Imperial College London

ProfessorStephenDurham

Faculty of MedicineNational Heart & Lung Institute

Professor of Allergy and Respiratory
 
 
 
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Contact

 

+44 (0)20 7351 8024s.durham

 
 
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Location

 

Fulham RoadRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

741 results found

Shamji MH, Singh I, Layhadi JA, Ito C, Karamani A, Kouser L, Sharif H, Tang J, Handijiev S, Parkin R, Durham SR, Kostic A, Orengo JM, DeVeaux M, Kamal M, Stahl N, Yancopoulos GD, Wang CQ, Radin ARet al., 2021, Passive Prophylactic Administration with a Single Dose of Anti-Fel d 1 Monoclonal Antibodies REGN1908-1909 in Cat Allergen-induced Allergic Rhinitis A Randomized, Double-Blind, Placebo-controlled Clinical Trial, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 204, Pages: 23-33, ISSN: 1073-449X

Journal article

Shamji MH, Valenta R, Jardetzky T, Verhasselt V, Durham SR, Wurtzen PA, van Neerven RJJet al., 2021, The role of allergen-specific IgE, IgG and IgA in allergic disease, ALLERGY, ISSN: 0105-4538

Journal article

Pfaar O, Bergmann KC, Bonini S, Compalati E, Domis N, de Blay F, de Kam PJ, Devillier P, Durham SR, Ellis AK, Gherasim A, Haya L, Hohlfeld JM, Horak F, Iinuma T, Jacobs RL, Jacobi HH, Jutel M, Kaul S, Kelly S, Klimek L, Larché M, Lemell P, Mahler V, Nolte H, Okamoto Y, Patel P, Rabin RL, Rather C, Sager A, Salapatek A, Sigsgaard T, Togias A, Willers C, Yang J, Zieglmayer R, Zuberbier T, Zieglmayer Pet al., 2021, Technical standards in allergen exposure chambers worldwide - an EAACI Task Force Report., Allergy

Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase 3 registration trials. The need for further validation in comparison with field exposure is clearly mandated. On this basis the European Academy of Allergy and Clinical Immunology (EAACI) initiated a Task Force in 2015 charged to gain a better understanding of how AECs can generate knowledge about respiratory allergies and can contribute to the clinical development of treatments. Researchers working with AECs worldwide were asked to provide technical information in eight sections: (i) dimensions and structure of the AEC, (ii) AEC staff, (iii) air flow, air processing, and operating conditions, (iv) particle dispersal, (v) pollen/particle counting, (vi) safety and non-contamination measures, (vii) procedures for symptom assessments, (viii) tested allergens/substances and validation procedures. On this basis, a minimal set of technical requirements for AECs applied to the field of allergology is proposed.

Journal article

Turner P, Ruiz-Garcia M, Patel N, Abrantes G, Burrell S, Vazquez-Ortiz M, Skypala I, Durham S, Boyle Ret al., 2021, Delayed symptoms and orthostatic intolerance following peanut challenge, Clinical and Experimental Allergy, Vol: 51, Pages: 696-702, ISSN: 0954-7894

BackgroundClinical reactions to Oral Food Challenge (OFC) in peanut‐allergic individuals have been well‐characterised, but rates and phenotypes of symptom recurrence beyond the first hour after objective symptoms are less well‐characterised.ObjectiveTo evaluate the rate of new‐onset symptoms occurring at least 1 h after stopping OFC in peanut‐allergic children and adults undergoing peanut‐OFC.MethodsWe prospectively collected data relating to adverse events following positive reactions at double‐blind, placebo‐controlled food challenges (DBPCFC) to peanut in children and adults evaluated for eligibility to participate in two clinical trials (NCT02149719, NCT02665793). The trials included people aged 8 to 45 with primary, IgE‐mediated peanut allergy at DBPCFC. The challenge protocol included consumption of a light meal 1 h after reaction.ResultsA total of 121 participants (64 children, 57 adults) had immediate, objective symptoms at DBPCFC, 25 (17 children, 8 adults) with anaphylaxis. Thirty‐three (27%) had progression or recurrence of symptoms ≥ 1 h after objective clinical reaction, of whom 8 developed anaphylaxis. In 23 cases, the onset of new symptoms was associated with consumption of a light meal. In eight cases, symptoms were limited to a symptomatic postural fall in blood pressure noted in preparation for discharge, without any other new features of an allergic reaction.Conclusions & Clinical RelevanceProgressive or new‐onset symptoms ≥1 h following initial allergic reaction at OFC are common and can include orthostatic hypotension. Recurrent symptoms may be temporally associated with food consumption.

