Clinical and Translational Allergy最新文献

{"title":"Predicting Blomia tropicalis allergens using a multiomics approach","authors":"Jan Hubert,&nbsp;Susanne Vrtala,&nbsp;Bruno Sopko,&nbsp;Scot E. Dowd,&nbsp;Qixin He,&nbsp;Pavel B. Klimov,&nbsp;Karel Harant,&nbsp;Pavel Talacko,&nbsp;Tomas Erban","doi":"10.1002/clt2.12302","DOIUrl":"https://doi.org/10.1002/clt2.12302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The domestic mite <i>Blomia tropicalis</i> is a major source of allergens in tropical and subtropical regions. Despite its great medical importance, the allergome of this mite has not been sufficiently studied. Only 14 allergen groups have been identified in <i>B. tropicalis</i> thus far, even though early radioimmunoelectrophoresis techniques (27 uncharacterized allergen complexes) and comparative data based on 40 allergen groups officially recognized by the World Health Organization (WHO)/IUIS in domestic astigmatid mites suggest the presence of a large set of additional allergens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we employ a multiomics approach to assess the allergome of <i>B. tropicalis</i> using genomic and transcriptomic sequence data and perform highly sensitive protein abundance quantification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Among the 14 known allergen groups, we confirmed 13 (one WHO/IUIS allergen, Blo t 19, was not found) and identified 16 potentially novel allergens based on sequence similarity. These data indicate that <i>B. tropicalis</i> shares 27 known/deduced allergen groups with pyroglyphid house dust mites (genus <i>Dermatophagoides</i>). Among these groups, five allergen-encoding genes are highly expressed at the transcript level: Blo t 1, Blo t 5, Blo t 21 (known), Blo t 15, and Blo t 18 (predicted). However, at the protein level, a different set of most abundant allergens was found: Blo t 2, 10, 11, 20 and 21 (mite bodies) or Blo t 3, 4, 6 and predicted Blo t 13, 14 and 36 (mite feces).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We report the use of an integrated omics method to identify and predict an array of mite allergens and advanced, label-free proteomics to determine allergen protein abundance. Our research identifies a large set of novel putative allergens and shows that the expression levels of allergen-encoding genes may not be strictly correlated with the actual allergenic protein abundance in mite bodies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50117356","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":"Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity","authors":"Michael A. Portelli,&nbsp;Sangita Bhaker,&nbsp;Vincent Pang,&nbsp;David O. Bates,&nbsp;Simon R. Johnson,&nbsp;Andrew P. Mazar,&nbsp;Dominick Shaw,&nbsp;Christopher Brightling,&nbsp;Ian Sayers","doi":"10.1002/clt2.12293","DOIUrl":"https://doi.org/10.1002/clt2.12293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Expression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To determine (i) the expression profile of uPAR in cultured human bronchial epithelial cells (HBEC) from asthma patients, (ii) the relationship between uPAR and the epithelial barrier, including blocking uPAR functions and (iii) the function of different uPAR isoforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>uPAR levels in HBECs isolated from asthma patients and cells at air liquid interface (ALI) during differentiation were quantified. Transepithelial electrical resistance or electrical cell impedance sensing was used to relate uPAR levels to barrier properties, including effects of uPAR blocking antibodies. The functional effects of gain of function was determined using transcriptomics, in cells over-expressing membrane (muPAR), soluble cleaved (scuPAR) or soluble spliced (ssuPAR) isoforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated expression of uPAR was a feature of cultured HBECs from asthma patients, suggesting intrinsic alterations in asthma patient cells. Soluble uPAR levels inversely correlated with barrier properties of the HBEC layer in 2D and ALI. Blocking uPAR-integrin interactions enhanced barrier formation. The gain of function cells showed limited transcriptomic changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides a significant advance in our understanding of the relationship between asthma, uPAR and the epithelial barrier, where elevated circulating uPAR results in a reduced cell barrier, a phenotype prevalent in asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50117353","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":"Reactivity