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Increased Levels of Inflammatory Proteins, Including TARC/CCL17, in Skin of AD Patients During JAK Inhibitor Treatment
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-02-04 DOI: 10.1111/cea.14637
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}
引用次数: 0
Food Allergy Prevalence, Diagnosis and Impact: Unexpected Findings
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-02-03 DOI: 10.1111/cea.14635
Robert J. Boyle, Mohamed H. Shamji
{"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}
引用次数: 0
Very Long-Term Stability of Tryptase in Frozen Serum Samples
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-02-03 DOI: 10.1111/cea.70009
Florent Broussal, Thomas Rouzioux, Dounia Khelifi-Touhami, Sibylle Bachelier, Brigitte Berthier, Aicha Abbas, Simone Choi, Yannick Chantran
{"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}
引用次数: 0
Acceptance and Commitment Therapy Eczema Management Program for Children With Eczema: A Pilot Randomised Controlled Trial.
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-02-03 DOI: 10.1111/cea.70003
Yuen Yu Chong, Wai Tong Chien, Huan Yu Mou, Sui Ping Leung, Oi Yin Wong, Shu Yan Lam
{"title":"Acceptance and Commitment Therapy Eczema Management Program for Children With Eczema: A Pilot Randomised Controlled Trial.","authors":"Yuen Yu Chong, Wai Tong Chien, Huan Yu Mou, Sui Ping Leung, Oi Yin Wong, Shu Yan Lam","doi":"10.1111/cea.70003","DOIUrl":"https://doi.org/10.1111/cea.70003","url":null,"abstract":"<p><strong>Introduction: </strong>Eczema significantly affects the quality of life of affected children and their families, with psychological stress often overlooked. Acceptance and Commitment Therapy (ACT) provides a supplementary approach to address these psychological challenges and enhance overall care.</p><p><strong>Objective: </strong>This pilot randomised controlled trial aimed to examine the feasibility, acceptability and preliminary effectiveness of the Family ACT-based Eczema Management Program (FACT-EMP).</p><p><strong>Methods: </strong>Parents and children aged 6-12 diagnosed with eczema from three outpatient clinics in Hong Kong were randomly assigned to either the FACT-EMP group, receiving four weekly ACT-based sessions plus eczema management education, or a waitlist control group receiving routine care. Feasibility and acceptability were assessed through recruitment, retention and completion rates, supplemented by focus group feedback on parental experiences. Primary clinical outcomes were children's eczema Severity Scoring of Atopic Dermatitis (SCORAD) and parental self-efficacy. Secondary outcomes included parental distress, quality of life, psychological flexibility and self-compassion of both parents and children.</p><p><strong>Results: </strong>From July 2021 to June 2023, 181 of 944 screened parent-child dyads met the inclusion criteria, and 78 were randomised and analysed (parents' mean [SD] age, 41.3 [11.0] years; 70 mothers [89.7%]; children's mean [SD] age, 8.3 [1.9] years; 53 boys [67.9%]). Recruitment, retention and completion rates were 43.1%, 87.2% and 76.9%, respectively. No significant between-group differences in SCORAD scores were observed immediately post-intervention. At 3-month post-intervention, SCORAD scores decreased significantly more in the FACT-EMP group than in the waitlist control group (adjusted mean difference, aMD, -7.73; 95% CI, -13.92 to -1.54). Parental self-efficacy scores also improved significantly more in the FACT-EMP group than the control, with an aMD of 18.69 (95% CI, 13.80 to 33.58) immediately post-intervention and 28.90 (95% CI, 13.93 to 43.84) at 3 months.</p><p><strong>Conclusion: </strong>FACT-EMP is potentially feasible, acceptable and effective in improving children's eczema symptoms and enhancing parents' self-efficacy in disease management over 3 months.</p><p><strong>Trial registration: </strong>NCT04919330.</p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122507","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}
引用次数: 0
Evaluation of Small Airways Dysfunction With Dupilumab Using Airway Oscillometry in Uncontrolled Severe Asthma
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-01-30 DOI: 10.1111/cea.70002
Kirsten E. Stewart, Chris RuiWen Kuo, Rory Chan, Brian J. Lipworth
