{"title":"Growth Trajectories and Body Composition in Preschoolers With Allergic Conditions: Findings From the Japan Environment and Children's Study Pilot Cohort.","authors":"Daisuke Harama, Miori Sato, Limin Yang, Yumiko Miyaji, Nathan Mise, Reiko Suga, Mayumi Tsuji, Masayuki Ochiai, Masako Oda, Maki Fukami, Shoji F Nakayama, Makiko Sekiyama, Yukihiro Ohya, Kiwako Yamamoto-Hanada","doi":"10.1111/cea.14625","DOIUrl":"https://doi.org/10.1111/cea.14625","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anet Laanesoo, Mariel Mäe, Anu Remm, Sebastian L. Johnston, Alan Altraja, Grazyna Bochenek, Bogdan Jakiela, Ana Rebane
{"title":"NLRP1 Is a Prominent Inflammasome Sensor Found in Bronchial Epithelial Cells in Asthma and Can Be Activated by Rhinovirus A16","authors":"Anet Laanesoo, Mariel Mäe, Anu Remm, Sebastian L. Johnston, Alan Altraja, Grazyna Bochenek, Bogdan Jakiela, Ana Rebane","doi":"10.1111/cea.70010","DOIUrl":"10.1111/cea.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Asthma exacerbations are frequently triggered by human rhinoviruses (RVs). Among other pro-inflammatory responses, RV infection of airway epithelium promotes the activation of the inflammasome pathway, the role of which in asthma exacerbations and disease progression is still poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bronchial brushing or biopsy specimens were collected from asthma patients and control subjects. Functional experiments were performed in cultured human bronchial epithelial cells (HBECs) using RV-A16, poly(I:C), and siRNA transfection. Gene expression was analysed by RNA-sequencing, RT-qPCR, immunofluorescence, western blot or ELISA. Caspase-1 activity was evaluated using FAM-FLICA assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression of NLRP1 was found to be the highest compared to other inflammasome sensors tested in brushed bronchial epithelium samples from asthma patients and control individuals, as well as in cultured primary HBECs. Additionally, we observed increased expression of CASP1 mRNA in bronchial epithelial cells from patients with neutrophilic asthma compared to those with paucigranulocytic and eosinophilic phenotypes. Changes in the expression of inflammasome pathway genes caused by RV-A16 infection were similar in HBEC cultures from asthma patients and controls, except for IL-1β, which showed increased response, and PYCARD, which exhibited decreased change in cells derived from asthma patients. Silencing of NLRP1 expression with siRNAs impeded RV-A16-induced activation of the inflammasome but had no effect on poly(I:C)-induced secretion of IL-1β and IL-18.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NLRP1 is highly expressed inflammasome sensor in both healthy and asthmatic bronchial epithelium and can be activated by RV-A16. RV-induced changes in the expression of inflammasome pathway genes suggest that there may be differences in HBECs derived from asthma patients, which may depend on the prevailing immunological phenotype of the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 3","pages":"239-246"},"PeriodicalIF":6.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398505","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}
D. Betancor, E. S. Castromil-Benito, J. Bernaola, J. Parrón-Ballesteros, C. Pastor-Vargas, J. Cuesta-Herranz
{"title":"Prevalence and Mite Allergen Recognition in an Area of Low Environmental Exposure","authors":"D. Betancor, E. S. Castromil-Benito, J. Bernaola, J. Parrón-Ballesteros, C. Pastor-Vargas, J. Cuesta-Herranz","doi":"10.1111/cea.70006","DOIUrl":"10.1111/cea.70006","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 3","pages":"267-269"},"PeriodicalIF":6.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R Bestwick, R Bhogal, K Kildonaviciute, B Y Ng, B Jackson, C Moriarty, C Thomas, L Savic, S A Misbah, M T Krishna, R Mujica-Mota