Journal article

Shamji MH, Layhadi JA, Sharif H, Penagos M, Durham SRet al., 2021, Immunological Responses and Biomarkers for Allergen-Specific Immunotherapy Against Inhaled Allergens, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 9, Pages: 1769-1778, ISSN: 2213-2198

Journal article

Eifan A, Scadding G, Durham S, Fedina Oet al., 2021, Comparison of nasal allergen challenges with dissolved Timothy Grass pollen tablets and aqueous extract, Allergy, Vol: 76, Pages: 1543-1545, ISSN: 0105-4538

Journal article

Han JK, Bachert C, Fokkens W, Desrosiers M, Wagenmann M, Lee SE, Smith SG, Martin N, Mayer B, Yancey SW, Sousa AR, Chan R, Hopkins C, SYNAPSE study investigatorset al., 2021, Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial., Lancet Respir Med

BACKGROUND: Chronic rhinosinusitis with nasal polyps affects approximately 2-4% of the general population, and long-term use of systemic corticosteroids is associated with adverse effects. The aim of this study was to assess the efficacy and safety of mepolizumab in adults with recurrent, refractory severe bilateral chronic rhinosinusitis with nasal polyps. METHODS: SYNAPSE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done at 93 centres, mainly hospitals, in 11 countries. Eligible patients were aged 18 years or older with recurrent, refractory, severe, bilateral nasal polyp symptoms (nasal obstruction symptom visual analogue scale [VAS] score of >5), were eligible for repeat nasal surgery (overall symptoms VAS score >7 and endoscopic nasal polyps score of ≥5, with a minimum score of 2 in each nasal cavity) despite standard of care treatment, and had to have at least one nasal surgery in the past 10 years. Patients were randomly assigned (1:1), using permuted block design, to receive either 100 mg mepolizumab subcutaneously or placebo once every 4 weeks, in addition to standard of care (mometasone furoate intranasal spray for at least 8 weeks before screening and during the study, saline nasal irrigations, systemic corticosteroids or antibiotics, or both), as required, for 52 weeks. Site staff, the central study team, and patients were masked to study treatment and absolute blood eosinophil counts. The coprimary endpoints were change from baseline in total endoscopic nasal polyp score at week 52 and in mean nasal obstruction VAS score during weeks 49-52, assessed in the intention-to-treat population (ITT). This study is registered with ClinicalTrials.gov, NCT03085797. FINDINGS: From May 25, 2017, to Dec 12, 2018, 854 patients were screened for eligibility. 414 patients were randomly assigned with 407 included in the ITT population; 206 received mepolizumab and 201 received placebo. Total endoscopic nasal polyp score signi

Journal article

Shamji MH, Larson D, Eifan A, Scadding GW, Qin T, Lawson K, Sever ML, Macfarlane E, Layhadi JA, Würtzen PA, Parkin RV, Sanda S, Harris KM, Nepom GT, Togias A, Durham SRet al., 2021, Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy., J Allergy Clin Immunol

INTRODUCTION: There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). OBJECTIVE: We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial. METHODS: Nasal fluid and serum were obtained yearly (per-protocol population, n = 84). TGP-specific IgA1, IgA2, IgG4, IgG, and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively. RESULTS: At years 2 and 3, TGP-IgA1/2 levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA1, 2.0- and 1.8-fold for IgA2, respectively; all P < .01). TGP-IgA1 level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P < .001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG4 level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P < .01). Serum IgG4 levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9-fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P < .05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P = .04) and placebo (3.1-fold; P = .02). IgA to TGP and IgE and IgG4 to TGP components stratified participants according to treatment group and clinical response. CONCLUSIONS: The observed induction of IgA1/2 in SLIT and IgG4 in SCIT suggest key differenc

Journal article

Pfaar O, Agache I, Bergmann K-C, Bindslev-Jensen C, Bousquet J, Creticos PS, Devillier P, Durham SR, Hellings P, Kaul S, Kleine-Tebbe J, Klimek L, Jacobsen L, Jutel M, Muraro A, Papadopoulos NG, Rief W, Scadding GK, Schedlowski M, Shamji MH, Sturm G, van Ree R, Vidal C, Vieths S, Wedi B, Gerth van Wijk R, Frew AJet al., 2021, Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper, ALLERGY, Vol: 76, Pages: 629-647, ISSN: 0105-4538

Journal article

Bousquet J, Anto JM, Czarlewski W, Haahtela T, Fonseca SC, Iaccarino G, Blain H, Vidal A, Sheikh A, Akdis CA, Zuberbier T, ARIA groupet al., 2021, Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19, Allergy, Vol: 76, Pages: 735-750, ISSN: 0105-4538

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT1 R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.

