = .02 in MAAS).</p><p><strong>Conclusion: </strong>FLG loss-of-function mutations are associated with persistent egg sensitization in both Japanese and European ethnicities, and the mutations might be a potential biomarker for identifying the risk of persistent egg sensitization/allergy in early infancy. Future studies should incorporate oral food challenges to confirm this relationship.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicklas Brustad, Jakob Stokholm, Klaus Bønnelykke, Bo L Chawes
{"title":"Vitamin D-FUT2 interaction and risk of lower respiratory tract infections in childhood.","authors":"Nicklas Brustad, Jakob Stokholm, Klaus Bønnelykke, Bo L Chawes","doi":"10.1111/all.16266","DOIUrl":"https://doi.org/10.1111/all.16266","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}