to allergenic food contaminants: A study on products on the market","authors":"Alessandro Fiocchi,&nbsp;Linda Monaci,&nbsp;Elisabetta De Angelis,&nbsp;Veronica Calandrelli,&nbsp;Lamia Dahdah,&nbsp;Rocco Valluzzi,&nbsp;Sara Urbani,&nbsp;Carmen Mazzuca,&nbsp;Stefania Arasi,&nbsp;Arianna Cafarotti,&nbsp;Carla Riccardi,&nbsp;Maria Cristina Artesani,&nbsp;Lorenza Putignani,&nbsp;Valentina Pecora,&nbsp;Valeria Marzano,&nbsp;Vincenzo Fierro","doi":"10.1002/clt2.12301","DOIUrl":"10.1002/clt2.12301","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%–5% of the population could react (ED01–ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35 mg total protein/kg food. In our dose model, these amounts exceeded 1.5–10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154551","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":"Could it be hereditary angioedema?—Perspectives from different medical specialties","authors":"Markus Magerl,&nbsp;Anna Sala-Cunill,&nbsp;Christina Weber-Chrysochoou,&nbsp;Susanne Trainotti,&nbsp;Ilaria Mormile,&nbsp;Giuseppe Spadaro","doi":"10.1002/clt2.12297","DOIUrl":"10.1002/clt2.12297","url":null,"abstract":"<p>Hereditary angioedema (HAE) is a rare autosomal dominant disease, with patients often suffering with associated symptoms for many years before receiving a correct diagnosis. The symptoms greatly impact a patient's quality of life (QoL) and include excruciating abdominal pain and angioedema of the skin and submucosa. Angioedema of the larynx represents a significant mortality risk in undiagnosed patients, and a large proportion of patients with HAE receive incorrect diagnoses and undergo unnecessary surgery. HAE-specific treatments can control and prevent acute life-threatening episodes, in addition to improving QoL, emphasizing the value of early diagnosis for patients. Diagnostic delay may be due to a lack of HAE awareness by healthcare professionals and the similarity of HAE symptoms with those of more common conditions, complicating differential diagnosis. The multifaceted nature of the condition may result in visits to one of many different medical settings, for example: the Emergency Room, pediatrics, general practice, otolaryngology, gastroenterology, and dermatology. Therefore, it is crucial that physicians in multiple healthcare specialties are aware of the disease to ensure that patients with HAE receive a timely diagnosis. Using patient cases from various medical specialties, this review highlights the necessity for cross-specialty awareness of HAE and outlines the essential information for the various healthcare professionals that may encounter a patient with HAE symptoms, in order to effectively treat and/or diagnose HAE.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112741","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":"A concept for integrated care pathways for atopic dermatitis—A GA2LEN ADCARE initiative","authors":"Torsten Zuberbier,&nbsp;Amir Abdul Latiff,&nbsp;Xenofon Aggelidis,&nbsp;Matthias Augustin,&nbsp;Radu-Gheorghe Balan,&nbsp;Christine Bangert,&nbsp;Lisa Beck,&nbsp;Thomas Bieber,&nbsp;Jonathan A. Bernstein,&nbsp;Marta Bertolin Colilla,&nbsp;Alejandro Berardi,&nbsp;Anna Bedbrook,&nbsp;Carsten Bindslev-Jensen,&nbsp;Jean Bousquet,&nbsp;Marjolein de Bruin-Weller,&nbsp;Dayanne Bruscky,&nbsp;Betul Buyuktiryaki,&nbsp;Giorgio Walter Canonica,&nbsp;Carla Castro,&nbsp;Natia Chanturidze,&nbsp;Herberto Jose Chong-Neto,&nbsp;Chia-Yu Chu,&nbsp;Leena Chularojanamontri,&nbsp;Michael Cork,&nbsp;Roberta F. J. Criado,&nbsp;Laia Curto Barredo,&nbsp;Adnan Custovic,&nbsp;Ulf Darsow,&nbsp;Arben Emurlai,&nbsp;Ana de Pablo,&nbsp;Stefano Del Giacco,&nbsp;Giampiero Girolomoni,&nbsp;Tanja Deleva Jovanova,&nbsp;Mette Deleuran,&nbsp;Nikolaos Douladiris,&nbsp;Bruno Duarte,&nbsp;Ruta Dubakiene,&nbsp;Esben Eller,&nbsp;Batya Engel-Yeger,&nbsp;Luis Felipe Ensina,&nbsp;Nelson Rosario Filho,&nbsp;Carsten Flohr,&nbsp;Daria Fomina,&nbsp;Wojciech Francuzik,&nbsp;Maria Laura Galimberti,&nbsp;Ana M. Giménez-Arnau,&nbsp;Kiran Godse,&nbsp;Charlotte Gotthard Mortz,&nbsp;Maia Gotua,&nbsp;Michihiro Hide,&nbsp;Wolfram Hoetzenecker,&nbsp;Nicolas Hunzelmann,&nbsp;Alan Irvine,&nbsp;Carolyn Jack,&nbsp;Ioanna Kanavarou,&nbsp;Norito Katoh,&nbsp;Tamar Kinaciyan,&nbsp;Emek Kocatürk,&nbsp;Kanokvalai Kulthanan,&nbsp;Hilde Lapeere,&nbsp;Susanne Lau,&nbsp;Mariana Machado Forti Nastri,&nbsp;Michael Makris,&nbsp;Eli Mansour,&nbsp;Alexander Marsland,&nbsp;Mara Morelo Rocha Felix,&nbsp;Ana Paula Moschione Castro,&nbsp;Eustachio