Journal article

Sahiner UM, Layhadi JA, Golebski K, István Komlósi Z, Peng Y, Sekerel B, Durham SR, Brough H, Morita H, Akdis M, Turner P, Nadeau K, Spits H, Akdis C, Shamji MHet al., 2021, Innate Lymphoid Cells: The Missing Part Of A Puzzle In Food Allergy., Allergy

Food allergy is an increasingly prevalent disease which is mainly driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5 and IL-13 with infiltration of mast cells, eosinophils and basophils. Recent studies raised a possible role for the involvement of innate lymphoid cells (ILCs) in driving food allergy. They represent a group of lymphocytes that lack specific, recombined antigen receptors. ILCs contribute to immune responses not only by releasing cytokines and other mediators but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces ofthe airways, gut and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidence on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs towards inflammatory processes and regulatory mechanisms.

Journal article

Golebski K, Layhadi JA, Sahiner U, Steveling-Klein EH, Lenormand MM, Li RCY, Bal SM, Heesters BA, Vilà-Nadal G, Hunewald O, Montamat G, He FQ, Ollert M, Fedina O, Lao-Araya M, Vijverberg SJH, Maitland-van der Zee A-H, van Drunen CM, Fokkens WJ, Durham SR, Spits H, Shamji MHet al., 2021, Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response., Immunity, Vol: 54, Pages: 291-307.e7, ISSN: 1074-7613

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.

Journal article

Sharif H, Acharya S, Dhondalay GKR, Varricchi G, Krasner-Macleod S, Laisuan W, Switzer A, Lenormand M, Kashe E, Parkin RV, Yi Y, Koc M, Fedina O, Vilà-Nadal G, Marone G, Eifan A, Scadding GW, Fear DJ, Nadeau KC, Durham SR, Shamji MHet al., 2021, Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 663-676, ISSN: 0091-6749

BACKGROUND: Allergen-specific immunotherapy (AIT) is a disease-modifying treatment that induces long-term T cell tolerance. OBJECTIVE: To evaluate the role of circulating CXCR5+PD-1+T follicular helper (cTFH) and T follicular regulatory (TFR) cells following grass pollen subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and the accompanying changes in their chromatin landscape. METHODS: Phenotype and function of cTFH cells were initially evaluated in grass pollen-allergics (GPA, n= 28) and non-atopic controls (NAC, n=13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cTFH and TFR cells were further enumerated in NAC (n=12), GPA (n=14), SCIT (n=10) and SLIT (n=8)-treated groups. Chromatin accessibility in cTFH and TFR cells was assessed by ATAC-seq to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT and SLIT. RESULTS: cTFH cells were shown to be distinct from TH2 and TH2A cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cTFH cell proliferation in GPA but not in NAC (P<.05). cTFH cells were higher in GPA compared to NAC and were lower in SCIT and SLIT (P<.01). Time-dependent induction of IL-4, IL-21 and IL-6 were observed in nasal mucosa following intranasal allergen challenge in GPA but not in SCIT and SLIT groups. TFR and IL-10+ cTFH cells were induced in SCIT and SLIT (all, P<.01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups. CONCLUSION: For the first time, we showed dysregulation of cTFH cells in GPA compared to NAC, SCIT and SLIT and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following AIT in cTFH and TFR cells.