{"title":"An Economic Evaluation of Direct Oral Penicillin Challenge for De-Labelling Low Risk Patients With a Penicillin Allergy Label.","authors":"R Bestwick, R Bhogal, K Kildonaviciute, B Y Ng, B Jackson, C Moriarty, C Thomas, L Savic, S A Misbah, M T Krishna, R Mujica-Mota","doi":"10.1111/cea.14633","DOIUrl":"https://doi.org/10.1111/cea.14633","url":null,"abstract":"<p><strong>Background: </strong>Removing inaccurate penicillin allergy labels (PALs) can reduce unnecessary exposure to 'watch' and 'reserve' groups of antibiotics and thereby reduce antimicrobial resistance. The most efficient model for a non-allergy-specialist-led penicillin allergy de-labelling (PADL) service has not been established.</p><p><strong>Objective: </strong>To determine the costs to the UK National Health Service of a direct oral penicillin challenge (DPC) for low-risk patients with a PAL in three hospitals in England, each with a different non-allergy-specialist delivery model: pharmacist-led, nurse-led, and mixed multidisciplinary.</p><p><strong>Methods: </strong>Cost analysis of the DPC pathway, including resources related to staff time and antibiotics. The effect of de-labelling on healthcare utilisation over 5 years was modelled using data from the published literature.</p><p><strong>Results: </strong>In total, 2257 patients from the Acute Medical or Infectious Disease Unit (AMU/IDU), Pre-surgical, and Haematology-Oncology departments were screened. Subsequently, 126 underwent DPC, and 122 were de-labelled. Twenty-two of these were de-labelled in time to affect their antibiotic regimen; 6 from AMU/IDU and 16 Pre-surgery. The DPC represented 22%-23% of the pathway cost in the pharmacist-led and mixed models, and 15% in the nurse-led model. Across departments and models, the cost per de-labelled patient varied between £577 (95% Credible Interval: 370, 633) for haematology-oncology patients to £2329 (947, 19,504) for AMU/IDU patients, both under the nurse-led model. After 5 years, recouping costs was unlikely for AMU/IDU patients under any model or for all patients combined under the mixed model.</p><p><strong>Conclusions: </strong>The penicillin allergy de-labelling pathway cost was ≥ 4-fold that of the DPC alone. Costs were up to 3 times higher in an acute compared to an elective setting. No short-term cost savings were identified from proactive or opportunistic penicillin allergy de-labelling in this study.</p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Jing Shi Ang, Haur Yueh Lee, Chaw Su Naing, Chiara Jiamin Chong, Chujie Li, Kavitha Garuna Murthee, Ibrahim Muhammad Hanif, Vivian Tan, Zi Teng Chai, Karen Jui Lin Choo
{"title":"Outcomes of Prolonged Provocation Testing in Penicillin Allergy Evaluation","authors":"Andrea Jing Shi Ang, Haur Yueh Lee, Chaw Su Naing, Chiara Jiamin Chong, Chujie Li, Kavitha Garuna Murthee, Ibrahim Muhammad Hanif, Vivian Tan, Zi Teng Chai, Karen Jui Lin Choo","doi":"10.1111/cea.70008","DOIUrl":"10.1111/cea.70008","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 3","pages":"273-275"},"PeriodicalIF":6.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Celeste M. Boesjes, Lian F. van der Gang, Daphne S. Bakker, C. F. den Hartog Jager, Marlies de Graaf, Marjolein S. de Bruin-Weller, Femke van Wijk, Edward F. Knol
{"title":"Increased Levels of Inflammatory Proteins, Including TARC/CCL17, in Skin of AD Patients During JAK Inhibitor Treatment","authors":"Celeste M. Boesjes, Lian F. van der Gang, Daphne S. Bakker, C. F. den Hartog Jager, Marlies de Graaf, Marjolein S. de Bruin-Weller, Femke van Wijk, Edward F. Knol","doi":"10.1111/cea.14637","DOIUrl":"10.1111/cea.14637","url":null,"abstract":"<p>Atopic dermatitis (AD) is a complex and heterogeneous inflammatory skin disease that not only involves T helper (Th)2 responses, but also Th1, Th17 and Th22 cytokine pathways. Thymus and activation-regulated chemokine (TARC)/CCL17 is a type 2 chemokine that is highly expressed in AD skin and blood. Previous research showed that serum TARC levels significantly correlate with disease severity [<span>1</span>]. To date, TARC has been identified as the most reliable clinical biomarker to measure AD severity and to evaluate treatment response [<span>2</span>]. However, we recently reported that serum TARC might not be an adequate biomarker in AD patients treated with Janus kinase (JAK)-inhibitors (JAKi), as we found persistently high serum TARC levels despite a good treatment response [<span>3</span>]. To further investigate this, we aimed to assess local skin levels of TARC and other inflammatory proteins of AD patients treated with JAKi.