{"title":"Evaluation of Small Airways Dysfunction With Dupilumab Using Airway Oscillometry in Uncontrolled Severe Asthma","authors":"Kirsten E. Stewart,&nbsp;Chris RuiWen Kuo,&nbsp;Rory Chan,&nbsp;Brian J. Lipworth","doi":"10.1111/cea.70002","DOIUrl":"10.1111/cea.70002","url":null,"abstract":"&lt;p&gt;Dupilumab acts on IL-4 receptor alpha inhibiting IL-4 and IL-13 signalling which in turn attenuates type 2 inflammation (T2I) in patients with asthma. The presence of small airway dysfunction (SAD) may be assessed using airway oscillometry (AO) which is performed during normal tidal breathing. AO may exhibit a high degree of sensitivity in detecting SAD in asthma, which can be evaluated using either peripheral lung resistance as the heterogeneity in resistance between 5 Hz and 20 Hz (R5-R20) or peripheral lung compliance as the area under the reactance curve (AX).&lt;/p&gt;&lt;p&gt;The presence of SAD as increased R5-R20 in asthmatic patients with an FEV&lt;sub&gt;1&lt;/sub&gt; &gt; 80% predicted is associated with significantly greater use of oral corticosteroids and salbutamol [&lt;span&gt;1&lt;/span&gt;]. Moreover, SAD as altered R5-R20 and AX, but not as FEV&lt;sub&gt;1&lt;/sub&gt;, is closely related to T2I biomarkers [&lt;span&gt;2&lt;/span&gt;]. A real-life retrospective study in patients with uncontrolled severe asthma receiving dupilumab revealed improved SAD detected through R5-R20 and AX [&lt;span&gt;3&lt;/span&gt;]. The objective of the present study was to prospectively assess the impact of 12 weeks of treatment with dupilumab on SAD in patients with type 2 high (T2H) poorly controlled severe asthma.&lt;/p&gt;&lt;p&gt;This was a phase 4 single-arm proof of concept clinical trial with a single-centre, open-labelled design which included adults aged 18–75 years with T2H poorly controlled severe asthma despite taking ICS/LABA with or without other second line controllers. Eligible patients entered a 4-week run-in period with standardisation of ICS/LABA as maintenance and reliever therapy (MART) 2–8 actuations per day using extra fine particle Fostair NEXThaler 100/6μg dry powder inhaler beclomethasone dipropionate/formoterol (BDP/FM). A treatment period of 12 weeks of dupilumab was then employed with an initial 600 mg loading dose followed by 300 mg 2 weekly doses in addition to BDP/FM MART. Participants were then followed for a subsequent 12-week washout period without dupilumab to week 24. ERS and ATS guidelines were followed for spirometry (Micromedical, Chatham, UK) and airwave oscillometry (AO) (TremoFlo c100, Thorasys, Montreal, Canada) according to the manufacturer's instructions and following published guidance [&lt;span&gt;4&lt;/span&gt;]. The study was approved by a local research ethics committee (21/WS/0151) and all participants gave written informed consent. The clinical trial was registered with ISRCTN:70810039. The presence of SAD at baseline was defined using values as follows: R5-R20 ≥ 0.1 kPa/L/s, R5-R20/R5 Ratio ≥ 19%, AX ≥ 1.0 kPa/L and FEF&lt;sub&gt;25–75&lt;/sub&gt; ≤ 60% predicted [&lt;span&gt;5&lt;/span&gt;]. Repeated measures analysis of variance (RM-ANOVA) was initially performed to compare results overall between baseline, week 12 and week 24. In the presence of a significant overall RM-ANOVA, pairwise Students &lt;i&gt;t&lt;/i&gt;-tests were used to assess differences between baseline (week 0) versus post dupilumab (week 12), and betwe","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 3","pages":"264-266"},"PeriodicalIF":6.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064113","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}
引用次数: 0
Chronic Urticaria Is Associated With an Increased Risk of Psoriasis: An Observational and Validation Study.
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-01-29 DOI: 10.1111/cea.70000
Lin-Hong Shi, An-Ping Huo, Yu-Hsun Wang, James Cheng-Chung Wei
{"title":"Chronic Urticaria Is Associated With an Increased Risk of Psoriasis: An Observational and Validation Study.","authors":"Lin-Hong Shi, An-Ping Huo, Yu-Hsun Wang, James Cheng-Chung Wei","doi":"10.1111/cea.70000","DOIUrl":"https://doi.org/10.1111/cea.70000","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064109","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}
引用次数: 0
Beyond Skin Deep: Olfactory Dysfunction as a Common Problem Among Chinese Hereditary Angioedema Patients.