Journal article

Ruiz-Garcia M, Bartra J, Alvarez O, Lakhani A, Patel S, Tang A, Sim M, Shamji MH, Skypala I, Mills ENC, Lyon AR, Hayward C, Durham SR, Turner PJ, Boyle RJet al., 2021, Cardiovascular changes during peanut-induced allergic reactions in human subjects, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 633-642, ISSN: 0091-6749

Background: Food allergy is the commonest cause of anaphylaxis. Changes in posture during acute reactions can trigger fatal outcomes, but the impact of allergic reactions on the cardiovascular system in non-fatal reactions remains poorly understood. Objective: To systematically evaluate changes in cardiovascular function during acute allergic reactions to peanut. Methods: Participants underwent double-blind placebo-controlled food challenge topeanut as part of a clinical trial. Changes in hemodynamic parameters (heart rate, stroke volume, blood pressure, peripheral blood flow) and electrocardiogram during food challenges were assessed using continuous monitoring. ClinicalTrials.gov Identifier: NCT02665793 Results: 57 adults (median age 24 (IQR 20-29) years, 53% female) participated; 22 (39%) had anaphylaxis. Acute reactions were associated with significant changes in stroke volume (mean decrease 4.2%, 95%CI 0.8 to 7.6; p=0.03), heart rate (mean increase 11.6%, 95%CI 8.4 to 14.8; p<0.0001) and peripheral blood flow (mean increase 19.7%, 95%CI 10.8 to 28.6; p<0.0001), irrespective of reaction severity. These changes were reproduced at subsequent repeat peanut challenge in 26 participants, and could be reversed with administration of intravenous fluids which resulted in faster resolution of abdominal symptoms. Conclusions: In this first detailed human study of cardiovascular changes during food-allergic reactions, we found evidence for significant fluid redistribution, independent of reaction severity. This provides a sound rationale for optimizing venous return during significant allergic reactions to food. Finally, these data provide a new paradigm for understanding severity in anaphylaxis, where poor outcomes occur due to a failure in compensatory mechanisms.Ruiz-Garcia et al 5 Clinical Implication: Significant changes in cardiovascular function, including decreased stroke volume, occur during peanut-induced allergic reactions in adults irrespective of severit

Journal article

Durham SR, Till SJ, Holgate ST, 2021, OBITUARY Anthony Barrington Kay 1939-2020, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 206-208, ISSN: 0954-7894

Journal article

Orban N, Jacobson MR, Nouri-Aria KT, Durham SR, Eifan AOet al., 2021, Repetitive nasal allergen challenge in allergic rhinitis: priming and Th2-type inflammation but no evidence of remodelling., Clinical and Experimental Allergy, Vol: 51, Pages: 329-338, ISSN: 0954-7894

BACKGROUND: Local tissue eosinophilia and Th2-cytokines are characteristic features of seasonal allergic rhinitis. Airway-remodelling is a feature of asthma whereas evidence for remodelling in allergic rhinitis (AR) is conflicting. OBJECTIVE: By use of a novel human repetitive nasal allergen challenge (RAC) model, we evaluated the relationship between allergic inflammation and features of remodelling in AR. METHODS: Twelve patients with moderate-severe AR underwent 5-alternate day challenges with diluent which after 4-weeks were followed by 5-alternate day challenges with grass pollen extract. Nasal symptoms, Th1/Th2 cytokines in nasal secretion and serum were evaluated. Nasal biopsies were taken 24 hours after the 1st and 5th challenges with diluent and with allergen. Sixteen healthy controls underwent a single challenge with diluent and with allergen. Using immunohistochemistry, epithelial and sub-mucosal inflammatory cells, and remodelling markers were evaluated by computed image analysis. RESULTS: There was an increase in early and late-phase symptoms after every allergen challenge compared to diluent (both p<0.05) with evidence of both clinical and immunological priming. Nasal tissue eosinophils and IL-5 in nasal secretion increased significantly after RAC compared to corresponding diluent challenges (p<0.01, p=0.01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r=0.79, p=0.007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r=0.69, p=0.06) in allergic rhinitis. No differences were observed after RAC with regards to epithelial integrity, reticular basement membrane thickness, glandular area, expression of markers of activation of airway-remodelling including α-SMA, HSP-47, extracellular matrix (MMP7, 9 and TIMP-1), angiogenesis and lymphangiogenesis for AR compared to healthy controls. CONCLUSION: Novel repetitive nasal allergen challenge in

Journal article

Turner P, Boyle R, Durham S, 2021, Limited effect of intramuscular epinephrine on cardiovascular parameters during peanut-induced anaphylaxis: an observational cohort study, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 527-530.e1, ISSN: 2213-2198