</p><p>We measured 11 inflammatory proteins, including TARC, in tape strips from adult AD patients with a good clinical response to JAKi (upadacitinib or abrocitinib, Eczema Area Severity Index [EASI] ≤ 7), who had either persistently elevated (JAKh, <i>n</i> = 5) or normalised (JAKn, <i>n</i> = 5) serum TARC levels. Patients were retrospectively selected by serum TARC levels measured during routine diagnostics. Tape strips were collected of lesional and non-lesional skin (time points [Tx] vary per patient, ≥ 1 year of treatment) and were compared to tape strips of lesional skin from patients with active AD without systemic treatment (ADcontrol, <i>n</i> = 5). Additionally, tape strips were collected from nonatopic healthy controls (HCs, <i>n</i> = 3). Besides TARC, disease-related proteins (pulmonary and activation-regulated chemokine [PARC], cutaneous T-cell-attracting chemokine [CTACK], interleukin [IL]-13 and periostin), pro-inflammatory proteins (IL-18, IL-8, IP-10 and IL-1α), and tissue remodelling proteins (matrix metalloproteinase-1 [MMP-1], IL-15) were measured. Tape stripping of stratum corneum was performed using D-Squame tape strips (3.8 cm<sup>2</sup>, Standard D-Squame, Clinical & Derm TX USA) as previously described [<span>4</span>]. Tape strips 5–7 were used for analysis and eluted overnight at 4°C in a PBS elution buffer containing 0.5% Tween 20 and complete protease inhibitor cocktail (Roche Diagnostics). Protein levels were measured by Luminex multiplex immunoassay [<span>5</span>]. In addition, clinical effectiveness was measured by the EASI. For statistical analysis, the Mann–Whitney <i>U</i> test was used to identify differences in skin protein levels, EASI scores and serum TARC levels between patient groups and the Wilcoxon Rank test to compare lesional and non-lesional skin within subgroups. All patients provided written informed consent and participated in the Dutch BioDay registry.</p><p>All patients were treated at the University Medical Center Utrecht (November 2021–February 2024). ","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 3","pages":"260-263"},"PeriodicalIF":6.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.14637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187773","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}
{"title":"Food Allergy Prevalence, Diagnosis and Impact: Unexpected Findings","authors":"Robert J. Boyle, Mohamed H. Shamji","doi":"10.1111/cea.14635","DOIUrl":"https://doi.org/10.1111/cea.14635","url":null,"abstract":"<p>In this issue, we present three studies which make important contributions to our understanding of food allergy epidemiology, food allergy diagnostics and food allergy's impact on populations. There are very few prior studies of changes in food allergy prevalence over time using robust methodology. Perhaps the only studies worldwide which have undertaken repeated, population-based assessments of confirmed food allergy prevalence are the UK Isle of Wight studies. In this issue, Carina Venter and colleagues summarise the findings of two birth cohorts on the Isle of Wight. They used these to evaluate whether a change in food allergy prevalence can be seen between a birth cohort born in 1989/90 and one born 12 years later in 2001/2 [<span>1</span>]. The significance of these years is that during this time, many reports have documented a sharp increase in hospital attendance and admission for food anaphylaxis in young children. Contrary to the popular narrative of a food allergy epidemic, Venter et al. did not identify a detectable change in food allergy overall between the two populations (Figure 1). This finding mirrors those of the US National Health and Nutrition Examination Surveys and the Australian HealthNuts and Melbourne Atopy Cohort studies, where no change in sensitisation to foods using blood specific IgE (US) or skin prick testing (Australia) to foods could be detected. Those studies compared children born in the 1970/80s with those born in the 1990s (US) and children born in 1993/4 versus 2010/11 (Australia) [<span>2, 3</span>]. The Isle of Wight findings are also consistent with a stable rate of fatal food anaphylaxis in national registry studies [<span>4</span>]. Taken together, these studies question whether food allergy has been increasing in high-income countries in recent decades.