Nettis,&nbsp;J. F. Nicolas,&nbsp;Audrey Nosbaum,&nbsp;Mikaela Odemyr,&nbsp;Niki Papapostolou,&nbsp;Claudio A. S. Parisi,&nbsp;Sushil Paudel,&nbsp;Jonny Peter,&nbsp;Prakash Pokharel,&nbsp;Luis Puig,&nbsp;Tamara Quint,&nbsp;German Dario Ramon,&nbsp;Frederico Regateiro,&nbsp;Giampaolo Ricci,&nbsp;Cristine Rosario,&nbsp;Cansin Sackesen,&nbsp;Peter Schmid-Grendelmeier,&nbsp;Esther Serra-Baldrich,&nbsp;Kristina Siemens,&nbsp;Cathrine Smith,&nbsp;Petra Staubach,&nbsp;Katarina Stevanovic,&nbsp;Özlem Su-Kücük,&nbsp;Gordon Sussman,&nbsp;Simona Tavecchio,&nbsp;Natasa Teovska Mitrevska,&nbsp;Diamant Thaci,&nbsp;Elias Toubi,&nbsp;Claudia Traidl-Hoffmann,&nbsp;Regina Treudler,&nbsp;Zahava Vadasz,&nbsp;Ingrid van Hofman,&nbsp;Maria Teresa Ventura,&nbsp;Zhao Wang,&nbsp;Thomas Werfel,&nbsp;Andreas Wollenberg,&nbsp;Ariana Yang,&nbsp;Yik Weng Yew,&nbsp;Zuotao Zhao,&nbsp;Ricardo Zwiener,&nbsp;Margitta Worm","doi":"10.1002/clt2.12299","DOIUrl":"https://doi.org/10.1002/clt2.12299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The GA²LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL²EN ADCARE centres.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50150900","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":"Patient-physician interactions in hereditary angioedema—Key learnings from the coronavirus disease 2019 pandemic","authors":"Marcus Maurer,&nbsp;Thomas Buttgereit,&nbsp;Markus Magerl,&nbsp;Kathrin Schön,&nbsp;Zsusanna Balla,&nbsp;Henriette Farkas","doi":"10.1002/clt2.12300","DOIUrl":"10.1002/clt2.12300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The coronavirus disease pandemic and its containing measures have caused concerns for patients with hereditary angioedema (HAE) and their treating physicians. Both faced challenges surrounding interaction, and communication had to adapt to facilitate appropriate management. Specifically, the pandemic resulted in reduced in-person contact in clinics. Where possible, telemedicine appointments were offered and treatment outside the hospital setting was encouraged.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Body</h3>\u0000 \u0000 <p>The pandemic markedly affected patient-physician communication, which is essential to maintain partnerships and optimize care. Although patients with HAE are often experts in their condition, guidance by their physicians is essential, especially with the recent shift toward patient-centered management for rare diseases and shared decision-making (SDM). SDM enables patients to take control of their disease and allows the risks and benefits of treatment to be discussed with their physicians. This review explores perspectives from patients and physicians in the HAE clinical setting, particularly regarding their experiences with communication throughout the pandemic. We discuss the importance of SDM in rare diseases such as HAE, factors that impact effective communication, and potential solutions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Since patient-centered care and SDM have particular relevance in rare diseases in general, we believe our findings could be transferrable and applicable in the management of other rare diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093049","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":"Novel, computational IgE-clustering in a population-based cross-sectional study: Mapping the allergy burden","authors":"Rebecca Czolk,&nbsp;Maria Ruiz-Castell,&nbsp;Oliver Hunewald,&nbsp;Naphisabet Wanniang,&nbsp;Gwenaëlle Le Coroller,&nbsp;Christiane Hilger,&nbsp;Michel Vaillant,&nbsp;Guy Fagherazzi,&nbsp;Françoise Morel-Codreanu,&nbsp;Markus Ollert,&nbsp;Annette Kuehn","doi":"10.1002/clt2.12292","DOIUrl":"10.1002/clt2.12292","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Even though the prevalence of allergies is increasing, population-based data are still scarce. As a read-out for chronic inflammatory information, new methods are needed to integrate individual biological measurements and lifestyle parameters to mitigate the consequences and costs of allergic burden for society.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>More than 480.000 data points were collected from 1462 Luxembourg adults during the representative, cross-sectional European Health Examination Survey, spanning health and lifestyle reports. Deep IgE-profiles based on unsupervised clustering were correlated with data of the health survey.