Journal article

Bousquet J, Anto JM, Bachert C, Haahtela T, Zuberbier T, Czarlewski W, Bedbrook A, Bosnic-Anticevich S, Walter Canonica G, Cardona V, ElisioCosta, Cruz AA, Erhola M, Fokkens WJ, Fonseca JA, Illario M, CarlosIvancevich J, Jutel M, Klimek L, PiotrKuna, Kvedariene V, Le L, Larenas-Linnemann D, Laune D, Lourenço OM, Melén E, Mullol J, Niedoszytko M, Odemyr M, Okamoto Y, Papadopoulos NG, Patella V, Pfaar O, Pham-Thi N, Rolland C, Samolinski B, Sheikh A, Sofiev M, SuppliUlrik C, Todo-Bom A, Tomazic PV, Toppila-Salmi S, Tsiligianni I, Valiulis A, Valovirta E, Ventura M-T, Walker S, Williams S, Yorgancioglu A, Agache I, Akdis CA, Almeida R, Ansotegui IJ, Annesi-Maesano I, Arnavielhe S, Basagaña X, Bateman E, Bédard A, Bedolla-Barajas M, Becker S, Bennoor KS, Benveniste S, Bergmann KC, Bewick M, Bialek S, Billo N, Bindslev-Jensen C, Bjermer L, Blain H, Bonini M, Bonniaud P, Bosse I, Bouchard J, Boulet LP, Bourret R, Boussery K, Braido F, Briedis V, Briggs A, Brightling CE, JanBrozek, Brusselle G, Brussino L, Buhl R, Buonaiuto R, Calderon MA, Camargos P, Camuzat T, Caraballo L, Carriazo AM, Carr W, Cartier C, Casale T, Cecchi L, Cepeda Sarabia AM, Chavannes N, Chkhartishvili E, Chu DK, Cingi C, Correia de Sousa J, Costa DJ, Courbis AL, Custovic A, Cvetkosvki B, D'Amato G, da Silva J, Dantas C, Dokic D, Dauvilliers Y, De Feo G, De Vries G, Devillier P, Di Capua S, Dray G, Dubakiene R, Durham SR, Dykewicz M, Ebisawa M, Gaga M, El-Gamal Y, Heffler E, Emuzyte R, Farrell J, Fauquert J-L, Fiocchi A, Fink-Wagner A, Fontaine J-F, Fuentes Perez JM, Gemicioğlu B, Gamkrelidze A, Garcia-Aymerich J, Gevaert P, Gomez M, González Diaz S, Gotua M, Guldemond NA, Guzmán M-A, Hajjam J, Huerta Villalobos YR, Humbert M, Iaccarino G, Ierodiakonou D, TomohisaIinuma, Jassem E, Joos G, Jung K-S, Kaidashev I, Kalayci O, Kardas P, Keil T, Khaitov M, Khaltaev N, Kleine-Tebbe J, Kouznetsov R, Kowalski ML, Kritikos V, Kull I, La Grutta S, Leonardini L, Ljungberg H, Lieberman P, Lipworth B, Lodrup Carlet al., 2021, ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice., Allergy, Vol: 76, Pages: 168-190, ISSN: 0105-4538

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis.It strengthens the ARIA change management strategy in the prevention and managementof airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