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-01-28 DOI: 10.1111/cea.70001
Hugo W F Mak, Valerie Chiang, Jackie S H Yim, Elaine Lee, Dorothy L Y Lam, Philip H Li
{"title":"Beyond Skin Deep: Olfactory Dysfunction as a Common Problem Among Chinese Hereditary Angioedema Patients.","authors":"Hugo W F Mak, Valerie Chiang, Jackie S H Yim, Elaine Lee, Dorothy L Y Lam, Philip H Li","doi":"10.1111/cea.70001","DOIUrl":"https://doi.org/10.1111/cea.70001","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051843","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}
引用次数: 0
Relationship Between Bronchodilator Reversibility and Spirometry Response to Dupilumab in Type 2 High Uncontrolled Severe Asthma
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-01-28 DOI: 10.1111/cea.14634
Robert Greig, Kirsten Stewart, Chris RuiWen Kuo, Rory Chan, Brian Lipworth
{"title":"Relationship Between Bronchodilator Reversibility and Spirometry Response to Dupilumab in Type 2 High Uncontrolled Severe Asthma","authors":"Robert Greig,&nbsp;Kirsten Stewart,&nbsp;Chris RuiWen Kuo,&nbsp;Rory Chan,&nbsp;Brian Lipworth","doi":"10.1111/cea.14634","DOIUrl":"10.1111/cea.14634","url":null,"abstract":"&lt;p&gt;Airway hyperresponsiveness is a key tenet of persistent asthma, along with the type 2 inflammatory phenotype in most patients, while bronchodilator reversibility (BDR) may be absent in patients with a preserved FEV&lt;sub&gt;1&lt;/sub&gt;. Biologics act on downstream type 2 cytokine pathways inhibiting signalling of interleukins (IL) 4, 5 and 13 [&lt;span&gt;1&lt;/span&gt;]. A retrospective study in severe asthma patients receiving anti-IL-5 or anti-IL-5Rα showed no difference in clinical outcomes when stratified by baseline BDR. Dupilumab is a monoclonal antibody which targets the alpha subunit of IL4 receptor which in turn inhibits IL4 and IL13 signalling, resulting in reduced exacerbations, improved symptom control and better lung function [&lt;span&gt;2&lt;/span&gt;]. We wanted to evaluate the putative relationship between baseline BDR to salbutamol and the lung function response to dupilumab, expressed as either force expiratory volume in 1 s (FEV&lt;sub&gt;1&lt;/sub&gt;) or forced mid-expiratory flow (FEF&lt;sub&gt;25-75&lt;/sub&gt;).&lt;/p&gt;&lt;p&gt;Here we assessed patients with uncontrolled severe asthma (EudraCT 2021-005593-25) who had BDR measured at their initial screening visit. Then after a 4 week run-in period patients also had lung function measured after receiving 12 weeks of dupilumab 300 mg given every 2 weeks. We assessed the spirometry response to either salbutamol or dupilumab calculated as % predicted changes from baseline, as well as relative % change from baseline (post–pre/pre), and absolute change (FEV&lt;sub&gt;1&lt;/sub&gt; in L and FEF&lt;sub&gt;25-75&lt;/sub&gt; as L/s). To ensure an equal comparison, the pre-salbutamol baseline at screening prior to run-in was used for both assessments.&lt;/p&gt;&lt;p&gt;Spirometry (Micromedical, Chatham, UK) measurements were performed in triplicate according to the ERS guidelines [&lt;span&gt;3&lt;/span&gt;]. 400 μg of salbutamol via a pressurised metered dose inhaler with an Aerochamber spacer device (Trudell Medical, London, Canada) was administered to all patients and after 20 min, the spirometry was repeated to assess BDR. Following the manufacturer's instructions and ERS guidelines, FeNO was obtained using NIOX Vero (NIOX, Oxford, UK) [&lt;span&gt;4&lt;/span&gt;]. SPSS version 29 was used for statistical analysis. Paired students &lt;i&gt;t&lt;/i&gt;-tests were applied with an alpha error of 5% and Pearsons test was used to evaluate correlations. Nominal &lt;i&gt;p&lt;/i&gt; values are quoted as either &lt;i&gt;p&lt;/i&gt; &lt; 0.05, &lt; 0.01 or &lt; 0.001 (two tailed).&lt;/p&gt;&lt;p&gt;The cohort consisted of 24 patients, 14 females, mean (SEM) age 52.3 (2.96); BMI 30.0 (1.23). The mean % predicted pre-bronchodilator pulmonary function values and type 2 inflammation markers were: FEV&lt;sub&gt;1&lt;/sub&gt; 88.1% (3.5); FEF&lt;sub&gt;25-75&lt;/sub&gt; 47.5% (3.0); FVC 105.8% (4.0) ACQ 3.0 (0.2); FeNO 68.0 ppb (8.9); eosinophils 510/μL (48), total IgE 204.7 kU/l (42.8).&lt;/p&gt;&lt;p&gt;There were significant improvements in FEV&lt;sub&gt;1&lt;/sub&gt; and FEF&lt;sub&gt;25-75&lt;/sub&gt; in response to salbutamol. However, the response to dupilumab was significant for FEV&lt;sub&gt;1&lt;/sub&gt; but not FEF&lt;sub&gt;25","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 3","pages":"253-255"},"PeriodicalIF":6.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.14634","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058035","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}
引用次数: 0
Urinary Lipid Production Profile of Patients With Food Allergy