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>42.6% of the participants reported a physician-diagnosed allergy and 44% were found to be IgE-positive to at least one allergen or extract. The main sensitization sources were tree pollens followed by grass pollens and mites (52.4%, 51.8% and 40.3% of sensitized participants respectively), suggesting seasonal as well as perennial burden. The youngest group of participants (25–34 years old) showed the highest burden of sensitization, with 18.2% of them having IgE to 10 or more allergen groups. Unsupervised clustering revealed that the biggest cluster of 24.4% of participants was also the one with the highest medical need, marked by their multi-sensitization to respiratory sources.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our novel approach to analyzing large biosample datasets together with health information allows the measurement of the chronic inflammatory disease burden in the general population and led to the identification of the most vulnerable groups in need of better medical care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41121299","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":"Evaluation of patient-reported outcome measures for on-demand treatment of hereditary angioedema attacks and design of KONFIDENT, a phase 3 trial of sebetralstat","authors":"Danny M. Cohn,&nbsp;Emel Aygören-Pürsün,&nbsp;Jonathan A. Bernstein,&nbsp;Henriette Farkas,&nbsp;William R. Lumry,&nbsp;Marcus Maurer,&nbsp;Andrea Zanichelli,&nbsp;Matthew Iverson,&nbsp;James Hao,&nbsp;Michael D. Smith,&nbsp;Christopher M. Yea,&nbsp;Paul K. Audhya,&nbsp;Marc A. Riedl","doi":"10.1002/clt2.12288","DOIUrl":"10.1002/clt2.12288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE) with C1-inhibitor deficiency (HAE-C1-INH) is characterized by recurrent, debilitating episodes of swelling. Sebetralstat, an investigational oral plasma kallikrein inhibitor, demonstrated promising efficacy for on-demand treatment of HAE-C1-INH in a phase 2 trial. We describe the multipronged approach informing the design of KONFIDENT, a phase 3 randomized, placebo-controlled, three-way crossover trial evaluating the efficacy and safety of sebetralstat in patients aged ≥12 years with HAE-C1-INH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To determine an optimal endpoint to measure the beginning of symptom relief in KONFIDENT, we engaged patients with HAE on clinical outcome measures and subsequently conducted analyses of phase 2 outcomes. Sample size was determined via a simulation-based approach using phase 2 data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patient interviews revealed a strong preference (71%) for the Patient Global Impression of Change (PGI-C) over other measures and indicated a rating of “A Little Better” as a clinically meaningful milestone. In phase 2, a rating of “A Little Better” demonstrated agreement with attack severity improvement and resolution on the Patient Global Impression of Severity and had better sensitivity than “Better.” Simulations indicated that 84 patients completing treatment would ensure at least 90% power for assessing the primary endpoint of time to beginning of symptom relief defined as a PGI-C rating of at least “A Little Better” for two time points in a row.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patient feedback and phase 2 data support PGI-C as the primary outcome measure in the phase 3 KONFIDENT trial evaluating sebetralstat, which has the potential to be the first oral on-demand treatment for HAE-C1-INH attacks.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113646","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":"Sensitivity to change and minimal clinically important difference of the angioedema control test","authors":"Lauré M. Fijen,&nbsp;Carolina Vera,&nbsp;Thomas Buttgereit,&nbsp;Hanna Bonnekoh,&nbsp;Marcus Maurer,&nbsp;Markus Magerl,&nbsp;Karsten Weller","doi":"10.1002/clt2.12295","DOIUrl":"10.1002/clt2.12295","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Angioedema Control Test (AECT) is a patient-reported outcome measure developed and validated for the assessment of disease control in patients with recurrent angioedema. Its sensitivity to change and minimal clinically important difference (MCID) have hitherto not been established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with recurrent angioedema due to chronic spontaneous urticaria, hereditary angioedema, or acquired C1-inhibitor deficiency were repeatedly asked to complete the AECT along with the Angioedema Quality of Life Questionnaire (AE-QoL), Dermatology Life Quality Index (DLQI), and anchors for disease control and whether treatment was sufficient