Journal article

Bousquet J, Cristol J-P, Czarlewski W, Anto JM, Martineau A, Haahtela T, Fonseca SC, Iaccarino G, Blain H, Fiocchi A, Canonica GW, Fonseca JA, Vidal A, Choi H-J, Kim HJ, Le Moing V, Reynes J, Sheikh A, Akdis CA, Zuberbier T, Abdul Latiff AH, Abdullah B, Aberer W, Abusada N, Adcock I, Afani A, Agache I, Aggelidis X, Agustin J, Akdis CA, Akdis M, Al-Ahmad M, Al-Zahab Bassam A, Alburdan H, Aldrey-Palacios O, Alvarez Cuesta E, Alwan Salman H, Alzaabi A, Amade S, Ambrocio G, Angles R, Annesi-Maesano I, Ansotegui IJ, Anto JM, Ara Bardajo P, Arasi S, Arrais M, Arshad H, Artesani M-C, Asayag E, Avolio F, Azhari K, Bachert C, Bagnasco D, Baiardini I, Bajrovic N, Bakakos P, Bakeyala Mongono S, Balotro-Torres C, Barba S, Barbara C, Barbosa E, Barreto B, Bartra J, Basagana X, Bateman ED, Battur L, Bedbrook A, Bedolla Barajas M, Beghe B, Bekere A, Bel E, Ben Kheder A, Benson M, Berghea E-C, Bergmann K-C, Bernardini R, Bernstein D, Bewick M, Bialek S, Bialoszewski A, Bieber T, Billo NE, Bilo M-B, Bindslev-Jensen C, Bjermer L, Blain H, Bobolea I, Bochenska Marciniak M, Bond C, Boner A, Bonini M, Bonini S, Bosnic-Anticevich S, Bosse I, Botskariova S, Bouchard J, Boulet L-P, Bourret R, Bousquet P, Braido F, Briggs A, Brightling CE, Brozek J, Brussino L, Buhl R, Bumbacea R, Buquicchio R, Burguete Cabanas M-T, Bush A, Busse WW, Buters J, Caballero-Fonseca F, Calderon MA, Calvo M, Camargos P, Camuzat T, Canevari FR, Cano A, Canonica GW, Capriles-Hulett A, Caraballo L, Cardona V, Carlsen K-H, Carmona Pirez J, Caro J, Carr W, Carreiro-Martins P, Carreon-Asuncion F, Carriazo A-M, Carrion y Ribas C, Casale T, Castor M-A, Castro E, Caviglia AG, Cecchi L, Cepeda Sarabia A, Chalubinski M, Chandrasekharan R, Chang Y-S, Chato-Andeza V, Chatzi L, Chatzidaki C, Chavannes NH, Chaves Loureiro C, Chavez Garcia A-A, Chelninska M, Chen Y, Cheng L, Chinthrajah S, Chivato T, Chkhartishvili E, Christoff G, Chrystyn H, Chu DK, Chua A, Chuchalin A, Chung KF, Ciceran A, Cingi C, Ciprandi G, Cirule I, Coelhoet al., 2020, Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies, Clinical and Translational Allergy, Vol: 10, Pages: 1-18, ISSN: 2045-7022

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.

Journal article

Bousquet J, Anto JM, Iaccarino G, Czarlewski W, Haahtela T, Anto A, Akdis CA, Blain H, Canonica GW, Cardona V, Cruz AA, Illario M, Ivancevich JC, Jutel M, Klimek L, Kuna P, Laune D, Larenas-Linnemann D, Mullol J, Papadopoulos NG, Pfaar O, Samolinski B, Valiulis A, Yorgancioglu A, Zuberbier Tet al., 2020, Is diet partly responsible for differences in COVID-19 death rates between and within countries?, Clinical and Translational Allergy, Vol: 10, ISSN: 2045-7022

Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.

Journal article

Kirtland ME, Tsitoura DC, Durham SR, Shamji MHet al., 2020, Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy, FRONTIERS IN IMMUNOLOGY, Vol: 11, ISSN: 1664-3224

Journal article

Bousquet J, Anto JM, Iaccarino G, Czarlewski W, Haahtela T, Anto A, Akdis CA, Blain H, Canonica GW, Cardona V, Cruz AA, Illario M, Ivancevich JC, Jutel M, Klimek L, Kuna P, Laune D, Larenas-Linnemann D, Mullol J, Papadopoulos NG, Pfaar O, Samolinski B, Valiulis A, Yorgancioglu A, Zuberbier Tet al., 2020, Is diet partly responsible for differences in COVID-19 death rates between and within countries? (vol 10, 16, 2020), Clinical and Translational Allergy, Vol: 10, Pages: 1-3, ISSN: 2045-7022

Journal article

Ruiz-Garcia M, Skypala I, Durham S, Boyle RJ, Turner PJet al., 2020, Intravenous fluids are effective for managing cardiovascular changes and gastrointestinal symptoms during food-related anaphylaxis, European-Academy-of-Allergology-and-Clinical-Immunology Digital Congress (EAACI), Publisher: WILEY, Pages: 239-240, ISSN: 0105-4538

Conference paper

Radauer C, Parkin R, Tang J, Schneider J, Durham SR, Breiteneder H, Shamji MHet al., 2020, YoaJ, an expansin-like protein from Bacillus subtilis, is a non-allergenic structural homologue of the major grass pollen allergen Phl p 1, European-Academy-of-Allergology-and-Clinical-Immunology Digital Congress (EAACI), Publisher: WILEY, Pages: 159-160, ISSN: 0105-4538

Conference paper

Jackson DJ, Busse WW, Bacharier LB, Kattan M, O'Connor GT, Wood RA, Visness CM, Durham SR, Larson D, Esnault S, Ober C, Gergen PJ, Becker P, Togias A, Gern JE, Altman MCet al., 2020, Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 146, Pages: 203-206, ISSN: 0091-6749