</p><p>If we look at two more studies published in this issue, we can start to understand why professionals and members of the public are convinced there is a food allergy epidemic, without good objective evidence to support that. The first issue is that food allergy diagnosis is difficult, so this health condition is susceptible to overdiagnosis. This is shown in the study of Chong et al. from Singapore, which involved evaluating the diagnostic accuracy of commonly used tests for milk, egg, wheat and peanut allergy in children [<span>5</span>]. They report poor diagnostic accuracy, especially for milk and wheat diagnostics, with the known issue of a high false positive rate for all testing modalities and allergens. Most children with food allergy do not have a supervised oral food challenge [<span>6</span>]. So, by relying on diagnostic tests and clinical history, and increasing the number of diagnostic tests performed, we may have allowed overdiagnosis to increase, fuelling a false food allergy epidemic [<span>7</span>].</p><p>The second issue is the social response to food allergy. There has been a marked increase in concern about food allergy in rec","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 2","pages":"108-110"},"PeriodicalIF":6.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.14635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111094","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}
{"title":"Very Long-Term Stability of Tryptase in Frozen Serum Samples","authors":"Florent Broussal, Thomas Rouzioux, Dounia Khelifi-Touhami, Sibylle Bachelier, Brigitte Berthier, Aicha Abbas, Simone Choi, Yannick Chantran","doi":"10.1111/cea.70009","DOIUrl":"10.1111/cea.70009","url":null,"abstract":"<p>Mast cells are key players in allergic manifestations, which will affect 50% individuals by 2050. In physiological conditions, tryptase is produced almost exclusively by mast cells. A transient serum tryptase elevation is the biological hallmark of systemic acute mast cell activation, for example, occurring during anaphylaxis or Mast Cell Activation Syndrome.</p><p>In contrast, basal serum tryptase (bST) is remarkably steady over years in a given individual [<span>1</span>]. The concentrations of bST are mainly determined by genetic factors like Hereditary alpha-Tryptasemia [<span>1, 2</span>] and by the number of mast cells, which evolves very slowly in most healthy and diseased individuals [<span>1</span>]. Inter-individual variability of bST is explained by several sociodemographic, environmental and health determinants [<span>3</span>]. Notably, we recently reported that higher bST concentrations were associated with higher risk of allergic sensitisation, FeNO values, allergic manifestations including IgE-mediated asthma, and poor asthma control, in teenagers from a birth cohort [<span>4</span>]. Given the lifelong intraindividual stability of bST, our results suggest that bST could be used as a predictive tool to stratify individuals at high risk of allergic manifestations. Provided sufficient tryptase stability in frozen biological samples, this hypothesis could be tested retrospectively on research and care setting biobanks. Long-term tryptase stability is highly suspected [<span>1</span>] but was never formally demonstrated to date.</p><p>The present study aimed to determine very long-term tryptase stability in a collection of serum samples frozen during several years.</p><p>Briefly, all samples were collected at the Armand-Trousseau (AP-HP) hospital allergology laboratory from January to December 2016 (T0), systematically frozen and stored at −20°C immediately after bST measurements, and reanalysed for bST in July 2024 (T8). Blood samples were collected on tubes with clot activator and send to the laboratory within 2 h at room temperature. After 2 h clotting, samples were centrifuged at 1500 <b><i>g</i></b>, 15°C. Sera were aliquoted, stored at +4°C, and bST was analysed within 7 days [<span>5</span>]. If enough sample remained, sera were stored right after bST measurement at −20°C until T8. The maintenance of adequate temperature during storage was monitored by a temperature probe (SPY RF, JRI (France)) connected to a live monitoring software (Sirius, JRI (France)). Samples were kept at −20°C (±4°C) during all the study, without major incident or defrosting. A total of exactly 100 samples with bST values at T0 within reference range (1–15 μg/L) [<span>1</span>] were retrieved. Samples were allowed to defrost in an upright position during 24 h at +4°C. After defrosting, sera were homogenised gently by a vortex at low intensity and centrifuged before reanalysis. Tryptase were re-assayed at T8 by the same method (ImmunoCAP Tryptase Test","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 3","pages":"276-277"},"PeriodicalIF":6.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122509","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}