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-01-28 DOI: 10.1111/cea.14636
Sakura Masuko, Shinichiro Inagaki, Taiki Hamabata, Takeru Ishii, Nanae Nagata, Kiwako Yamamoto-Hanada, Tatsuki Fukuie, Masami Narita, Tatsuo Shimosawa, Yukihiro Ohya, Takahisa Murata
{"title":"Urinary Lipid Production Profile of Patients With Food Allergy","authors":"Sakura Masuko,&nbsp;Shinichiro Inagaki,&nbsp;Taiki Hamabata,&nbsp;Takeru Ishii,&nbsp;Nanae Nagata,&nbsp;Kiwako Yamamoto-Hanada,&nbsp;Tatsuki Fukuie,&nbsp;Masami Narita,&nbsp;Tatsuo Shimosawa,&nbsp;Yukihiro Ohya,&nbsp;Takahisa Murata","doi":"10.1111/cea.14636","DOIUrl":"10.1111/cea.14636","url":null,"abstract":"&lt;p&gt;Upon immediate allergic inflammation, activated mast cells produce abundant bioactive lipid mediator prostaglandin (PG) D&lt;sub&gt;2&lt;/sub&gt;. PGD&lt;sub&gt;2&lt;/sub&gt; is metabolised and excreted in urine as tetranor-PGDM. We have previously reported urinary tetranor-PGDM as a sensitive biomarker for food allergy (FA) reactions in children [&lt;span&gt;1&lt;/span&gt;]. However, the production profile of other lipid mediators in the urine of FA patients remains unknown. Bioactive lipids are produced by enzyme-dependent or independent metabolism of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA), linoleic acid (LA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DGLA). There are three types of oxidative enzymes for PUFAs: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP). The produced lipid mediators regulate inflammation and are extracted mainly in urine, thus their production profile can reflect the inflammatory status of our bodies. In this study, we comprehensively analysed the production profile of lipid mediators in the urine of subjects who received oral food challenge (OFC).&lt;/p&gt;&lt;p&gt;We collected the same urine samples from subjects as previously reported [&lt;span&gt;1&lt;/span&gt;]. Children suspected of having FA who underwent OFC to milk, egg, peanut or sesame were recruited between December 2014 and August 2015, and urine samples were collected before (pre) and 4 h after OFC (post). Of a total of 42 children, 31 were assessed as having positive results (OFC-positive; FA). This study received ethical approval from the Committee, University of Tokyo School of Medicine (2017,10586). All participants provided informed consent.&lt;/p&gt;&lt;p&gt;Initially, we confirmed that OFC and/or its positivity did not influence urinary pH, or specific gravity, while they did influence the lipid content (Figure 1A). There was no difference in urinary lipid content in children who ingested offending food, suggesting that lipid content may reflect the inflammatory reaction in the body. Next, we analysed the levels of 196 types of lipid metabolites in urine using LC–MS/MS and detected 19 lipid metabolites. These methods are available in the following repository (https://zenodo.org/records/14207617).&lt;/p&gt;&lt;p&gt;Figure 1B shows the AA metabolites levels in subjects' urine. As reported previously, the urinary levels of tetranor-PGDM were increased in OFC-positive-post urine, and its levels were higher than those of OFC-negative-post urine [&lt;span&gt;1&lt;/span&gt;]. The levels of other PGD&lt;sub&gt;2&lt;/sub&gt; metabolites, 13,14-dihydro-15-keto-tetranor-PGD&lt;sub&gt;2&lt;/sub&gt; and tetranor-PGJM (precursor and non-enzymatic metabolite of tetranor-PGDM, respectively), were also higher in the OFC-positive-post urine. It is well known that mast cells express H-PGDS and produce PGD&lt;sub&gt;2&lt;/sub&gt; [&lt;span&gt;2&lt;/span&gt;]. During the progression of FA, mast cells infiltrate into the relatively large area of intestinal mucosa and release PGD&lt;sub&gt;2&lt;/sub&gt;. This phenomenon presumably re","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 3","pages":"256-259"},"PeriodicalIF":6.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.14636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058038","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}
引用次数: 0
From Anxiety to Work Productivity and Activity Impairment: The Mediating Role of Fatigue in Hereditary Angioedema.
IF 6.3 2区 医学
Clinical and Experimental Allergy Pub Date : 2025-01-24 DOI: 10.1111/cea.14632
Hugo W F Mak, Jane C Y Wong, Valerie Chiang, Dorothy L Y Lam, Philip H Li
{"title":"From Anxiety to Work Productivity and Activity Impairment: The Mediating Role of Fatigue in Hereditary Angioedema.","authors":"Hugo W F Mak, Jane C Y Wong, Valerie Chiang, Dorothy L Y Lam, Philip H Li","doi":"10.1111/cea.14632","DOIUrl":"https://doi.org/10.1111/cea.14632","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037488","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}
引用次数: 0
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