Journal article

Hoof I, Schulten V, Layhadi JA, Stranzl T, Christensen LH, de la Mata SH, Seumois G, Vijayanand P, Lundegaard C, Niss K, Lund A, Ahrenfeldt J, Holm J, Steveling E, Sharif H, Durham SR, Peters B, Shamji MH, Andersen PSet al., 2020, Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses, Journal of Allergy and Clinical Immunology, Vol: 146, Pages: 180-191, ISSN: 0091-6749

BACKGROUND: Immunoglobulin E (IgE) are least abundant, tightly regulated and IgE producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood. OBJECTIVE: To investigate the cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT). METHODS: In a randomized double-blind, placebo-controlled, time-course SLIT study, peripheral blood mononuclear cells (PBMCs) and nasal biopsies were collected from forty adults with seasonal allergic rhinitis at baseline, 4, 8, 16, 28 and 52 weeks. RNA was extracted from PBMCs, sorted B cells and nasal biopsies for VH repertoire sequencing. Moreover, monoclonal antibodies were derived from single B cell transcriptomes. RESULTS: Combining VH repertoire sequencing and single cell transcriptomics yielded direct evidence of a parallel boost of two clonally and functionally related B cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells (termed IgGE). Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relative stable as per heavy chain isotype, somatic hypermutations and clonal composition. Single IgGE + memory B cell and IgE+ pre-plasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and were able to elicit basophil activation at very low allergen concentrations. CONCLUSION: For the first time, we have shown that upon mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These rapidly switch isotype and expand into short-lived IgE+ plasmablasts and serve as a potential target for therapeutic intervention.

Journal article

Bédard A, Antó JM, Fonseca JA, Arnavielhe S, Bachert C, Bedbrook A, Bindslev-Jensen C, Bosnic-Anticevich S, Cardona V, Cruz AA, Fokkens WJ, Garcia-Aymerich J, Hellings PW, Ivancevich JC, Klimek L, Kuna P, Kvedariene V, Larenas-Linnemann D, Melén E, Monti R, Mösges R, Mullol J, Papadopoulos NG, Pham-Thi N, Samolinski B, Tomazic PV, Toppila-Salmi S, Ventura MT, Yorgancioglu A, Bousquet J, Pfaar O, Basagaña X, MASK study groupet al., 2020, Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air® App, Allergy, Vol: 75, Pages: 1672-1688, ISSN: 0105-4538

BACKGROUND: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. METHODS: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. RESULTS: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. CONCLUSIONS: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.

Journal article

Larson D, Patel P, Salapatek AM, Couroux P, Whitehouse D, Pina A, Johnson JL, Sever ML, Sanda S, Poyser J, Allio T, Scadding GW, Qin T, Shamji MH, Kwok WW, James EA, French D, Lelic A, Larche M, Altman MC, Togias A, Durham SRet al., 2020, Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 145, Pages: 1585-1597, ISSN: 0091-6749

Journal article

Alvaro-Lozano M, Akdis CA, Akdis M, Alviani C, Angier E, Arasi S, Arzt-Gradwohl L, Barber D, Bazire R, Cavkaytar O, Comberiati P, Dramburg S, Durham SR, Eifan AO, Forchert L, Halken S, Kirtland M, Kucuksezer UC, Layhadi JA, Matricardi PM, Muraro A, Ozdemir C, Pajno GB, Pfaar O, Potapova E, Riggioni C, Roberts G, Rodriguez del Rio P, Shamji MH, Sturm GJ, Vazquez-Ortiz Met al., 2020, Allergen Immunotherapy in Children User’s Guide, Pediatric Allergy and Immunology, Vol: 31, Pages: 1-101, ISSN: 0905-6157

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.

Journal article

Pfaar O, Karatzas K, Bastl K, Berger U, Buters J, Darsow U, Demoly P, Durham SR, Galan C, Gehrig R, Gerth van Wijk R, Jacobsen L, Katsifarakis N, Klimek L, Saarto A, Sofiev M, Thibaudon M, Werchan B, Bergmann K-Cet al., 2020, Pollen season is reflected on symptom load for grass and birch pollen-induced allergic rhinitis in different geographic areas-An EAACI Task Force Report, ALLERGY, Vol: 75, Pages: 1099-1106, ISSN: 0105-4538

Journal article

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