during routine care visits. The sensitivity to the change of the AECT was determined by correlating changes in its scores over time with changes in the applied anchors. The MCID was determined using anchor-based and distributional criterion-based approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-six cases were used for this analysis. Changes in AECT scores correlated well with AE-QoL changes (but less with changes in the DLQI) as well as other applied anchors, demonstrating its sensitivity to change. The MCID was found to be three points for improvement of angioedema control. The available number of cases with meaningful deterioration in our dataset was too low to reach a definite conclusion on the MCID for deterioration of angioedema control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The AECT is a valuable tool to assess changes in disease control in patients with recurrent angioedema over time. The lowest AECT score change that reflects a meaningful improvement of disease control to patients (MCID) is three points.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105412","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":"Anti-polyethylene glycol (PEG) antibody isotypes may predict PEG-associated allergy and COVID-19 protection among patients with history of suspected COVID-19 vaccine allergy","authors":"Andy Ka Chun Kan,&nbsp;Valerie Chiang,&nbsp;Wai Ki Ip,&nbsp;Elaine Y. L. Au,&nbsp;Philip H. Li","doi":"10.1002/clt2.12284","DOIUrl":"10.1002/clt2.12284","url":null,"abstract":"<p>Different anti-polyethylene glycol (PEG) antibody isotypes develop following exposure to PEG-containing substances, including many mRNA COVID-19 vaccines.<span>¹</span> For example, one study of 14 patients indicated that patients allergic to PEG-containing mRNA vaccines have significantly higher anti-PEG titres than controls.<span>²</span> Two COVID-19 vaccines are available in Hong Kong—PEG-containing Pfizer-BioNTech Comirnaty (BNT) and non-PEG-containing Sinovac CoronaVac (SV). Since their introduction, cases of vaccine-/PEG-associated allergy have exacerbated vaccine hesitancy.<span>³</span> Following suspected allergic reactions, subsequent vaccination decisions depend on balancing the risk of genuine allergy with existing COVID-19 protection. However, allergist evaluation or tests for COVID-19 protection remain limited.<span>⁴</span> Studies have shown that true COVID-19 vaccine allergy patients are exceedingly rare, and most reactions are unlikely to be genuine.<span>⁵</span> However, PEG/vaccine skin tests were found to have high specificity but low sensitivity for COVID-19 vaccine allergy on meta-analysis.<span>⁶</span> Therefore, markers and adjunct tests are needed to aid screening and confirm diagnosis. We hypothesise that specific anti-PEG isotypes (IgE/IgG/IgM) may serve as predictors of PEG allergy and COVID-19 protection among individuals who received PEG-containing COVID-19 vaccines. We analysed clinical data and blood samples of patients evaluated for suspected vaccine-associated allergy following either BNT or SV vaccination. Patients gave informed consent and this study was approved by the Institutional Review Board of HKU/HA HKWC.</p><p>The Vaccine Allergy Safety pathway evaluated all patients with suspected COVID-19 vaccine allergy in Hong Kong, with ‘high-risk’ cases assigned for allergist assessment; ‘high-risk’ patients were defined as those with a history of immediate-type allergic reaction (onset &lt;1 h) with systemic symptoms to previous COVID-19 vaccination.<span>^{4, 7}</span> We recruited all ‘high-risk’ patients who received 1 dose of either BNT or SV, between March 2021 and November 2022. Blood samples for anti-PEG IgE, IgG and IgM as well as COVID-19 neutralising antibody titres were measured, with a median interval between vaccination and blood sample collection of 3.3 months (inter-quartile range: 2.5–4.2). Anti-PEG IgG and IgM were measured using commercial human anti-PEG IgG and IgM ELISA kits respectively (Alpha Diagnostic Intl. Inc.). Results were expressed as Antibody Activity Threshold Index, which values ≥ 1.0 were positive for antibody. For anti-PEG IgE measurement, the anti-PEG IgG ELISA kit was modified and performed according to the manufacturer's instructions. Human anti-PEG reference IgE monoclonal antibody obtained from Academia Sinica was used as the ELISA standard, while horseradish peroxidase-conjugated mouse anti-hum","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108666","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}